An integrated strategy of UPLC-Q-TOF/MS and HPTLC/PAD-DESI-MSI for the analysis of chemical variations: A case study of Tibetan medicine Tiebangchui.

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LC-MS based metabonomics study on protective mechanism of ESWW in cerebral ischemia via CYTC/Apaf-1/NDRG4 pathway.

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.

Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling. Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored. Methods: Ultra-performance liquid chromatography-tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models. Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue. Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

Rapid visual characterization of alkaloid changes in traditional processing of Tibetan medicine Aconitum pendulum by high-performance thin-layer chromatography coupled with desorption electrospray ionization mass spectrometry imaging.

Radix Aconiti, also known as Tie-bang-chui (TBC), Pang-a-na-bao, and Bang-na, is a typical aconitum Tibetan medicine and a perennial herb of the genus Aconitum pendulum Busch. and A. flavum Hand. -Mazz. dry roots. It has high toxicity and remarkable efficacy; as such, it is a typical "highly toxic and effective" drug that needs be processed and used. Processing methods of this Tibetan medicine include non-heating of highland barley wine (HBW) and fructus chebulae soup (FCS). This work aimed to understand differences in chemical composition between non-heat processed products and raw TBC. In this study, high-performance thin-layer chromatography (HPTLC) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) were used to analyze the chemical composition of TBC processed by FCS (F-TBC) and HBW (H-TBC). The MRM mode of HPLC-QqQ-MS/MS was selected to determine the changes of several representative alkaloids to comparison with the former results. A total of 52 chemical constituents were identified in raw and processed products, and the chemical composition of F-TBC and H-TBC changed slightly compared with that of raw TBC. The processing mechanism of H-TBC was also different from that of F-TBC, which might be related to the large amount of acidic tannins in FCS. It was found that the content of all six alkaloids decreased after processing by FCS, and all five alkaloids decreased except aconitine increased after processing by HBW. The combination of HPTLC and DESI-MSI could be an effective method for rapid identification of chemical components and changing rules in ethnic medicine. The wide application of this technology provides not only an alternative method for the traditional separation and identification of secondary metabolism but also a reference for research on the processing mechanism and quality control of ethnic medicine.

Astragaloside IV, as a potential anticancer agent.

Cancer is a global intractable disease, and its morbidity and mortality are increasing year by year in developing countries. Surgery and chemotherapy are often used to treat cancer, but they result in unsatisfactory outcomes, such as severe side effects and drug resistance. With the accelerated modernization of traditional Chinese medicine (TCM), an increasing body of evidence has shown that several TCM components have significant anticancer activities. Astragaloside IV (AS-IV) is considered the main active ingredient of the dried root of Astragalus membranaceus. AS-IV exhibits various pharmacological effects, such as anti-inflammatory, hypoglycemic, antifibrotic, and anticancer activities. AS-IV possesses a wide range of activities, such as the modulation of reactive oxygen species-scavenging enzyme activities, participation in cell cycle arrest, induction of apoptosis and autophagy, and suppression of cancer cell proliferation, invasiveness, and metastasis. These effects are involved in the inhibition of different malignant tumors, such as lung, liver, breast, and gastric cancers. This article reviews the bioavailability, anticancer activity, and mechanism of AS-IV and provides suggestions for further research of this TCM.

