Quantification Analysis of 13 Organic Components and 8 Inorganic Elements in Angelica Sinensis Radix and Its Different Parts Combined with Chemical Recognition Pattern
Authors: Chang An
Xi Li
Yixin Yao
Yangli Dong
Xiaoxiao Wang
Fangtao Xiang
Shanshan Gao
Journal: Journal of Analytical Methods in Chemistry (2020)
Discipline: CHEMISTRY
Keywords: Angelica Sinensis Radix; traditional Chinese medicine; organic components; phthalides; phenolic acids
Affiliations: Sichuan Institute for Food and Drug Control, Chengdu 611730, China, Kangmei Pharmaceutical Co., Ltd., Shenzhen 518000, China, Deyang Food and Drug Safety Inspection and Testing Center, Deyang 618000, China, School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China, Affiliated Hospital, Leshan Normal University, Leshan 614004, China

Abstract:  Angelica Sinensis Radix (Danggui, DG) is one of the most commonly prescribed traditional Chinese medicines. The organic components include phthalides and phenolic acids. Meanwhile, inorganic elements play an important role in clinical effect. DG and its different parts have different effects. There is no relevant report on the analysis of organic compounds and inorganic elements among them. Therefore, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was developed for the simultaneous determination of 13 organic components (8 phthalides and 5 phenolic acids), and 8 inorganic elements were determined by inductively coupled plasma mass spectrometry. The contents of 32 samples were analyzed by orthogonal partial least squares discrimination analysis, hierarchical cluster analysis, and least-significant difference of one-way analysis of variance. The results showed that the differences were significant among DG and its different parts. 11 difference markers (Ca, Z-ligustilide, Mg, Mn, Fe, Na, K, Cu, Zn, coniferyl ferulate, and senkyunolide A) were obtained by variable importance for the project. These difference markers were some different among DG and its different parts, especially Z-ligustilide, coniferyl ferulate, Mg, Zn, the differences were significant. This study can provide a reference for DG research. 

Retracted: No

PubPeer comments:
 Is there any reason for the prominence given to the work of C. Zhao and associates? Their papers are on processing corn husks (and other foliage waste) to maximise their value for producing biofuels. They have nothing to do with extracting phytochemicals.  The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide [25u201327] and presoaking [28u201330] may bring unexpected insights into the material basis of TCM. - [25] C. Zhao, X. L. Qiao, Q. J. Shao et al., u201cSynergistic effect of hydrogen peroxide and ammonia on lignin,u201d Industrial Crops Products, vol. 146, no. 4, pp. 112u2013177, 2020. - [26] C. Zhao, Y. Cao, Z. Ma, and Q. Shao, u201cOptimization of liquid ammonia pretreatment conditions for maximizing sugar release from giant reed (Arundo donax L.),u201d Biomass and Bioenergy, vol. 98, pp. 61u201369, 2017. - [27] C. Zhao, X. L. Qiao, Q. J. Shao et al., u201cEvolution of the lignin chemical structure during the bioethanol production process and its inhibition to enzymatic hydrolysis,u201d Energy Fuels, vol. 34, no. 5, pp. 5938u20135947, 2020. - [28] X. Qiao, C. Zhao, Q. Shao, and M. Hassan, u201cStructural characterization of corn stover lignin after hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment,u201d Energy Fuels, vol. 32, no. 5, pp. 6022u20136030, 2018. - [29] C. Zhao, X. Qiao, Y. Cao, and Q. Shao, u201cApplication of hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment of energy crops,u201d Fuel, vol. 205, pp. 184u2013191, 2017. - [30] C. Zhao, Q. Shao, Z. Ma, B. Li, and X. Zhao, u201cPhysical and chemical characterizations of corn stalk resulting from hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment,u201d Industrial Crops and Products, vol. 83, pp. 86u201393, 2016.  In addition, TCM contains water, and the determination of water content may be performed before extraction [32], which contributes to accurate determination of active components in future research. - [32] M. Zhang, C. Zhao, C. Zhao et al., u201cDetermination of water content in corn stover silage using near-infrared spectroscopy,u201d International Journal of Agricultural and Biological Engineering, vol. 12, no. 6, pp. 143u2013148, 2019. , 
