The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury.

BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

The effective combination therapies with irinotecan for colorectal cancer.

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini.

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor, with active ingredients of bufadienolides and indole alkaloids. With further research and clinical applications, it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells, promoting apoptosis, inhibiting formation of tumor neovascularization, reversing multidrug resistance, and regulating immune response; it also has the functions of relieving cancer pain and regulating immune function. In this paper, the chemical composition, pharmacological effects, clinical applications, and adverse reactions of cinobufacini are summarized. However, the extraction of monomer components of cinobufacini, the relationship between different mechanisms, and the causes of adverse reactions need to be further studied. Also, high-quality clinical studies should be conducted.

[Identification of quality markers of Gei Herba based on analytic hierarchy process-entropy weight method and network pharmacology].

Analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacology were employed to identify the potential quality markers(Q-markers) of Gei Herba. According to the new concept of Q-markers in traditional Chinese medicine(TCM), the AHP-EWM was applied to quantitatively identify the Q-markers of Gei Herba. The AHP was used for the weight analysis of primary indicators(factor layer), and the EWM for the analysis of literature and experimental data of secondary indicators(control layer). In addition, network pharmacology was employed to build the "component-target-disease-efficacy" network for Gei Herba, and the components showing strong associations with the Qi-replenishing, spleen-invigorating, blood-tonifying, Yin-nourishing, lung-moistening, and phlegm-resolving effects of Gei Herba were screened out. According to the results of AHP-EWM and network pharmacology, four components, i.e., ellagic acid, gallic acid, gemin G, and gemin C, were finally identified as potential Q-markers of Gei Herba. In this study, the AHP-EWM and network pharmacology were employed to screen the Q-markers of Gei Herba, which provided ideas for the quantitative evaluation and identification of Q-markers of TCM.

The serum lipidomics reveal the action mechanism of Danggui-Yimucao herbal pair in abortion mice.

Medical abortion is a common medical procedure that women choose to terminate an unwanted pregnancy, but it often brings post-abortion complications. Danggui (Angelica sinensis Radix)-Yimucao (Leonuri Herba), as a herbal pair (DY) in clinical prescriptions of traditional Chinese medicine, is often used in the treatment of gynecological diseases and has the traditional functions of tonifying the blood, promoting blood circulation, removing blood stasis and regulating menstruation. In this study, serum lipidomics were adopted to dissect the mechanism of DY in promoting recovery after medical abortion. A total of 152 differential metabolites were screened by lipidomics. All metabolites were imported into MetaboAnalyst for analysis, and finally key metabolic pathways such as glycerophospholipid metabolism, linoleic acid metabolism and pentose and glucuronate interconversions were enriched. Our results indicated that metabolic disorders in abortion mice were alleviated by DY through glycerophospholipid metabolism, while prostaglandin and leukotriene metabolites might be the key targets of DY to promote post-abortion recovery.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

ETHNOPHARMACOLOGICAL RELEVANCE: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. AIM OF THE STUDY: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). MATERIALS AND METHODS: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. RESULTS: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. CONCLUSION: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

Potential Medicinal Value of Rhein for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.

A three-dimensional integration strategy for Q-markers identification: Taken Euphorbia Pekinensis Radix as an example.

Euphorbia Pekinensis Radix (EPR) is an important antitumor medicinal resource. However, quality control of EPR has not been well established due to the lack of quality markers (Q-markers) research. In this study, a three-dimensional integration strategy was developed to systematically characterize Q-markers and this method was successfully applied to identify Q-markers of EPR. Firstly, three core quality attributes-effectiveness, testability and specificity-were considered as three dimensions, and the weights of each dimension were calculated by analytical hierarch process. Then, the values of each dimension were evaluated by multi-indicators. For EPR with antitumor activity, cytotoxic assay and network pharmacology, UPLC analysis and literature search, compound belonging search were employed to calculate the values of effectiveness, testability and specificity, respectively. Finally, the weights and values were multiplied as the scores of each component on that dimension, and the total scores of the three dimensions were further integrated based on the radar plot and expressed as regression area, by which Q-markers were quantified and visualized. Five components were identified as Q-markers of EPR due to their high-ranked antitumor capacity, ease of measurement and excellent specificity, which laid an important foundation for the quality control improvement of EPR. Furthermore, the integrated strategy summarized here is helpful for the quantitative identification of Q-markers and promote the quality standard of traditional Chinese medicine.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice.

OBJECTIVE: To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice. METHODS: Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing. RESULTS: Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism. CONCLUSION: APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

[Quantitative identification of Q-markers of Euphorbiae Humifusae Herba based on AHP-CRITIC comprehensive weighting method].

