# An overview of the phytochemistry of medicinal bark (trunk, stem or root) from the most popular southern African species

Nicholas John Sadgrove, Anne-Claire Mitaine-Offer, Khumalo Gugulethu, Ben-Erik van Wyk

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## To cite this version:

Nicholas John Sadgrove, Anne-Claire Mitaine-Offer, Khumalo Gugulethu, Ben-Erik van Wyk. An overview of the phytochemistry of medicinal bark (trunk, stem or root) from the most popular southern African species. Phytochemistry Reviews, 2025, pp.1-21. 10.1007/s11101-024-10059-5 hal-04971668

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Submitted on 28 Feb 2025

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# An overview of the phytochemistry of medicinal bark (trunk, stem or root) from the most popular southern African species

Nicholas John Sadgrove ID • Anne-Claire Mitaine-Offer • Gugulethu Khumalo • Ben-Erik Van Wyk

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PSE
Learning to be nature

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Received: 17 November 2023 / Accepted: 17 December 2024
© The Author(s) 2025

**Abstract** The ten countries that make up southern Africa are collectively a hot-spot of medicinal plant knowledge, with a unique preference for the utilization of bark over leaves from possibly hundreds of species. The most popular 86 medicinal bark species were identified in an earlier survey of various muthi markets around Johannesburg, and are listed in the current review, out of which chemical data was found for 63 and tabulated. The chemistry of medicinal bark species is, however, incomplete, since many scholars focused their research on metabolites of interest to their research groups, such as essential oils, lipophilic compounds, alkaloids or saponins, to the exclusion of other specialized metabolites present in the respective biota. From the current phytochemical analysis, the medicinal potential of bark relative to leaves is not obvious, as it is dependent on factors such as quantity of specialized metabolites (potency), their identities

and anecdotal accounts from traditional healers. Nevertheless, the preference for bark may be due to empirical outcomes in therapy. Southern African medicinal bark species demonstrate an extremely diverse pool of unique/new or relatively unheard of natural products, such as calondendrolide from *C. capense*, combretastatin from *C. caffrum*, capensin from *C. capense*, crotohalimaneic acid from *C. sylvaticus*, ekebergins from *E. capensis*, entandrophragmin from *E. caudatum*, lysisteisoflavone from *E. lysistemon*, kigelinone from *K. africana*, holstinones from *O. holstii*, piptadeniaoside from *P. africanum*, rauvolfianoids from *R. caffra*, tetrapterosides from *T. tetraptera*, voacangine from *V. thouarsii*, warburganal from *W. salutaris* and mucronine from *Z. mucronata*. The review concludes by briefly commenting on pharmacokinetic aspects associated with ingestion or topical application of bark metabolites.

**Keywords** Bark · Medicinal bark · Phytochemistry · Southern Africa

## Introduction

Bark is defined as all external tissues that surround the vascular cambium, occupying a much smaller volume as compared to the wood. This is mostly because wood tissue is preserved for structural maintenance of the organism, while the outermost bark cells are

<footnote>N. J. Sadgrove (✉) · G. Khumalo · B.-E. Van Wyk
Department of Botany and Plant Biotechnology,
University of Johannesburg (Auckland Park Campus),
Auckland Park, P.O. Box 524, Johannesburg 2006, South
Africa
e-mail: nicholas.sadgrove@gmail.com</footnote>

<footnote>B.-E. Van Wyk
e-mail: bevanwyk@uj.ac.za</footnote>

<footnote>A.-C. Mitaine-Offer
Centre Des Sciences du Goût et de l'Alimentation, CNRS,
INRAE, Institut Agro, Université de Bourgogne,
21000 Dijon, France
e-mail: Anne-Claire.Offer@u-bourgogne.fr</footnote>
continuously discarded. The outer bark is non-living tissue, and the living inner bark is external to vital cells, making it an adequate site for the accumulation of specialized metabolites to levels above those tolerated by internal tissues (Hon and Shiraishi 2000). Hence, bark is a suitable site for the elimination of metabolites from the organism, conveniently creating a barrier to phytopathogens and herbivores, but in traditional medicinal practice it serves as a reservoir of bioactive products.

In traditional medicinal practice, selection of tree, stem or root bark over leaves is common. In such cases bark was determined to be superior to other organs, via iterative trial and error selection. Medicinal bark species are used in all cultures across the world, for example, the Egyptians and Sumerians utilized the bark of willow (*Salix* spp.) and poplar (*Populus* spp.) trees, containing salicin and salicylic acid respectively (Norn et al. 2009), and the South Americans utilized bark from *Cinchona*, containing quinine (Permin et al. 2016). There are also ethnobotanical records of medicinal bark use from Australia (Lassak and McCarthy 2011), China (Kopp et al. 2003), Thailand (Phumthum et al. 2018) and India (Biswas and Mukherjee 2003), just to name a few.

Southern Africa represents a hot-spot of medicinal bark selection and chemical diversity (Khumalo 2018; Khumalo et al. 2021). Research on the chemistry of the various bark species used in traditional practice demonstrates that they contain a diverse array of unique, novel, or new specialized metabolites, ranging from polar to non-polar ingredients, belonging to multiple classees of compound, alkaloids, terpenes, flavonoids, phenylpropanoids, phenols and many more.

In comparing the accumulation of specialized metabolites in bark against leaves, the taxonomic level is most important in determining differences between the levels, yields or concentration of specialized metabolites. There are several examples from Lamiaceae (Sadgrove et al. 2020b) or Scrophulariaceae (Sadgrove et al. 2011, 2021; Sadgrove and Jones 2014a) where leaves (not bark) accumulate volatile organic compounds at yields ranging from 1 to 8% of the fresh weight. In another example, it is the fruit of *Maclura pomifera* (Rafinesque) Schneider that accumulate the highest yield of the prenylated flavonoids, osajin and pomiferin at nearly 1% (Tsao et al. 2003).

However, there are many other examples of metabolite accumulation in bark or wood pulp that greatly exceeds the density in leaves. For example, the accumulation of tryptamines in the bark of *Mimosa tenuiflora* (Willd.) Poir. (syn. *Mimosa hostilis* Benth.) far exceeds the content in the leaves (Pilar Nicasio et al. 2005). In another example, the wood pulp of *Artocarpus heterophyllus* Lam., yielded 1% of the prenylated isoflavone artocarpin, significantly higher than the concentration in leaves (Morrison et al. 2021).

The yield of specialized metabolites is not always why there is a preference for bark in *Materia medica* selection of specific taxa. In most cases, chemical differences between leaves and bark are the reason for the differences of therapeutic attributes, and this is evident in a significant number of phytochemical studies. In the published literature, the vast majority of plant-organ comparisons are made between essential oils from bark and leaves, such as in studies of *Pinus* (Bagci et al. 2011), *Cinnamomum* (Singh et al. 2007), or *Boswellia* (Geetha and Chakravarthula 2018). But mass spectral and NMR studies are also available that compare the various plant organs and identify chemical dissimilarities among the non-volatile metabolites, such as in fruits of *Aesculus* (Green et al. 2021), bark and leaves of *Flindersia* (Picker et al. 1976), and the same for *Ficus* (Ramadan et al. 2009).

While such comparisons are not available for the majority of medicinal bark species of southern African origin, chemical data from bark is regarded as independent of the chemistry of leaves for reasons mentioned above. Therefore, the identities of metabolites in the bark of medicinal-bark species is considered more relevant to the discussion of therapeutic outcomes than the comparison between plant organs. In the current narrative, the specialized metabolites of popular southern African bark medicines are summarized and discussed in the context of human health, using information from published sources.

## Materials and methods

The most popular medicinal bark species were identified from previous work (Khumalo 2018; Khumalo et al. 2021) and via a search of the published literature. A popular species is defined as one that is traded in commerce. While there are many more medicinal bark species, they are not traded in the muthi markets, so
they are not regarded as popular. To obtain chemical data of medicinal bark species, google scholar was used and the search phrases were “genus,” “species,” “bark,” and “chemistry.” The accepted names, genus and species, were determined by searching plants of the world online, Kew, and synonyms were also used in the literature search. Exclusion criteria included studies only of leaves or wood pulp, or studies that used qualitative phytochemical assays, or only thin layer chromatography, and not more up to date methods. Inclusion criteria were for studies of bark, either stem, tree or root bark.

## Results

By focusing on the most popular medicinal bark species in southern Africa, a list of 86 medicinal bark species were compiled (Table 1). The vast majority of these were identified by Khumalo (2018) and Khumalo et al. (2021), and details related to usage modalities and targeted ailments are provided in their studies. English vernacular names are provided, as are the Zulu names, which are the names used in muthi market trade. Out of the 86 listed in Table 1, chemical data of specifically the bark of either root, stem or tree, was found for 63 species (Table 2).

The chemical data listed in Table 2 (bark of either root, stem or tree) is limited to the metabolites of interest to the authors of the chemical studies. This leaves open many avenues for further research. Authors that focused on alkaloids neglected to study terpenes or flavonoids, and so on. Some studies also focused on essential oils only, or characterized the chemistry using LC-MS and spectral identification, so the data in Table 2 should not be considered complete. Nevertheless, the chemical data is comprehensive, since much of it was determined through chromatographic isolation and assignment by nuclear magnetic resonance spectroscopy.

A chemical overview of medicinal bark species in southern Africa conveys that there is a high chemical diversity across species, with no patterns or salient features that identify them as bark per se. Several of the species contain previously undescribed compounds that were named according to their etymological connection to the genus or species. Examples include the furanosesquiterpene lactone calondrolide (1) from *C. capense* (Kiprop et al. 2005), the

stilbene combretastatin (2) from *C. caffrum* (Pettit et al. 1987), the coumarin capensin (3) from *C. capense* (Okwemba et al. 2018), the halimane diterpene crotohalimaneic acid (4) from *C. sylvaticus* (Maroyi 2017), the ekebergin limonoid (5) from *E. capensis* (Irungu et al. 2014), the limonoid entan-drophragmin (6) from *E. caudatum* (Ansell and Taylor 1988), the prenylated isoflavone lysisteisoflavone (7) from *E. lysistemon* (Sadgrove et al. 2020a), the furanonapthaquinone kigelinone (8) from *K. africana* (Gupta and Jain 2019), the holstinone sterol (9) from *O. holstii* (Kalenga et al. 2021), the pentacyclic triterpene saponin piptadeniaoside (10) from *P. africanum* (Noté et al. 2013), the indole rauvolfianoid alkaloid (11) from *R. caffra* (Bitombo et al. 2022), the pentacyclic triterpene monoglucosides called tetrapterosides (12) from *T. tetraptera* (Noté et al. 2009), the methoxylated indole alkaloid methyl ester voacangine (13) from *V. thouarsii* (Goldblatt et al. 1970), the sesquiterpene dialdehyde warburganal (14) from *W. salutaris* (Khumalo et al. 2019b) and the macrolide mucronine (15) from *Z. mucronata* (Auvin et al. 1996; Barboni et al. 1994). These examples capture the diversity of metabolite profiles across species (Figs. 1, 2).

While medicinal bark of southern Africa is chemically diverse, there are also several compounds that are somewhat ubiquitous across the plant kingdom, such as the sterols and triterpenes, including lupeol, the amyrin isomers, sitosterol, ursolic acid and oleanolic acid. These triterpenes are often at the core of more complex structures, such as saponins (with complex patterns of sugars bonded). Other relatively ubiquitous compounds belong to the flavonoids class, such as catechin, apigenin and quercetin, as well as phenols, such as ellagic acid, gallic acid or benzoic acid (including derivatives). Fatty acids are infrequently reported, but this may be due to the disinterest across the science community. Fatty acids are frequently ignored in spectroscopic studies due to their lack of novelty, but often include palmitic acid, linoleic acid, stearic acid or oleic acid.