The study of chemical components in Qishiwei Zhenzhu pills and its anti-apoptotic mechanism in cerebral ischemic based on LC-MS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishiwei Zhenzhu pills are one of the most representative precious treasure proprietary medicines and have been used for nearly 500 years in clinical practice in Chinese. This medicine can prevent diseases and play a certain role in fighting altitude sickness with cerebral ischemia. AIM OF THE STUDY: This study used LC-MS to analyse the chemical constituents of Qishiwei Zhenzhu pills, which laid a foundation for the improvement of the quality standard and the basic research of pharmacodynamics substances. This study aims to reveal the mechanism of Qishiwei Zhenzhu pills on cerebral ischemia from the perspective of the inflammatory and apoptotic pathway. MATERIALS AND METHOD: UPLC-Q-TOF-MS was used to analyse the chemical constituents of Qishiwei Zhenzhu pills qualitatively. HPLC-QQQ-MS was used to analyse the contents of Qishiwei Zhenzhu pills quantitatively. The therapeutic target and pathway of Qishiwei Zhenzhu pills in the treatment of ischemic stroke were predicted on the basis of network pharmacology. On the basis of the MCAO rat model, the cerebral infarction rate (TTC staining) and the number of Nissl bodies (toluidine blue staining) were measured, the pathological morphologies of cortex and hippocampus were observed (HE staining), and the mRNA levels were determined by RT-PCR. The protein expressions of Bax, Bcl-2, and Caspase3 in the ischemic brain tissue of rats were determined using the WB method. RESULTS: A total of 42 chemical constituents, including 11 triterpenoids, 10 flavonoids, 8 organic acids and their derivatives, 4 diterpenoids, 4 tannins, 2 steroids, and 3 other components, were identified from Qishiwei Zhenzhu pills by UPLC-Q-TOF-MS. HPLC-QQQ-MS results found that among the 16 different batches, the content difference between the two batches of preparations with the national drug approval number was small and that the quality was stable. However, significant differences were observed among the preparations of nine medical institutions. Network pharmacology study found that the effect of Qishiwei Zhenzhu pills might be related to the AGE-rage and tumour necrosis factor signalling pathways. Qishiwei Zhenzhu pills could improve the neurobehavioral abnormalities of MCAO rats, reduce the rate of cerebral infarction, improve the pathological changes in the hippocampal area of brain tissue, and increase the number of Nissl body in the brain tissue. Qishiwei Zhenzhu pills tended to reduce the mRNA transcription levels of Bax, Caspase-3, p65, c-fos and VEGF-A and increase the expression of Bcl-2 and MAPK8 mRNA. Moreover, the Bax protein expression tended to decrease, and the bcl-2 protein expression tended to increase. CONCLUSIONS: A total of 42 chemical components were qualitatively identified from Qishiwei Zhenzhu pills, and 16 chemical components from 16 batches were determined. These components improved the quality standard level of Qishiwei Zhenzhu pills and provided reference for the later exploration of its pharmacodynamics substance basis. The protective mechanism of Qishiwei Zhenzhu pills against ischemic stroke might be related to the downregulation of the apoptosis factor caspase-3.

[Distribution of bioactive compounds in different tissues of Paeonia lactiflora roots by DESI-MSI and UPLC].

The quality of Paeoniae Radix Alba and Paeoniae Radix Rubra is evaluated by root thickness, and paeoniflorin serves as a common quality indicator of them. However, the correlation between the content of bioactive compounds and the root size is still unclear. Therefore, this study characterized the distribution patterns and content of seven bioactive compounds including paeoniflorin in different tissues of Paeonia lactiflora roots, analyzed the correlation between the root size and the content of bioactive compounds based on the xylem-to-bark ratio, and further determined the index components for quality assessment. Nine samples of fresh P. lactiflora roots were collected from the genuine cultivation area. The distribution of bioactive compounds in different tissues on the cross-section of the root was firstly analyzed by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI). Subsequently, the content of bioactive compounds was determined in the xylems and barks of the roots by UPLC. The compounds with the largest difference between the xylem and the bark were selected by orthogonal partial least squares discriminant analysis(OPLS-DA). The results indicated that paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, gallic acid, and 1,2,3,4,6-pentagalloylglucose were significantly accumulated in the xylems, while albiflorin and catechin were mainly distributed in the barks. Paeoniflorin and albiflorin, with the largest differences in the xylem and the bark, had the highest content in the two tissues. The root diameter was positively correlated with paeoniflorin content and negatively correlated with albiflorin content. As isomers with different efficacies, paeoniflorin or albiflorin can be chosen as the quality marker corresponding to specific clinical application to launch quality classification evaluation of multi-functional Chinese medicines.