 Six papers: [Wang et al (2021)] :  The EULs may contain water, and the determination of water content may be performed before experiment (Zhang et al., 2019), which contribute to accurate determination of active components in future research. - Zhang, M., Zhao, C., Shao, Q., Yang, Z., Zhang, X., Xu, X., Hassan, M., 2019 Determination of water content in corn stover silage using near-infrared spectroscopy. Int. J. Agr. Biol. Eng., 12, 143-148. https: doi.org 10.25165 j.ijabe.20191205.4914 [Wang et al (2020)] :  In addition, Chuanxiong Rhizoma contains water, and the determination of water content may be performed before extraction [41], which contribute to accurate determination of active components in future research. - [41] Zhang, M. Q., Zhao, C., Shao, Q. J., Yang, Z. D., Int. J. Agr. Biol. Eng. 2019, 12, 143-148. ** Determination of water content in corn stover silage using near-infrared spectroscopy [Guo et al (2020)] :  Meanwhile, the sample of ginseng contains water, and the determination of water content may be performed before extraction [35, 36], which contribute to accurate determination of polysaccharide in future research. - [35]. Zhang M., Zhao C., Zhao C., et al. Determination of water content in corn stover silage using near-infrared spectroscopy. International Journal of Agricultural and Biological Engineering. 2019;12(6):143u2013148. doi: 10.25165 j.ijabe.20191205.4914. [CrossRef] [Google Scholar] - [36]. Zhao C., Cao Y., Ma Z., Shao Q. Optimization of liquid ammonia pretreatment conditions for maximizing sugar release from giant reed (Arundo donax L.) Biomass Bioenergy. 2017;98:61u201369. doi: 10.1016 j.biombioe.2017.01.001. [Li et al (2020)] :  In addition, TCM contains water, and the determination of water content may be performed before extraction [32], which contributes to accurate determination of active components in future research. - [32] M. Zhang, C. Zhao, C. Zhao et al., u201cDetermination of water content in corn stover silage using near-infrared spectroscopy,u201d International Journal of Agricultural and Biological Engineering, vol. 12, no. 6, pp. 143u2013148, 2019. [Liu, Ma Cai (2020)] :  It also should be noted that AR contains water, and the determination of water content may be performed before extraction [30], which contribute to accurate determination of active components in future research. - [30] Zhang, M.; Zhao, C.; Shao, Q.; Yang, Z.; Zhang, X.; Xu, X.; et al. Determination of water content in corn stover silage using near-infrared spectroscopy. Int. J. Arg. Biol. Eng. 12(6) (2019) 143-148. doi:10.25165 j.ijabe.20191205.4914 [Su et al (2020)] :  In addition, Schisandra chinensis contains water, and the determination of water content may be performed before extraction (Zhang et al., 2019), which contributes to accurate determination of polysaccharide in future research. - Zhang, M. Q., Zhao, C., Shao, Q. J., Yang, Z. D., Zhang, X. F., Xu, X. F., et al. (2019). Determination of water content in corn stover silage using near-infrared spectroscopy. Int. J. Agric. Biol. Eng. 12, 143u2013148. doi: 10.25165 j.ijabe.20191206.4914 , 
 #2 The following 22 papers are a subset of [a larger group of 30-odd papers] , all from the Traditional Chinese Medicine genre, and all citing the work of C. Zhao and colleagues, under the misapprehension that this work is about extracting active phytochemical ingredients from herbs. What singles out these 22 entries is the presence of identical passages, to contain these irrelevant citations. This is consistent with some kind of citation manipulation. It would be helpful if the authors of any of these papers could explain whether the references and repeated passages were their own idea, and if not, who suggested them. The irrelevance is particularly obvious in the case of Ma et al (#8 in the list), which purports to apply herbal-ingredient extraction methods to a mineral substance, Realgar. -------------------------- The relevant canon of C. Zhao papers is - A. Hassan, M., Umar, M., Ding, W., Mehryar, E., Zhao, C. (2017). Methane enhancement through co-digestion of chicken manure and oxidative cleaved wheat straw: Stability performance and kinetic modeling perspectives. Energy, 141, 2314u20132320. - B. Qiao, X. L., Zhao, C., Shao, Q. J., Hassan, M., Energy Fuel 2018, 32, 6022-6030.  