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Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5′-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro , HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT. [Display omitted] • XYT reduces cardiac dysfunction in TAC mice. • XYT reduces AngII-induced cardiomyocyte injury. • RIPK3/FUNDC1-mediated UPRmt and mitophagy is an important pathway for the efficacy of XYT. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a chronic lung dysfunction disease with a poor prognosis and poor recovery. The clinically used therapeutic drugs, such as glucocorticoids and immunosuppressants, have no significant therapeutic effect and are accompanied with severe side effects. In recent years, considerable progress has been made in exploring and applying natural herb components for treating ILD. Traditional Chinese Medicine (TCM) possesses innate, non-toxic characteristics and offers advantages in preventing and treating pulmonary ailments. However, a comprehensive study of TCM on ILD therapy has not yet been reviewed. This review aimed to provide a comprehensive summary of the monomer components, total extracts, and prescriptions of TCM for ILD therapy, elucidating their molecular mechanisms to serve as a reference in treating ILD. The literature information was searched in the PubMed, Web of Science databases. The search keywords included 'interstitial lung disease', 'lung fibrosis' or 'pulmonary fibrosis', and 'traditional Chinese medicine', 'traditional herbal medicine', or 'herb medicine'. The active components of single herbs, such as alkaloids, flavonoids, terpenoids, phenols, and quinones, have potential therapeutic effects on ILD. The active extracts and prescriptions were also summarized and analyzed. The herbs, Glycyrrhiza uralensis Fisch. (Gancao), Astragalus membranaceus Fisch. Bunge. (Huangqi) and Angelicasinensis (Oliv.) Diels (Danggui), play significant roles in the treatment of ILD. The mechanisms involve the inhibition of inflammatory factor release, anti-oxidative injury, and interference with collagen production, etc. This review examines the therapeutic potential of TCM for ILD and elucidates its molecular mechanisms, demonstrating that mitigating inflammation and oxidative stress, modulating the immune system, and promoting tissue repair are efficacious strategies for ILD therapy. The depth research will yield both theoretical and practical implications. [Display omitted] • The active components derived from TCM have potential therapeutic effects against ILD. • The total extract from TCM is effective for the treatment of ILD. • The therapeutic mechanisms of TCM for ILD include anti-inflammatory, antioxidant and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In the genus Curculigo, Curculigo orchioides Gaertn, Curculigo capitulata (Lour) O. Ktze and Curculigo pilosa (Schumach. & Thonn.) Engl are often used in traditional medicine. Curculigo orchioides is used for the treatment of impotence, limb limpness, arthritis of the lumbar and knee joints, and watery diarrhea in traditional Chinese medicine, and also used as a potent immunomodulator and aphrodisiac in the Ayurvedic medical system. Curculigo capitulata is used for the treatment of consumptive cough, kidney asthenia, impotence and spermatorrhea, hemorrhoids, asthma, jaundice, diarrhea, colic and gonorrhea in traditional Chinese and India medicine, and to treat urinary tract infection, acute renal pelvis and nephritis, nephritis-edema, cystitis, nephrolithiasis, hypertension and rheumatic arthritis in traditional Dai medicine. Curculigo pilosa are applied to treat gastrointestinal and heart diseases in Africa. Aim of the review: This review aims to exhibit up-to-date and comprehensive information about traditional uses, phytochemistry, pharmacology and toxicology of medicinal plants in the genus Curculigo, and has an insight into the opportunities for the future research and development of Curculigo plant. Methods: A bibliographic investigation was performed by analyzing the information available on Curculigo plant from worldwide accepted scientific databases (Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo). Furthermore, information also was obtained from some local and foreign books on ethnobotany and ethnomedicines. Results: Curculigo orchioides, Curculigo capitulata and Curculigo pilosa have been used as traditional medicine to treat kinds of diseases such as impotence, limb limpness, gastrointestinal and heart diseases, etc. Phytochemical investigation of eight species of the genus Curculigo has resulted in identification of more than 110 compounds. The content of curculigoside is used as an indicator to evaluate the quality of rhizome of Curculigo orchioides. The medicinal plants have showed a wide spectrum pharmacological activities, including adaptive, immunostimulatory, taste-modifying and sweet-tasting, antioxidant, mast cell stabilization, antihistaminic and antiasthmatic, hepatoprotective and neuroprotective activity. Toxicological test indicated that Curculigo orchioides at the dose of 120g/kg after administrating rats for 180 days may cause injury of liver and kidney. Conclusion: The medicinal plants of genus Curculigo have emerged as a good source of the traditional medicines. Some uses of these plants in the traditional medicines have been validated by pharmacological investigation. However, the mechanism of their actions should be further elucidated; the particular constituent responsible for toxicity should be isolated and identified, and the target tissue and mechanism of toxic ingredients also deserve to be further investigated; more reference substances should be prepared, and sophisticated analytical technologies should be developed to comprehensively assess the quality of Curculigo herbs. These investigations will be helpful for further utilization of the plants of genus Curculigo. [Copyright &y& Elsevier]

