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Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases. An updated ETCM v2.0 database may be a major data warehouse for quality marker identification and pharmacological mechanism investigation of TCMs against human diseases, and TCM-derived drug discovery and repurposing. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is the most common respiratory disease with high morbidity and mortality. Shema oral liquid (Shema) is a traditional Chinese medicine (TCM) approved for the treatment of respiratory diseases. Clinical applications have shown that Shema has antitussive, expectorant, and anti-asthmatic effects, but its definite efficacy to COPD is still unclear. This study aimed to explore the therapeutic capacity and potential mechanism of Shema in treatment of COPD. Methods: Network pharmacology was used to investigated the possible pharmacological mechanism of Shema against COPD. A rat model of lipopolysaccharide (LPS)-induced COPD was established to determine pulmonary ventilatory function, serum inflammatory cytokines, and pulmonary pathological change. Subsequently, tandem mass tag (TMT)-based quantitative proteomics was used to further reveal the therapeutic targets related with Shema against COPD. Western blot was finally performed to validate the expression of targeted proteins screened by proteomics research. Results: Network pharmacology analysis indicated that Shema against COPD mainly inhibited the inflammation and affected the immune system. The animal experiment demonstrated that Shema treatment protected the lung tissue from LPS induced injury, inhibited the levels of serum inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and improved the respiratory ventilatory function by upregulating forced expiratory volume in 0.1 s (FEV0.1), FEV0.3, forced vital capacity (FVC), and the ratios of FEV0.1 (0.3)/FVC. Proteomic analysis and western blot both proved that Shema inhibited the expression of DNA methyltransferase 1 (DNMT1) in the lung tissue. Conclusion: The therapeutic mechanism of Shema in treatment of COPD may involve inhibiting inflammatory response, improving pulmonary ventilatory function, and alleviating LPS-induced lung injury through regulating the expression of DNMT1. This study also shed light on the development of therapeutic strategies in treating COPD by intervening DNMT-related pathways. [ABSTRACT FROM AUTHOR]

Gastrointestinal disorder (GID) is a global health disease which leads to heavy public medical burden. Disorders in the intestinal flora have been found in gastrointestinal disorder patients. However, the interaction between GID and the intestinal flora in faecal has not been studied comprehensively. In addition, multicomponent drugs represented by traditional Chinese medicine (TCM) are widely used for treating GID, but their modulation of the intestinal flora has not been investigated. Therefore, in this study, a high-throughput sequencing strategy was used to investigate alterations in the intestinal flora in a rat GID model, followed by an investigation of the modulation by a representative TCM, Xiaoerfupi (XEFP) granule. The results showed that in rats with GID, the relative abundances of Erysipelotrichaceae, Lachnospiraceae, Streptococcaceae increased and that of Ruminococcaceae decreased. At the macro level, the levels of LysoPC(16:0), LysoPC(20:2), LysoPC(15:0), LysoPC(20:2 (11Z, 14Z)), LysoPC(20:1), LysoPC(15:0), LysoPC(20:0) and LysoPE (0:0/20:0) in serum increased and levels of PC(36:4), PC(38:4), PC(o-36;4), PE (MonoMe(13,5)/MonoMe(11,5)) decreased. The imbalance of metabolites was restored by XEFP through ether lipid metabolism pathway. Increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio of the GID rats was restored by XEFP as well. Moreover, XEFP can relief the symptoms of GID rats by increasing bacteria Ruminococcaceae and decreasing Streptococcaceae , Erysipelotrichaceae and Lachnospiraceae in faecal microbiota level. This study represents a comprehensive survey of the interaction between GID and the intestinal flora and a systematic evaluation of modulation by a multicomponent drug. [ABSTRACT FROM AUTHOR]

Xinglou Chengqi (XLCQ) decoction, composed of three botanical drugs and one inorganic drug, is used in clinics during the treatment of acute stroke complicated with Tanre Fushi (TRFS) syndrome in China. However, its active ingredients and the molecular mechanism have not been clarified. So, we aimed to preliminarily characterize its chemical constituents and investigate its pharmacological mechanisms using an integrative pharmacology strategy, including component analysis, network prediction, and experimental verification. We employed UPLC-QTOF-MS/MS to describe the chemical profile of XLCQ, Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP v2.0, http://www.tcmip.cn/), to assist in identifying the chemical components and predict the putative molecular mechanism against acute stroke complicated with TRFS, and LPS-stimulated BV-2 cells to verify the anti-neuroinflammatory effects of luteolin, apigenin, and chrysoeriol. Altogether, 197 chemical compounds were identified or tentatively characterized in the water extraction of XLCQ, 22 of them were selected as the key active constituents that may improve the pathological state by regulating 27 corresponding targets that are mainly involved in inflammation/immune-related pathways, and furthermore, luteolin, apigenin, and chrysoeriol exhibited good anti-neuroinflammatory effects from both protein and mRNA levels. In summary, it is the first time to employ an integrative pharmacology strategy to delineate 22 constituents that may improve the pathological state of stroke with TRFS by regulating 27 corresponding targets, which may offer a highly efficient way to mine the scientific connotation of traditional Chinese medicine prescriptions. This study might be a supplement for the deficiency of the basic research of XLCQ. [ABSTRACT FROM AUTHOR]

To improve the treatment of patients with coronary heart disease (CHD), personalized treatments based on potential biomarkers could make a difference. To investigate if such potential biomarkers could be found for CHD inhomogeneous, we combined traditional Chinese medicine based diagnosis with untargeted and targeted metabolomics analyses. Shi and Xu patient subtype groups of CHD with angina pectoris were identified. Different metabolites including lipids, fatty acids and amino acids were further analyzed with targeted metabolomics and mapped to disease-related pathways. The long-chain unsaturated lipids ceramides metabolism, bile acid metabolism were differentially affected in the Xu subtype groups. While, Shi-subtype patients seemed to show inflammation, anomalous levels of bioactive phospholipids and antioxidant molecules. Furthermore, variations in the endothelial damage response and energy metabolism found based on ELISA analysis are the key divergence points between different CHD subtypes. The results showed Xu subtype patients might benefit from long-chain unsaturated lipids ceramides as therapeutic targets. Shi subtype patients might benefit more from levels of polyunsaturated fatty acid consumption and treatments that help in restoring energy balance. Metabolic differences can be essential for treatment protocols. Thus, patient group specific differences can serve as important information to refine current treatment approaches in a personalized manner. [ABSTRACT FROM AUTHOR]

