Compatibility Of Traditional Chinese Medicine Research Articles

Unveiling the Mechanism of Compound Ku-Shen Injection in Liver Cancer Treatment through an Ingredient–Target Network Analysis

Background: Compound Ku-Shen Injection (CKI) is a traditional Chinese medicine preparation derived from Ku-Shen and Bai-Tu-Ling, commonly used in the adjunctive treatment of advanced cancers, including liver cancer. However, the underlying mechanisms of CKI’s effectiveness in cancer treatment are not well defined. Methods: This study employs network pharmacology to investigate the traditional Chinese medicine (TCM) compatibility theory underlying CKI’s action in treating liver cancer, with findings substantiated by molecular docking and in vitro experiments. Sixteen active components were identified from CKI, along with 193 potential targets for treating liver cancer. Key therapeutic target proteins, including EGFR and ESR1, were also identified. KEGG enrichment results showed that the neuroactive ligand–receptor interaction, cAMP signaling pathway, and serotonergic synapses make up the key pathway of CKI in the treatment of liver cancer. Molecular docking results confirmed that the key active ingredients effectively bind to the core targets. CCK-8 cytotoxic experiment results show that the CKI key components of oxymatrine and matrine can inhibit the growth of HepG2 liver cancer cell proliferation. A Western blot analysis revealed that oxymatrine suppresses the expression of EGFR, contributing to its therapeutic efficacy against liver cancer. Conclusion: our study elucidated the therapeutic mechanism of CKI in treating liver cancer and unveiled the underlying principles of its TCM compatibility through its mode of action.

A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet

BackgroundCinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified. PurposeOur study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary. MethodsThe toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS. ResultsCin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed. ConclusionAs a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.

Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.Graphical

Scientific connotation of the compatibility of traditional Chinese medicine from the perspective of the intestinal flora.

Revealing the connotation of the compatibility of Chinese medicines (CM) is a requirement for the modernization of traditional Chinese medicine (TCM). However, no consensus exists on the specific mechanism of traditional Chinese medicine compatibility (TCMC). Many studies have shown that the occurrence and development of diseases and the efficacy of CM are closely related to intestinal flora (IF), which may provide a new perspective to understand the theory of TCM. This study aimed to summarize the relationship between the changes in IF before and after the compatibility of different drugs and the synergistic, toxicity reduction, and incompatibility effects of drug pairs from the perspective of the effects of CM on the IF and the regulation of microbial metabolites. These studies showed that the effect of drug pairs on the composition of the IF is not a simple superposition of two single drugs, and that the drug pairs also play a specific role in regulating the production of intestinal bacterial metabolites; therefore, it has a different pharmacodynamic effect, which may provide a perspective to clarify the compatibility mechanism. However, research on the interpretation of the scientific connotations of TCMC from the perspective of the IF is still in its infancy and has limitations. Therefore, this study aimed to summarize previous research experience and proposed to conduct a deep and systematic study from the perspective of drug pair dismantling, IF, intestinal bacteria metabolite, organism, and disease to provide a reference for scientific research on the compatibility mechanism of CM.

Combining lipidomics and efficacy-oriented compatibility revealed that Qi Ge decoction compatibility improved lipid metabolism in hyperlipidemic rats.

The mechanism underlying traditional Chinese medicine (TCM) compatibility is difficult to understand. This study combined lipidomics and efficacy-oriented compatibility to explore underlying compatibility mechanisms of Qi Ge decoction (QG) for improving lipid metabolism in hyperlipidemic rats. The QG was divided into three groups according to the efficacy group strategy: the Huangqi-Gegen (HG), Chenpi (CP), and QG groups. Hyperlipidemic rats were treated with QG, HG, CP, or atorvastatin for 3 weeks. The mass spectral data of widely targeted lipidomics were used to evaluate lipid changes. Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess the lipidomic differences between the groups. MetaboAnalyst 5.0 was used to explore metabolic pathways. Compared with the model group, serum cholesterol, triglyceride, and hepatic steatosis were significantly reduced by QG, whereas HG and CP had no significant effects on these indexes. Lipidomics showed that QG, HG, and CP back-regulated 60, 11, and 14 lipids, respectively. Compared with HG and CP, QG had more metabolic targets in diglycerides, triglycerides, ceramides, and phosphatidylethanolamines. Pathway analysis indicated that QG mainly regulated glycerophospholipid and glycerolipid metabolism. This study provided a new method of combining lipidomics and efficacy-oriented compatibility for exploring the scientific connotation of TCM compatibility.

