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QiLing decoction (QLD) is a traditional Chinese medicine compound. This study aims to explore the therapeutic effect of QLD in castration-resistant prostate cancer (CRPC) and its potential bio-targets. A total of 51 active components and QLD 149 targets were identified using bioinformatics analysis. Additionally, five optimal hub target genes were screened including tumor protein P53 (TP53), interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), caspase-3 (CASP-3), and estrogen receptor- 1 (ESR-1). The interrelated network between active components of QLD and their potential targets was constructed. The molecular function, biological processes, and signaling pathways of QLD-against CRPC were identified. Moreover, QLD was found to efficiently exert a repressive effect on CRPC tumor growth mainly by suppressing the activation of HIF-α/VEGFA and TNF-α/IL6 signaling pathways, and increasing the P53 expression level. These results successfully indicated the potential anti-CRPC mechanism of the active components of QLD. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor. [ABSTRACT FROM AUTHOR]

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria. [ABSTRACT FROM AUTHOR]

Paeonia is a well‐known species of ornamental plants, traditional Chinese medicines, and emerging oilseed crops. Apart from nutritional unsaturated fatty acids, the seeds of peonies are rich in stilbenes characterized by their wide‐ranging health‐promoting properties. Although the typical stilbene resveratrol has been widely reported for its multiple bioactivities, it remains uncertain whether the trimer of resveratrol trans‐gnetin H has properties that regulate cancer cell viability, let alone the underlying mechanism. Autophagy regulated by trans‐gnetin H was detected by western blotting, immunofluorescence, and quantitative real‐time PCR. The effects of trans‐gnetin H on apoptosis and proliferation were examined by flow cytometry, colony formation and Cell Counting Kit‐8 assays. Trans‐gnetin H significantly inhibits cancer cell viability through autophagy by suppressing the phosphorylation of TFEB and promoting its nuclear transport. Mechanistically, trans‐gnetin H inhibits the activation and lysosome translocation of mTORC1 by inhibiting the activation of AMPK, indicating that AMPK is a checkpoint for mTORC1 inactivation induced by trans‐gnetin H. Moreover, the binding of TSC2 to Rheb was markedly increased in response to trans‐gnetin H stimulation. Similarly, trans‐gnetin H inhibited the interaction between Raptor and RagC in an AMPK‐dependent manner. More importantly, trans‐gnetin H‐mediated autophagy highly depends on the AMPK‐mTORC1 axis. We propose a regulatory mechanism by which trans‐gnetin H inhibits the activation of the mTORC1 pathway to control cell autophagy. [ABSTRACT FROM AUTHOR]

Threatened abortion (TA) is the most common complication in early pregnancy and is caused by anxiety and depressive symptoms. The Zishen Yutai Pill (ZYP) is a traditional herbal formula that is commonly used to treat TA. However, the pharmacological mechanisms underlying the effect of ZYP have yet to be elucidated. To disclose the mechanism of ZYP in the treatment of TA, first, we identified the chemical constituents of ZYP from multiple databases and then predicted the potential targets of TA by applying the GeneCards database. A protein-protein interaction (PPI) network was then constructed to allow the screening of hub targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) enrichment analyses were also performed and the Database for Annotation Visualization and Integrated Discovery server was used to identify critical biological processes and signaling pathways. Cytoscape software was used to construct a Compound-Target-Pathway. Furthermore, we analyzed ZYP by UPLC-Q-TOF/MS, then the RU486-induced TA rat model was established, and the reliability of the network pharmacology prediction results was verified. Finally, the mechanisms responsible for the action of ZYP on TA were revealed by qRT-PCR and molecular docking. Database screening identified a total of 161 active compounds in ZYP and 324 TA-related targets. And, we identified 42 compounds from ZYP by UPLC-Q-TOF/MS. Inflammation and apoptosis were identified as the main biological processes. GO and KEGG analyses identified that the MAPK and PI3K/Akt pathways were the key functional pathways that respond to ZYP. The results showed that ZYP treatment significantly increased maternal weight, significantly increased the levels of estradiol and progesterone, and attenuated histopathological changes in a rat model of TA. Data indicated that ZYP treatment improved pregnancy outcomes in the rat model of TA. QRT-PCR data showed that ZYP reduced inflammation and apoptosis by regulating the MAPK and PI3K/Akt pathways. In addition, molecule docking results identified a range of key compounds, including Pik3a, Mapk14, Mapk1, Mapk3, Mapk8 Tnf, Il6, and Cas8. In summary, we performed network pharmacological analysis and experimental validation and identified that ZYP exerts an effect on TA by regulating the MAPK and PI3K/Akt pathways and by inhibiting the expression levels of proinflammatory cytokines and genes related to apoptosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the potential targets and mechanism of action of Danshen in treating concurrent ischemic heart disease (IHD) and depression using network pharmacology, molecular docking, and molecular dynamics simulation (MDS). Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain active ingredients and targets of Danshen. Candidate targets for IHD and depression were obtained from the Genecards and DisGeNet databases. The protein–protein interaction (PPI) network was constructed using the STRING database and the Cytoscape 3.8.2 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Metascape database and the GlueGO package of the Cytoscape 3.8.2 software. Molecular docking was performed using Autodock 1.5.6 and Vina, and the MDS was completed using GROMACS 5.1.2. Results: We obtained 65 active ingredients of Danshen with 131 candidate targets and 39 intersection targets of the active ingredients and diseases. Luteolin, tanshinone IIA, and salviolone were the core active ingredients, and AKT1, TNF, IL-6, MMP9, CASP3, IL-10, PTGS2, STAT3, PPARG, IL-4, EGFR, MAPK14, NOS3, and EDN1 were the core targets. The GO and KEGG pathway enrichment analyses revealed that the intersection targets were mainly enriched in positive regulation of protein phosphorylation, blood circulation, IL-17 signaling pathway, VEGF signaling pathway, and JAK/STAT signaling pathway. The molecular docking revealed that the core active ingredients had a good affinity for the core targets. The results of MDS revealed that the protein-ligand complexes were stable. Conclusions: This study used network pharmacology to analyze the potential mechanism of action of Danshen in the treatment of concurrent IHD and depression. Additionally, the study provided a theoretical basis for further studying the pharmacological mechanisms and targets of Danshen. [ABSTRACT FROM AUTHOR]