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics–pharmacodynamics (PK–PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK–PD processes in vivo. Then, the main research contents of TCMIP are introduced as follows: chemical and ADME/PK profiles of TCM formulas; confirming the three forms of active substances and the three action modes; establishing the qualitative PK–PD correlation; and building the quantitative PK–PD correlations, etc. After that, we summarize the existing data resources, computational models and experimental methods of TCMIP and highlight the urgent establishment of mathematical modeling and experimental methods. Finally, we further discuss the applications of TCMIP for the improvement of TCM quality control, clarification of the molecular mechanisms underlying the actions of TCMs and discovery of potential new drugs, especially TCM-related combination drug discovery. This review focuses on the presentation of the novel concept and the main research contents, methodologies and applications of integrative pharmacology-based traditional Chinese medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the leading causes of death worldwide. However, there is no effective treatment for MI. In this study, trimetazidine (TMZ) and Danhong injection (DHI), representing western medicine and traditional Chinese medicine for MI, were used as tools to identify vital processes in alleviating MI injury. Administration of DHI and TMZ obviously decreased myocardial infarct size, improved ultrasonic heart function, and reduced creatine kinase (CK), lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (AST) levels after MI. RNA-seq results indicated calcium ion handling and negative regulation of apoptotic process were vital processes and DHI and TMZ obviously reduced the expression of CaMK II and inhibited cleaved caspase-3 and Bax. Furthermore, DHI and TMZ increased p-S16-PLB, p-S16T17-PLB, CACNA1C, p-RyR2, and p-PKA expression but did not affect SERCA2a expression. In addition to the enhancement of cardiac myocyte shortening amplitude, maximum shortening velocity, and calcium transients, DHI and TMZ increased sarcoplasmic reticulum calcium content and enhanced SERCA2a calcium uptake capability by upregulating the phosphorylation of PLB but did not affect calcium exclusion by NCX. In conclusion, DHI and TMZ protect against MI through inhibiting apoptosis by downregulating CaMKII pathway and enhancing cardiac myocyte contractile functions possibly through the PKA signaling pathway. [ABSTRACT FROM AUTHOR]

Yunnan is a multiethnic province in southwest China, rich in Materia medica resources, and is popularly known as the kingdom of plants. Biomedicine and public health industry have been the industrial pillars of Yunnan since 2016, which is the important pharmaceutical industrial base for Dai and Yi medicine in China. This review of the Yunnan ethnic medicine industry describes some of the problems to be solved in the development of sustainable ethnomedicine in China. We investigated Chinese patent medicines (CPMs) declared as ethnomedicine on the drug instructions and identified 28 Dai patent medicines (DPMs) and 73 Yi patent medicines (YPMs) that were approved for clinical use in China. In further research, the clinical indications of these CPMs were determined, and the quality standard of medicinal materials and their usage frequencies in DPMs and YPMs were investigated. We also collected and analyzed the data on use of botanical and animal sources of medicines, the rare and endangered medicinal materials, and toxic medicines in DPMs and YPMs. The application of zootherapy in Yi traditional medicine was introduced from its abundant ancient documents and records; based on the "YaGei" theory in Dai traditional medicine, toxic medicines can be relatively safe in DPMs. However, for promoting the Yunnan traditional medicine industry, it is necessary to strengthen medical research to expand evidence-based clinical practice and balance ethnomedicine production and sustainable utilization of Materia medica resources, especially the animal sources of medicines, toxic medicines, and the protected wild resources reported in this survey. Only in this way can industrialization of ethnomedicine promote the improvement of human health. [ABSTRACT FROM AUTHOR]

Clostridium difficile infection (CDI) is featured as the dysbiosis of gut microbiota and consequent mild diarrhoea or severe pseudomembranous colitis. However, the frequent recurrence of CDI following treatment course challenged the antibiotic therapy. Currently, to address the relapse of CDI, several novel therapeutic approaches have emerged, including Bezlotoxumab, SYN-004 (Ribaxamase), RBX2660, and faecal microbial transplant. Traditional Chinese Medicine (TCM) is an old medical system accumulated for thousands of years. Orientated by syndrome-based treatment, TCM functions in a multicomponent and multitarget mode. This old medical system showed superiority over conventional medical treatment, particularly in the treatment of complex disorders, including CDI. In the present review, we will elaborate the TCM intervention in the management of CDI and others disorders via restoring the gut microbiota dysbiosis. We hope that this review will deepen our understanding of TCM as an alternative to CDI treatment. However, more rigorously designed basic researches and randomised controlled trials need to conduct to appraise the function mechanisms and effects of TCM. Finally, it is concluded that the combined therapeutic potentials of TCM and western medicine could be harness to resolve the recurrence and improve the outcome of CDI. [ABSTRACT FROM AUTHOR]

Gingivitis is an inflammatory disease that affects gingival tissues through a microbe-immune interaction. Huanglian Jiedu decoction (HLJD) is used traditionally for clearing and detoxifying in China, which had been reported to possess many pharmacological effects. Rat gingival inflammation model was established by lipopolysaccharide (LPS) injection for 3 consecutive days, and HLJD was given by gavage before LPS injection. After 3 days rats were sacrificed and tissue samples were evaluated. Serum cytokine levels such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoabsorbent assay (ELISA). Oxidative stress related molecules such as total antioxidant capacity (T-AOC), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined. Expression of AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway were inspected by western blotting. Histological changes of gingival tissues were tested with hematoxylin-eosin (HE) staining. HLJD significantly decreased serum levels of IL-6 and TNF-α, suppressed generation of MDA and ROS, and enhanced T-AOC creation. Moreover, HLJD inhibited expressions of AMPK and ERK1/2. The inflammation severity of gingival tissue by HE staining was severe in model group but relieved in HLJD group obviously. HLJD exhibited protective effects against gingival damage through suppressing inflammation reaction and elevating antioxidation power. [ABSTRACT FROM AUTHOR]

Background: QiXueHe Capsule (QXHC) is a Chinese patent drug that is extensively used for the treatment of menstrual disorders. However, its underlying pharmacological mechanisms have not been fully elucidated. Methods: A list of QXHC putative targets were predicted using MetaDrug. An interaction network using links between QXHC putative targets and the known therapeutic targets of menstrual disorders was constructed. QXHC candidate targets were also identified via calculating the topological feature values of nodes in the network. Additionally, molecular docking simulation was performed to determine the binding efficiency of QXHC compound-putative target pairs. Results: A total of 1022 putative targets were predicted for 311 chemical components containing in QXHC. Following the calculation of topological features of QXHC putative target-known therapeutic target of menstrual disorder network, 66 QXHC candidate targets for the treatment of menstrual disorders were identified. Functionally, QXHC candidate targets were significantly associated with several biological pathways, such as VEGF and Chemokine signaling pathways, Alanine/aspartate/glutamate metabolism, Long-term depression and T/B cell receptor signaling pathway. Moreover, molecular docking simulation demonstrated that there were 20 pairs of QXHC chemical component-candidate target had the strong binding free energy. Conclusions: This novel and scientific network pharmacology-based study holistically deciphers that the pharmacological mechanisms of QXHC in the treatment of menstrual disorders may be associated with its involvement into hemopoiesis, analgesia, nutrients absorption and metabolism, mood regulation, as well as immune modulation. [ABSTRACT FROM AUTHOR]

The current ear is a time of agriculture civilization, industrial civilization and information intelligence in parallel. In this time traditional Chinese medicine (TCM) is much valued but it is still in an opportunity period of transformation from a vulnerable science. TCM development should comply with development direction of big science, and keep pace with the times based on image thinking and original creativity. Aiming at 2 important issues in medical development-medical moral education and clinical research, the authors propose that the characteristics of high concept age should be grasped, medical ethics should be remodeling according to benevolence and virtue concepts, humanistic care should be blended in medicine, innovative academic team should be built, and harmonious academic atmosphere should be constructed. Medical research should be based on clinical practice, and clinical practice should be guided by original derivation and development of sciences. The talents of general medicine should be cultivated through early and frequent clinical practice. Basic and clinical researches should be guided by TCM original thinking. It is historical inevitability to integrate TCM and Western medicine. The update of disciplinary framework should be mobilized by curative effect of TCM pattern differentiation and treatment, and medical system will be completed with philosophic wisdom of Chinese ethnic peoples. [ABSTRACT FROM AUTHOR]

