bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rutin prevents inflammation induced by lipopolysaccharide in RAW 264.7 cells via conquering the TLR4-MyD88-TRAF6-NF-κB signalling pathway
Authors: Tian Chunlian , Liu Xin , Chang Yu , Wang Ruxia , Yang Mei , Liu Mingchun 
Published: January 2021

Abstract

Objectives
Inflammation widely exists in many diseases and poses a great threat to human and animal health. Rutin, quercetin-3-rhamnosyl glucoside, has a variety of pharmacological effects, including anti-oxidant, anti-inflammatory, antibacterial, anticancer and radioresistance effects. The current study focused on evaluation of its anti-inflammatory activity and described the mechanism of rutin in lipopolysaccharide-induced RAW 264.7 cells.

Methods
The related gene and protein expression levels were investigated by quantification real-time PCR and western blotting, respectively.

Key findings
This study revealed that rutin can decrease inducible nitric oxide synthase (iNOS) gene and protein expression levels, effectively increase IκB gene expression, reduce toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6) and p65 gene expression and inhibit the phosphorylation of IκB and p65 and the proteins expression of TLR4, MyD88 and TRAF6.

Conclusions
These results suggest that rutin might exert anti-inflammatory effect on LPS-stimulated RAW 264.7 cells and will be potentially useful as an adjuvant treatment for inflammatory diseases.
Hypericin-mediated photodynamic therapy for the treatment of cancer: a review
Authors: Dong Xiaoxv , Zeng Yawen , Zhang Zhiqin , Fu Jing , You Longtai , He Yuanyuan , Hao Yang , Gu Zili , Yu Zhenfeng , Qu Changhai , Yin Xingbin , Ni Jian , Cruz Luis J 
Published: January 2021

Abstract

Objectives
Hypericin is a polycyclic aromatic naphthodianthrone that occurs naturally. It is also an active ingredient in some species of the genus Hypericum. Emerging evidence suggests that hypericin has attracted great attention as a potential anticancer drug and exhibits remarkable antiproliferative effect upon irradiation on various tumour cells. This paper aims to summarise the anticancer effect and molecular mechanisms modulated by hypericin-medicated photodynamic therapy and its potential role in the cancer treatment.

Key findings
Hypericin-medicated photodynamic therapy could inhibit the proliferation of various tumour cells including bladder, colon, breast, cervical, glioma, leukaemia, hepatic, melanoma, lymphoma and lung cancers. The effect is primarily mediated by p38 mitogen-activated protein kinase (MAPK), JNK, PI3K, CCAAT-enhancer-binding protein homologous protein (CHOP)/TRIB3/Akt/mTOR, TRAIL/TRAIL-receptor, c-Met and Ephrin-Eph, the mitochondria and extrinsic signalling pathways. Furthermore, hypericin-medicated photodynamic therapy in conjunction with chemotherapeutic agents or targeted therapies is more effective in inhibiting the growth of tumour cells.

Summary
During the past few decades, the anticancer properties of photoactivated hypericin have been extensively investigated. Hypericin-medicated photodynamic therapy can modulate a variety of proteins and genes and exhibit a great potential to be used as a therapeutic agent for various types of cancer.
Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-κB transcription factor and NLRP3 inflammasome activation
Authors: Ogunrinade Folashade A , Guetchueng Stephanie T , Katola Folashade O , Aderogba Mutalib A , Akande Idowu S , Sarker Satyajit D , Olajide Olumayokun A 
Published: January 2021

Abstract

Objectives
The effects of a root extract of Zanthoxylum zanthoxyloides on neuroinflammation in BV-2 microglia stimulated with LPS and hemozoin were investigated.

Methods
ELISA, enzyme immunoassay and Griess assay were used to evaluate levels of cytokines, PGE2 and NO in culture supernatants, respectively. Microglia-mediated neurotoxicity was evaluated using a BV-2 microglia-HT-22 neuron transwell co-culture.

Key findings
Treatment with Z. zanthoxyloides caused reduced elevated levels of TNFα, IL-6, IL-1β, NO and PGE2, while increasing the levels of IL-10. In addition, there were reduced levels of iNOS and COX-2 proteins. This was accompanied by a prevention of microglia-mediated damage to HT-22 mouse hippocampal neurons. Z. zanthoxyloides reduced elevated levels of phospho-IκB and phospho-p65, while preventing degradation of IκB protein and DNA binding of p65. Further mechanistic studies revealed that Z. zanthoxyloides reduced the levels of pro-IL-1β and IL-1β in hemozoin-activated BV-2 microglia. This was accompanied by a reduction in caspase-1 activity and NLRP3 protein expression. Bioassay-guided fractionation resulted in the isolation of skimmianine as an anti-inflammatory compound in Z. zanthoxyloides.