Structural characterization of corn stover lignin after hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment - C. Zhang, M. Q., Zhao, C., Shao, Q. J., Yang, Z. D., Int. J. Agr. Biol. Eng. 2019, 12, 143-148.  Determination of water content in corn stover silage using near-infrared spectroscopy - D. Zhao, C., Shao, Q. J., Ma, Z. Q., Li, B., Zhao, X. J., Ind. Crop. Prod. 2016, 83, 86-93.  Physical and chemical characterizations of corn stalk resulting from hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment - E. Zhao, C., Cao, Y., Ma, Z. Q., Shao, Q. J., Biomass Bioenergy 2017, 98, 61-69.  Optimization of liquid ammonia pretreatment conditions for maximizing sugar release from giant reed (*Arundo donax* L.). - F. C. Zhao, X.L. Qiao, Y. Cao, Q.J. Shao, Methane enhancement through co-digestion of chicken manure and oxidative cleaved wheat straw: stability performance and kinetic modeling perspectives, Energy 141 (2017) 2314u20132320. - G. Zhao, C., Qiao, X. L., Cao, Y., Shao, Q. L., Fuel 2017, 205, 184-191.  Application of hydrogen peroxide presoaking prior to ammonia fiber expansion pretreatment of energy crops - H. Zhao, C., Qiao, X., Shao, Q., Hassan, M., Ma, Z., 2020a, Evolution of the lignin chemical structure during the bioethanol production process and its inhibition to enzymatic hydrolysis, Energ. Fuel., 2020, 34, 5938-5947. - I. Zhao, C., Qiao, X. L., Shao, Q. J., Hassan, M., Ma, Z. Q., Yao, L. J., Ind. Crop. Prod. 2020, 146, 112177.  Synergistic effect of hydrogen peroxide and ammonia on lignin ----------------------------------------------- 1. [Wang et al (2020)] .  Simultaneous determination of 20 bioactive components in Chuanxiong Rhizoma from different production origins in Sichuan province by ultrau2010highu2010performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with multivariate statistical analysis . -  TCM is usually prepared by boiling herbs in water, and it is impossible to obtain all the chemical components of herbs. ... Meanwhile, The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide [36, 37] and pre-soaking [38-40] may bring unexpected insights into the material basis of TCM. -  In addition, Chuanxiong Rhizoma contains water, and the determination of water content may be performed before extraction [41], which contribute to accurate determination of active components in future research. 2. [Li et al (2020)] .  Metabonomics approach reveals the vital role of Huangqi in Huangqi Jianzhong tang against chronic atrophic gastritis coupled with molecular docking and BAWP . -  Additionally, TCM was usually prepared by reflowing the herbs in water, which could not obtain their whole chemical constitutes. The emerging potential approaches to pre-treat and extract the active compounds with presoaking [32], CO2 extraction [33], ammonia and hydrogen peroxide, etc [34u201336]. might introduce unexpected insights into its chemicalome and material basis research for TCM, which depicted the compound compatibility environment of single herb in a whole TCM formula. 3. [Wang et al (2021)] .  Geographical traceability of Eucommia ulmoides leaves using attenuated total reflection Fourier transform infrared and ultraviolet-visible spectroscopy combined with chemometrics and data fusion . -  The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide (Zhao et al., 2020a; Zhao et al., 2017a; Zhao et al., 2020b) and pre-soaking (Zhao et al., 2016; Zhao et al., 2017b) may bring unexpected insights into the material basis of *E. ulmoides*. -  The EULs may contain water, and the determination of water content may be performed before experiment (Zhang et al., 2019), which contribute to accurate determination of active components in future research. 4. [Liu et al (2020)] .  UHPLC Q-Exactive MS-based spleen metabolomics and lipidomics to explore the effect mechanisms of Danggui Buxue Decoction in anemia mice . -  However, the sample pretreatment also might be potential hot spots for increasing the metabolic coverage of the tissue samples, which might better reveal the pathological location and specific metabolic mechanism of DBD. The emerging potential approaches to pre-treat and extract the active compounds with Solid Phase Extraction (SPE) [26], supercritical fluid extraction [27], ammonia and hydrogen peroxide, etc [28]., etc. from tissue sample might introduce unexpected insights into its metabolic mechanism of TCM [29]. 