Yindan xinnaotong, a compound preparation used in traditional Chinese medicine, is composed of eight herbs: Ginkgo biloba leaf (yinxingye), Salvia miltiorrhizae (danshen), Herba gynostemmatis (jiaogulan), Erigerontis herba (dengzhanxixin), Allii sativi bulbus (dasuan), Notoginseng radixe rhizoma (sanqi), Crataegi fructus (shanzha), and Borneolum (tianranbingpian). Yindan xinnaotong is primarily used to treat cardiovascular and cerebrovascular diseases. However, to date, no scientific methods have been established to assess the quality of Yindan xinnaotong. Therefore, a combinatorial method was developed based on chemical constituent identification and fingerprint analysis to assess the consistency of Yindan xinnaotong quality. In this study, ultra high performance liquid chromatography coupled with time-of-flight mass spectrometry was used to identify the chemical components of Yindan xinnaotong soft capsules. Approximately 74 components were detected, of which 70, including flavonoids, ginkgolide, phenolic acid, diterpenoid tanshinones, and ginsenoside, were tentatively identified. A fingerprint analysis was also conducted to evaluate the uniformity of the quality of Yindan xinnaotong soft capsules. Ten batches of Yindan xinnaotong soft capsules were analyzed. All of the resulting chromatograms were imported into the 'Similarity Evaluation System for Chromatographic Fingerprints of TCM' (Chinese Pharmacopoeia Commission, version 2004A). The similarity scores of common peaks from these samples ranged from 0.903-1.000, indicating that samples from different batches were highly correlated. [ABSTRACT FROM AUTHOR]

For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were regarded as real modules. MixMod could identify the most accurate mixed modules from the drug-target 2-HN (normalized mutual information 0.62 and classification accuracy 0.4524). In the end, MixMod was applied to the 2-HN of Buchang naoxintong capsule (BNC) and detected 49 mixed modules. By using enrichment analysis, we investigated five mixed modules that contained primary constituents of BNC intestinal absorption liquid. As a matter of fact, the findings of in vitro experiments using BNC intestinal absorption liquid were found to highly accord with previous analysis. Therefore, MixMod is an effective method to detect accurate mixed modules from chemical-gene heterogeneous networks and further uncover the molecular mechanism of multicomponent therapies, especially TCM formulae. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment. [ABSTRACT FROM AUTHOR]

Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM). Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ), which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G), berberine (B) and jasminoidin (J) was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G): 2(B): 0.5(J), and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could greatly improve the efficiency in finding new combination drug from TCM. [ABSTRACT FROM AUTHOR]

An ultra-performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry (UPLC/Q-TOF-MS) was first employed to establish the chromatographic fingerprint and thereby identify the major components of Yuanhu Zhitong tablet (YZT), a traditional Chinese medicine. Fingerprint was established by analyzing 15 different batches of YZT, in which we obtained 17 common peaks with 18 constituents. Fifteen components were identified in the fingerprint with reference to the standards and literature data, including protopine, α-allocryptopine, coptisine, tetrahydropalmatine, tetrahydroberberine, corydaline, palmatine, berberine, byakangelicol, dehydrocorydaline, oxypeucedanin, imperatorin, phelloptorin, isoimperatorin, and osthole. Each of these was separated by using a Waters Acquity UPLC BEH C18(2.1 × 50 mm, 1.7 µm) column with linear gradient elution of 0.2% formic acid water-acetonitrile. Meanwhile, the hierarchical cluster analysis was applied to evaluate the variation of the YZTs based on the characteristics of the common peaks in the UPLC/Q-TOF-MS profiles. This established method with high sensitivity and high speed may become a powerful tool for quality evaluation of YZT and related preparation. [ABSTRACT FROM AUTHOR]

Context: Chinese herbal medicine (CHM) is a complex multicomponent complex system that interacts with multiple targets and functions via multiple pathways based on the whole human system. Therefore, identification of key constituents of Chinese herbals (CH) not only plays a critical role in the quality control of CHM, but also paves a basis for redevelopment of them. Objective: Identification of key constituents in volatile oil (VO) of Ligusticum chuanxiong Hort (Umbelliferae) (LCH), which is a CHM clinically used in China thousands of years ago. Materials and methods: The VO of LCH was pharmacologically demonstrated to have blood vessel activity (BVA) in vitro and chemically investigated by gas chromatography-mass spectrometry (GC-MS) analysis. Data mining approaches were used to bridge the gap between chemical constituents (CCS) and bioactivities as well as contribute to select key constituents of LCH automatically. Results: Thirteen effective constituents of LCH with significant association with BVA were identified. Conclusion: The combination of 13 key constituents would accurately predict the bioactivities of blood vessel of LCH. Furthermore, the strategy presented here paves a strong basis for identification of key constituents of CH and elucidation of material basis of CHM. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) documented about 100,000 formulae during past 2500 years. To use and customize them by modern pharmaceutical industry, we make an interdisciplinary effort to study the activity of new drug research and development (R&D) in TCM by introducing data mining approaches to it. We used the migraine formulae as a training set to investigate the possibility of developing new prescription by means of data mining. The activity of new drug R&D of TCM consists of two steps. The first step is to discover new prescriptions (candidates for drugs) from migraine formulae. We present an unsupervised clustering approach based on data mining theory to address the problem in the first step and automatically discover ten new prescriptions from the formulae data. The second step is to develop and optimize the prescriptions discovered by current biomedical approaches. Since Ligusticum chuanxiong Hort (LCH), a kind of herb, is often used to treat migraine and appears in the new prescriptions, we use it as an example and apply supervised regression method based on data mining theory to study the drug R&D activity of TCM. We revised two linear regression methods in order to establish the nonlinear association between three chemical ingredients of LCH and corresponding pharmacological activity and used it to predict the activities. The association is validated by in vitro experiments and we found that the experimental results are consistent with the prediction. Unsupervised clustering and supervised regression cover most part of data mining theory, which means that data mining approaches play a crucial role in new drug R&D in TCM and present a better solution to establish the platform of drug R&D in TCM. [ABSTRACT FROM AUTHOR]

Andrographis Herba (AH), the dry aerial segments of Andrographis paniculata (Burm.f.) Nees, is a common herbal remedy with bitter properties in traditional Chinese medicine (TCM) theory. Although bitterness is one of the features representing Chinese medicine, it has not been implemented as an index to assess the quality and efficacy of TCM because of peoples' subjectivity to taste. In this study, 30 batches of AH with different commercial classifications (leaves, stems, or mixtures of both) were collected. Bitterness of AH was quantified by electronic tongue technology. Meanwhile, chemical compositions were characterized through establishing high-performance liquid chromatography fingerprints. The result indicated that the radar curves of the bitterness from different AH commercial classifications displayed different taste fingerprint information. Based on six taste factors, a Principal Component Analysis (PCA) score three-dimensional (3D) plot exhibited a clear grouping trend (R2X, 0.912; Q2, 0.763) among the three different commercial classifications. Six compounds (Peaks 2, 3, 4, 6, 7, 8) with positive correlation to bitterness were discovered by a Spearman correlation analysis. Peaks 2, 6, 7, 8 were identified as andrographolide, neoandrographolide, 14-deoxyandrographolide, and dehydroandrographolide, respectively. The electronic tongue can be used to distinguish AH samples with different commercial classifications and for quality evaluation. [ABSTRACT FROM AUTHOR]