Conclusion
This is the first report showing the inhibition of neuroinflammation in LPS- and hemozoin-activated BV-2 microglia by the root extract of Z. zanthoxyloides by targeting the activation of both NF-κB and NLRP3 inflammasome.
Crude polysaccharide from the milky mushroom, Calocybe indica, modulates innate immunity of macrophage cells by triggering MyD88-dependent TLR4/NF-κB pathway
Authors: Ghosh Sandipta , Khatua Somanjana , Dasgupta Adhiraj , Acharya Krishnendu 
Published: January 2021

Abstract

Objectives
Calocybe indica is a famous nutritious food in Asian countries and one of the most widely cultivated mushrooms in the world. Here, we have isolated crude polysaccharides from this mushroom, characterized it and investigated its antioxidant and immunostimulatory potential.

Methods
The polysaccharide was chemically characterized by spectrophotometry, FTIR and high-performance thin layer chromatography and tested its antioxidant potential by in vitro assays. Immunomodulatory activity and its underlying signalling process were ascertained in RAW 264.7 cells.

Key findings
The polysaccharide consisted of D-glucose (β-linked sugars), D-mannose and D-galactose, where backbone was organized in random coil structure. Preliminary investigation of the bioactivity of the polysaccharide revealed its antioxidant potential. The polysaccharide could noticeably induce phagocytic activity and production of immune mediators in macrophage cells. The polysaccharide was found to enhance the expression of pro-inflammatory cytokines and activate NF-κB signalling pathway by overexpressing MyD88, Iκ-Bα and NF-κB. Further studies indicated the polysaccharide binds to the toll-like receptor 4 to manifest its immunostimulatory activity in macrophage cells.

Conclusions
Our findings indicate potential therapeutic properties of the crude polysaccharide of C. indica which might provide the means to treat various radical induced and immunodeficiency disorders in the days to come.
Combination of urine and faeces metabolomics to reveal the intervention mechanism of Polygala tenuifolia compatibility with Magnolia officinalis on gastrointestinal motility disorders
Authors: Ma Rong , Xie Qian , Wang Jian , Huang Lihua , Guo Xiaoqing , Fan Yamei 
Published: January 2021

Abstract

Objectives
To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT.

Methods
Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT–MO on PT-induced disorders.

Key findings
PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT–MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT–MO intervention mechanism.

Conclusions
The PT–MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.
Pharmacological characterisation of anticonvulsant effects elicited by erythrartine
Authors: dos Reis Suelen Lorenzato , Gelfuso Erica A , Fachin Ana Lúcia , Pereira Ana Maria Soares , Beleboni Renê O 
Published: January 2021

Abstract

Objectives
The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants.

Methods
Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination.

Results
Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals.

Conclusion
Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.
Physcion-8-O-β-d-glucoside interferes with the nuclear factor-κB pathway and downregulates P-glycoprotein expression to reduce paclitaxel resistance in ovarian cancer cells
Authors: Li Xue , He Yuanqi , Wei Liqun , Zhang Jianzhong , Li Xiaoxiao , Cui Weiwei , Zhang Shihong 
Published: January 2021

Abstract

Objective
This study assessed whether physcion-8-O-beta-D-monoglucoside (PG) sensitises paclitaxel (PTX)-resistant ovarian cancer cells and explored the underlying mechanism.

Methods
Ovarian cancer SK-OV-3 cells were used to establish PTX-resistant SK-OV-3 (SK-OV-3/PTX) cells. The Cell Counting Kit-8 assay and crystal violet staining were used to determine cell viability. P-glycoprotein (P-gp) and nuclear factor (NF)-κB expression and cell distributions were detected using immunofluorescence. Cell apoptosis and protein expression changes were detected using flow cytometry and western blotting, respectively. Effect of PG in vivo was evaluated using a xenograft tumour model. P-gp expression in tumour tissues was detected using immunohistochemical staining.