This study investigated the quality markers(Q-markers) of Euphorbiae Humifusae Herba based on the analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) comprehensive weighting method. The Q-markers evaluation system was constructed based on the AHP-CRITIC comprehensive weighting method with quantitative identification of Q-markers of Euphorbiae Humifusae Herba as the target layer. The index weights of the factor layer and the control layer were integrated based on the weights of three indicators(effectiveness, testability, and specificity) in the factor layer calculated by the AHP method and weights of eight indicators(anti-inflammatory inhibitory rate, coagulation shortening rate, anti-cancer inhibition rate, component degree value, component test batch, component average content, content variation coefficient, and number of medicinal materials retrieved according to components) in the control layer calculated by the CRITIC method. The comprehensive score of the chemical components of Euphorbiae Humifusae Herba was weighted and ranked to identify the Q-markers of Euphorbiae Humifusae Herba. In terms of comprehensive scores, top 10 potential Q-markers of Euphorbiae Humifusae Herba were ranked as cynaroside > quercetin > gallic acid > apigenin > luteolin > apigenin-7-O-glucoside > quercetin-7-O-glucoside > ellagic acid > astragalin > ethyl gallate. This study provides a reference for the quality control of Euphorbiae Humifusae Herba and a methodological reference for the quantitative identification of Q-markers of Chinese medicine.

Integrated dose-response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose-response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. METHODS: The proposed methodology of integrated dose-response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose-response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. RESULTS: This developed strategy was successfully applied to rhubarb. The dose-response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. CONCLUSION: An integrated dose-response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.

Traditional Chinese Medicine: A promising strategy to regulate inflammation, intestinal disorders and impaired immune function due to sepsis.

Sepsis is described as a dysregulation of the immune response to infection, which leads to life-threatening organ dysfunction. The interaction between intestinal microbiota and sepsis can't be ignored. Furthermore, the intestinal microbiota may regulate the progress of sepsis and attenuate organ damage. Thus, maintaining or restoring microbiota may be a new way to treat sepsis. Traditional Chinese medicine (TCM) assumes a significant part in the treatment of sepsis through multi-component, multi-pathway, and multi-targeting abilities. Moreover, TCM can prevent the progress of sepsis and improve the prognosis of patients with sepsis by improving the imbalance of intestinal microbiota, improving immunity and reducing the damage to the intestinal barrier. This paper expounds the interaction between intestinal microbiota and sepsis, then reviews the current research on the treatment of sepsis with TCM, to provide a theoretical basis for its clinical application.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.

Modern research thoughts and methods on bio-active components of TCM formulae.

TCM formulae are the important guidances for clinical application of traditional Chinese medicines, which follow the principles of diagnosis and treatment in TCM. Elucidating the bio-active components of TCM formulae is the key to the modernization and internationalization of traditional Chinese medicines. With the rapid development of modern instruments and technology, many new theories, methods and strategies are emerging, which upgrade the research of TCM formulae into a higher level. Only when the medicinal efficacy, bio-active components, function mechanism of TCM formulae are understood, we can guarantee TCM safety and quality control. In this paper, we summarized the latest modern research thoughts and methods on bio-active components of TCM formulae including formula decomposition study, serum pharmacology and serum pharmacochemistry, association analysis, biochromatography, network pharmacology, metabolomics and proteomics, so as to provide reference for the research and development of TCM in the future.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS: LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

[Research on Q-markers of Polygoni Perfoliati Herba based on analytic hierarchy process-entropy weight method and fingerprints].

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati Herba.

Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MSE and integrated effects.

BACKGROUND: Rhei Radix et Rhizoma (rhubarb), as one of the typical representatives of multi-effect traditional Chinese medicines (TCMs), has been utilized in the treatment of various diseases due to its multicomponent nature. However, there are few systematic investigations for the corresponding effect of individual components in rhubarb. Hence, we aimed to develop a novel strategy to fuzzily identify bioactive components for different efficacies of rhubarb by the back propagation (BP) neural network association analysis of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for every data (UPLC-Q-TOF/MSE) and integrated effects. METHODS: Through applying the fuzzy chemical identification, most components of rhubarb were classified into different chemical groups. Meanwhile the integration effect values of different efficacies can be determined by animal experiment evaluation and multi-attribute comprehensive indexes. Then the BP neural network was employed for association analysis of components and different efficacies by correlating the component contents determined from UPLC-Q-TOF/MSE profiling and the integration effect values. Finally, the effect contribution of one type of components may be totaled to demonstrate the universal and individual characters for different efficacies of rhubarb. RESULTS: It suggested that combined anthraquinones, flavanols and their polymers may be the universal character to the multi-functional properties of rhubarb. Other components contributed to the individuality of rhubarb efficacies, including stilbene glycosides, anthranones and their dimers, free anthraquinones, chromones, gallic acid and gallotannins, butyrylbenzenes and their glycosides. CONCLUSIONS: Our findings demonstrated that the bioactive components for different efficacies of rhubarb were not exactly the same and can be systematically differentiated by the network-oriented strategy. These efforts will advance our knowledge and understanding of the bioactive components in rhubarb and provide scientific evidence to support the expansion of its use in clinical applications and the further development of some products based on this medicinal herb.