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics.

Fuzi is a famous toxic traditional herbal medicine, which has long been used for the treatment of various diseases in China and many other Asian countries because of its extraordinary pharmacological activities and high toxicity. Different processing methods to attenuate the toxicity of Fuzi are important for its safe clinical use. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with a metabolomics-combined multivariate statistical analysis approach was applied to investigate a series of Aconitum alkaloids and explore potential metabolic markers to understand the differences between raw and processed Fuzi with different steaming time points. Moreover, the selected metabolic markers were visualized by DESI-MSI, and six index alkaloids' contents were determined through HPLC. The results indicated visible differences among raw and processed Fuzi with different steaming times, and 4.0 h is the proper time for toxicity attenuation and efficacy reservation. A total of 42 metabolic markers were identified to discriminate raw Fuzi and those steamed for 4.0 and 8.0 h, which were clearly visualized in DESI-MSI. The transformation from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids and then to non-esterified diterpene alkaloids through hydrolysis is the major toxicity attenuation process during steaming. DESI-MSI combined with metabolomics provides an efficient method to visualize the changeable rules and screen the metabolic markers of Aconitum alkaloids during steaming. The wide application of this technique could help identify markers and reveal the possible chemical transition mechanism in the "Paozhi" processes of Fuzi. It also provides an efficient and easy way to quality control and ensures the safety of Fuzi and other toxic traditional Chinese medicine.

Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. AIM OF THE STUDY: This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. MATERIALS AND METHODS: Relevant information about Tiebangchui (A. pendulum and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra, and Jing Zhu Materia Medica, and official drug standards were reviewed. RESULTS: A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. CONCLUSIONS: The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored.

[Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics].

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Tibetan Medicine Duoxuekang Capsule Ameliorates High-Altitude Polycythemia Accompanied by Brain Injury.

Objective: Duoxuekang (DXK) capsule is an empirical prescription for Tibetan medicine in the treatment of hypobaric hypoxia (HH)-induced brain injury in the plateau. This study aimed to investigate the protective effects and underlying molecular mechanisms of DXK on HH-induced brain injury. Methods: UPLC-Q-TOF/MS was performed for chemical composition analysis of DXK. The anti-hypoxia and anti-fatigue effects of DXK were evaluated by the normobaric hypoxia test, sodium nitrite toxicosis test, and weight-loaded swimming test in mice. Simultaneously, SD rats were used for the chronic hypobaric hypoxia (CHH) test. RBC, HGB, HCT, and the whole blood viscosity were evaluated. The activities of SOD and MDA in the brain, and EPO and LDH levels in the kidney were detected using ELISA. H&E staining was employed to observe the pathological morphology in the hippocampus and cortex of rats. Furthermore, immunofluorescence and Western blot were carried out to detect the protein expressions of Mapk10, RASGRF1, RASA3, Ras, and IGF-IR in the brain of rats. Besides, BALB/c mice were used for acute hypobaric hypoxia (AHH) test, and Western blot was employed to detect the protein expression of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the cerebral cortex of mice. Results: 23 different chemical compositions of DXK were identified by UPLC-Q-TOF/MS. The anti-hypoxia test verified that DXK can prolong the survival time of mice. The anti-fatigue test confirmed that DXK can prolong the swimming time of mice, decrease the level of LDH, and increase the hepatic glycogen level. Synchronously, DXK can decrease the levels of RBC, HGB, HCT, and the whole blood viscosity under the CHH condition. Besides, DXK can ameliorate CHH-induced brain injury, decrease the levels of EPO and LDH in the kidney, reduce MDA, and increase SOD in the hippocampus. Furthermore, DXK can converse HH-induced marked increase of Mapk10, RASGRF1, and RASA3, and decrease of Ras and IGF-IR. In addition, DXK can suppress the ratio of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 under the HH condition. Conclusion: Together, the cerebral protection elicited by DXK was due to the decrease of hematological index, suppressing EPO, by affecting the MAPK signaling pathway in oxidative damage, and regulating the RAS signaling pathway.