## Discussion

While medicinal bark selection is of high cultural importance to the people of southern Africa, conservationists have been exploring the potential impact on
<table><caption>**Table 1** The 86 most popular medicinal bark species used in southern Africa, most of which are available in the Johannesburg muthi markets and prescribed by herbal practitioners</caption><thead><tr><th>Genus</th><th>Species</th><th>Authority (Family)</th><th>Zulu</th><th>English vernacular</th><th>Chemical data (yes/no)</th></tr></thead><tbody><tr><td>Albizia</td><td>Adianthifolia</td><td>(Schumach.) W.Wight (Fabaceae)</td><td>Umgadankawu</td><td>Flat-crown tree</td><td>Yes</td></tr><tr><td>Araucaria</td><td>Heterophylla</td><td>(Salisb.) Franco (Araucariaceae)</td><td>Abangqongqozi</td><td>Monkey puzzle</td><td>Yes</td></tr><tr><td>Balanites</td><td>Maughamii</td><td>Sprague (Zygophyllaceae)</td><td>Iphamba</td><td>Torchwood</td><td>Yes</td></tr><tr><td>Berchemia</td><td>Discolor</td><td>(Klotzsch) Hemsl. (Rhamnaceae)</td><td>Uvuka</td><td>Bird plum</td><td>Yes</td></tr><tr><td>Bersama</td><td>Lucens</td><td>(Hochst.) Szyszyl. (Melianthaceae)</td><td>Undiyaza</td><td>Glossy bersama</td><td>Yes</td></tr><tr><td>Bersama</td><td>Swinnyi</td><td>E. Phillips (Melianthaceae)</td><td>Undiyaza</td><td>Glossy white ash</td><td>Yes</td></tr><tr><td>Bersama</td><td>Tysoniana</td><td>Oliv. (Melianthaceae)</td><td>Undiyaza</td><td>Common white ash</td><td>No</td></tr><tr><td>Bobgunnia</td><td>Madagascariensis</td><td>(Desv.) J.H. Kirkbr. et Wiersema</td><td>No record found</td><td>Snake bean plant</td><td>Yes</td></tr><tr><td>Brackenridgea</td><td>Zanguebarica</td><td>Oliv. (Ochnaceae)</td><td>Mutavhatsindi</td><td>Yellow peeling plane</td><td>Yes</td></tr><tr><td>Bridelia</td><td>Micrantha</td><td>(Hochst.) Baill. (Phyllanthaceae)</td><td>Umhlahle/ umhlahla</td><td>Coastal goldenleaf</td><td>Yes</td></tr><tr><td>Calodendrum</td><td>Capense</td><td>(L.f.) Thunb. (Rutaceae)</td><td>Umemezi omhlophe</td><td>Cape chestnut</td><td>Yes</td></tr><tr><td>Carissa</td><td>Bispinosa</td><td>(L.) Desf. Ex Brenan (Apocynaceae)</td><td>Umvusankunzi</td><td>Num-num</td><td>No</td></tr><tr><td>Cassine</td><td>Papillosa</td><td>(Hochst.) Kuntze (Celastraceae)</td><td>No record found</td><td>No record found</td><td>Yes</td></tr><tr><td>Cassipourea</td><td>fFanaganii</td><td>(Schinz) Alston (Rhizophoraceae)</td><td>Umemezi obomvu</td><td>Cape onionwood</td><td>Yes</td></tr><tr><td>Cinnamomum</td><td>Camphora</td><td>(L.) J.Presl (Lauraceae)</td><td>Uloselina</td><td>Camphor tree</td><td>Yes</td></tr><tr><td>Combretum</td><td>Caffrum</td><td>(Eckl. & Zeyh.) Kuntze (Combretaceae)</td><td>Isidubu</td><td>Cape bushwillow</td><td>Yes</td></tr><tr><td>Commiphora</td><td>Africana</td><td>(A. Rich.) Engl. var. africana (Burseraceae)</td><td>Iminyela</td><td>Hairy corkwood</td><td>Yes</td></tr><tr><td>Croton</td><td>Gratissimus</td><td>Burch. (Euphorbiaceae)</td><td>Isikhumampuphu</td><td>Lavender croton</td><td>Yes</td></tr><tr><td>Croton</td><td>Sylvaticus</td><td>Hochst. (Euphorbiaceae)</td><td>Umahlabekufeni</td><td>Forest fever-berry</td><td>Yes</td></tr><tr><td>Cryptocarya</td><td>Latifolia</td><td>Sond. (Lauraceae)</td><td>Umkhondweni</td><td>Broad-leaved laurel</td><td>Yes</td></tr><tr><td>Cunonia</td><td>Capensis</td><td>L. (Cunoniaceae)</td><td>Umlulama</td><td>Butterspoon tree</td><td>No</td></tr><tr><td>Curtisia</td><td>Dentata</td><td>(Burm.f.) C.A.Sm. (Curtisiaceae)</td><td>Umlahleni</td><td>Assegai-tree</td><td>No</td></tr><tr><td>Dichrostachys</td><td>Cinerea</td><td>(L.) Wight & Arn. (Fabaceae)</td><td>Ugagane</td><td>Sicklebush</td><td>Yes</td></tr><tr><td>Dombeya</td><td>Rotundifolia</td><td>(Hochst.) Planch. (Malvaceae)</td><td>Unhliziyonkulu</td><td>Wild pear</td><td>Yes</td></tr><tr><td>Ekebergia</td><td>Capensis</td><td>Sparm. (Meliaceae)</td><td>Umnyamathi/ Umathunzin' entaba</td><td>Cape ash</td><td>Yes</td></tr><tr><td>Elaeodendron</td><td>Croceum</td><td>(Thunb.) DC (Celastraceae)</td><td>Lisithundu</td><td>Common saffron</td><td>No</td></tr></tbody></table>
<table><caption>**Table 1 continued**</caption><thead><tr><th>Genus</th><th>Species</th><th>Authority (Family)</th><th>Zulu</th><th>English vernacular</th><th>Chemical data (yes/ no)</th></tr></thead><tbody><tr><td>Elaeodendron</td><td>Transvaalensis</td><td>(Burtt Davy) R.H.Archer (Celastraceae)</td><td>Ingwavuma</td><td>Transvaal saffronwood</td><td>Yes</td></tr><tr><td>Entandrophragma</td><td>Caudatum</td><td>(Sprague) Sprague (Meliaceae)</td><td>Umgugudo</td><td>Bushveld saffron</td><td>Yes</td></tr><tr><td>Eriocoelum</td><td>Microspermum</td><td>Radlk. ex De wild. (Sapindaceae)</td><td>No record found</td><td>No record found</td><td>Yes</td></tr><tr><td>Erythrina</td><td>Lysistemon</td><td>Hutch. (Fabaceae)</td><td>Umnsinsi</td><td>Common coral tree</td><td>Yes</td></tr><tr><td>Erythrophleum</td><td>Lasianthum</td><td>Corbishley (Fabaceae)</td><td>Umbhemiso/ umkhwangu</td><td>Swazi ordeal tree</td><td>No</td></tr><tr><td>Eucalyptus</td><td>Sideroxylon</td><td>A.Cunn. Ex Wools (Myrtaceae)</td><td>Umdlavuza</td><td>Red ironbark</td><td>Yes</td></tr><tr><td>Euclea</td><td>Natalensis</td><td>A.DC. (Ebenaceae)</td><td>Isizimane</td><td>Natal guarri</td><td>Yes</td></tr><tr><td>Ficus</td><td>Glumosa</td><td>Delile (Moraceae)</td><td>Inkokhokho</td><td>Mountain rock fig</td><td>Yes</td></tr><tr><td>Garcinia</td><td>Gerrardii</td><td>Harv. Ex Sim (Clusiaceae)</td><td>Umbinda</td><td>Forest mangosteen</td><td>Yes</td></tr><tr><td>Garcinia</td><td>Lvingstonei</td><td>T. Anderson (Clusiaceae)</td><td>Igobandlovu</td><td>African mangosteen</td><td>Yes</td></tr><tr><td>Haplocoelum</td><td>Accuminatum (syn. congolanum)</td><td>Radlk. Ex Engl. (Sapindaceae)</td><td>No record found</td><td>No record found</td><td>Yes</td></tr><tr><td>Harpephyllum</td><td>Caffrum</td><td>Bernh. (Anacardiaceae)</td><td>Umgwenya</td><td>Wild plum</td><td>Yes</td></tr><tr><td>Heteromorpha</td><td>Arborescens</td><td>(Spreng.) Cham. & Schltdl. (Apiaceae)</td><td>Umbangandlala</td><td>Tropical parsley</td><td>No</td></tr><tr><td>Hippobromus</td><td>Pauciflorus</td><td>(L.f.) Radlk. (Sapindaceae)</td><td>Isiphahluka</td><td>False horsewood</td><td>No</td></tr><tr><td>Ilex</td><td>Mitis</td><td>(L.) Radlk. (Aquifoliaceae)</td><td>Xidumo/ udumaphansi</td><td>African holly</td><td>No</td></tr><tr><td>Kigelia</td><td>Africana</td><td>(Lam.) Benth. (Bignoniaceae)</td><td>Umvongothi</td><td>Sausage tree</td><td>Yes</td></tr><tr><td>Lannea</td><td>Schweinfurthii var. stuhlmannii</td><td>(Engl.) Engl. var. stuhlmannii (Engl.) Kokwaro (Anacardiaceae)</td><td>Umganunkomo</td><td>False-marula</td><td>Yes</td></tr><tr><td>Macaranga</td><td>Capensis</td><td>(Baill.) Sim (Euphorbiaceae)</td><td>Unompumelelo</td><td>River macaranga</td><td>Yes</td></tr><tr><td>Maytenus</td><td>Undata</td><td>(Thunb.) Blakelock (Celastraceae)</td><td>Undabulavalo</td><td>Koko tree</td><td>Yes</td></tr><tr><td>Ochna</td><td>Holstii</td><td>Engl. (Ochnaceae)</td><td>Isibhanku</td><td>Red ironwood</td><td>Yes</td></tr><tr><td>Ocotea</td><td>Bullata</td><td>(Burch.) Baill. (Lauraceae)</td><td>Unukani</td><td>Black stinkwood</td><td>Yes</td></tr><tr><td>Olax</td><td>Obtusifolia</td><td>De Wild. (Olacaceae)</td><td>No record found</td><td>Large-fruited olax</td><td>Yes</td></tr><tr><td>Ozoroa</td><td>Paniculosa</td><td>(Sond.) R.Fern & A.Fern (Anacardiaceae)</td><td>Isifice/isifuce</td><td>Common resin tree</td><td>No</td></tr><tr><td>Pappea</td><td>Capensis</td><td>Eckl. & Zeyh (Sapindaceae)</td><td>Iletha, umhuluka</td><td>Jacket plum</td><td>No</td></tr><tr><td>Peltophorum</td><td>Africanum</td><td>Sond. (Fabaceae)</td><td>Msehla/ umsenhla</td><td>African-wattle</td><td>Yes</td></tr><tr><td>Philenoptera</td><td>Volacea</td><td>(Klotzsch) Schrire (Fabaceae)</td><td>Isihomohomo</td><td>Apple-leaf</td><td>No</td></tr><tr><td>Piptadeniastrum</td><td>Africanum</td><td>(Hook.f.) Brenan (Fabaceae)</td><td>No record found</td><td>African greenheart</td><td>Yes</td></tr><tr><td>Pleurostylia</td><td>Capensis</td><td>(Turcz.) Loes. (Celastraceae)</td><td>Umthunyelwa</td><td>Bastard saffronwood</td><td>No</td></tr></tbody></table>
<table><caption>**Table 1** continued</caption><thead><tr><th>Genus</th><th>Species</th><th>Authority (Family)</th><th>Zulu</th><th>English vernacular</th><th>Chemical data (yes/ no)</th></tr></thead><tbody><tr><td>Protorhus</td><td>Longifolia</td><td>(Bernh.) Engl. (Anacardiaceae)</td><td>unhlangothi</td><td>Red-beech</td><td>Yes</td></tr><tr><td>Prunus</td><td>Africana</td><td>(Hook.f.) Kalkman (Rosaceae)</td><td>Inyazangoma elimnyama</td><td>Stinkwood</td><td>Yes</td></tr><tr><td>Ptaeroxylon</td><td>Obliquum</td><td>(Thunb.) Radlk. (Rutaceae)</td><td>Umthathe</td><td>Sneeze wood</td><td>Yes</td></tr><tr><td>Pterocarpus</td><td>Angolensis</td><td>DC. (Fabaceae)</td><td>Umvangazi</td><td>Bloodwood</td><td>Yes</td></tr><tr><td>Pterocelastrus</td><td>Rostratus</td><td>Walp. (Celastraceae)</td><td>Usehlulabanye/ Usehlulamanye</td><td>Red candlewood</td><td>No</td></tr><tr><td>Rapanea</td><td>Melanophloeos</td><td>(L.) Mez (Primulaceae)</td><td>Umaphipha</td><td>Cape beech</td><td>No</td></tr><tr><td>Rauvolfia</td><td>Caffra</td><td>Sond. (Apocynaceae)</td><td>Umhlambamanzi</td><td>Quinine tree</td><td>Yes</td></tr><tr><td>Schotia</td><td>Brachypetala</td><td>Sond. (Fabaceae)</td><td>Umgxamu/ihluze</td><td>Weeping boer-bean</td><td>No</td></tr><tr><td>Sclerocarya</td><td>Birrea</td><td>(A. Rich.) Hochst. (Anacardiaceae)</td><td>Umganu</td><td>Marula</td><td>Yes</td></tr><tr><td>Searsia</td><td>Chirindensis</td><td>(Baker.f.) Moffett (Anacardiaceae)</td><td>Inyazangoma elibomvu</td><td>Red current</td><td>No</td></tr><tr><td>Securidaca</td><td>Longepedunculata</td><td>Fresen (Polygalaceae)</td><td>Mpesu/ iphuphuma</td><td>Violet tree</td><td>Yes</td></tr><tr><td>Securidaca</td><td>Welwitschii</td><td>Oliv. (Polygalaceae)</td><td>No record found</td><td>No record found</td><td>Yes</td></tr><tr><td>Sideroxylon</td><td>Inerme</td><td>L. (Sapotaceae)</td><td>Amasethole</td><td>White milkwood</td><td>Yes</td></tr><tr><td>Spirostachys</td><td>Africana</td><td>Sond. (Euphorbiaceae)</td><td>Umthombothi</td><td>Tamboti</td><td>Yes</td></tr><tr><td>Strychnos</td><td>Henningsii</td><td>Gilg (Loganiaceae)</td><td>Umqalothi</td><td>Red bitter berry</td><td>Yes</td></tr><tr><td>Syzygium</td><td>Cordatum</td><td>Hochst. Ex Krauss (Myrtaceae)</td><td>Umdoni</td><td>Water berry</td><td>Yes</td></tr><tr><td>Terminalia</td><td>Catappa</td><td>L. (Combretaceae)</td><td>No record found</td><td>Indian almond</td><td>Yes</td></tr><tr><td>Terminalia</td><td>Sericea</td><td>Burch. ex DC. (Combretaceae)</td><td>Amangwe</td><td>Silver cluster-leaf</td><td>Yes</td></tr><tr><td>Terminalia</td><td>Superba</td><td>Engl. & Diels. (Combretaceae)</td><td>Mususu (Venda)</td><td>Silver cluster-leaf</td><td>Yes</td></tr><tr><td>Tetrapleura</td><td>Tetraptera</td><td>(Schumach. & Thonn.) Taub. (Fabaceae)</td><td>No record found</td><td>Aridan</td><td>Yes</td></tr><tr><td>Trichilia</td><td>Dregeana</td><td>Sond. (Meliaceae)</td><td>Umathunzini</td><td>Forest mahogany</td><td>No</td></tr><tr><td>Trichilia</td><td>Emetica</td><td>Vahl (Meliaceae)</td><td>Umkhuhlu</td><td>Natal mahogany</td><td>No</td></tr><tr><td>Turraea</td><td>Floribunda</td><td>Hochst. (Meliaceae)</td><td>Umadlozane</td><td>Honeysuckle-tree</td><td>Yes</td></tr><tr><td>Turraea</td><td>Obtusifolia</td><td>Hochst. (Meliaceae)</td><td>Ikunzi</td><td>Small honeysuckle tree</td><td>No</td></tr><tr><td>Vachellia</td><td>Natalitia</td><td>(E.Mey.) Kyal. & Boatwr. (Fabaceae)</td><td>Umunga</td><td>Pale-barked sweet thorn</td><td>No</td></tr><tr><td>Vachellia</td><td>Robusta</td><td>(Burch.) Kyal. & Boatwr. subsp. robusta (Fabaceae)</td><td>Umngamanzi</td><td>Broadpod robust thorn</td><td>No</td></tr><tr><td>Vachellia</td><td>Xanthophloea</td><td>(Benth.) Banfi & Galasso (Fabaceae)</td><td>Umkhanyakude</td><td>Fever tree</td><td>Yes</td></tr><tr><td>Vitex</td><td>Obovata</td><td>E.Mey. (Verbenaceae)</td><td>Umluthu</td><td>Hairy finger leaf</td><td>No</td></tr></tbody></table>
<table><caption>**Table 1** continued</caption><thead><tr><th>Genus</th><th>Species</th><th>Authority (Family)</th><th>Zulu</th><th>English vernacular</th><th>Chemical data (yes/no)</th></tr></thead><tbody><tr><td>Voacanga</td><td>Thouarsii</td><td>Roem. & Schult (Apocynaceae)</td><td>Indlabalozi/indlabaloyi</td><td>Wild frangipani</td><td>Yes</td></tr><tr><td>Warburgia</td><td>Salutaris</td><td>(G. Bertol.) Chiov. (Cannellaceae)</td><td>Isibhaha</td><td>Pepper-bark tree</td><td>Yes</td></tr><tr><td>Zanthoxylum</td><td>Capense</td><td>(Thunb.) Harv. (Rutaceae)</td><td>Umlungumabele</td><td>Small knobwood</td><td>Yes</td></tr><tr><td>Ziziphus</td><td>Mucronata</td><td>Wild. (Rhamnaceae)</td><td>Umlahlankosi</td><td>Buffalo-thorn</td><td>Yes</td></tr></tbody></table>