Gut microbiome and tissue metabolomics reveal the compatibility effects of Xiaoyaosan on depression based on “gut-liver-kidney” axis

BackgroundDepression affects not only the central nervous system, but also the peripheral system. Xiaoyaosan (XYS), a classical traditional Chinese medicine (TCM) prescription, exhibits definite anti-depression effects demonstrated both clinically and experimentally. However, its compatibility has not been entirely revealed due partly to the complex compositions of herbs contained. AimBased on the strategy of “Efficacy Group”, this study aimed to reveal the compatibility of XYS from the perspective of “gut-liver-kidney” axis. MethodsFirstly, XYS was divided into two efficacy groups, i.e. Shugan (SG) and Jianpi (JP) groups. Classic behaviors of rats were measured to confirm the anti-depression effects of XYS and its two efficacy groups. On top of this, gut microbiota analysis and kidney metabolomics were performed by 16S rRNA sequencing and 1H NMR, respectively. ResultsWe found that XYS and its efficacy groups significantly regulated the abnormalities of behaviors and kidney metabolism of depressed rats, as well as intestinal disorders, but to different degrees. The regulatory effects of XYS and its efficacy groups on behaviors and kidney metabolomics of depressed rats had the same order, i.e. XYS > SG > JP, while the order of regulating gut microbiota was XYS > JP > SG. Both XYS and its efficacy groups significantly ameliorated gut microbiota disturbed, especially significant modulation of Peptostreptococcaceae. XYS significantly regulated nine kidney metabolites, while SG and JP regulated four and five differential metabolites, respectively, indicating that the two efficacy groups synergistically exhibited anti-depression effects, consequently contributing to the overall anti-depression effects of XYS. ConclusionThe current findings not only innovatively demonstrate the anti-depression effects and compatibility of XYS from the perspective of “gut-liver-kidney” axis, comprehensively using “Efficacy Group” strategy, macro behavioristics, metabolome and microbiome, and also provide a new perspective, strategy, and methodology for studying complex diseases and the compatibility of TCMs.

Metabolomic Analysis of Stephania tetrandra-Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway.

The Stephania tetrandra−Astragalus membranaceus herbal pair (FH) is a classic herbal pair widely used in the treatment of nephrotic syndrome (NS). The effects of Stephania tetrandra (FJ) and Astragalus membranaceus (HQ) on NS have been reported, but the mechanism of their combination on the improvement of NS are still unclear. The NS model was established by injecting adriamycin into the tail vein. FH intervention reduced the levels of serum triglyceride, total cholesterol, interleukin-6 (IL-6), blood urea nitrogen (BUN), urinary protein, and the gene expression levels of aquaporin 2 (AQP2) and arginine vasopressin (AVP) in NS rats. In addition, FH improved kidney injury in NS rats by inhibiting the expression of interleukin 13 (IL-13), phospho-signal transducers, and activators of transcription 6 (p-STAT6), Bax, cleaved-caspase3, while promoting the expression of Bcl-2. By comprehensive comparison of multiple indexes, the effects of FH on lipid metabolism, glomerular filtration rate, and inflammation were superior to that of FJ and HQ. Metabonomic studies showed that, compared with FJ and HQ, FH intervention significantly regulated tricarboxylic acid (TCA) cycle, cysteine and methionine metabolism, and alanine, aspartic acid and glutamic acid metabolism. Pearson correlation analysis showed that succinic acid and L-aspartic acid were negatively correlated with urinary protein, cystatin C (Cys C) and BUN (p < 0.05). In summary, FH could reduce renal injury and improve NS through inhibiting the IL-13/STAT6 signal pathway, regulating endogenous metabolic pathways, such as TCA cycle, and inhibiting the expression of AQP2 and AVP genes. This study provides a comprehensive strategy to reveal the mechanism of FH on the treatment of NS, and also provides a reasonable way to clarify the compatibility of traditional Chinese medicine.

Gut microbiota: The key to the treatment of metabolic syndrome in traditional Chinese medicine - a case study of diabetes and nonalcoholic fatty liver disease.