BACKGROUD: Astragali Radix (AR) and Codonopsis Radix (CR) are widely used as the tonic herbal medicine with efficacy of tonifying qi in traditional Chinese medicine (TCM), which showed significant antifatigue activities. In this study, AR and CR were combined, with Jujubae Fructus (JF) further added to improve the taste, to afford the ACJ extracts in the ratio of 2:1:2. RESULTS: The results showed that ACJ water extract exhibited antifatigue effect by the weight‐loaded exhaustive swimming test in mice. The untargeted fecal metabolomic approach and 16S rRNA gene sequencing analysis showed that ACJ could improve exercise performance by regulating changes of gut metabolites and microbiota to alleviate fatigue. Four pathways were determined as the key pathways relating with its antifatigue effect, which included sphingolipid metabolism, glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis and d‐arginine and d‐ornithine metabolism. Correlation analysis showed the complex association among bacteria, metabolites and phenotypes. CONCLUSION: In conclusion, this study revealed new perspectives to study the antifatigue mechanism of ACJ extracts from the gut microbiota, which provided the basis for further functional food development. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Currently, there are many different drugs to improve Alzheimer's disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients. Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of ß-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models. Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of ß-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP. Results: For the primary endpoint, compared with the modeling group, ß-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31-2.70). For the secondary endpoint, ß-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = -2.25, 95% CI: -2.49 to -2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = -2.40, 95% CI: -3.51 to -1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38-0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = -0.70, 95% CI: -0.93 to -0.47) over the control group. Conclusion: ß-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) has become the second most common disease worldwide, making it a threat to human health. Cyperi Rhizoma (CR) is a traditional herbal medicine with antidepressant properties. Traditional Chinese medicine theory states that CR relieves MDD by dispersing stagnated liver qi to soothe the liver, but the material basis and underlying mechanism have not been elucidated. In this study, we identified the active compounds and potential anti-MDD targets of CR by network pharmacology-based approaches. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we hypothesized that the anti-MDD effect of CR may be mediated by an altered response of the liver to lipopolysaccharide (LPS) and glucose metabolism. Through bioinformatics analysis, comparing normal and MDD liver tissue in rats with spontaneous diabetes, we identified differentially expressed genes (DEGs) and selected PAI-1 (SERPINE1) as a target of CR in combating MDD. Molecular docking and molecular dynamics analysis also verified the binding of the active compound quercetin to PAI-1. It can be concluded that quercetin is the active compound of CR that acts against MDD by targeting PAI-1 to enhance the liver response to LPS and glucose metabolism. This study not only reveals the material basis and underlying mechanism of CR against MDD through soothing the liver but also provides evidence for PAI-1 as a potential target and quercetin as a potential agent for MDD treatment. [ABSTRACT FROM AUTHOR]