biodiversity and conservation. This is due to the destructive nature of removing bark from the trunk or roots of medicinal species. Scholars continue to deliberate over the perceived threat to biodiversity and contest the necessity of using bark in favour of stems and leaves. Suggestions have also been made on how to preserve biodiversity without having an impact on the freedom of cultural practice (Kalaba et al. 2010; van Wyk and Prinsloo 2018; Wiersum et al. 2006). An understanding of the chemical uniqueness of bark compared to leaves may add essential information to this ongoing discussion. Unfortunately, studies that quantitatively explore the comparison between leaves and bark are scarce.

The harvesting of bark in preference to leaves or stems requires considerably greater manual labour, implicating that this practice is motivated by empirically determined superiority in therapy. In exploring this further, prospective chemical studies are undertaken, but they merely characterize chemical profiles, which is a limited approach in understanding the therapeutic attributes of the species. Thus, chemical studies are often complemented with bioassay data. Both approaches help to build the picture of the diversity of metabolites and the therapeutic potency of bark, reported in ethnobotanical studies.

A major criticism of ethnopharmacological studies is in relation to the feasibility that the bioactive metabolites are extracted by traditional methods. These metabolites may be significant to therapeutic applications, but the modality of use determines which metabolites are transferred from the bark to the person, either via ingestion, inhalation or contact with the dermis. For example, several bark therapies are used in smoke fumigation practice, driving a range of

molecules onto skin surfaces, or into the lungs. Smoke fumigation promotes transfer of volatile organic compounds and other metabolites as aerosols, which increases the human dose of semi-volatile ingredients that are not regarded as essential oil components (Khumalo et al. 2019b; Sadgrove et al. 2014; Sadgrove and Jones 2014b).

Extraction of specialized metabolites into water for use in medicine is also common practice (Khumalo 2018). Extractions that are performed using water at room temperature result in preferential dissolution of polar metabolites, which may improve solubility of lipophilic ingredients, particularly when the biota is rich in surfactants, such as saponins or lecithins. The pH of the extract will also determine solubility of ionizable compounds, such as free carboxylic acids or alkaloids. Alternatively, extractions using boiled water may liquidate lipophilic ingredients, causing flocculants to form upon cooling. Thereafter, flocculants are ingested when the solution is drunk, entering the body as particles (nanoparticles) rather than as solutes. This phenomenon is familiar to traditional Chinese medicine, recently demonstrated by boiling liquorice to produce nanoparticles of proteins that encapsulate lipophilic ingredients (Zhou et al. 2019).