Classical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, Asini Corii Colla, and Poria. This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. To evaluate the therapeutic effect of KTC on POI and its underlying mechanism. Healthy and specific pathogen-free (SPF) female Kunming mice aged 6–8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A "drug-component-target-pathway-disease" network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting. Compared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids, 15 terpenoids, 2 lignans, 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. KTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI. [Display omitted] [ABSTRACT FROM AUTHOR]

Neurological diseases (NDs) are a leading cause of death worldwide and tend to mainly affect people under the age of 50. High rates of premature death and disability caused by NDs undoubtedly constrain societal development. However, effective therapeutic drugs and methods are very limited. Schisandra chinensis Fructus (SCF) is the dry ripe fruit of Schisandra chinensis (Turcz.) Baill, which has been used in traditional Chinese medicine for thousands of years. Recent research has indicated that SCF and its active ingredients show a protective role in NDs, including cerebrovascular diseases, neurodegenerative diseases, or depression. The key neuroprotective mechanisms of SCF and its active ingredients have been demonstrated to include antioxidation, suppression of apoptosis, anti-inflammation, regulation of neurotransmitters, and modulation of brain-derived neurotrophic factor (BDNF) related pathways. This paper summarizes studies of the role of SCF and its active ingredients in protecting against NDs, and highlights them as promising resources for future treatment. Furthermore, novel insights on the future challenges of SCF and its active ingredients are offered. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) has emerged as a condition with high incidence and mortality rates in recent years. Dengzhan Shengmai capsule (DZSMC) is a Chinese patent medicine based on the classic recipe "Shengmai powder". The relevant Chinese medicine ratio of Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A.Mey., Schisandra chinensis (Turcz.) Baill., and Ophiopogon japonicus (Thunb.) Ker Gawl. Is 30 : 6: 6 : 11. Traditional Chinese medicine (TCM) is being increasingly explored as a safe and effective treatment modality for HFpEF. Clinical studies have shown that DZSMCs can effectively treat heart failure, however, the mechanism of action of DZSMCs in the treatment of HFpEF are still not clear. Aim of the study: To investigate the efficacy and underlying mechanisms of Dengzhan Shengmai capsule (DZSMC), in the treatment of HFpEF by focusing on its ability to treat microvascular inflammation. First, the efficacy of DZSMCs against HFpEF was predicted by network pharmacology. After 3 days of adaptive feeding in SPF-grade polypropylene cages, the mice in the Model group, DZSMC group, and Captopli group underwent single kidney resection, and micropumps were implanted in their backs for continuous infusion of aldosterone at a rate of 0.3 μg/h for 4 weeks. Moreover, the mice were given DZSMCs or Captopli via oral gavage for four weeks. Overall, cardiac function was evaluated in mice, and cardiac ultrasound and blood biochemical indices were evaluated in HFpEF mice. DZSMCs can ameliorate myocardial hypertrophy and cardiomyocyte damage caused by excessive myocardial stress, ultimately mitigating long-term cardiac impairment; it aids in the restoration of myocardial fibre proliferation and enhances mitochondrial morphology and function. In a murine model of ventricular hypertrophy and left ventricular dysfunction, which are indicative of cardiac insufficiency, the administration of DZSMCs resulted in notable improvements. Echocardiographic and overall assessments of cardiac function revealed a reduction in cardiac dysfunction and ventricular hypertrophy post-DZSMC intervention. Moreover, intervention with DZSMCs led to a reduction in the serum levels of several markers associated with chronic systemic inflammation, such as sST2, IL1RL1, CRP, and IL-6. Simultaneously, the levels of indicators of microvascular inflammation, including VCAM and E-SELECTIN, also decreased following DZSMC intervention. These findings suggest the potential multifaceted impact of DZSMCs in alleviating cardiac abnormalities, mitigating systemic inflammation, and reducing microvascular inflammatory markers, highlighting their promising therapeutic role in managing myocardial health. These results provide novel evidence that DZSMCs improve HFpEF by regulating microvascular inflammation. [Display omitted] • Key targets and mechanisms of DZSMC for HEpEF was found by Network pharmacology. • Mice receiving DZSMC have an improvement in left ventricular function. • DZSMC can regulate the overall inflammation level in HFpEF mice. • DZSMC have an advantage in adjusting chronic and microvascular inflammation. [ABSTRACT FROM AUTHOR]

Yuanhu Zhitong Prescription (YZP) is a well-known traditional Chinese medicine (TCM) formula for neuropathic pain (NP) therapy with a satisfying clinical efficacy. However, the underlying pharmacological mechanism and its compatibility principle remain unclear. This study aims to investigate the analgesic and compatibility mechanisms of YZP on neuropathic pain (NP) at the gene and biological process levels. The chronic constriction injury (CCI) rats were intragastrically administrated with extracts of YZP, YH and BZ separately, and then mechanical hypersensitivity were measured to evaluate the analgesic effects between YH and BZ before and after compatibility. Then, RNA-seq and bioinformatics analyses were performed to elucidate the potential mechanisms underlying YZP's analgesia and compatibility. Finally, the expression levels and significant differences of key genes were analyzed. Behaviorally, both YZP and YH effectively alleviated mechanical allodynia in CCI rats, with YZP being superior to YH. In contrast, we did not observe an analgesic effect of BZ. Genetically, YZP, YH, and BZ reversed the expression levels of 52, 34, and 42 aberrant genes in the spinal cord of CCI rats, respectively. Mechanically, YZP was revealed to alleviate NP mainly by modulating the inflammatory response and neuropeptide signaling pathway, which are the dominant effective processes of YH. Interestingly, the effective targets of YZP were especially enriched in leukocyte activation and cytokine-mediated signaling pathways. Moreover, BZ was found to exert an adjunctive effect in enhancing the analgesic effect of YH by promoting skeletal muscle tissue regeneration and modulating calcium ion transport. YH, as the monarch drug, plays a dominant role in the analgesic effect of YZP that effectively relieves NP by inhibiting the spinal inflammation and neuropeptide signaling pathway. BZ, as the minister drug, not only synergistically enhances analgesic processes of YH but also helps to alleviate the accompanying symptoms of NP. Consequently, YZP exerted a more potent analgesic effect than YH and BZ alone. In conclusion, our findings offer new insights into understanding the pharmacological mechanism and compatibility principle of YZP, which may support its clinical application in NP therapy. [Display omitted] • The analgesic effect of YZP is more efficient than that of YH and BZ alone. YH plays a dominant role in the analgesic effect of YZP. • YZP ameliorates NP by inhibiting the inflammatory response and regulating neuropeptide signaling. • BZ alleviates skeletal muscle atrophy, which facilitates the analgesic effects of YH. • Ucn, Gal, and Ptgs2 may be pivotal targets associated with YZP analgesia as well as YH-BZ synergism. [ABSTRACT FROM AUTHOR]