Traditional uses, phytochemistry, pharmacology, and toxicology of Pterocephalus hookeri (C. B. Clarke) Höeck: a review.

Pterocephalus hookeri (C. B. Clarke) Höeck is a member of the Dipsacaceae family and has been used in traditional Tibetan medicine for thousands of years. P. hookeri clears heat, detoxifies, stops dysentery, eliminates distemper, dispels wind, and relieves stagnation and is mainly prescribed for heat syndrome, dysentery, arthritis, and plague. Approximately 93 chemical compounds have been isolated and identified from P. hookeri, including iridoid glycosides, lignan and triterpenoids. Meanwhile, modern pharmacological studies have shown that P. hookeri has anti-inflammatory, anti-rheumatoid arthritis, analgesic, anticancer, and neuroprotection activities. However, studies on the in vivo pharmacokinetics and mechanism of action, discovery of quality markers, and qualitative and quantitative analysis are still insufficient. Hence, this paper provides a comprehensive review of the ethnic medicine, phytochemistry, pharmacology, and toxicology of P. hookeri to increase the understanding of the medicinal value of P. hookeri.

Pterocephanoside A, a new iridoid from a traditional Tibetan medicine, Pterocephalus hookeri.

This work obtained and identified pterocephanoside A (1), one new iridoid glucoside derivative with rare structure of three iridoid glycosides linked to cyclopenta[c]pyran-3(1H)-one, and 10 known iridoids (2-11) from Pterocephalus hookeri through silica gel column chromatography and semi-preparative HPLC. The structure of the new compound was confirmed by 1D and 2D NMR and HRMS data analysis. Compounds 1 and 2 were isolated from this plant for the first time. The iridoids mostly possessed seco-iridoid subtype and iridoid subtype skeletons from P. hookeri. Compounds 1, 3, 4, and 6-11 showed weak anti-inflammatory activity.

Virtual Screening Technique Used to Estimate the Mechanism of Adhatoda vasica Nees for the Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking.

Adhatoda vasica Nees (AVN) is commonly used to treat joint diseases such as rheumatoid arthritis (RA) in ethnic minority areas of China, especially in Tibetan and Dai areas, and its molecular mechanisms on RA still remain unclear. Network pharmacology, a novel strategy, utilizes bioinformatics to predict and evaluate drug targets and interactions in disease. Here, network pharmacology was used to investigate the mechanism by which AVN acts in RA. The chemical compositions and functional targets of AVN were retrieved using the systematic pharmacological analysis platform PharmMapper. The targets of RA were queried through the DrugBank database. The protein-protein interaction network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets were constructed in the STRING database, and the network visualization analysis was performed in Cytoscape. Maestro 11.1, a type of professional software, was used for verifying prediction and analysis based on network pharmacology. By comparing the predicted target information with the targets of RA-related drugs, 25 potential targets may be related to the treatment of RA, among which MAPK1, TNF, DHODH, IL2, PTGS2, and JAK2 may be the main potential targets for the treatment of RA. Finally, the chemical components and potential target proteins were scored by molecular docking, and compared with the ligands of the protein, the prediction results of network pharmacology were preliminarily verified. The active ingredients and mechanism of AVN against RA were firstly investigated using network pharmacology. Additionally, this research provided a solid foundation for further experimental studies.