Metabolic syndrome mainly includes obesity, type 2 diabetes (T2DM), alcoholic fatty liver (NAFLD) and cardiovascular diseases. According to the ancient experience philosophy of Yin-Yang, monarch-minister compatibility of traditional Chinese medicine, prescription is given to treat diseases, which has the advantages of small toxic and side effects and quick effect. However, due to the diversity of traditional Chinese medicine ingredients and doubts about the treatment theory of traditional Chinese medicine, the mechanism of traditional Chinese medicine is still in doubt. Gastrointestinal tract is an important part of human environment, and participates in the occurrence and development of diseases. In recent years, more and more TCM researches have made intestinal microbiome a new frontier for understanding and treating diseases. Clinically, nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) often co-occur. Our aim is to explain the mechanism of interaction between gastrointestinal microbiome and traditional Chinese medicine (TCM) or traditional Chinese medicine formula to treat DM and NAFLD. Traditional Chinese medicine may treat these two diseases by influencing the composition of intestinal microorganisms, regulating the metabolism of intestinal microorganisms and transforming Chinese medicinal compounds.

UGTs-mediated metabolic interactions contribute to enhanced anti-inflammation activity of Jinhongtang

Ethnopharmacological relevanceJinhongtang, a traditional Chinese medicine (TCM) formula consisting of dry stems of Rheum palmatum L. (Polygonaceae) and Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson (Lardizabalaceae) and whole plant of Taraxacum mongolicum Hand.-Mazz. (Asteraceae), is widely used for the treatment of infection diseases including severe sepsis and COVID-19. Aim of the studyThe present study aimed to explore the compatibility mechanism in the prescription of Jinhongtang based on the pharmacokinetic interaction. Materials and methodsCLP-induced sepsis mice and LPS-induced RAW264.7 cells were used to explore the anti-inflammatory effect of Jinhongtang and herbs in this clinical prescription. Pharmacokinetics of active components in Jinhongtang (Rhein, Emodin and Aloe emodin) was studied in rats. In vitro analysis of metabolic pathways and interactions mediated by metabolic enzymes were conducted using human liver microsomes (HLMs) and recombinant UGT isoforms. ResultsJinhongtang exhibited much more potent anti-inflammatory effect than its single herbs on CLP-induced sepsis mice and LPS-induced RAW264.7 cells. Next, the bioavailability of active ingredients (Rhein, Emodin and Aloe emodin) in R. palmatum was significantly improved through reduced metabolic clearance when co-administered with S. cuneata and T. mongolicum as Jinhongtang during the in vivo pharmacokinetic study, which presented the rational herbal compatibility mechanism. In detailed, the components in S. cuneata and T. mongolicum including Sargentodoxoside A, Chanitracin Ia, Quercetin and Luteolin inhibited the UGT1A9-mediated glucuronidation of active ingredients in R. palmatum, with Ki values of 2.72 μM, 1.25 μM, 2.84 μM and 0.83 μM, respectively. ConclusionT. mongolicum and S. cuneata, the adjuvant herbs of Jinhongtang, could reduce the metabolic clearance of key active components of R. palmatum, prolong their action time and further enhance their anti-inflammatory activity via inhibition of UGTs. Our findings provided deep insight for the rational compatibility of TCMs and useful guidance for the development of TCM formula.

CPMCP: a database of Chinese patent medicine and compound prescription.

Although several traditional Chinese medicine (TCM)-related databases have emerged, they focus on researching single medicinal materials, which is far from sufficient for clinical research and application. In comparison, compound prescriptions are more informative and meaningful in TCM, for they embody the information on the compatibility of TCM besides the relatively isolated information about single medicinal materials. The compatibility information is essential in TCM because it conveys not only what components are involved to treat special diseases but also how to combine these single medical materials. We established a database of Chinese patent medicine and compound prescription (CPMCP). It demonstrates the prescription information of Chinese patent medicines (CPMs) and ancient Chinese medicine prescriptions (CMPs). CPMCP reports their comprehensive and standardized information such as the components, indications and contraindications. It is worth mentioning that we organized relevant experts and spent lots of time manually mapping the functions of compound prescriptions in ancient Chinese to the standardized TCM symptom vocabularies, obtaining a total of 71 414 associations between compound prescriptions and TCM symptoms. In this way, CPMCP established the associations between TCM and modern medicine (MM) according to the associations between TCM symptoms and MM symptoms. In addition, to further exhibit the compatibility mechanism of compound prescriptions, CPMCP summarizes a set of common drug combination principles by analyzing the existing prescriptions. We believe that CPMCP can promote the modernization of TCM and make greater contributions to MM. Database URL http://cpmcp.top

Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.

Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.

Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress

Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored. Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San. Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting. Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting. Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San.

Exploratory Compatibility Regularity of Traditional Chinese Medicine on Osteoarthritis Treatment: A Data Mining and Random Walk-Based Identification.