Mailuo Shutong Pill (MLST), a traditional Chinese medicine (TCM), has been widely used for clearing heat and detoxifying, eliminating stasis and dredging meridians, dispelling dampness and diminishing swelling. Earlier study found that MLST could improve cerebral ischemic-reperfusion injury, however, the potential mechanism has not been well evaluated. In this study, a well established and widely used mice model of middle cerebral artery occlusion/reperfusion (MCAO/R) was preformed to evaluate the protective function of MLST on cerebral ischemic-reperfusion injury and further discuss the potential pharmacological mechanisms. Chemical profiling of MLST was analyzed based on Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry. ICR mice were challenged by MCAO/R surgery. The protective effect of MLST on MCAO/R injury was evaluated by neurological deficit score, cerebral infarct rate, brain water content, H&E and nissl staining. The blood-brain barrier (BBB) integrity was detected by Evans blue staining. The potential pharmacological mechanism of MLST in treating MCAO/R injury was further elucidated by the methods of proteomics, central carbon targeted metabolomics, as well as Western blot. Immunohistochemistry was used to detect the microglia infiltration, enzyme linked immunosorbent assay (ELISA) kit was explored to evaluate the content of IL-1β, TNF-α and IL-6 in brain tissue, and Western blot was used to detect proteins expression in brain tissue. A total of 76 chemical compounds have been determined in MLST. MLST effectively protected mice from MCAO/R injury, which was confirmed by lower neurological deficit score, cerebral infarct rate, brain water content and nissl body loss, and improved brain pathology. Meanwhile, MLST upregulated the expression of ZO-1, Occludin and Claudin 5 by downregulating the ratio of TIMP1/MMP9 to suppress the entrance of Evans blue to brain tissue, indicating that MLST maintained the integrity of BBB. Further studies indicated that MLST inhibited the inflammatory level of brain tissue by inhibiting microglia infiltration and downregulating NLRP3 inflammasome signaling pathway. The results of proteomics, Western blot, and central carbon targeted metabolomics confirmed that MLST regulated Glycolysis/Gluconogenesis, Pyruvate metabolism and TCA cycle in brain tissue of mice with MCAO/R. MLST inhibits neuroinflammation by regulating glucose metabolism disorders to interfere with immune metabolism reprogramming and inhibit the NLRP3 inflammasome signaling pathway, and finally improve cerebral ischemia-reperfusion injury. This study confirms that MLST is a potential drug for treating Cerebral ischemic stroke. [Display omitted] • Mailuo Shutong Pill (MLST) alleviates cerebral ischemia-reperfusion injury (I/R). • MLST induces regression of I/R by inhibiting neuroinflammation. • MLST regulates the glucose metabolism disorders in mice with MCAO/R. [ABSTRACT FROM AUTHOR]

Angong Niuhuang Wan (AGNHW) is a prescription from traditional Chinese medicine (TCM) that has been used for centuries to treat ischemic stroke (IS) and hemorrhagic stroke (HS). According to a recent study, targeting ferroptosis might be effective in the management of IS and HS. However, the ferroptosis-related effects and mechanisms of AGNHW have not yet been reported. This research examines the anti-ferroptosis mechanisms of AGNHW in the treatment of IS and HS. A system pharmacological approach including in vivo experiment, UHPLC-Q-Orbitrap HRMS, network pharmacology, molecular docking, microscale thermophoresis, and in vitro experiment was utilized to study the anti-ferroptosis mechanisms of AGNHW against IS and HS. In vivo experiments indicated that AGNHW enhanced nerve function, decreased cerebral infarct volume, ameliorated histological brain injuries, improved the structural integrity of the blood-brain barrier, ameliorated the mitochondrial dysfunction and morphology disruption, and inhibits ROS, LPO and Fe2+ accumulations in IS and HS rats. Using UHPLC-Q-Orbitrap HRMS, the key ingredients of AGNHW-containing serum were identified as bilirubin, berberine, baicalin, and wogonoside. According to the network pharmacology analyses, AGNHW could inhibit ferroptosis by modulating the PPAR and PI3K/AKT signaling pathways. The core targets are PPARγ, AKT, and GPX4. Molecular docking and microscale thermophoresis experiments further revealed that the key ingredients have strong interactions with ferroptosis-regulating core proteins. Moreover, in vitro experiment results showed that AGNHW alleviated ferroptosis injury induced by erastin in PC12 cells, increased cell viability, reduced the LPO and Fe2+ levels, and up-regulated mRNA expressions of PPARγ, AKT, and GPX4. AGNHW also up-regulated protein expressions of PPARγ, p-AKT/AKT, and GPX4 in IS and HS rats. AGNHW attenuated ferroptosis in treating IS and HS by targeting the PPARγ/AKT/GPX4 pathway. This work reveals AGNHW's anti-ferroptosis mechanism against IS and HS, but it also develops an integrated approach to demonstrate the common characteristics of drugs in treating different diseases. [Display omitted] • Angong Niuhuang Wan (AGNHW) is used for treating ischemic stroke (IS) and hemorrhagic stroke (HS) by eliminating phlegm and clearing heat. • Mechanism of AGNHW against IS and HS was related to inhibiting oxidative stress-induced ferroptosis in neurons. • Regulation of oxidative stress-induced ferroptosis in neurons was mediated by PPARγ/AKT/GPX4 pathway. • Bilirubin, berberine, baicalin, and wogonoside were the key active ingredients of AGNHW against IS and HS. [ABSTRACT FROM AUTHOR]

• Clinical trials of drug research and development approved by NMPA. • A total of 9,401 clinical trials were analyzed in this article. • Analyzed the phase, indication, dosage form, applicant of the clinical trials. • Analyzed the status and provided proposal for drug R&D in China. The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs. [ABSTRACT FROM AUTHOR]

Migraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) plays an important role. TG is composed of multiple neuronal and non-neuronal cell types, which is related to "neuro-inflammation-vascular" disorder in migraine. Tou Tong Ning capsule (TTNC), a CFDA-approved traditional Chinese medicine for treating migraine, has the characteristics of "multicomponents, multitargets, multipathways". To clarify the mechanism of TTNC and elucidate crosstalk between multicomponent drugs and neuronal and non-neuronal functions and cells in migraine. We integrated single-nucleus RNA sequencing and a quantitative evaluation algorithm of the disturbance of multitarget drugs on the disease network and explored the specific pathology of migraine and corresponding compounds. A cerebrovascular smooth muscle spasmolytic activity experiment was carried out to verify the results of the bioinformatics analysis. TTNC exhibited its regulation activities in neuronal and non-neuronal aspects based on drugs attack to four subnetworks and cell specific networks, which explored the MoA of TTNC in comprehensive and refined perspectives. Compared to neuronal regulation, TTNC showed more significant attack score on non-neuronal biological function (smooth muscle and vessel). And TTNC compound clusters C1, C6 and C7, targeting non-neuronal function and cells, had larger group area than C10, C4 and C6 for neuronal function and cell, which implied that TTNC may mainly regulate the non-neuronal function, e.g., vessel smooth muscle contraction. Contraction of cerebrovascular smooth muscle of mice ex vivo confirmed the vasodilation activity of TTNC and active compounds from C1, C6, C9 (Emodin, Luteolin and Levistilide A). Literature mining confirmed the vasospasmodolytic activity and neuroprotective effect of TTNC. The study found that TTNC may primarily alleviate non-neuronal functional disorders in migraine by relaxing cerebral vascular smooth muscle cell spasm to alleviate migraine. Integrating single-nucleus RNA sequencing data and network disturbance tools provides a new strategy for the pharmacological mechanism of multicomponent drugs through cell subtyping. [Display omitted] • Integrating snRNA-seq and network disturbance provides a new strategy for the MoA of multicomponent drugs through cell atlas. [ABSTRACT FROM AUTHOR]