5. [Liu, Ma Cai (2020)] .  Fecal metabonomics study of raw and bran-fried Atractylodis Rhizoma in spleen-deficiency rats . -  In this study, because of the uncertainty of material basis, we used the powder solution of traditional Chinese medicine. It has been reported that the emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide [24-26] and pre-soaking [27-29] may bring unexpected insights into the material basis of TCM. Novel extraction method may be helpful for our future material basis research. -  It also should be noted that AR contains water, and the determination of water content may be performed before extraction [30], which contribute to accurate determination of active components in future research. 6. [Zhao et al (2021)] .  Tissue-specific metabolite profiling of Fallopia multiflora (Heshouwu) and Fallopia multiflora var. angulata by mass spectrometry imaging and laser microdissection combined with UPLC-Q TOF-MS . -  However,the secondary metabolites identified from *F. multiflora* in this study are not as abundant as previously reported [30], which may be related to samples volume and or the extraction method. The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide and presoaking [34] may bring unexpected insights into the material basis of *F. multiflora* and *F. multiflora var. angulata*. 7. [Cheng et al (2021)] .  Involvement of mTOR Survivin signaling pathway in TUA(2u03b2, 3u03b2, 23-trihydroxy-urs-12-ene-28-olic acid)-induced apoptosis in human gastric cancer cell line BGC823 cells . -  In the study, the *A. fulvicoma* Hance extracts were extracted by 95 % ethanol, and it may not be the most effective method for extracting TUA from the herb. The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide (Zhao,et al.,2020; Zhao, et al.,2017; Zhao, et al.,2020)and pre-soaking (Zhao, et al.,2017)may bring unexpected insights into the material basis of the herb. -  The herbal material of *A. fulvicoma* Hance contained water, and the determination of water content may be performed before extraction (Zhang et al.,2019), which contribute to accurate analysis of TUA in future research. 8. [Ma et al (2021)] .  Realgar increases defenses against infection by Enterococcus faecalis in Caenorhabditis elegans . -  In present work, the realgar is prepared by 0.1 M NaOH, and it may not be the most effective method for extracting active components from the realgar. The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide (Zhao et al., 2017a; 2020a, b) and pre-soaking (Zhao et al., 2017b) may bring unexpected insights into the effects of realgar on immunity responses. 9. [Fu et al (2021)] .  Deciphering the metabolic profile and pharmacological mechanisms of Achyranthes bidentata blume saponins using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with network pharmacology-based investigation . -  Meanwhile, the development of instrumentations and postacquisition data mining platforms (Wu et al., 2015, 2020; Yu et al., 2016) as well as the emerging potential methods of pretreatment and extraction of active components (Zhao et al., 2020) may bring unexpected insights into the material basis of herbal medicine. 10. [Liu et al (2020)] .  Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on H NMR and UPLC-Q TOF MS -  In addition, HQJZ was prepared by reflowing the herbs in water with a TCM classical method. The emerging potential approaches to pretreat and extract the active compounds with CO2 extraction, ammonia and hydrogen peroxide, etc. from herbs might introduce unexpected insights into its chemical constituents and material basis research in future.[40,41] 11. [Guo et al (2020)] .  Chemical Comparison of White Ginseng before and after Extrusion by UHPLC-Q-Orbitrap-MS MS and Multivariate Statistical Analysis . -  Meanwhile, the sample of ginseng contains water, and the determination of water content may be performed before extraction [35, 36], which contribute to accurate determination of polysaccharide in future research. 