Osteoarthritis (OA) is a degressive and complex disease which is a growing public health problem on a global scale. On basis of an in-house database consisting of clinical records of 13,083 OA patients, the Traditional Chinese Medicine (TCM) was divided into 4 categories of medicines on the basis of the curative properties of herbs. Due to the lack of depth and internal relationship in the calculation results of TCM compatibility law data mining methods such as statistics and frequency analysis, we use a variety of multidimensional complex network methods that can efficaciously find the compatibility law of TCM, including similarity measure, graphical visualization of network diagram, random walking, and propensity score methods. We summarize common couplet medicines utilized for the treatment of osteoarthritis. The similarity measure method was used to investigate the commonly used drugs for the treatment of osteoarthritis. The method of association rule analysis is used to recognize the compatibility between the components. On basis of the propensity score methods, the evaluation displayed that, compared with single drug, the drug group increased ESR, CRP, C3, C4, IgG, and IgA more efficiently. Concluding, a random walk model was constructed to assess drug efficacy. After applying a random walk model, while revealing the compatibility among different components of TCM, their therapeutic efficacy against OA is analyzed. We obtained four groups of drug combination clusters by similarity measure and 11 pairs of highly connected drugs by association rules, which are cardinal drug combinations in the prescription for the treatment of OA. We also found that different traditional drug pairs were associated with different laboratory indexes, and drug combinations could better optimize laboratory indexes. This study presented that the TCM constituents complement one another. Besides, the therapeutic effects resulting from a variety of combinations of these constituents are quite different.

Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets"

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a &quot;double reduction network pharmacology&quot;(2 R network pharmacology) research method based on &quot;prediction of dominant components-potential target selection&quot;. Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is &quot;reducing constituents&quot;; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is &quot;reducing targets&quot;. To improve the efficiency and accuracy of effective component screening, the network relationship of &quot;component target&quot; was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Wutou decoction ameliorates experimental rheumatoid arthritis via regulating NF-kB and Nrf2: Integrating efficacy-oriented compatibility of traditional Chinese medicine

BackgroundThousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown. PurposeThis study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms. MethodsThe anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments. ResultsOur data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro. ConclusionThe ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.

The synergistic anti-depression effects of different efficacy groups of Xiaoyaosan as demonstrated by the integration of network pharmacology and serum metabolomics

Compatibility investigations are vital but also the most difficult aspect of traditional Chinese medicine (TCM) prescriptions. Previous researches have demonstrated that Xiaoyaosan (XYS) is an effective treatment for depression. However, the compatibility rules of XYS and the underlying mechanisms remain unclear. Herein, we combined network pharmacology and serum metabolomics to investigate the scientific connotations and the compatibility effects of XYS. First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and the GeneCards databases were applied to identify the chemical components and the putative targets of XYS, and its efficacy groups. We then analyzed the herb-component-target pathways and constructed PPI networks. Potential pathways were determined by gene ontology (GO) and pathway enrichment analyses. Additionally, a chronic unpredictable mild stress (CUMS) model was applied on rats. A proton nuclear magnetic resonance spectrometry (1H NMR) based serum metabolomics was then used to identify potential metabolites and the corresponding pathways that were involved in depression and the potential anti-depression effects of XYS and its efficacy groups. A total of 121 components of XYS and 111 targets were associated with depression. Additionally, we screened 105 targets of 24 components in Shugan (SG) group and 106 targets of 95 components in Jianpi (JP) group. 13 targets were common to all three groups. Protein-protein interaction network analysis showed that Caspase-3 and Nitric oxide synthase-3 were nodes that overlapped with proteins known to be associated with depression. Pathway enrichment analysis further indicated that the putative targets of XYS and its efficacy groups mostly participated in pathways associated with cancer. Also, XYS and its efficacy groups significantly reversed abnormalities of serum metabolites and metabolic pathways, but to different degrees. Overall, different efficacy groups of XYS exhibit synergistic anti-depression effects and contribute to the whole prescription against depression. This study shows that the combination of network pharmacology and metabolomics is an effective approach to demonstrate scientific connotations and compatibility of TCMs from a holistic perspective.