Shengmai injection (SMI), consisting of Panax ginseng , Fructus schisandrae, and Radix ophiopogonis , has been widely used in the treatment of cardiovascular and cerebrovascular diseases. This study aimed to uncover the chemical profile of SMI, tissue distribution and pharmacokinetic characteristics of the main compounds after administration by combing UPLC-LTQ-Orbitrap-MS and UPLC-QQQ-MS. UPLC-LTQ-Orbitrap-MS method was firstly established for the chemical profiling analysis of SMI. Then UPLC-QQQ-MS method was used to quantitatively analyze the contents of the main identified compounds in SMI and in the different tissues after intravenous dosing SMI in rats with cerebral ischemia. Finally, a new method was developed for the pharmacokinetic study of ginsenosides with considerable exposure. A total of 59 compounds were identified in SMI, including 25 ginsenosides, 25 lignans, four ophiopogon saponins, and five flavonoids. Among them, 26 compounds were confirmed by the standard substance. By UPLC-QQQ-MS, 23 chemical compounds were then quantitatively identified with their contents in SMI. Ginsenosides, as the main active compounds from Panax ginseng , showed the highest contents in SMI. Fifteen compounds including ginsenosides and Schisandrol were further found to have considerable exposure in different tissues. A rapid, sensitive, and specified method was then developed for simultaneously detecting the seven ginsenosides in the plasma and had good method validation. Pharmacokinetic evaluation showed that PPD type ginsenosides (Rd, Rb1, Rc) were all exhibited at higher levels of exposure in the plasma and had a much slower elimination rate, whereas PPT type ginsenosides (Re, Rg1, Rf, Rg2) underwent fast elimination. This study systematically revealed the ingredients of SMI and their tissue distribution. The pharmacokinetic characteristics of ginsenosides were also discovered. The findings provide a helpful reference for the pharmacological, toxicological, and clinical research on SMI. [Display omitted] • Identification of the components in SMI by UPLC- LTQ-Orbitrap-MS. • Quantitative analysis of the main components in SMI and their tissues distribution after administering by UPLC-QQQ-MS. • Pharmacokinetic analysis of ginsenosides after intravenous dosing SMI in rats with cerebral ischemia. [ABSTRACT FROM AUTHOR]

• Employing 2D-UHPLC-Q-Orbitrap HRMS for ANP component analysis. • A comprehensive metabolic profile of ANP was achieved. • In rats, 60 prototype components and 164 metabolites were identified. • Novel prototypes and metabolites from animal-oriented medicines were detected in vivo. Angong Niuhuang Pill (ANP) is a traditional Chinese medicine (TCM) formula with significant clinical efficacy in the treatment of stroke. Due to its complex composition, little attention has been directed toward the analysis of chemical composition and absorption characteristics of ANP. In this study, a reliable two-dimensional ultra-high-performance liquid chromatography (2D-UHPLC) coupled with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS) method was established to characterize the chemical constituents in ANP as well as the prototype components and metabolites absorbed in plasma, urine, feces, and brain tissues after oral administration. The prototype components were identified by a high mass accuracy (within 5 ppm) and MS/MS data based on online, local, and ANP self-built databases. The metabolites were predicted and identified using Compound Discoverer metabolic platform. A total of 154 compounds mainly including 37 flavonoids, 35 alkaioids, 19 organic acid, 19 bile acid, 32 terpenoids and 12 others were identified in this way. In addition, 60 prototype components mainly including flavonoids, alkaioids, organic acid, terpenoids and 164 metabolites were confirmed or preliminarily identified in rats. The metabolic pathways phase I reaction (hydration, reduction, oxidation, demethylation, and hydroxylation) and phase II reaction (acetylation, stearyl conjugation, and methylation) for the absorbed constituents were explored and summarized. This is the first systematic and comprehensive chemical characterization in ANP and its metabolism in vivo by 2D-UHPLC-Q-Orbitrap HRMS. This approach provides an effective strategy for the characterization of compounds and metabolites in traditional Chinese medicine formulas. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Yuanhu Zhitong prescription (YZP) is a commonly used and relatively simple clinical herb preparation recorded in the China Pharmacopoeia. It contains Corydalis yanhusuo (Chinese name, Yanhusuo [YH]) and Angelica dahurica (Hoffm.) (Chinese name, Baizhi [BZ]), and has a long history of use in traditional Chinese medicine (TCM) for the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea. Aim of the study A TCM-ADMEpred method is developed for novel strategy for poly-pharmacokinetics prediction of TCM. To predict the pharmacokinetic characteristics of the main YZP constituents in rat plasma using in silico models, based on the theory that structurally similar constituents show similar pharmacokinetic properties. This approach may facilitate in silico prediction of the pharmacokinetics of TCM. Materials and methods A robust platform using ultra-performance liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for simultaneous determination of seven active YZP constituents in rat plasma. These seven compounds were divided into two structural classes, alkaloids and coumarins. The correlation between AUC profiles within a structural class was expressed as Γ+, and this variable was used to develop two novel in silico models to predict constituent AUC values. The pharmacokinetics of tetrahydropalmatine, tetrahydroberberine, and corydaline following YZP administration were predicted using the Γ+-values of α-allocryptopine observed following YH administration, while those of imperatorin and isoimperatorin following BZ administration were predicted using the Γ+-values of byakangelicin observed following YZP administration. Results The UPLC-ESI-MS/MS method was successfully used to evaluate pharmacokinetic parameters after oral YZP, YH, or BZ administration. Our findings showed that co-administration of YH and BZ increased the AUC of four alkaloid constituents and reduced the AUC of three coumarin constituents, which might provide a scientific rationale for co-administering these herbs clinically as a YZP preparation, thus increasing their efficacy and reducing toxicity. The AUC values of imperatorin and isoimperatorin were predicted 3 h after oral BZ administration, with the bias ratios between the theoretical values and the observed experimental values ranging from 0.61% to 11.4%, and average bias ratios of 5.8% and 8.0%, respectively. The AUC values of tetrahydropalmatine, tetrahydroberberine, and corydaline were predicted 3 h after oral YZP administration, with bias ratios ranging from 3.7% to 46.4%, and average bias ratios of 23.8%, 15.4%, and 25.8%, respectively. Conclusion The UPLC-ESI-MS/MS method was successfully applied to pharmacokinetic evaluations after oral administration of YZP, YH, and BZ to rats. The Γ+ variable was used to express the correlation between the AUC profiles of structurally similar compounds. This facilitated the development of an in silico model that was used to predict the AUC of three alkaloids in YZP and of two coumarins in BZ. Calculation of the bias ratios between the predicted and experimental values suggested that this in silico model provided a viable approach for the prediction of TCM pharmacokinetics. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