Efficacy and safety of total glucosides of paeony for rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by erosion of joints and surrounding tissues. RA not only causes the decline of patients' physical function and quality of life, but also brings huge economic burden to patients' families and society. Total glucosides of paeony (TGP) is commonly used in treating RA in China. At present, there are many clinical reports about this medicine, but these reports have their own flaws. Therefore, there is an urgent need for systematic review and meta-analysis of the existing clinical evidence. METHODS AND ANALYSIS: Literature search will be carried out in 6 databases, and the literatures will be screened according to the inclusion and exclusion criteria. The clinical effective rate will be taken as primary outcome. Serum rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, Western Ontario and McMaster before and after treatment and adverse effects will be secondary outcomes. The heterogeneity of the study will be examined by χ and I test. To identify the source of heterogeneity, subgroup analysis will be carried out. The sensitivity test will be conducted investigate the stability of results. Funnel plot and Egger test will be used to evaluate publication bias. Finally, the quality of evidence will be summarized. RESULTS: The results will be published in peer-reviewed journals. CONCLUSIONS: This study will systematically evaluate the efficacy of TGP in the treatment of RA. The results of this study can better guide clinical practice. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/85QVF.

Traditional Tibetan Medicine in Cancer Therapy by Targeting Apoptosis Pathways.

Cancer is a leading cause of death around the world. Apoptosis, one of the pathways of programmed cell death, is a promising target for cancer therapy. Traditional Tibetan medicine (TTM) has been used by Tibetan people for thousands of years, and many TTMs have been proven to be effective in the treatment of cancer. This paper summarized the medicinal plants with anticancer activity in the Tibetan traditional system of medicine by searching for Tibetan medicine monographs and drug standards and reviewing modern research literatures. Forty species were found to be effective in treating cancer. More importantly, some TTMs (e.g., Ophiocordyceps sinensis, Phyllanthus emblica L. and Rhodiola kirilowii (Regel) Maxim.) and their active ingredients (e.g., cordycepin, salidroside, and gallic acid) have been reported to possess anticancer activity by targeting some apoptosis pathways in cancer, such as Bcl-2/Bax, caspases, PI3K/Akt, JAK2/STAT3, MAPK, and AMPK. These herbs and natural compounds would be potential drug candidates for the treatment of cancer.

[Correlation study on Tibetan medicine Pterocephalus hookeri of bitter taste receptors based on molecular docking technology].

In order to study the interaction between Pterocephalus hookeri and bitter taste receptors,three-dimensional structural models of bitter taste receptors TAS2 R16,TAS2 R14 and TAS2 R13 were established by homology modeling in this paper. Maestro software was used for docking the chemical constituents of P. hookeri with bitter taste receptors. The results showed that 25 chemical components of P. hookeri can regulate three bitter taste receptors. And these components were mainly iridoid glycosides and phenolic acids.This research focused on the comprehensive application of homology modeling and molecular docking technology to explore the interaction between bitter chemical constituents of P. hookeri and bitter taste receptors. This study provided assistance in revealing pharmacodynamic basis of bitter Tibetan medicine at molecular level. It also provided new ideas and methods for the study of Tibetan medicine.

[Investigation on intestinal absorption ingredients and their absorption characteristics in Pterocephali Herba by everted intestinal sac method].

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.

[Potential distribution of the traditional Tibetan herb Pterocephalus hookeri by Maxent model].

In order to study the ecology suitability of Pterocephalus hookeri, and provide a reference for GAP planting location and regional development, the Maxent model and GIS technology were used to investigate ecology suitability regions for P. hookeri based on the distribution points collected from Chinese virtual herbarium, the references and field trips. The potential distribution areas mainly concentrated in the eastern Tibet, western Sichuan, southern Qinghai, northwest Yunnan, and southern Gansu. There were 7 major environmental factors to have obvious influence on ecology suitability distributions of P. hookeri, including altitude (contribution rate of 62%), precipitation of warmest quarter (contribution rate of 14.4%), coefficient of variation of precipitation seasonality (contribution rate of 7.2%), mean temperature of driest quarter (contribution rate of 3.5%), the electrical conductivity of top and sub-soil (contribution rate of 3%), the total exchangeable bases in the top- and subsoil (contribution rate of 2.4%) and SD of temperature seasonality (contribution rate of 2.2%). The study of the ecological suitability regionalization of P. hookeri based on Maxent model can provide scientific basis for the selection of artificial planting base and GAP planting location.