## Comment on the comparison of leaves to bark

While there are limited studies that compare leaves to twigs, some examples were found. From the comparison of *Curtisia dentata* (Burm.f.) C.A.Sm., an apparent paradox was revealed. In an antimicrobial assay, extracts of leaves and twigs were more active against microorganisms than the extracts of the stem bark (Shai et al. 2009). The authors didn't isolate and
<table><caption>**Table 2** Phytochemical data related to 63 of the species listed in Table 1</caption><thead><tr><th>Species</th><th>Bark type</th><th>Chemistry</th></tr></thead><tbody><tr><td>Albizia adianthifolia</td><td>Stem &amp; root bark</td><td>Essential oils, β-caryophyllene, α-humulene, selin-11-en-4-α-ol, other sesquiterpenes (Akande et al. 2018)</td></tr><tr><td>Araucaria heterophylla</td><td>Resin from stem bark</td><td>Three labdane diterpenes, abda-8(17),14-diene, 13-epicupressic acid, and 13-O-acetyl-13-epicupressic. Essential oils, α-copaene (29.9%), germacrene D (21.4%), γ-gurjunene (9.7%), δ-cadinene (7.1%), and sandaracopimara-8(14),15-diene (6.5%) (Abdel-Sattar et al. 2009; Verma et al. 2014)</td></tr><tr><td>Balanites maughamii</td><td>Tree bark</td><td>Scopoletin and stigmasterol (Langlois 2000)</td></tr><tr><td>Berchemia discolor</td><td>Root bark</td><td>Putative new prenylated flavonoids and pterocarpans, plus the known analogues nitidulin, amorphigenin, and dabinol (Chin et al. 2006)</td></tr><tr><td>Bersama lucens</td><td>Tree &amp; root bark</td><td>New and known triterpenes, such as lup-30-al-3b-ol and lup-20-(30)-en-3,29-diol-7-one (Koorbanally et al. 2008)</td></tr><tr><td>Bersama swinnyi</td><td>Tree &amp; root bark</td><td>New and known triterpenes, such as 24-propylcholestan-7,15,20-triol (Koorbanally et al. 2008)</td></tr><tr><td>Bobgunnia madagascariensis</td><td>Tree bark</td><td>Triterpenes, lup-20(29)-en-3-one (Adeyemi and Amupitan 2011). Flavonoids, quercetin (Adeyemi et al. 2010)</td></tr><tr><td>Brackenridgea zanguebarica</td><td>Stem bark</td><td>Chalcone dimers, such as calodenin B, isochamaejasmine, and brackenin (Issa et al. 2013)</td></tr><tr><td>Bridelia micrantha</td><td>Stem bark</td><td>Phenols, trans-triacontyl-4-hydroxy-3-methoxycinnamate and catechin, triterpenes, friedelin and betulinic acid (Munayi 2016)</td></tr><tr><td>Calodendrum capense</td><td>Root bark</td><td>Sesquiterpene, calodendrolide, and the limonoids, limonin and limonin diosphenol (Kiprop et al. 2005). Alkaloids, capensenin and confusamine, furanocoumarins psolaren and bergapten (Okwemba et al. 2018)</td></tr><tr><td>Cassine papillosa</td><td>Stem bark</td><td>Peltogynoids, (+)-6R,13R-11,1 dimethyl-1,3,8,10-tetrahydroxy-9-methoxypeltogynan and (-)-4'-0-methoxyepigallocatechin, proanthocyanidins, galactitol, tingenone, and tingenin B, pentacyclic triterpenes, canophyllol, 3-hydroxylupeol and 30-hydroxylup 20(29)-en-3-one (Drewes and Mashimbye 1993)</td></tr><tr><td>Cassipourea flanaganii</td><td>Stem bark</td><td>Diterpenes, ent-atis-16-en-19-al, ent-atis-16-en-19-oic acid, ent-atis-16-en-19-ol, ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-manoyl oxide, amines, guinesine A, guinesine B, guinesine C, phenols, lichenxanthone, 2,4-dihydroxy-3,6-dimethyl benzoic acid methyl ester, docosyl ferulate, lynoside, triterpenes, lupeol, β-amyrin, sterols, stigmasterol, sitosterol and sitosterol-O-glucoside (Langat et al. 2021)</td></tr><tr><td>Cinnamomum camphora</td><td>Tree bark</td><td>Essential oils, D-camphor (51.3%), 1,8-cineole (4.3%), and α-terpineol (3.8%) (Guo et al. 2016). Phenols, hydroxy and methoxy benzoic acid derivatives (Shu et al. 2022)</td></tr><tr><td>Combretum caffrum</td><td>Stem bark</td><td>Phenols, combretastatin, 3,3',4'-tri-O-methylellagic acid and acacetin (Pettit et al. 1987, 1995)</td></tr><tr><td>Commiphora africana</td><td>Stem bark</td><td>Resveratrol derivatives (phenols), (E)-resveratrol 3-O-rutinoside, 5-methoxy-(E)-resveratrol 3-O-rutinoside, pinostilbene, and 3-hydroxy-5-methoxybenzoic acid (Segun et al. 2019)</td></tr><tr><td>Croton gratissimus</td><td>Stem bark</td><td>Cembranolides, (+)-[1R*,2S*,7S*,8S*,12R*]-7,8-epoxy-2,12-cyclocembra-3E,10Z-dien-20,10-olide, among others (Mulholland et al. 2010)</td></tr><tr><td>Croton sylvaticus</td><td>Tree bark</td><td>Diterpenes, crotohalimaneic acid, 15-acetoxy-2-oxo-trans-ent-cleroda-3,13-diene, and hardwickiic acid among others. Triterpenes and sterols, lupeone, β-amaryn, and sitosterol, among others (Maroyi 2017)</td></tr><tr><td>Cryptocarya latifolia</td><td>Tree bark</td><td>α-Pyrone derivatives, 6-substituted-5,6-dihydro-α-pyrones and dioxabicyclo [3,3,1]nonan-2-one derivatives (Drewes et al. 1995b)</td></tr><tr><td>Dichrostachys cinerea</td><td>Root &amp; tree bark</td><td>Meroterpenes in root bark, dichrostachines A-R (Long et al. 2009). Triterpenes and sterols in tree bark, friedelan-3-one, friedelan-3-β-ol, betulinic acid, and 3-O-β-D-glucopyranosyl-β-sitosterol, fatty acid derivatives and flavonoids, apigenin, luteonin, and related derivatives (Fotie et al. 2004)</td></tr><tr><td>Dombeya rotundifolia</td><td>Stem bark</td><td>Sterols, lupeol and sitosterol (Ndwigah et al. 2005)</td></tr></tbody></table>
<table><caption>**Table 2 continued**</caption><thead><tr><th>Species</th><th>Bark type</th><th>Chemistry</th></tr></thead><tbody><tr><td>Ekebergia capensis</td><td>Tree &amp; root bark</td><td>Tree bark, acyclic triterpenes, 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene and 2-hydroxymethyl-2,3,22,23-tetrahydroxy-6,10,15,19,23-pentamethyl-6,10,14,18-tetracosatetraene, plus known pentacyclic triterpenes (Nishiyama et al. 1996; Oyedeji-Amusa et al. 2021). Root bark, oleanonic acid, 3-epi-oleanolic acid, oleanolic acid, ekeberin A, 2-hydroxymethyl-2,3,22,23-tetrahydroxy-6,10,15,19,23-pentamethyl-6,10,14,18-tetracosatetraene, and 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (Irungu et al. 2014)</td></tr><tr><td>Elaeodendron transvaalensis</td><td>Tree bark</td><td>Triterpenes and sterols, lup-20(29)-ene-30-hydroxy-3-one, 3,28-dihydroxylbetuli-20(29)-ene, 3-oxo-28-hydroxylbetuli-20(29)-ene, 6β-hydroxy-lup-20(29)-ene-3-one, β-sitosterol, Ψ-taraxastanol and lup-20(30)-ene-3α,29-diol, flavonoid, 4'-O-methyl-epigallocatechin, canophyllol, canophyllal, a peltopgynoid, (+)-11,11-dimethyl-1,3,8,10-tetrahydroxy-9-methoxypeltogynan (Drewes et al. 1991; Khumalo et al. 2019a; Maroyi and Semenya 2019; Tshikalange and Hussein 2010)</td></tr><tr><td>Entandrophragma caudatum</td><td>Tree &amp; root bark</td><td>Limonoids and protolimonoids, phragmalin; phragmalin 3,30-diisobutyrate, phragmalin 3-isobutyrate-30-propionate, entandrophragmin B (12α-acetoxyphragmalin 3-nicotinate-30-isobutyrate), bussein A and B; entandrophragmin, 3α-turreanthin, and melianone (Ansell and Taylor 1988; Oyedeji-Amusa et al. 2021)</td></tr><tr><td>Eriocoeium microspermum</td><td>Root bark</td><td>Terpenoid glycosides, 3-O-α-L-rhamnopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-[β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-[β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin 28-O-β-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-α-L-arabinopyranosyl-(1 → 4)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-β-D-xylopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 3)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-α-L-arabinopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosylhederagenin, 1-O-[β-D-xylopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 6)]-[β-D-xylopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-(2E,6E)-farnes-1-ol, 1-O-[β-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 6)]-[β-D-xylopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-(2E,6E)-farnes-1-ol (Pertuit et al. 2018a)</td></tr><tr><td>Erythrina lysistemon</td><td>Tree bark</td><td>Prenylated isoflavones and pterocarpans, erybraedin A, phaseollidin, abyssinone V-4' methyl ether, eryzerin C, alpumisoflavone, cristacarpin and lysisteisoflavone (Sadgrove et al. 2020a)</td></tr><tr><td>Eucalyptus sideroxylon</td><td>Tree bark</td><td>Flavonoids, quercetin-O-dihexoside, engeletin (dihydrokaempferol rhamnoside), engeletin isomers, naringenin and sideroxylin. Ellagic acid, related derivative such methyl ellagic, dimethyl ellagic, and trimethyl ellagic acids. Triterpenes, such as trihydroxy oleanenoic (arjunolic) acid, O-p coumaroyl pentacyclic triterpene, oleanolic, ursolic, morolic acid, eucalyptanoic acid, methyl morolate 1, β-sitosterol 2, phenols, syringaldehyde, and 7'-Deoxyguajavadial A (Ashour et al. 2019)</td></tr><tr><td>Euclea natalensis</td><td>Stem bark</td><td>Phenol, shinanolone, phenol dimer, octahydroeuclein and triterpenes, 20(29)-lupene-3β-isoferulate, lupeol, and botulin (Weigenand et al. 2004)</td></tr><tr><td>Ficus glumosa</td><td>Stem bark</td><td>Ceramides, (2R,7E)-2-hydroxy-N-[(2S,3S,4R)-1,3,4-trihydroxyhexadecan-2-yl]hexacos-7-enamide and (2R)-N-[(2S,3S,4R,9Z)-1-O-[(β-D-glucopyranosyl]-3,4-dihydroxyheptadec-9-en-2-yl]-2-hydroxypentacosanamide (Nana et al. 2012)</td></tr><tr><td>Garcinia gerrardii</td><td>Stem bark</td><td>Xanthones, such as xanthone, garcigerrin A, and B (Sordat-Diserens et al. 1989)</td></tr></tbody></table>
<table><caption>**Table 2** continued</caption><thead><tr><th>Species</th><th>Bark type</th><th>Chemistry</th></tr></thead><tbody><tr><td>Garcinia livingstonei</td><td>Root bark</td><td>Prenylated and dimeric xanthones, 1,4,5-trihydroxy-3-(3-methylbut-2-enyl)-9H-xanthen-9-one, garcilivin A, B & C, 12β-hydroxy-des-D-garcigerrin A. A biflavanoid, ent-naringeninyl-(1-3α,II-8)-4'-O-methylnaringenin (Mbwambo et al. 2006; Sordat-Diserens et al. 1992a, 1992b)</td></tr><tr><td>Haplocoelum congolanum</td><td>Root bark</td><td>Triterpenoid saponins, 3-O-(4-O-[3-hydroxy-3-methylglutaryl])-α-l-arabinopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)]-α-l-arabinopyranosyloleanolic acid and 3-O-α-l-arabinofuranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)]-α-l-arabinopyranosyloleanolic acid (Pertuit et al. 2019)</td></tr><tr><td>Harpephyllum caffrum</td><td>Stem bark</td><td>Phenols, cardanols, an alkyl p-coumaric acid ester, and (+)-catechin (Moodley et al. 2014)</td></tr><tr><td>Kigelia africana</td><td>Stem & root bark</td><td>Stem bark: Napthaquinones, kigelinone, isopinnatal, and 2-(hydroxyethyl)naphtho[2,3-b]furan-4,9-dione. Root bark: Napthaquinones: Isopinnatal, kigelinol, isokigelinol, 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone, isopinnatal, kigelinol, and isokigelinol (Gupta and Jain 2019)</td></tr><tr><td>Lannea schweinfurthii</td><td>Root bark</td><td>3-((E)-nonadec-16'-enyl)phenol, 1-((E)-heptadec-14'-enyl)cyclohex-4-ene-1,3-diol, catechin, and 1-((E)-pentadec-12'-enyl)cyclohex-4-ene-1,3-diol (Yaouba et al. 2018)</td></tr><tr><td>Macaranga capensis</td><td>Tree bark</td><td>Triterpenes, 3α-hydroxyalleuritic acid 2-p-hydroxybenzoate and 3-acetoxyoleanolic acid (Majeed 2020)</td></tr><tr><td>Maytenus undata</td><td>Stem bark</td><td>Triterpenes, oleanolic acid, β-sitosterol, 3-oxo-28-friedelanoic acid, β-amyrin, lupeol and lupenone (Muthaura et al. 2017)</td></tr><tr><td>Ochna holstii</td><td>Stem bark</td><td>Flavonoids and chalconoids, ouratein D, isochamaejasmin A, 7',7"-di-O-methylisochamaejasmin, campylospermone A, liquiritigeninyl-(1-3,II-3)-naringenin, isoliquitigenin, terminalionone, flavumchalcone, lophirone F, 2,3-dihydrocalodenin B, holstiinone A, holstiinone B, holstiichalcone I, holstiichalcone II, holstiichalcone III, and calodenin B (Kalenga et al. 2021)</td></tr><tr><td>Ocotea bullata</td><td>Stem bark</td><td>Neolignans, ocobullenone, iso-ocobullenone, a neolignan ketone (Drewes et al. 1995a) and a diastereomer (Zschocke et al. 2000)</td></tr><tr><td>Olax obtusifolia</td><td>Root bark</td><td>Triterpenoid saponins, 3-O-α-l-rhamnopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucuronopyranosyloleanolic acid, 3-O-α-l-rhamnopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucuronopyranosyloleanolic acid 28-O-β-d-glucopyranosyl ester, 3-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 3)]-β-d-glucuronopyranosyloleanolic acid and 3-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-glucopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 3)]-β-d-glucuronopyranosyloleanolic acid 28-O-β-d-glucopyranosyl ester (Pertuit et al. 2018b)</td></tr><tr><td>Peltophorum africanum</td><td>Tree bark</td><td>Formyl phloroglucinols, 1-O-(E)-p-coumaroylbergenin, bergenin and norbergenin (Mebe and Makuhunga 1992). Flavonoids and phenolics but details of plant organ are scanty (Mazimba 2014)</td></tr><tr><td>Piptadeniastrum africanum</td><td>Stem bark</td><td>Triterpenoid saponins, piptadeniaoside, 3-O-β-[α-L-arabinopyranosyl-(1 → 2)-α-L-arabinopyranosyl-(1 → 3)-β-D-glucopyranosyl]maslinic acid-28-[β-D-glucopyranosyl-(1 → 2)-α-L-rhamnopyranosyl] ester, and 3-O-β-[α-L-arabinopyranosyl-(1 → 2)-α-L-arabinopyranosyl-(1 → 3)-β-D-glucopyranosyl]maslinic acid-28-[β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl-(1 → 2)-α-L-rhamnopyranosyl] ester (Noté et al. 2013)</td></tr><tr><td>Protorhus longifolia</td><td>Stem bark</td><td>Triterpenes, 3-oxo-5α-lanosta-8,24-dien-21-oic acid, 3β-hydroxylanosta-9,24-dien-24-oic acid, and methyl-3β-hydroxylanosta-9,24-dienoate (Mosa et al. 2014, 2011)</td></tr><tr><td>Prunus africana</td><td>Tree bark</td><td>Fatty acids, myristic acid, palmitic acid, linoleic acid, lignoceric acid, behenic acid, and oleic acid. Sterols and triterpenes, ursolic acid and sitosterol (Hass et al. 1999)</td></tr><tr><td>Ptaeroxylon obliquum</td><td>Tree bark</td><td>Aromadendrone diterpene, cneorubin X (prenylated sesquiterpene) (Mulholland and Mahomed 2000)</td></tr><tr><td>Pterocarpus angolensis</td><td>Tree bark</td><td>Epicatechin derivatives, [(-)-epicatechin, epicatechin-3-O-galate, epicatechin (4β-8)-epicatechin (B2), and a hexamer of epicatechin (Samie et al. 2009)</td></tr></tbody></table>
<table><caption>**Table 2** continued</caption><thead><tr><th>Species</th><th>Bark type</th><th>Chemistry</th></tr></thead><tbody><tr><td>Rauvolfia caffra</td><td>Stem bark</td><td>Indole alkaloids, such as ajmaline, norajmaline (dihydroindoles), ajmalicinine, ajmalicine (heteroyohimbines), geissoschizol (E-seco indole), pleiocarpamine (Nasser and Court 1984) raucaffricine, N-methylsarpagine, spegatrine (Tlhapi et al. 2019) rauvolfianoids A and B (Bitombo et al. 2022)</td></tr><tr><td>Sclerocarya birrea</td><td>Tree bark</td><td>Phenols, digalloylated procyanidin B, epicatechin 3-O-gallate and related derivatives (Russo et al. 2013)</td></tr><tr><td>Securidaca longepedunculata</td><td>Tree &amp; root bark</td><td>Tree bark: Phenols, β-D-(3,4-disinapoyl)fructofuranosyl-α-D-(6-sinapoyl)glucopyranoside, β-D-(3-sinapoyl)fructofuranosyl-α-D-(6-sinapoyl)glucopyranoside, sinapoic acid, caffeic acid, 4,5-dicaffeoyl-D-quinic acid, and 3,4,5-tricaffeoyl-D-quinic acid (De Tommasi et al. 1993). Root bark: methyl salicylate (Alitonou et al. 2012), 3-hydroxybenzoic acid, 3-hydroxy-4-methoxybenzoic acid, and 3,4-dimethoxy-7-hydroxyxanthone (Tiksa et al. 2019)</td></tr><tr><td>Securidaca welwitschia</td><td>Stem bark</td><td>Presenegenin glycosides, 3-O-(β-D-glucopyranosyl)presenegenin 28-[O-β-D-xylopyranosyl-(1 → 4)-O-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-β-D-fucopyranosyl] ester, 2,3-O-(β-D-glucopyranosyl)presenegenin 28-[O-β-D-galactopyranosyl-(1 → 4)-O-β-D-xylopyranosyl-(1 → 4)-O-3-O-acetyl-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-β-D-fucopyranosyl] ester and presenegenin (Timité et al. 2010)</td></tr><tr><td>Sideroxylon inerme</td><td>Stem bark</td><td>Epigallocatechin gallate and procyanidin B1 (Momtaz et al. 2008)</td></tr><tr><td>Spirostachys africana</td><td>Stem bark</td><td>Triterpenes, D-friedoolean-14-en-oic acid (3-acetyl aleuritic acid), lupeol, diterpenes, ent-2,6α-dihydroxy-norbeyer-1,4,15-trien-3-one (diosphenol 2) and ent-3β-hydroxy-beyer-15-ene-2-one (Mathabe et al. 2008)</td></tr><tr><td>Strychnos henningsii</td><td>Stem &amp; root bark</td><td>Alkaloids, holstiine, splendoline, 23-hydroxyspermostrychnine, 19-epi-23-hydroxyspermostrychnine, retuline, henningsiine, deshydroxyacetylhenningsiine, O-acetylhenningsiine, 3-hydroxyhenningsiine, henningsiine-N(4)-oxide, 23-hydroxyspermostrychnine-N(4)-oxide, 17,23-dihydroxyspermostrychnine, spermostrychnine, henningsamide, O-acetylhenningsamide, deshydroxyacetylhenningsamide and cyclostrychnine (Massiot et al. 1991)</td></tr><tr><td>Syzygium cordatum</td><td>Tree bark</td><td>Anthocyanins, leucodelphinidin and leucocyanidin, triterpenes, friedelin, epi-friedelinol, β-sitosterol, arjunolic acid, phenols, gallic acid, ellagic acid hexahydroxydiphenic acid, and a gallic acid-ellagic acid heterodimer (Candy et al. 1968; Maroyi 2018)</td></tr><tr><td>Terminalia catappa</td><td>Stem bark</td><td>Phenol, 3,4,5-trimethoxyphenyl-1-O-(4-sulfo)-β-D-glucopyranoside, and triterpene saponins, chebuloside II, arjunoglucoside II, triterpenes, arjunolic acid and 3-betulinic acid, and the sterol, sitosterol-3-O-β-D-glucopyranoside (Pertuit et al. 2015)</td></tr><tr><td>Terminalia sericea</td><td>Root bark</td><td>Triterpenes and sterols, sericic acid, sericoside (Mbunde et al. 2021), β-sitosterol, β-sitosterol-3-acetate, lupeol and stigmasterol-3-one, phenols, epicatechin, catechin, and epigallocatechingallocatechin (Nkobole 2011)</td></tr><tr><td>Terminalia superba</td><td>Stem bark</td><td>Pentacyclic triterpenes, 2α,3β-dihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside, 2α,3β, 21β-trihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside, 2α,3β, 29-trihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside, 2α,3β,23,27-tetrahydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside, and 2α,3β,23-trihydroxyolean-12-en-28-oic acid (Pertuit et al. 2015)</td></tr><tr><td>Tetrapleura tetraptera</td><td>Stem bark</td><td>Oleanane-type saponins, tetrapterosides A and B (Noté et al. 2009)</td></tr><tr><td>Turraea floribunda</td><td>Stem bark</td><td>Liminoid, floribundin F (1α,7α-12α-triacetoxy-4α-carbomethoxy-11β-(2-methylpropanoyloxy)-14β,15β-epoxyhavanensin) (Oyedeji-Amusa et al. 2021)</td></tr><tr><td>Vachellia xanthophloea</td><td>Tree bark</td><td>Hydrolysable tannins, gallic acid, tannic acid, catechin, catechol, m-hydroxy benzoic acid (Duraisamy et al. 2020)</td></tr></tbody></table>
<table><caption>**Table 2** continued</caption><thead><tr><td>Species</td><td>Bark type</td><td>Chemistry</td></tr></thead><tbody><tr><td>Voacanga thouarsii</td><td>Tree bark</td><td>Alkaloids, voacangine, ibogaine, voacamine, vobtusine, voacristine, iboluteine, vobasine, 18'-decarbomethoxyvoacamine and voaluteine (Goldblatt et al. 1970)</td></tr><tr><td>Warburgia salutaris</td><td>Stem & tree bark</td><td>Drimane sesquiterpenes, drimenol, 12α-acetal-polygodial, polygodial, ugandensidial, and warburganal, linear sesquiterpene, E-nerolidol (Khumalo et al. 2019b)</td></tr><tr><td>Zanthoxylum capense</td><td>Stem bark & knobs</td><td>The amide, pellitorine, the lignan xanthoxylol-γ,γ-dimethylallyl ether, and the sterol sitosterol-β-D-glucoside (Steyn et al. 1998). Alkaloids, chelerythrine, 6-hydroxydihydrochelerythrine, and rutaecarpine. Phenols, dodecyl-trans-p-coumarate, a lignan, sesamin, a flavanol, catechin, triterpenes, lupeol and sitosterol, pigments (possibly only in leaves), pheophytin a and lutein (Bodede et al. 2017)</td></tr><tr><td>Ziziphus mucronata</td><td>Root bark</td><td>Cyclopeptide alkaloids, mucronine J (Auvin et al. 1996), and derivatives (Barboni et al. 1994)</td></tr></tbody></table>