Key findings
PG (1–10 μm) did not significantly affect SK-OV-3/PTX cell proliferation but significantly downregulated P-gp expression. PG pretreatment (1–10 μm) enhanced PTX cytotoxicity. PG treatment decreased the quantity of phosphorylated-NF-κB p65 in SK-OV-3/PTX cell total proteins and upregulated IKBα expression. Simultaneously, it decreased NF-κB p65 levels in nuclear proteins. PG (1–10 μm) inhibited NF-κB p65 entry into the nucleus. PTX plus PG significantly inhibited SK-OV-3/PTX xenograft tumour growth. PG (1–10 μm) reduced P-gp expression in transplanted tumour tissue.

Conclusions
PG can enhance the sensitivity of PTX-resistant ovarian cancer cells SK-OV-3/PTX to PTX, and this effect is related to inhibiting NF-κB from entering the nucleus and down-regulating the expression of P-gp protein.
Comparing the pharmacokinetics of 13α,21-dihydroeurycomanone and eurycomanone exclusively enriched in Eurycoma longifolia extracts and their spermatogenesis enhancement in andrographolide-induced oligospermia in rats
Authors: Chung Wan-Jie , Chan Kit-Lam , Lee Chong-Yew 
Published: January 2021

Abstract

Objectives
The quassinoids eurycomanone (EN) and 13α,21-dihydroeurycomanone (DHY) of Eurycoma longifolia Jack are reported to enhance spermatogenesis. This study aims to profile the pharmacokinetics of DHY, a minor and hitherto unstudied constituent, evaluate its spermatogenesis enhancement property and compare these attributes with that of the predominant EN.

Methods
Crude Eurycoma longifolia extract was chromatographed into a DHY-enriched extract (DHY-F) and an EN-enriched extract (EN-F). Male Sprague–Dawley rats were administered intravenously and orally with both extracts and their plasma levels of both quassinoids were determined. The extracts were then tested for their spermatogenesis augmentation ability in normal rats and an andrographolide-induced oligospermia model.

Key findings
Chromatographic enrichment resulted in a 28-fold increase of DHY in DHY-F and a 5-fold increase of EN in EN-F compared with non-chromatographed crude extracts. DHY showed better oral bioavailability (1.04 ± 0.58%) than EN (0.31 ± 0.19%). At 5 mg/kg, EN exhibited higher efficacy in spermatogenesis enhancement in normal rats and restoration of oligospermia to normal sperm profile versus DHY.

Conclusions
Despite the better pharmacokinetic profile of DHY, EN remains the main chemical contributor to plant bioactivity. DHY-F and EN-F represent improvements in developing Eurycoma longifolia as a potential phytomedicine for male infertility particularly oligospermia.
Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma
Authors: Xue Danfeng , Zhou Xiongming , Qiu Jiaxuan 
Published: January 2021

Abstract

Objectives
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.

Methods
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.

Key findings
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.

Conclusions
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.
l-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats
Authors: Zhang Wenwen , Wen Jianxia , Jiang Yinxiao , Hu Qichao , Wang Jian , Wei Shizhang , Li Haotian , Ma Xiao 
Published: January 2021

Abstract

Objectives
Stroke is one of the leading causes of disability and death worldwide, and ischaemic stroke is the most common subtype. Moreover, we found that L-borneol has an obvious therapeutic effect on cerebral ischaemia. This study aimed to investigate the potential mechanism of L-borneol in permanent middle cerebral artery occlusion (pMCAO) rats via the mitochondrial calcium uniporter (MCU)-related apoptosis cascade.

Methods
A pMCAO model was used to simulate cerebral ischaemia, and neurological function was evaluated. Cerebral infarction was observed by TTC staining. HE staining was also used to reflect the pathophysiological changes in the rat hippocampus and cortex. Furthermore, MCU-related signals and apoptosis signalling pathways were detected at both the gene and protein levels.

Results
The neurological function scores of the high-dose L-borneol (H-B) group, medium-dose L-borneol (M-B) group and low-dose L-borneol (L-B) group were significantly lower than that of the model group at 24 h (P &lt; 0.05, P &lt; 0.01). High and medium doses of L-borneol could reverse the cerebral infarction area, similar to Nimotop. After HE staining, the cells in the H-B group and M-B group were neatly and densely arranged, with largely normal morphological structures. High-dose L-borneol could significantly reduce the gene and protein levels of Apaf-1, Bad and Caspase-3 and increase the expression of Bcl-2 (P &lt; 0.05, P &lt; 0.01). In addition, the MCU expression of the H-B group was significantly decreased compared with that of the model group at both the gene and protein levels (P &lt; 0.05, P &lt; 0.01). The expression of IDH2 was similar to that of MCU but not MEP (P &lt; 0.05, P &lt; 0.01).