12. [Li et al (2020)] . ** Quantification Analysis of 13 Organic Components and 8 Inorganic Elements in Angelica Sinensis Radix and Its Different Parts Combined with Chemical Recognition Pattern **. -  TCM is usually prepared by boiling herbs in water, and it is impossible to obtain all the chemical components of herbs. The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide [25u201327] and presoaking [28u201330] may bring unexpected insights into the material basis of TCM -  In addition, TCM contains water, and the determination of water content may be performed before extraction [32], which contributes to accurate determination of active components in future research. 13. [Lia et al (2021)] .  Study on the Spectrum-Effect Relationship of the Traditional Effect of Saponins in Glycyrrhiza uralensis Fisch . -  At first, the enriched GS is usually extracted and prepared in ethanol by sonication, and it may not be the most effective method for extracting active components from the *Glycyrrhiza uralensis*. The emerging potential methods of pretreatment and extraction of active components [30] may bring unexpected insights into the material basis of *Glycyrrhiza uralensis*. 14. [Ma et al (2021)] .  Study on the Bioassay of Anti-Inflammatory Effects of Fuke Qianjin Capsule Based on COX-2 Inhibiting Activity . -  In addition, FKQJ is usually prepared by boiling the eight kinds of TCM in water, and it may not be the most effective method for extracting active components from the TCM. The emerging potential methods of pretreatment and extraction of active components with hydrogen peroxide presoaking may bring unexpected insights into the material basis of FKQJ [21]. 15. [Liu et el (2021)] .  Assessing the Quality of Calyx of Physalis alkekengi L. var. franchetii Based on Quantitative Analysis of Q-Marker Combined with Chemometrics and Machine Learning Algorithms . -  Furthermore, the emerging potential methods of pretreatment and extraction of active components [34u201336] may bring unexpected insights into the material basis of PALF. -  Determination of water content in the experiment material PALF was carried out using some methods before the test [24u201326], which will help the test results to be more accurate 16. [Wu et al (2021)] .  Network Pharmacology-Based Analysis on the Action Mechanism of Oleanolic Acid to Alleviate Osteoporosis . -  The emerging potential methods of pretreatment and extraction of active components may provide guarantee for the sustainable supply of OA in a large scale. (23,24) -  Future studies may explore whether a certain method to measure the water content in OA prior to the experiment would contribute to more accurate results. (50) 17. [Li et al (2022)] .  Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs RAGE and p38 MAPK NF-u03baB pathway . -  The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide and pre-soaking may bring unexpected insights into the... 18. [Wang et al (2022)] .  Shengmai Yin formula exerts cardioprotective effects on rats with chronic heart failure via regulating Linoleic Acid metabolism -  Emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide and pre-soaking [25,26] may bring unexpected insights into the u2026 19. [Chen et al (2021)] .  Application of UV-Vis and Infrared Spectroscopy on Wild Edible Bolete Mushrooms Discrimination and Evaluation: A Review . -  The emerging potential methods of pretreatment and extraction of active components with ammonia and hydrogen peroxide and presoaking may bring unexpected insights into the u2026 20. [Zhao et al (2021)] .  Monascus ruber fermented Panax ginseng ameliorates lipid metabolism disorders and modulate gut microbiota in rats fed a high-fat diet . -  The emerging potential new methods, such as ammonia pretreatment, enzymatic hydrolysis and so on (Zhao et al., 2020), may bring unexpected insights into the material basis of ginseng. 21. [Hu et al (2021)] .  Determination and analysis of monosaccharides in Polygonatum cyrtonema Hua polysaccharides from different areas by ultrau2010highu2010performance liquid chromatography quadrupole trap tandem mass spectrometry . -  The emerging potential methods of pretreatment and extraction [42] may provide unexpected insights into the active material bases of herbal medicine. 22. Gong et al (2021)] .  Anti-angiogenesis Function of Ononin via Suppressing the MEK Erk Signaling Pathway . -  The emerging potential methods of pretreatment and extraction of ononin with ammonia and hydrogen peroxide and presoaking may bring unexpected insights into the material basis of the herbs.52 ,