<figure><img src="image_5.png" /><figcaption>**Fig. 1** Structures 1–9, illustrating the range of compounds isolated from medicinal barks in southern Africa</figcaption></figure>

identify the antimicrobial compounds, but used thin layer chromatography to determine that the lipophilic fraction of the three organs was chemically similar. In another study, pentacyclic triterpenes were identified

in leaves, including lupeol, betulinic acid, ursolic acid and 2α-hydroxyursolic acid (Shai et al. 2008). The latter two are potently active against various
<figure><img src="image_6.png" /><figcaption>**Fig. 2** Structures 10–15, illustrating the range of compounds isolated from medicinal barks in southern Africa</figcaption></figure>

microorganisms (Jesus et al. 2015) and probably explain the antimicrobial activity observed.

The above example does not conclusively prove that leaves are more useful in anti-infective applications, because an artefact of the scientific method may obscure other factors. Without further interpretation, it conveys that the antimicrobial compounds are more abundant in leaves. However, another possibility is that a higher yield of other metabolites in bark diluted the active ingredients in the respective extract, i.e., while the authors did not report extract yields, if a tenfold greater mass was extracted from bark compared to leaves, with only a fivefold reduction in antimicrobial potency, then the pre-extracted bark is

more potent than the pre-extracted leaves. This possibility should be considered in moving forward, to understand why the bark is chosen for anti-infective applications by herbalists.

In another example of a species from the genus *Strychnos* (*S. henningsii* Gilg) the diversity of alkaloids in the leaves was higher compared to the bark. While the same bark alkaloids were identified in leaves, another 13 were assigned in leaves, including cyclostrychine, an alkaloid that is similar to the highly toxic alkaloid strychnine (Massiot et al. 1991). The implication is that the choice of bark in preference to leaves in medicinal practice is a matter of safety, rather than potency.
In a similar study of *Elaeodendron croceum* (Thunb.) DC., it was revealed that most compounds in the leaves are very toxic, containing the toxic substances 20-hydroxy-20-epi-tingenone, tingenone, and tingenine B, and the non-toxic substances 11α-hydroxy-β-amyrin and naringenin (Yelani et al. 2010). Unfortunately, no studies were found on the bark of this species, but the comparison of leaves to bark is necessary to understand this further.

A toxicity study of *Ekebergia capensis* Sparrm against carcinoma cell lines and vero (normal) cells demonstrated that root bark extracts were substantially more toxic than leaves, and toxicity was relatively uniform between cancerous and normal mammalian cells (Irungu et al. 2014). Despite this, most of the EC50 values reported were relatively high to be considered replicable in vivo, due to pharmacokinetic factors (Sadgrove and Jones 2019). The chemical analysis revealed that the two organs were completely different at the level of chemical class, with triterpenes dominating in the root bark compared to a limonoid and several flavonoid glycosides in the leaves. Ethnobotanical reports convey that all plant parts are used in traditional medicine, either internally or topically for various applications to achieve anti-infective, anti-cancerous and cardiovascular effects (Oyedeji-Amusa et al. 2021). Thus far, the mechanisms are not explained by the in vitro data (Sadgrove and Jones 2019), and the toxicity studies need to be interpreted in the context of pharmacokinetics and pharmacodynamics.

In a final example, a comparison of the major compounds in the leaves and bark of *Croton gratisimus* Burch (Langat et al. 2011; Mulholland et al. 2010), demonstrated a greater diversity of cembranolides in the leaves (16 isolates, compared to 4 in bark). While the two plant organs shared a common biosynthetic group, being the the cembranolides, there was minimal overlap of chemical identities.

In the context of therapeutic attributes of this species, there may be a geographical component controlling local use or efficacy. This is because another study on the chemistry of *C. gratissimus* revealed that specimens growing in other parts of the country are dominated by abietane and halimane dieterpenes (Sadgrove et al. 2019), and do not contain the cembranolides described for the specimen cultivated in Durban of coastal South Africa. In this regard, geographical specificity, plasticity of metabolite

expression (chemophenetics) (Ramos et al. 2023), and chemotypes (Sadgrove 2020) should be considered when interpreting chemical data of any African species.

Comment on metabolites as indicators of therapeutic value: pharmacokinetics

The vast majority of chemical studies found in the literature did not follow up with bioassays. Where bioassay data was found, scholars predominantly focus on anti-infective activity, or cytotoxicity against cancer cell lines. Unfortunately, routine bioassays are limited in their ability to explain therapeutic mechanisms of medicinal species. Many of the bioassays were developed to guide the synthesis of drugs as selective targets of isolated biochemical processes, but for natural products it would be too much of a coincidence if their mechanisms are via the same singular biochemical process. More importantly, pharmacokinetic processes in the body drastically change natural product extracts; it is difficult to ascertain which of the xenobiotic intermediates play a role in the therapeutic results (Sadgrove and Jones 2019).

The medicinal bark species of southern Africa are predominantly anti-infective, i.e., they are antimicrobial against select pathogens or a broad spectrum of pathogens that are Gram-positive, Gram-negative, a fungi or yeast. Antimicrobial assays of bark extracts made in a laboratory are therefore translatable to topical applications where direct contact between the bark extracts and microorganisms is feasible. For example, placing extracts directly onto a skin infection, wound, rash or fungal infection will conceivably reproduce the in vitro data. It is also feasible where targetted pathogens are in the gastrointestinal space, because concoctions and decoctions carry metabolites directly to the pathogens in the alimentary canal. In a final example, anti-infective compounds that are either volatile or semi-volatile, are easily transferred to the lungs by smoke fumigation, achieving direct contact with respiratory pathogens (Khumalo et al. 2019b).

However, medicinal bark extracts that are taken to target infections via the systemic passage (portal circulation, metabolism and elimination) require expert interpretation, particularly where in vitro studies are performed without consideration to pharmacokinetic viability (Sadgrove and Jones 2019). Not
only do digestive processes alter the metabolites, but
gut microbes catabolize them. Another factor to
determine translation is the transdermal transport of
specific metabolites across the intestinal wall into
portal circulation, or the exclusion and elemination of
others.

For example, where saponins are present in medicinal bark species, the pharmacokinetic interpretation becomes more complex. Saponins are known to soothe skin and topical autoimmune-related inflammatory afflictions (Passos et al. 2022), which may enact therapeutic effects to the intestinal epidermis. But ingested saponins are not absorbed through the intestinal wall into portal circulation, rather, the sugars are hydrolyzed in the digestive process and a simpler triterpene conjugates, or triterpene aglycones, are absorbed. These triterpenes tend to enact the same anti-inflammatory effects as the more complex saponin, after binding to blood albumin and being transported to various sites in the human body (Sadgrove and Jones 2019).

One exception to the poor dermal penetration ability of saponins is the highly complex structures that are aminated. An example is the group of saponins known as the avicins, which have a geranly moiety and an acetamide group. These types of saponins travel across dermal layers as efficiently as moderately lipophilic molecules (Pino et al. 2014), which appears to be a glaring contradiction to pharmacokinetic theory, but constitutes an exception to the rule. Not surprisingly, the bark of one southern African species, *Piptadeniastrum africanum* (Hook.f.) Brenan., contains acetamide saponins, known as the piptadenioasides (Fig. 2) (Noté et al. 2013). Currently there is no research examining transdermal potential of these saponins, but it is a worthy future endeavour.

Another pharmacokinetic issue related to bioassay
data is the concentration reported for in vitro studies,
which are commonly reported for antimicrobial
effects or inhibition of cancer cells. It is common for
reported concentrations to far exceed maximum
concentrations achieved in human plasma, due to the
rate of conjugation and elimination in metabolism.
Such concentrations are generally above 10 µg mL⁻¹.
While some natural products can reach concentrations
as high as 5 µg mL⁻¹, most natural products will only
achieve systemic concentrations of up to 1 µg mL⁻¹.

