Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: a review.

BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.

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.

[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.

[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.

[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.

Qualitative and quantitative analysis of chemical components in Eupatorium lindleyanum DC. by ultra-performance liquid chromatography-mass spectrometry integrated with anti-inflammatory activity research.

As a traditional Chinese medicine, Eupatorium lindleyanum DC. has an effect on resolving phlegm, relieving cough, and relieving asthma. In this study, an ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was established for qualitative analysis of Eupatorium lindleyanum. Besides, we developed an ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry method in positive and negative multiple reaction monitor modes for the quantitative analysis of 27 chemical constituents from 19 different batches of Eupatorium lindleyanum. The methodology validated linearity, intraday and interday precision, stability, repeatability, and recovery. The results showed that there were some differences in different batches of Eupatorium lindleyanum, which might be attributed to the influence of different growth environments and climatic conditions on the accumulation of compounds. The variable importance of projection value of orthogonal partial least square discriminant analysis and anti-inflammatory activity test showed that eupalinolide A, B, C, and K have high content and strong activity, which could provide a reference for the follow-up study of the quality markers of Eupatorium lindleyanum. Collectively, we developed a rapid and efficient method for the qualitative analysis and simultaneous quantification of Eupatorium lindleyanum, which was beneficial for the comprehensive utilization and development of resources.

[Research on Q-markers of Eupatorium lindleyanum based on analytic hierarchy process-entropy weight method and network pharmacology].

The potential quality markers( Q-markers) of Eupatorium lindleyanum were studied with analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacological method. Based on the concept of Q-markers of traditional Chinese medicine, AHP-EWM was employed to quantitatively identify the Q-markers of E. lindleyanum. AHP method was applied to the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM method was used to analyze the secondlevel indexes supported by literature and experimental data. At the same time, based on the theory and method of network pharmacology, the component-target-disease-efficacy network of E. lindleyanum was built, and the components most closely related to the efficacy of resolving phlegm and relieving cough and asthma were screened out. Through the integrated analysis of the results obtained with AHP-EWM and network pharmacological method, 13 compounds including rutin, quercetin, nepetin, cirsiliol, luteolin, hyperoside,isoquercitrin, kaempferol, caffeic acid, eupalinolide K, eupalinolide A, eupalinolide B, and eupalinolide C were comprehensively identified as the potential Q-markers of E. lindleyanum. The results provide a basis for the quality control of E. lindleyanum.

[Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods].

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

[Exploring the best dried processing condition of fresh Gastrodia elata].

OBJECTIVE: To study the processing conditions that influenced the contents of gastrodine in dried processing of fresh Gastrodia elata. METHODS: The optimized processing condition were established by using single-factor and orthogonal experimental design, which was guided by the contents of gastrodine. Fresh Gastrodia elata were harvested in the day, cleaned sediment, cooked in atmospheric pressure for 25 min, cut into 0.5 - 1.0 cm thick slices and dried in 105 degrees C. The gastrodine content was measured by HPLC. RESULTS: The gastrodine content was 0.532%, which was higher than that of traditional processing method. CONCLUSION: Dried processing condition can influence the content of gastrodine in Gastrodia elata significantly.

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.

Traditional uses, botany, phytochemistry, pharmacology and applications of Labisia pumila: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, antiinflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

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.

The identification of metabolites from gut microbiota in coronary heart disease via network pharmacology.

Although the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota-metabolites-targets-signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.

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.

Exploring the effective compounds and potential mechanisms of Shengxian Decoction against coronary heart disease by UPLC-Q-TOF/MS and network pharmacology analysis.

As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1ß, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1ß, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.

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.

Celastrol induced the autophagy of spermatogonia cells contributed to tripterygium glycosides-related testicular injury.

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.

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.