A cytokine storm (CS) is a rapidly occurring, complex, and highly lethal systemic acute inflammatory response induced by pathogens and other factors. Currently, no clinical therapeutic drugs are available with a significant effect and minimal side effects. Given the pathogenesis of CS, natural products have become important resources for bioactive agents in the discovery of anti-CS drugs. This study aimed to provide guidance for preventing and treating CS-related diseases by reviewing the natural products identified to inhibit CS in recent years. A comprehensive literature review was conducted on CS and natural products, utilizing databases such as PubMed and Web of Science. The quality of the studies was evaluated and summarized for further analysis. This study summarized more than 30 types of natural products, including 9 classes of flavonoids, phenols, and terpenoids, among others. In vivo and in vitro experiments demonstrated that these natural products could effectively inhibit CS via nuclear factor kappa-B, mitogen-activated protein kinase, and Mammalian target of rapamycin (mTOR) signaling pathways. Moreover, the enzyme inhibition assays revealed that more than 20 chemical components had the potential to inhibit ACE2, 3CL-protease, and papain-like protease activity. The experimental results were obtained using advanced technologies such as biochips and omics. Various natural compounds in traditional Chinese medicine (TCM) extracts could directly or indirectly inhibit CS occurrence, potentially serving as effective drugs for treating CS-related diseases. This study may guide further exploration of the therapeutic effects and biochemical mechanisms of natural products on CS. [Display omitted] • Initially reviews the potential natural products for the treatment of cytokine storm. • Initially summarizes target proteins for natural products treating cytokine storm. • Initially summarizes the pathways of natural products inhibiting cytokine storm. • Investigates the potential targets- ACE2、3CLpro、PLpro based enzyme inhibition assays. • Initially summarizes technical methods in investigated relevant research experiments. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Trichosanthis Fructus (ripe fruits of Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms) is an essential traditional Chinese medicine to treat thoracic obstruction, angina, cardiac failure, myocardial infarction, pulmonary heart disease, some cerebral ischaemic diseases, etc. The present report reviews the advancements in research on the botany, traditional uses, phytochemistry and pharmacology of Trichosanthis Fructus. Finally, perspectives on future research and its possible directions are discussed. Aim of the study This review provides up-to-date information about the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Trichosanthis Fructus and discusses the perspectives on future research and possible directions of this traditional Chinese Medicine and its origin plants. Materials and methods The information on Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms was collected from published scientific materials, including books; monographs on medicinal plants; pharmacopoeia and electronic databases such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, CNKI and Google Scholar. Results Approximately 162 compounds, including terpenoids, phytosterols, flavonoids, nitrogenous compounds and lignans, have been isolated and identified from Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms. Numerous studies have shown that the extracts and compounds isolated from these two plants exhibit pharmacological activities, including protection against myocardial ischaemia, calcium antagonist, endothelial cell protection, anti-hypoxic, anti-platelet aggregation, expectorant, anti-inflammatory, cytotoxic and antioxidant. Conclusions Trichosanthis Fructus is an essential traditional Chinese medicine with pharmacological activities that mainly affect the cardiovascular system. This review summarises its botany, traditional uses, phytochemistry and pharmacology. Future research is needed to clarify the different uses of the seeds, pericarps and fruits. Quality control of investigations of the fruits should be improved, and the potential uses of the flesh, leaves and twigs should be further explored. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Buchang Naoxintong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. However, the therapeutic effects and mechanisms are not yet well understood. Materials and methods In this study, a UPLC/TOF-MS-based metabolomic study was conducted to explore potential biomarkers that will increase our understanding of cerebral ischemia and to assess the integral efficacy of BNC in a middle cerebral artery occlusion (MCAO) rat model. Plasma metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. Results Clear separations were observed between the sham, MCAO and BNC-treated groups. We identified 28 biomarkers in the MCAO rats using variable importance for the projections (VIP) values (VIP>1) and a t -test ( P <0.05). The identified biomarkers were mainly related to disturbances in monoamine neurotransmitter metabolism, amino acid metabolism, energy metabolism and lipid metabolism. Moreover, a correlation network diagram of the plasma biomarkers perturbed by MCAO was constructed. Some biomarkers, such as glutamine, PE (17:0), LysoPE (20:1), LysoPE (24:0), and the ratios of LysoPE (24:1) to LysoPE (24:0), LysoPE (24:2) to LysoPE (24:0), showed obvious changes and a tendency for returning to baseline values in BNC-treated MCAO rats. In addition, MCAO rats receiving BNC treatment had improved neurological deficits and reduced cerebral infarct size demonstrating the therapeutic potential of BNC for treating cerebral ischemia. Conclusion This study provides a useful approach for exploring the mechanism of MCAO-induced cerebral ischemia and evaluating the efficacy of BNC. [ABSTRACT FROM AUTHOR]

Abstract: A rapid resolution liquid chromatography coupled with a triple quadrupole mass spectrometry (RRLC-QQQ) was employed to identify and quantify the major bioactive constituents in Yuanhu Zhitong tablet (YZT), a traditional Chinese medicine. Seventeen constituents were simultaneously determined and quantified by reference standards in 9min, namely scopoletin, protopine, α-allocryptopine, tetrahydropalmatine, coptisine, tetrahydroberberine, corydaline, berberine, byakangelicin, byakangelicol, xanthotoxin, bergapten, pimpinellin, oxypeucedanin, imperatorin, osthole and isoimperatorin. All of them were performed on an Agilent XDB C18 column (4.6mm×50mm, 1.8μm) with linear gradient elution of acetonitrile–0.3% formic acid water (pH 2.7). The proposed method was applied to analyze 15 batches of samples with acceptable linearity (r 2, 0.9938–0.9999), precisions (RSD, 1.01–4.92%), repeatability (RSD, 1.33–4.91%), stability (RSD, 1.46–4.86%), recovery (RSD, 1.11–4.81%) of the seventeen compounds. Furthermore, the Hierarchical Cluster Analysis was applied to classify 15 samples based on characteristics of the 17 compound markers. As a result, the analytical method possessing high sensitivity and speed is suitable for the quality control of YZT. [Copyright &y& Elsevier]

Heart failure (HF) after myocardial infarction (MI) is one of the most common disabling and painful diseases. A traditional Chinese medicine (TCM) formula, Shengmaisan, is known as a multitarget medicine that is widely used clinically to treat heart failure (HF) in Asian countries. However, its mechanism has not been comprehensively demonstrated. To use a prediction network to figure out which disease link SMZ mainly alleviates in HF and find biomarkers related to myocardial fibrosis in the serum for clinical reference. In this article, we collected a large amount of actual measurement data and our own proteomics data, along with the biomarkers of heart failure staging under study to establish a precise network. Then, we tested and verified the medicinal effect of SMZ in treatment of HF after MI by Measurement of left ventricular wall thickness and ejection fraction by echocardiography. Then we tested the serum level of the potential targets of SMZ predicting by the network we developed using ELISA. Results: the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle increased after treating with SMZ. The serum level of EGFR and MAPK1 decreased in the groups treated with SMZ. SMZ can improve the cardiac function of rats with MI by increasing the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle. In addition, SMZ could delay heart failure mainly by inhibiting the progression of myocardial fibrosis through decreasing the EGFR and MAPK1 levels. [Display omitted] [ABSTRACT FROM AUTHOR]

• An LC-Q-TOF/MS- and LC-MS/MS-based metabolomics approach were used in coronary heart disease. • An untargeted and targeted metabolomic were used in Chinese medicine subtypes. • The integrated metabolomics-based diagnostic method can facilitate personalized TCM approaches. The World Health Organization has shown that coronary heart disease (CHD) is a more common cause of death than cancer. In traditional Chinese medicine (TCM), CHD is classified as a form of thoracic obstruction that can be divided in different subtypes including Qi stagnation with blood stasis (QS) and Qi deficiency with blood stasis (QD). Different treatment strategies are used based on this subtyping. Owing to the lack of scientific markers in the diagnosis of these subtypes, subjective judgments made by clinicians have limited the objective manner for utility of TCM in the treatment of CHD. Untargeted (UHPLC-QTOF-MS) and targeted (UHPLC-MS/MS) metabolomics approaches were employed to search significantly different metabolites related to the QS or QD subtypes of CHD with angina pectoris in this study. A total of 42 metabolites were obtained in the untargeted metabolomics analysis and 34 amino acids were detected in the targeted metabolomics analysis. In total, 16 metabolites were found significantly different among different groups. The results showed distinct metabolic profiles of urine samples not only between CHD patients and healthy controls, but also between the two subtypes of CHD. Pathway analysis of the significantly varied metabolites revealed that there were subtype-related differences in the activity of pathways. Therefore, urinary metabolomics can reveal the pathological changes of CHD in different subtypes, make the diagnosis of CHD in different subtypes in an objective manner and comprehensive and contribute to personalized treatment by providing scientific evidence. [ABSTRACT FROM AUTHOR]