Nevertheless, some of the bioassay data found in
the course of this review is indeed of interest, where

low values of 1–5 µg mL⁻¹ were reported. Examples
of bioactivity studies and their outcomes include the
antioxidant activity of phenolics in bark of *P. africaanum* (Mazimba 2014), anti-cancerous effect
of trans-triacontyl-4-hydroxy-3-methoxycinnamate
from *B. micrantha* (Munayi 2016), the anti-cancerous
effect of pellitorine (Ee et al. 2010) assigned in bark of
*Z. capense* (Steyn et al. 1998), or the anti-inflamma-
tory effects of sibyllenone, a meroterpene from *O. bullata* (Zschocke et al. 2000).

As mentioned above, there are also various studies
that report bioassay data requiring further interpreta-
tion, or even dismissal. But this does not nullify the
therapeutic attributes of species, it merely fails to
explain them. In many cases, the phytochemical
diversity of orally ingested nutraceutical items may
be considered prophylactic for numerous diseases
(Sadgrove 2022; Sadgrove and Simmonds 2022), by
facilitating a return to homeostasis in cells (i.e., restore
redox balance). For example, species that are rich in
flavonoids may be regarded as facilitating a recovery
to the redox balance of cells in stressed tissues (Crown
et al. 2019), either by stimulating the expression of
endogenous antioxidants (glutathione, superoxide
dismutase or catalase) (Kameoka et al. 1999) or by
participating at complex 1 of the electron transport
chain, producing heterodimers referred to as ‘spent
antioxidants’ (Huvaere et al. 2012). Such effects can
be behind reducing the symptoms of disease, improv-
ing diabetes, and strengthening the immune system,
supporting the body’s resistance and recovery from
infections.

Various studies that describe effects such as anti-
inflammatory, anti-infectious or anti-cancerous activ-
ity, but report EC50 or MIC values that are not reached
in human blood plasma (due to pharmacokinetic
obstacles), may still be of relevance due to the
accumulation of lipophilic ingredients in inflamed
tissues. This is due to the metabolic process in the liver
that generates glucuronide conjugates of natural
products entering portal circulation from the digestive
tract. Although glucuronides are conjugates that are
made more polar to enable elimination via the kidneys,
they will be deconjugated when in contact with any of
the β-glucuronidase isozymes. β-Glucuronidases are
expressed when macrophages and neutrophils are
stimulated (Kawai 2014; Shimoi and Nakayama
2005), which is relevant to the modulation of inflam-
mation by the body’s conjugated androgens (Bianchi
2019). Thus, when natural product glucuronide conjugates enter tissues that are inflamed, such as infections or cancers, the removal of the glucuronic acid moiety decreases the plasma solubility of the compound, causing it to accumulate on-site to concentrations exceeding the safe levels in plasma and enacting biological affects, such as anti-infection, anti-cancer or anti-inflammation. Thus, some of the biological effects ascribed to natural products in medicinal bark species may be considered relevant, but nevertheless, requiring further research.

In a final example, hydrolyzable and condensed tannins are ubiquitous in medicinal bark species. They are so common that they are frequently ignored in chemical studies and not reported. Tannins are generally determined as mixtures of hydrolysable and condensed forms. The two most common types of hydrolyzable tannin are ellagitannin and gallotannin. Ellagitannins are the most diverse and common group of hydrolyzable tannin, found for example, in the Myrtales (Yoshida et al. 2010), in some fruits (Barbara and Janja 2021), in the bark of most species in the genus *Eucalyptus* (Cadahía et al. 1997), and in multiple species from Nigeria (Ucella-Filho et al. 2022).

Ellagitannins are sugar conjugates of ellagic acid. They are instantly hydrolyzed in the acid conditions of the human stomach, converting to a mixture of sugars and ellagic acid. While some of the ellagic acid is absorbed into portal circulation of the human body, a large portion is catabolized by gut microbiota, producing urolithin isomers, such as urolithin A, urolithin B, isourolithin, or any of the 10 others that are so far known (García-Villalba et al. 2022). The most common catabolites are urolithin A or B. Their presence/absence or ratio is determined by the nature of species in the gut microbiome, and potentially other factors, creating the supposed "urolithin phenotypes" that have been identified in studies (Tomás-Barberán et al. 2014).

A role for the therapeutic effects of urolithins and their potential as prophylactic agents against lifestyle disease, has been explored in the literature. When urolithins are produced from ellagic acid in the microbiome, they cross into portal circulation and circulate in the human system as either their free form, or as a conjugate produced in liver metabolism, with a urolithin glucuronide being the most common. Out of the 35 studies reviewed by Garcia-Villalba et al.

(2022) it was concluded that they are not only prophylactic against cardiovascular disease, but they confer systemic anti-inflammatory effects, they are neuroprotective, and may decrease risk of cancers. Thus, the efficacy of bark medicines that are ingested goes beyond what is conveyed in routine bioassays of crude extracts produced in the lab, due to pharmacokinetic processes occurring in the human body.

**Acknowledgements** The authors would like to acknowledge the herbalists that volunteered information during the compilation of previous work leading up to this review.

**Author contributions** Conceptualization, B.-E.V.W. and N.S.; methodology, N.S.; writing—original draft preparation, N.S.; writing—review and editing, all authors. All authors have read and agreed to the published version of the manuscript.

**Funding** Open access funding provided by University of Johannesburg. This research received no external funding.

**Data availability** Not applicable.

### Declarations

**Conflict of interest** The authors declare that they have no conflict of interest.

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### References

Abdel-Sattar E, Monem ARA, Ezzat SM, El-Halawany AM, Mouneir SM (2009) Chemical and biological investigation of *Araucaria heterophylla* Salisb. Resin Z Naturforsch C 64:819–823

Adeyemi MH, Amupitan J (2011) Chemical and biological evaluation of the stem bark of *Bobgunnia madagascariensis* (Desv.) JH Kirkbr. & Wiersema). J Basic Appl Chem 1:46–51

Adeyemi M, Adebote D, Amupitan J, Oyewale A, Agbaji A (2010) Antifeedant activity of quercetin isolated from the stem bark of *Bobgunnia madagascariensis* (Desv.) JH
Kirkbr & Wiersema. (Caesalpiniaceae). Aust J Basic Appl
Sci 4:3342–3346

Akande A, Aboaba S, Flamini G (2018) Constituents and
anthelmintic activity evaluation of *Albizia adiantifolia*
(Schumach) W.F. Wright essential oils from Nigeria. Int J
Chem. https://doi.org/10.5539/ijc.v5510n5532p5510

Alitonou GA, Koudoro AY, Dangou JS, Yehouenou B, Avlessi F, Adeoti S, Menut C, Sohounhloue DC (2012) Volatile constituents and biological activities of essential oil from *Securidaca longepedunculata* Fers. growing in Benin. Sci Stud Res Chem Chem Eng Biotechnol Food Ind 13:33

Ansell SM, Taylor DAH (1988) Limonoids from the seed of *Entandrophragma caudatum*. Phytochemistry 27:1218–1220

Ashour RMS, Okba MM, Menze ET, El Gedaily RA (2019) *Eucalyptus sideroxylon* bark anti-inflammatory potential, Its UPLC-PDA-ESI-qTOF-MS profiling, and isolation of a new phloroglucinol. J Chromatogr Sci 57:565–574

Auvin C, Lezenven F, Blond A, Augeven-Bour I, Pousset J-L, Bodo B, Camara J (1996) Mucronine J, a 14-membered cyclopeptide alkaloid from *Zizyphus mucronata*. J Nat Prod 59:676–678

Bagci E, Hayta S, Dogan G (2011) Chemical composition of essential oils from bark and leaves of *Pinus brutia* Ten. from Turkey. Asian J Chem 23:2782–2784

Barbara B, Janja K (2021) A Review of Tannins in Berries. Agricultura Scientia 17:27–36

Barboni L, Gariboldi P, Torregiani E, Verotta L (1994) Cyclopeptide alkaloids from *Ziziphus mucronata*. Phytochemistry 35:1579–1582

Bianchi VE (2019) The anti-inflammatory effects of testosterone. J Endocr Soc 3:91–107

Biswas TK, Mukherjee B (2003) Plant medicines of Indian origin for wound healing activity: a review. Int J Low Extrem Wounds 2:25–39

Bitombo AN, Zintchem AAA, Atchadé AdT, Moni Ndedi EDF, Khan A, Ngono Bikobo DS, Pegnyemb DE, Bochet CG (2022) Antimicrobial and cytotoxic activities of indole alkaloids and other constituents from the stem barks of *Rauvolfia caffra* Sond (*Apocynaceae*). Nat Prod Res 36:1467–1475

Bodeo E, Shaik S, Singh M, Moodley R (2017) Phytochemical analysis with antioxidant and cytotoxicity studies of the bioactive principles from *Zanthoxylum capense* (Small knobwood). Anticancer Agent Med Chem 17(4):627–634.
https://doi.org/10.2174/1871520616666160627091939

Cadahía E, Conde E, Simón BFd, García-Vallejo MC (1997) Tannin composition of *Eucalyptus camaldulensis*, *E. globulus* and *E. rudis*. Part II. Bark. Holzforschung 51:125–129

Candy HA, McGarry EJ, Pegel KH (1968) Constituents of *Syzygium cordatum*. Phytochemistry 7:889–890

Chin Y-W, Mdee LK, Mbwambo ZH, Mi Q, Chai H-B, Cragg GM, Swanson SM, Kinghorn AD (2006) Prenylated flavonoids from the root bark of *Berchemia discolor*, a Tanzanian medicinal plant. J Nat Prod 69:1649–1652

Crown OO, Ogundele OO, Akinmoladun AC, Famusiwa CD, Josiah SS, Olaleye MT, Akindahunsi AA (2019) Effects of catechin, quercetin and taxifolin on redox parameters and metabolites linked with renal health in rotenone-toxified rats. Niger J Physiol Sci 34:1–10

De Tommasi N, Piacente S, De Simone F, Pizza C (1993) New sucrose derivatives from the bark of *Securidaca longipedunculata*. J Nat Prod 56:134–137

Drewes SE, Mashimbye MJ (1993) Flavanoids and triterpenoids from *Cassine papillosa* and the absolute configuration of 11, 11-dimethyl-1, 3, 8, 10-tetra-hydroxy-9-methoxypeltogynan. Phytochemistry 32:1041–1044

Drewes SE, Horn MM, Sehlapelo BM, Ramesar N, Field JS, Shaw S, Sandor P (1995a) Iso-ocobullenone and a neolignan ketone from *Ocotea bullata* bark. Phytochemistry 38:1505–1508

Drewes SE, Sehlapelo BM, Horn MM, Scott-Shaw R, Sandor P (1995b) 5,6-Dihydro-α-pyrones and two bicyclic tetrahydro-α-pyrone derivatives from *Cryptocarya latifolia*. Phytochemistry 38:1427–1430

Duraisamy R, Shuge T, Worku B, Berekete AK, Ramasamy KM (2020) Extraction, screening and spectral characterization of tannins from *Acacia xanthophloea* (Fever Tree) bark. Res J Text Leather 1:1–10. https://doi.org/10.46590/rjtl.2020.010101

Drewes ES, Mashimbye MJ, Field JS, Ramesar N (1991) 11,11-dimethyl-1,3,8,10-tetrahydroxy-9-methoxypeltogynan and three pentacyclic triterpenes from *Cassine transvaalensis*. Phytochemistry 30:3490–3493

Ee GCL, Lim CM, Rahmani M, Shaari K, Bong CFJ (2010) Pellitorine, a potential anti-cancer lead compound against HL60 and MCT-7 cell lines and microbial transformation of piperine from *Piper nigrum*. Molecules 15:2398–2404

Fotie J, Nkengfack AE, Peter MG, Heydenreich M, Fomum ZT (2004) Chemical constituents of the ethyl acetate extracts of the stem bark and fruits of *Dichrostachys cinerea* and the roots of Parkia bicolor. Bull Chem Soc Ethiop. https://doi.org/10.4314/bcse.v18i1.61646

García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, Ávila-Gálvez MÁ, Tomás-Barberán FA, Selma MV, Espín JC, González-Sarías A (2022) Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota. Mol Nutr Food Res 66:2101019

Geetha V, Chakravarthula SN (2018) Chemical composition and anti-inflammatory activity of *Boswellia ovalifoliolata* essential oils from leaf and bark. J for Res 29:373–381

Goldblatt A, Hootele C, Pecher J (1970) The alkaloids of *Voa-canga thouarsii* var. *obtusa*. Phytochemistry 9:1293–1298

Green A, Padilla-Gonzalez GF, Phumthum M, Simmonds MSJ, Sadgrove NJ (2021) Comparative metabolomics of reproductive organs in the genus *Aesculus* (*Sapindaceae*) reveals that immature fruits are a key organ of procyanidin accumulation and bioactivity. Plants 10:2695