Conclusion
L-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.
Transcriptomic and metabonomic profiling reveal the anti-obesity effects of Chikusetsusaponin V, a compound extracted from Panax japonicus
Authors: Qiu Yixing , Yu Huanghe , Hu Yi , Guo Shiyin , Lei Xinnuo , Qin Yan , Jian Yuqing , Li Bin , Liu Leping , Peng Caiyun , Wang Aibing , Wang Wei 
Published: January 2021

Abstract

Objectives
To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods.

Methods
The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively.

Key findings
Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes.

Conclusions
The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.
Antimicrobial and anthelmintic activities of the ethanolic extract, fractions and isolated compounds from Manilkara zapota L. P. Royen (Sapotaceae)
Authors: Mourão Mulvaney Layany Carolyny , Xavier-Júnior Francisco Humberto , Rodrigues Alice M S , Stien Didier , Allegretti Silmara Marques , Garcia Vera Lúcia 
Published: January 2021

Abstract

Objectives
To evaluate the antibacterial, antifungal and anthelmintic activities of the ethanolic extract (EEMz), fractions (LPFMz and HPFMz) and compounds isolated from the leaves of Manilkara zapota L. P. Royen.

Methods
Extract and fractions were produced by turbolization. LPFMz fraction was analysed by gas chromatography–mass spectrometry. The isolated compounds from HPFMz were purified by flash and preparative chromatographic methods, and chemically characterised by UPLC-ESITOFMS, optical rotation, and one- and two-dimensional 1H and 13C NMR techniques. Anthelmintic against Strongyloides venezuelensis and antimicrobial activities against Candida albicans, Trichophyton rubrum and Staphylococcus aureus were evaluated.

Key findings
EEMz showed mainly phenolic compounds and pentacyclic triterpenes from Δ12-oleane/Δ12-ursane series. Chlorogenic acid, myricetin-3-O-β-D-glucopyranoside, mearnsitrin, germanicol and germanicol acetate were reported to M. zapota leaves for the first time in this work. EEMz, HPFMz, LPFMz showed significative activity against C. albicans (16 µg/mL), while isolated flavonoids were active against S. aureus (&lt;32 µg/mL). EEMz, phenolic-rich compounds (F2), and chlorogenic acid were potentially active against S. venezuelensis at 24 h.

Conclusions
M. zapota and its bioactive compound can be eligible such as a potential phytomedicine for the treatment of microbial and strongyloidiasis drug-resistant infections.
Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway
Authors: Zhang Zheng-kun , Zhou Yan , Cao Jun , Liu Dan-yang , Wan Li-hong 
Published: January 2021

Abstract

Objectives
Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis.

Methods
Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS.

Key findings
RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.

Conclusions
These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.
The phytochemistry and biological diversity of Ferulago genus (Apiaceae): a systematic review
Authors: Salleh Wan Mohd Nuzul Hakimi Wan , Abed Salam Ahmed , Taher Muhammad , Kassim Hakimi , Tawang Alene 
Published: January 2021

Abstract

Objectives
The genus Ferulago belonging to the family Apiaceae is a flora widely distributed in Central Asia and the Mediterranean and used in folk medicine. It is administered as a sedative, tonic, digestive, aphrodisiac, also as a treatment for intestinal worms and haemorrhoids. Herein, we reported a review on phytochemistry and its biological activities reported from 1990 up to early 2020. All the information and reported studies concerning Ferulago plants were summarized from the library and digital databases (e.g. Scopus, Medline, Scielo, ScienceDirect, SciFinder and Google Scholar).

Key findings
The phytochemical investigations of Ferulago species revealed the presence of coumarins as the main bioactive compounds, including daucane derivatives, sesquiterpenes aryl esters, phenol derivatives, flavonoids and essential oils. Moreover, the therapeutic potentials of the pure compounds isolated from the genus Ferulago possess promising properties namely anticholinesterase, antimicrobial, anticoagulant, antileishmanial, antioxidant, antibacterial and antiproliferative.

Summary
Today, significant advances in phytochemical and biological activity studies of different Ferulago species have been revealed. The traditional uses and reported biological results could be correlated via the chemical characterization of these plants. All these data will support the biologists in the elucidation of the biological mechanisms of these plants.