Abstract: In order to improve the biomedical property of Bletilla striata polysaccharide (BSP), this study presents a new method of BSP fiber preparation and its mechanical properties were preliminarily tested. BSP with excellent biocompatibility was extracted from a traditional Chinese herb, B. striata, by using an immersion precipitation phase-inversion approach. BSP fibers were prepared by wet spinning using ethanol as the coagulant at room temperature. The morphology of BSP fibers was observed by scanning electron microcopy (SEM), and it has been found that the shape of the fibers was flat. The formation of the flat shape contributed to the slow exchange rate between the solvent and the nonsolvent. The stress at break, strain at break, initial modulus and energy at break point of the BSP fibers increased with increasing BSP concentration in the spinning solutions. The excellent spinnability, mechanical property and biocompatibility enable the BSP fibers to be an ideal material in the potential applications such as tissue engineering scaffold and wound dressing. [Copyright &y& Elsevier]

'Polypharmacology' is usually used to describe the network-wide effect of a single compound, but traditional Chinese medicine (TCM) has a polypharmacological effect naturally based on the 'multi-components, multi-targets and multi-pathways' principle. It is a challenge to investigate the polypharmacology mechanism of TCM with multiple components. In this study, we used XiaoErFuPi (XEFP) granules as an example to describe an unsupervised learning strategy for polypharmacology research of TCM and to explore the mechanism of XEFP polypharmacology against multifactorial disease function dyspepsia (FD). Unsupervised clustering of compounds based on similarity evaluation of cellular function fingerprints showed that compounds of TCM without similar targets and chemical structure could also exert similar therapeutic effects on the same disease, as different targets participate in the same pathway closely associated with the pathological process. In this study, we proposed an unsupervised machine learning strategy for exploring the polypharmacology-based mechanism of TCM, utilizing hierarchical clustering based on cellular functional similarity, to establish a connection from the chemical clustering module to cellular function. Meanwhile, FDA-approved drugs against FD were used as references for the mechanism of action (MoA) of FD. First, according to the compound-compound network built by the similarity of cellular function of XEFP compounds and FDA-approved FD drugs, the possible therapeutic function of TCM may represent a known mechanism of FDA-approved drugs. Then, as unsupervised learning, hierarchical clustering of TCM compounds based on cellular function fingerprint similarity could help to classify the compounds into several modules with similar therapeutic functions to investigate the polypharmacology effect of TCM. Furthermore, the integration of quantitative omics data of TCM and approved drugs (from LINCS datasets) provides more quantitative evidence for TCM therapeutic function consistency with approved drugs. A spasmolytic activity experiment was launched to confirm vanillic acid activity to repress smooth muscle contraction; vanillic acid was also predicted to be active compound of XEFP, supporting the accuracy of our strategy. In summary, the approach proposed in this study provides a new unsupervised learning strategy for polypharmacological research investigating TCM by establishing a connection between the compound functional module and drug-activated cellular processes shared with FDA-approved drugs, which may elucidate the unique mechanism of traditional medicine using FDA-approved drugs as references, facilitate the discovery of potential active compounds of TCM and provide new insights into complex diseases. [ABSTRACT FROM AUTHOR]

There is a lack of systematic descriptions and characterization of strokes and their effects in both the cerebral hippocampus and cortex. Shuxuetong (SXT) injection was reported to have good therapeutic effects in the clinic; therefore, it was selected as a drug intervention method for cerebral ischemia repair in rat models. The aim of this study was to understand the features of molecules and pathways and to reveal key processes of SXT repair. Evaluation of neurological deficit and infarct volume measurement was used to estimate the pharmacological effects of SXT injection on Ischemia-reperfusion(I/R) model rats. LC-MS/MS and RNA-Seq analysis were used to analyze the proteins and mRNA expression in the cerebral hippocampus and cortex 6 h and 24 h after ischemic injury and repair. A label-free approach (IBAQ) for proteomics analysis and FPKM based on gene read count for transcriptomics analysis were used to quantify the differences among the three experimental groups (Sham, Model and SXT-treated groups). Transcriptomics and proteomics analyses were verified by RT-qPCR and western blotting. By combining LC-MS/MS and RNA-Seq, eight larger datasets (two time points and two tissues) were confidently identified in more than three biological replicates. An average of 4500 unique proteins and 8200 protein-coding genes were confidently identified. By combining the subcellular localization, hierarchical clustering, pathway enrichment analysis in the injury and repair phase, six core proteins and related genes that were significantly expressed were verified as candidates for cerebral ischemic injury by western blotting and quantitative real-time PCR. Meanwhile, the results indicated that there was better expression in the 6 h group by significant proteomics analysis during the development and progression of cerebral ischemia. Two primary co-enriched pathways, the PI3K-AKT and MAPK signaling pathways, and six related core candidates may play key roles in molecular mechanisms related to cerebral ischemic injury and repair by SXT injection. Our data not only identified six core candidates and two key signaling pathways for cerebral ischemic injury and verification but also provided evidence for the explanation, prevention and treatment of cerebral ischemia by SXT injection. The results of the present study provide evidence for the explanation, prevention and treatment of cerebral ischemia by SXT injection. Image 1 [ABSTRACT FROM AUTHOR]

• Xiaoerfupi (XEFP) increased the gastric emptying and gastrin of the rats with functional dyspepsia (FD). • HTR3A and c-FOS were predicted to the key targets of XEFP by bioinformatics tools. • XEFP diminished the level of HTR3A and c-FOS in the stomach of rats with FD. To evaluate whether Xiaoerfupi (XEFP), a traditional Chinese medicine formula, can ameliorate functional dyspepsia (FD) through regulation of the HTR3A and c-FOS. The FD rat model was established through administration of iodoacetamide (IA) and interval fasting. XEFP group rats received XEFP for 3 weeks. Detection of gastric emptying and gastrin were performed to assess the interventional effect of XEFP. The constituents of XEFP were submitted to BATMAN-TCM, an online bioinformatics analysis tool, to predict the targets related to dyspepsia. Furthermore, the prediction was validated via Western blot assay. XEFP enhanced gastric emptying of rats (XEFP middle dose vs. FD model: 71.87 ± 15.21% vs. 30.07 ± 12.76%, P < 0.01) and simultaneously increased gastrin in FD rats (XEFP middle dose vs. FD model: 63.61 ± 17.90 vs. 26.14 ± 7.78 pg/ml, P < 0.01). KEGG enrichment analysis revealed that the neuroactive ligand-receptor interaction was successfully enriched (P -value = 2.2E-13, Benjamini = 2.0E-11). Combining different Bioinformatics analysis implied that XEFP regulates HTR3A and c-FOS. Subsequently molecular biological studies confirmed that the expression of HTR3A and c-FOS in the model group was upregulated in rats in comparison with the control group. Furthermore, the expression of HTR3A and c-FOS in the XEFP group (middle dose) compared with the model group was significantly reduced (P < 0.01). XEFP may ameliorate FD through regulation of the HTR3A and c-FOS. [ABSTRACT FROM AUTHOR]