Guo S, Geng Z, Zhang W, Liang J, Wang C, Deng Z, Du S (2016) The chemical composition of essential oils from *Cinnamomum camphora* and their insecticidal activity against the stored product pests. Int J Mol Sci 17:1836

Gupta AK, Jain A (2019) Phyto-chemical and therapeutic briefing of *Kigelia africana* (Lam.) Benth. Indian J Pharm Biol Res 7:14–22

Hass MA, Nowak DM, Leonova E, Levin RM, Longhurst PA (1999) Identification of components of *Prunus africana* extract that inhibit lipid peroxidation. Phytomedicine 6:379–388

Hon DN, Shiraishi N (2000) Wood and cellulosic chemistry, revised, and expanded. CRC Press
Huvaere K, Sinnaeve B, Van Bocxlaer J, Skibsted LH (2012) Flavonoid deactivation of excited state flavins: reaction monitoring by mass spectrometry. J Agric Food Chem 60:9261–9272

Irungu BN, Orwa JA, Gruhonjic A, Fitzpatrick PA, Landberg G, Kimani F, Midiwo J, Erdélyi M, Yenesew A (2014) Constituents of the roots and leaves of *Ekebergia capensis* and their potential antiplasmodial and cytotoxic activities. Molecules 19:14235–14246

Issa HH, Abe N, Ali Z, Khan IA (2013) Chalcone oligomers from the stem bark of *Brackenridgea zanguebarica*. Planta Med 79:P32

Jesus JA, Lago JH, Laurenti MD, Yamamoto ES, Passero LF (2015) Antimicrobial activity of oleanolic and ursolic acids: an update. Evid Based Complement Alternat Med 2015:620472

Kalaba KF, Chirwa P, Syampungani S, Ajayi CO (2010) Contribution of agroforestry to biodiversity and livelihoods improvement in rural communities of Southern African regions. In: Tscharntke T, Leuschner C, Veldkamp E, Faust H, Guhardja E, Bidin A (eds) Tropical rainforests and agroforests under global change: ecological and socio-economic valuations. Springer, Berlin, Heidelberg, pp 461–476

Kalenga TM, Ndoile MM, Atilaw Y, Gilissen PJ, Munissi JJE, Rudenko A, Bourgard C, Sunnerhagen P, Nyandoro SS, Erdélyi M (2021) Biflavanones, chalconoids, and flavonoid analogues from the stem bark of *Ochna holstii*. J Nat Prod 84:364–372

Kameoka S, Leavitt P, Chang C, Kuo S-M (1999) Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids. Cancer Lett 146:161–167

Kawai Y (2014) β-Glucuronidase activity and mitochondrial dysfunction: the sites where flavonoid glucuronides act as anti-inflammatory agents. J Clin Biochem Nutr 54:145–150

Khumalo GP, Sadgrove NJ, Van Vuuren SF, Van Wyk B-E (2018) An inventory of the most popular medicinal barks sold on Johannesburg muthi markets and the antimicrobial activity of selected extracts and isolated chemical compounds. S Afr J Bot 115:290. https://doi.org/10.1016/j.sajb.2018.02.054

Khumalo GP, Sadgrove NJ, van Vuuren S. Van Wyk B-E (2019a) Antimicrobial lupenol triterpenes and a polyphenol from *Elaedendron transvaalense*, a popular southern African medicinal bark. S Afr J Bot 122:518–521

Khumalo GP, Sadgrove NJ, Van Vuuren SF, Van Wyk B-E (2019b) Antimicrobial activity of volatile and non-volatile isolated compounds and extracts from the bark and leaves of *Warburgia salutaris* (*Canellaceae*) against skin and respiratory pathogens. S Afr J Bot 122:547–550

Khumalo GP, Sadgrove NJ, Van Vuuren SF, Van Wyk B-E (2021) South Africa's best BARK medicines prescribed at the Johannesburg Muthi markets for skin, gut, and lung infections: MIC's and brine shrimp lethality. Antibiotics 10(6):681. https://doi.org/10.3390/antibiotics10060681

Kiprop A, Rajab M, Wanjala F (2005) Isolation and characterization of larvicidal components against mosquito larvae (*Aedes aegypti* Linn.) from *Calodendrum capense* Thunb. Bull Chem Soc Ethiop 19:145–148

Koorbanally NA, Makatini M, Crouch NR (2008) Novel triterpenoids from South African *Bersama* species. Planta Med. https://doi.org/10.1055/s-0028-1084458

Kopp J, Wang GY, Horch RE, Pallua N, Ge SD (2003) Ancient traditional Chinese medicine in burn treatment: a historical review. Burns 29:473–478

Langat MK, Crouch NR, Smith PJ, Mulholland DA (2011) Cembranolides from the leaves of *Croton gratissimus*. J Nat Prod 74:2349–2355

Langat MK, Dlova NC, Mulcahy-Ryan LE, Schwikkard SL, Opara EI, Crouch NR, Hiles JD, Mulholland DA (2021) The effect of isolates from *Cassipourea flanaganii* (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition. J Ethnopharmacol 264:113272

Langlois A (2000) The chemical investigation of four medicinal plants. Durban, South Africa. University of Natal. Master of Science, Department of Chemistry

Lassak EV, McCarthy T (2011) Australian medicinal plants. Methuen Australia Pty Ltd, North Rhyde, Australia

Long C, Marcourt L, Raux R, David B, Gau C, Menendez C, Gao M, Laroche M-F, Schambel P, Delaude C, Ausseil F, Lavaud C, Massiot G (2009) Meroterpenes from *Dichrostachys cinerea* inhibit protein farnesyl transferase activity. J Nat Prod 72:1804–1815

Majeed A (2020) Identification of α-glucosidase inhibiting natural products from *Macaranga capensis* and *Sapium integerrimum*. Department of Chemistry. Winnipeg, Manitoba; Faculty of Graduate Studies. University of Manitoba. Master of Science

Maroyi A (2017) Traditional usage, phytochemistry and pharmacology of *Croton sylvaticus* Hochst. ex C. Krauss. Asian Pac J Trop Med 10:423–429

Maroyi A (2018) *Syzygium cordatum* Hochst. ex Krauss: an overview of Its ethnobotany, phytochemistry and pharmacological properties. Molecules 23(5):1084. https://doi.org/10.3390/molecules23051084

Maroyi A, Semenya SS (2019) Medicinal uses, phytochemistry and pharmacological properties of *Elaedendron transvaalense*. Nutrients 11:545

Massiot G, Thepenier P, Jacquier M-J, Henin J, Le Men-Olivier L, Delaude C (1991) Alkaloids from *Strychnos henningsii*. Phytochemistry 30:3449–3456

Mathabe MC, Hussein AA, Nikolova RV, Basson AE, Meyer JJM, Lall N (2008) Antibacterial activities and cytotoxicity of terpenoids isolated from *Spirostachys africana*. J Ethnopharmacol 116:194–197

Mazimba O (2014) Pharmacology and phytochemistry studies in *Peltophorum africanum*. Bull Fac Pharm Cairo Univ 52:145–153

Mbunde MVN, Innocent E, Mabiki F, Andersson PG (2021) In vitro study for antifungal compounds from *Parinari curatellifolia* (Chrysobalanaceae) and *Terminalia sericea* (Combretaceae). Int J Biol Chem Sci 15:367–378

Mbwambo ZH, Kapingu MC, Moshi MJ, Machumi F, Apers S, Cos P, Ferreira D, Marais JPJ, Vanden Berghe D, Maes L, Vlietinck A, Pieters L (2006) Antiparasitic activity of some xanthones and biflavonoids from the root bark of *Garcinia livingstonei*. J Nat Prod 69:369–372
Mebe PP, Makuhunga P (1992) 11-(E)-p-Coumaric acid ester of
bergenin from *Peltophorum africanum*. Phytochemistry
31:3286–3287

Momtaz S, Mapunya BM, Houghton PJ, Edgerly C, Hussein A,
Naidoo S, Lall N (2008) Tyrosinase inhibition by extracts
and constituents of *Sideroxylon inerme* L. stem bark, used
in South Africa for skin lightening. J Ethnopharmacol
119:507–512

Moodley R, Koorbanally NA, Shahidul Islam MD, Jonnala-
gadda SB (2014) Structure and antioxidant activity of
phenolic compounds isolated from the edible fruits and
stem bark of *Harpephyllum caffrum*. J Environ Sci Health
B 49:938–944

Morrison IJ, Zhang J, Lin J, Murray JE, Porter R, Langat MK,
Sadgrove NJ, Barker J, Zhang G, Delgoda R (2021)
Potential chemopreventive, anticancer and anti-inflamma-
tory properties of a refined artocarpin-rich wood extract of
*Artocarpus heterophyllus* Lam. Sci Rep 11:6854

Mosa RA, Oyedeji AO, Shode FO, Singh M, Opoku AR (2011)
Triterpenes from the stem bark of *Protorhus longifolia*
exhibit anti-platelet aggregation activity. Afr J Pharm
Pharmacol 5:2698–2714

Mosa RA, Nhleko ML, Dladla TV, Opoku AR (2014)
Antibacterial activity of two triterpenes from stem bark of
*Protorhus longifolia*. J Med Plant Res 8:686–670

Mulholland DA, Mahomed HA (2000) Isolation of Cneorubin
X, an unusual diterpenoid from *Ptaeroxylon obliquum*
(Ptaeroxylaceae). Biochem Syst Ecol 28:713–716

Mulholland DA, Langat MK, Crouch NR, Coley HM, Mutambi
EM, Nuzillard JM (2010) Cembranolides from the stem
bark of the southern African medicinal plant, *Croton
gratissimus* (Euphorbiaceae). Phytochemistry
71:1381–1386

Munayi RR (2016) Phytochemical investigation of *Bridelia micrantha* and *Tabernaemontana ventircosa* for cytotoxic principles against drug sensitive leukemia cell lines. University of Nairobi

Muthaura NC, Keriko MJ, Mutai C, Yenesew A, Heydenreich
M, Atilaw Y, Gathirwa WJ, Irungu NB, Derese S (2017)
Antiplasmodial, cytotoxicity and phytochemical con-
stituents of four *Maytenus* species used in traditional
medicine in Kenya. Nat Prod J 7:144–152

Nana F, Sandjo LP, Keumedjio F, Ambassa P, Malik R, Kuete
V, Rincheval V, Choudhary MI, Ngadjui BT (2012) Cer-
amides and cytotoxic constituents from *Ficus glumosa* Del.
(Moraceae). J Braz Chem Soc 23(3):482–487. https://doi.
org/10.1590/S0103-50532012000300015

Nasser AMAG, Court WE (1984) Stem bark alkaloids of *Rau-
volcia caffra*. J Ethnopharmacol 11:99–117

Ndwigah SN, Thoithi G, Mwangi J, Kibwage IO (2005) Con-
stituents of the stem bark of *Dombeya rotundifolia* Hochst.
East Cent Afr J Pharm Sci 8:40–42

Nishiyama Y, Moriyasu M, Ichimaru M, Tachibana Y, Kato A,
Mathenge SG, Nganga JN, Juma FD (1996) Acyclic
triterpenoids from *Ekebergia capensis*. Phytochemistry
42:803–807

Nkobole NK (2011) Antidiabetic activity of pentacyclic triter-
penes and flavonoids isolated from stem bark of *Terminalia
sericea* Burch. University of Pretoria, Ex DC

Norn S, Permin H, Kruse PR, Kruse E (2009) From willow bark
to acetylsalicylic acid. Dansk Medicinhistorisk Arbog
37:79–98

Noté OP, Mitaine-Offer A-C, Miyamoto T, Paululat T, Peg-
nyemb DE, Lacaille-Dubois M-A (2009) Tetrapterosides A
and B, two new oleanane-type saponins from *Tetrapleura
tetraptera*. Magn Reson Chem 47:277–282

Noté OP, Tapondjou AL, Mitaine-offer A-C, Miyamoto T,
Pegnyemb DE, Lacaille-Dubois M-A (2013) Triterpenoid
saponins from *Piptadeniastrum africanum* (Hook. f.) Bre-
nan. Phytochem Lett 6:505–510

Okwemba R, Tarus P, Machocho A, Wanyonyi A, Waweru I,
Onyancha J, Onani M, Amuka O (2018) Isolation, char-
acterization and biological activity of organic extractives
from *Calodendrum capense* (Lf) Thunb. (Rutaceae). J Med
Plants Res 12:139–163

Oyedeji-Amusa MO, Sadgrove NJ, Van Wyk B-E (2021) The
ethnobotany and chemistry of South African Meliaceae: a
review. Plants 10:1796

Passos FRS, Araújo-Filho HG, Monteiro BS, Shanmugam S,
Araújo AAdS, Almeida JRGdS, Thangaraj P, Júnior LJQ,
Quintans JdSS (2022) Anti-inflammatory and modulatory
effects of steroidal saponins and sapogenins on cytokines: a
review of pre-clinical research. Phytonomedicine 96:153842

Permin H, Norn S, Kruse E, Kruse PR (2016) On the history of
*Cinchona* bark in the treatment of Malaria. Dansk
Medicinhistorisk Arbog 44:9–30