Synergistic Effect of Berberine-Based Chinese Medicine Assembled Nanostructures on Diarrhea-Predominant Irritable Bowel Syndrome In Vivo

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one common chronic functional disease of the digestive system with limited treatments. The microbiota–gut–brain axis (MGBA) has a central function in the pathogeny of IBS-D, which includes the participation of many various factors, such as brain-gut peptides (BGPs), immune inflammation, and intestinal flora. Inspired by the drug combination in traditional Chinese medicine (TCM), our previous study discovered that berberine (BBR) and baicalin (BA) could form natural self-assemblies as BA-BBR nanoparticles (BA-BBR NPs) and showed synergistic effects against IBS-D. Here, we investigated the synergistic effects of BA-BBR NPs on IBS-D model mice induced by chronic restraint stress plus Senna alexandrina Mill decoction with the influence on MGBA. BA-BBR NPs showed the best therapeutic effect on improving visceral hypersensitivity and diarrhea on IBS-D model mice, compared with BBR, BA, and BA/BBR mixture. Furthermore, BA-BBR NPs significantly (P<0.05) reduced the levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and choline acety transferase (CHAT) in colon tissues or of serum from BGPs; it lowered the expressions of the nuclear factor kappa-B (NF-κB) in colon tissues and changed the levels of basophil granulocyte (BASO) and leukomonocyte (LYMPH) in whole blood from immune inflammation; it altered the intestinal flora of Bacteroidia, Deferribacteres, Verrucomicrobia, Candidatus_Saccharibacteria, and Cyanobacteria from intestinal flora. In conclusion, BA-BBR NPs, after forming the natural self-assembly between BBR and BA, promoted the synergistic effect on IBS-D mice than the sum of BBR and BA effects, based to the formation of self-assemblies rather than the simple mixing. It further proved that synergistic effect of BA-BBR NPs on IBS-D mice might be related to BGPs, immune inflammation, and intestinal flora from three important interrelated components of MGBA. This study will provide a novel idea for the interpretation of TCM compatibility theory and provide the basis for BA-BBR NPs as a medicinal plant-derived natural and efficient nanomaterial for clinical use.

Review of Constituents and Biological Activities of Triterpene Saponins from Glycyrrhizae Radix et Rhizoma and Its Solubilization Characteristics.

Glycyrrhizae Radix et Rhizoma is regarded as one of the most popular and commonly used herbal medicines and has been used in traditional Chinese medicine (TCM) prescriptions for over 2000 years. Pentacyclic triterpene saponins are common secondary metabolites in these plants, which are synthesized via the isoprenoid pathway to produce a hydrophobic triterpenoid aglycone containing a hydrophilic sugar chain. This paper systematically summarizes the chemical structures of triterpene saponins in Glycyrrhizae Radix et Rhizoma and reviews and updates their main biological activities studies. Furthermore, the solubilization characteristics, influences, and mechanisms of Glycyrrhizae Radix et Rhizoma are elaborated. Solubilization of the triterpene saponins from Glycyrrhizae Radix et Rhizoma occurs because they contain the nonpolar sapogenin and water-soluble sidechain. The possible factors affecting the solubilization of Glycyrrhizae Radix et Rhizoma are mainly other crude drugs and the pH of the decoction. Triterpene saponins represented by glycyrrhizin from Glycyrrhizae Radix et Rhizoma characteristically form micelles due to amphiphilicity, which makes solubilization possible. This overview provides guidance regarding a better understanding of Glycyrrhizae Radix et Rhizoma and its TCM compatibility, alongside a theoretical basis for the further development and utilization of Glycyrrhizae Radix et Rhizoma.

Analysis and monitoring of traditional Chinese medicines for tumor based on data mining

The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.

Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment.

The research field of systems biology has greatly advanced and, as a result, the concept of network pharmacology has been developed. This advancement, in turn, has shifted the paradigm from a “one-target, one-drug” mode to a “network-target, multiple-component-therapeutics” mode. Network pharmacology is more effective for establishing a “compound-protein/gene-disease” network and revealing the regulation principles of small molecules in a high-throughput manner. This approach makes it very powerful for the analysis of drug combinations, especially Traditional Chinese Medicine (TCM) preparations. In this work, we first summarized the databases and tools currently used for TCM research. Second, we focused on several representative applications of network pharmacology for TCM research, including studies on TCM compatibility, TCM target prediction, and TCM network toxicology research. Third, we compared the general statistics of several current TCM databases and evaluated and compared the search results of these databases based on 10 famous herbs. In summary, network pharmacology is a rational approach for TCM studies, and with the development of TCM research, powerful and comprehensive TCM databases have emerged but need further improvements. Additionally, given that several diseases could be treated by TCMs, with the mediation of gut microbiota, future studies should focus on both the microbiome and TCMs to better understand and treat microbiome-related diseases.