Pertuit D, Mitaine-Offer A-C, Miyamoto T, Tanaka C, Dele-
masure S, Dutartre P, Lacaille-Dubois M-A (2015) A new
aromatic compound from the stem bark of *Terminalia
catappa*. Nat Prod Commun. https://doi.org/10.1177/
1934578X1501000652

Pertuit D, Mitaine-Offer A-C, Miyamoto T, Tanaka C, Delaude
C, Lacaille-Dubois M-A (2018a) Terpenoid glycosides
from the root's barks of *Eriocoelum microspermum* Radlk.
ex Engl. Phytochemistry 152:182–190

Pertuit D, Mitaine-Offer A-C, Miyamoto T, Tanaka C, Delaude
C, Lacaille-Dubois M-A (2018b) Triterpene saponins of
the root bark of *Olax obtusifolia* De Wild. Phytochem Lett
28:174–178

Pertuit D, Mitaine-Offer A-C, Miyamoto T, Tanaka C, Tran DK,
Delaude C, Lacaille-Dubois M-A (2019) Triterpenoid
saponins from the root bark of *Haplocoelum congolanum*.
Nat Prod Commun 14:1934578X19851369

Pettit GR, Cragg GM, Singh SB (1987) Antineoplastic agents,
122. Constituents of *Combretum caffrum*. J Nat Prod
50:386–391

Pettit GR, Singh SB, Boyd MR, Hamel E, Pettit RK, Schmidt
JM, Hogan F (1995) Antineoplastic agents. 291. Isolation
and synthesis of combretastatins A-4, A-5, and A-6. J Med
Chem 38:1666–1672

Phumthum M, Srithi K, Inta A, Junsongduang A, Tangjitman K,
Pongamornkul W, Trisonthi C, Balslev H (2018) Eth-
nomedicinal plant diversity in Thailand. J Ethnopharmacol
214:90–98

Picker K, Ritchie E, Taylor W (1976) The chemical constituents
of Australian *Flindersia* species. XXI. An examination of
the bark and the leaves of *F. laevicarpa*. Aust J Chem
29:2023–2036

Pilar Nicasio MD, Villarreal ML, Gillet F, Bensaddek L,
Fliniaux M-A (2005) Variation in the accumulation levels
of n, n-dimethyltryptamine in micro-propagated trees and in in vitro cultures of *Mimosa tenuiflora*. Nat Prod Res 19:61–67

Pino CJ, Scherer MA, Shastri VP (2014) Investigation of the transdermal transport of charged local anesthetics in the presence of triterpene saponin glycosides. Drug Deliv Transl Res 4:131–138

Ramadan MA, Ahmad AS, Nafady AM, Mansour AI (2009) Chemical composition of the stem bark and leaves of *Ficus pandurata* Hance. Nat Prod Res 23:1218–1230

Ramos YJ, Gouvêa-Silva JG, de Brito MD, Felisberto JS, Pereira RC, Sadgrove NJ, de Lima MD (2023) Chemophenetic and chemodiversity approaches: new insights on modern study of plant secondary metabolite diversity at different spatiotemporal and organizational scales. Rev Bras 33:49–72

Russo D, Kenny O, Smyth TJ, Milella L, Hossain MB, Diop MS, Rai DK, Brunton NP (2013) Profiling of phytochemicals in tissues from *Sclerocarya birrea* by HPLC-MS and their link with antioxidant activity. Int Sch Res Not 2013:283462

Sadgrove NJ (2020) Southern Africa as a ‘cradle of incense’ in wider African aromatherapy. Sci Afr 9:e00502. https://doi.org/10.1016/j.sciaf.2020.e00502

Sadgrove NJ (2022) Are South African wild foods the answer to rising rates of cardiovascular disease? Diversity 14:1014

Sadgrove NJ, Jones GL (2014a) Cytogeography of essential oil chemotypes of *Eremophila longifolia* F. Muell (*Scrophulariaceae*). Phytochemistry 105:43–51

Sadgrove NJ, Jones GL (2016b) Reviewing the importance of aromatic medicinal plants in the traditional pharmacopoeia of Australian aboriginal people. Acta Hort 1125:297–302. https://doi.org/10.17660/ActaHortic.2016.1125.38

Sadgrove NJ, Jones GL (2019) From petri dish to patient: bioavailability estimation and mechanism of action for antimicrobial and immunomodulatory natural products. Front Microbiol 10:2470

Sadgrove NJ, Simmonds MSJ (2022) Advances in understanding the role of plant phytochemicals in preventing cardiovascular disease. In: Preedy VR, Patel V (eds) Understanding and optimising the nutraceutical properties of fruit and vegetables. Burleigh Dodds Science Publishing Limited, Sawston, Cambridge, UK

Sadgrove N, Mijajlovic S, Tucker DJ, Watson K, Jones GL (2011) Characterization and bioactivity of essential oils from novel chemotypes of *Eremophila longifolia* (F. Muell) (*Myoporaceae*): a highly valued traditional Australian medicine. Flavour Fragr J 26:341–350

Sadgrove N, Jones GL, Greatrex BW (2014) Isolation and characterisation of (-)-genifuranal: the principal antimicrobial component in traditional smoking applications of *Eremophila longifolia* (*Scrophulariaceae*) by Australian aboriginal peoples. J Ethnopharmacol 154:758–766

Sadgrove NJ, Madeley LG, Van Wyk B-E (2019) Volatiles from African species of *Croton* (*Euphorbiaceae*), including new diterpenes in essential oil from *Croton gratissimus*. Heliyon 5:e02677

Sadgrove NJ, Oliveira TB, Khumalo GP, van Vuuren SF, van Wyk B-E (2020a) Antimicrobial isoflavones and derivatives from *Erythrina* (*Fabaceae*): structure activity

perspective (Sar & QSar) on experimental and mined values against *Staphylococcus aureus*. Antibiotics 9:223

Sadgrove NJ, Padilla-González GF, Telford IRH, Greatrex BW, Jones GL, Andrew R, Bruhl JJ, Langat MK, Melnikovaova I, Fernandez-Cusimamani E (2020b) *Prostanthera (Lamiaceae)* as a “cradle of incense”: chemophenetics of rare essential oils from both new and forgotten Australian ‘mint bush’ species. Plants 9:1570

Sadgrove NJ, Padilla-González GF, Green A, Langat MK, MasClaret E, Lyddiard D, Klepp J, Legendre SVA-M, Greatrex BW, Jones GL, Ramli IM, Leuner O, Fernandez-Cusimamani E (2021) The diversity of volatile compounds in Australia’s semi-desert genus *Eremophila* (*Scrophulariaceae*). Plants 10:785

Samie A, Housein A, Lall N, Meyer JJM (2009) Crude extracts of, and purified compounds from, *Pterocarpus angolensis*, and the essential oil of *Lippia javanica*: their in-vitro cytotoxicities and activities against selected bacteria and *Entamoeba histolytica*. Ann Trop Med Parasitol 103:427–439

Segun PA, Ogbole OO, Ismail FMD, Nahar L, Evans AR, Ajaiyeoba EO, Sarker SD (2019) Resveratrol derivatives from *Commiphora africana* (A. Rich.) Endl. display cytotoxicity and selectivity against several human cancer cell lines. Phytother Res 33:159–166

Shai LJ, McGaw LJ, Aderogba MA, Mdee LK, Eloff JN (2008) Four pentacyclic triterpenoids with antifungal and antibacterial activity from *Curtisia dentata* (Burm.f) C.A. Sm. leaves. J Ethnopharmacol 119:238–244

Shai LJ, McGaw LJ, Eloff JN (2009) Extracts of the leaves and twigs of the threatened tree *Curtisia dentata* (*Cornaceae*) are more active against *Candida albicans* and other microorganisms than the stem bark extract. S Afr J Bot 75:363–366

Shimoi K, Nakayama T (2005) Glucuronidase deconjugation in inflammation. Methods Enzymol 400:263–272

Shu P-H, Fei Y-Y, Li Y-M, Xu T, Lou Y-Y, Yang Y, Zhang H, Li N-C, Wei X-L, Xiao F-G, Huang J-H (2022) Isolation and characterization of bioactive phenolic compounds from *Cinnamomum camphora* barks. Holzforschung 76:391–396

Singh G, Maurya S, deLampasona MP, Catalan CAN (2007) A comparison of chemical, antioxidant and antimicrobial studies of cinnamon leaf and bark volatile oils, oleoresins and their constituents. Food Chem Toxicol 45:1650–1661

Sordat-Diserens I, Marston A, Hamburger M, Hostettmann K, Rogers C (1989) Novel prenylated xanthones from *Garcinia gerrardii* HARVEY. Helv Chim Acta 72:1001–1007

Sordat-Diserens I, Hamburger M, Rogers C, Hostettmann K (1992a) Dimeric xanthones from *Garcinia livingstonei*. Phytochemistry 31:3589–3593

Sordat-Diserens I, Rogers C, Sordat B, Hostettmann K (1992b) Prenylated xanthones from *Garcinia livingstonei*. Phytochemistry 31:313–316

Steyn PS, Van den Heerver JP, Vosloo HCM, Ackerman LGJ (1998) Biologically active substances from *Zanthoxylum capense* (thumb.) Harv. S Afr J Sci 94:391–393

Tiksa T, Abdissa D, Abdissa N (2019) Chemical constituents of *Securidaca longipedunculata* root bark and evaluation of their antibacterial activities. Ethiop J Educ Sci 14:1–8
Timité G, Mitaine-Offer A-C, Miyamoto T, Tanaka C, Paululat T, Delaude C, Lacaille-Dubois M-A (2010) Presenegenin glycosides from *Securidaca welwitschii*. Helv Chim Acta 93:2237–2244

Tlhapi DB, Ramaite IDI, Van Ree T, Anokwuru CP, Orazio T-S, Hoppe HC (2019) Isolation, chemical profile and antimalarial activities of bioactive compounds from *Rauvolfia caffra* Sond. Molecules 24:39

Tomás-Barberán FA, García-Villalba R, González-Sarrías A, Selma MV, Espín JC (2014) Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J Agric Food Chem 62:6535–6538

Tsao R, Yang R, Young JC (2003) Antioxidant isoflavones in osage orange, *Maclura pomifera* (Raf.) Schneid. J Agric Food Chem 51:6445–6451

Tshikalange TE, Hussein AA (2010) Cytotoxicity activity of isolated compounds from *Elaeodendron transvaalense* ethanol extract. J Med Plants Res 4:1695–1697

Ucella-Filho JGM, Freire AdSM, Carréra JC, Lucas FMF, Zucolotto SM, Dias Júnior AF, Mori FA (2022) Tannin-rich bark extract of plants as a source of antimicrobial bioactive compounds: a bibliometric analysis. S Afr J Bot 150:1038–1050

van Wyk AS, Prinsloo G (2018) Medicinal plant harvesting, sustainability and cultivation in South Africa. Biol Cons 227:335–342

Verma RS, Padalia RC, Goswami P, Verma SK, Chauhan A, Darokar MP (2014) Chemical composition and antibacterial activity of foliage and resin essential oils of *Araucaria cunninghamii* Aiton ex D. Don and *Araucaria heterophylla* (Salisb.) Franco from India. Ind Crops Prod 61:410–416

Weigenand O, Hussein AA, Lall N, Meyer JJM (2004) Antibacterial activity of naphthoquinones and triterpenoids from *Euclea natalensis* root bark. J Nat Prod 67:1936–1938

Wiersum KF, Dold AP, Husselman M, Cocks M (2006) Cultivation of medicinal plants as a tool for biodiversity conservation and poverty alleviation in the Amatola region, South Africa. In: Bogers RJ, Craker LE, Lange D (eds) Medicinal and aromatic plants. Springer Netherlands, Dordrecht, pp 43–57

Yaouba S, Koch A, Guantai EM, Derese S, Irungu B, Heydenreich M, Yenesew A (2018) Alkenyl cyclohexanone derivatives from *Lannea rivae* and *Lannea schweinfurthii*. Phytochem Lett 23:141–148

Yelani T, Hussein AA, Meyer JJM (2010) Isolation and identification of poisonous triterpenoids from *Elaeodendron croceum*. Nat Prod Res 24:1418–1425

Yoshida T, Amakura Y, Yoshimura M (2010) Structural features and biological properties of ellagitannins in some plant families of the order myrtales. Int J Mol Sci 11:79–106

Zhou J, Zhang J, Gao G, Wang H, He X, Chen T, Ke L, Rao P, Wang Q (2019) Boiling licorice produces self-assembled protein nanoparticles: a novel source of bioactive nanomaterials. J Agric Food Chem 67:9354–9361

Zschocke S, van Staden J, Paulus K, Bauer R, Horn MM, Munro OQ, Brown NJ, Drewes SE (2000) Stereostructure and anti-inflammatory activity of three diastereomers of ocobullenone from *Ocotea bullata*. Phytochemistry 54:591–595

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