Echinops latifolius Tausch (ELT) is traditional Mongolian medicine in China, and often used to against osteoporosis, strengthen tendons and bones, clear bones heat. To study efficacy of ELT on ovariectomized (OVX) rats and underly metabolic pathways related to trabecular micro-architecture changing of OVX. Three-month-old female Wistar rats were randomly divided into 4 groups (n = 6) including normal group (without surgery), sham group (bilateral laparotomy), OVX group (bilateral ovariectomy), and ELT-treated groups (ELT-treated after bilateral ovariectomy). The effects of ELT on trabecular micro-architecture and biochemical markers of OVX rat were investigated by dual-energy X-ray absorptiometry machine and Enzyme-linked immunosorbent assay (ELISA), respectively. Untargeted metabolomics strategy was applied to discover the potential biomarkers and related metabolic pathways involving the progression of OVX-induced osteoporosis. The trabecular micro-architecture and biochemical markers of OVX rats were improved by ELT. We found 36 potential biomarkers and 21 related metabolic pathways were involved in progression of OVX-induced osteoporosis. Amino acids metabolism and glycerophospholipids metabolism were mainly intervened in ELT treatment on ovariectomized rats. The disordered amino acids and glycerophospholipids metabolism closely related to the imbalance between bone resorption and formation were reversed by administration of ELT, indicating that the influences of ELT on OVX rats' trabecular micro-architecture may possible be associated with intervening amino acids and glycerophospholipids metabolism. This approach may provide the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of ELT, to further explain how ELT works in postmenopausal patients with bone loss. Image 1 • Anti-osteoporosis efficacy of Echinops latifolius Tausch on ovariectomized rats was evaluated by trabecular micro-architecture changing for the first time. • Pharmacodynamics and metabolomics were combined to elucidate the mechanism of Echinops latifolius Tausch in the treatment of osteoporosis for the first time. • The influences of Echinops latifolius Tausch on ovariectomized rats' trabecular micro-architecture were uncovered in this paper for the first time. • This work provides the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of Echinops latifolius Tausch. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb–gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels. Materials and methods Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α -naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC–MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma. Results The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone. Conclusions The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP. [ABSTRACT FROM AUTHOR]

Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF- α , IL-1 β and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. Among crude extracts from C. chinensis , ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N -[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2 E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p - N , N -dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)- α , interleukin (IL)-6 and IL-1 β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: To investigate the synergistic property of Platycodonis Radix (PG) in a classic Traditional Chinese Medicine (TCM) prescription Shengxian Decoction (SXT) by combining chemical profile with pharmacokinetic analysis strategy. The synergized prescription consisted of Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, and Cimicifuage Rhizoma. Materials and methods: Ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry (UPLC–Q-TOF/MS) was employed to investigate the chemical fingerprints of SXT and decreased SXT (SXT that removed Platycodonis Radix, SXT-PG). A reliable LC–MS/MS method was developed to examine the pharmacokinetics of 9 marker compounds (including formononetin, calycosin-7-O-β-d-glucoside, ononin, caffeic acid, isoferulic acid, mangiferin, timosaponin E1, timosaponin B-II and timosaponin B) following oral administration of SXT and SXT-PG in rats. Both in vitro chemical profiles and in vivo pharmacokinetic parameters differences between SXT and SXT-PG were conducted. Results: By using UPLC–Q-TOF/MS method, a total of 25 compounds identified from SXT, including 13 triterpenoids, 5 caffeinic derivatives, 4 isoflavonoids and 3 xanthone glycosides. Comparing the chemical fingerprints between SXT and decreased SXT did not reveal significant difference in the chemical profile of other four TCMs. The improved pharmacokinetic profiles of mangiferin, timosaponin E1, timosaponin B-II and timosaponin B were found in SXT group, suggesting the quicker distribution and more effective absorption, when compared with those in the SXT-PG group. Conclusions: These results indicated that PG did not increase the dissolution of synergized prescription when co-decocting, but guided the synergized prescription to target location, reflecting the courier role of PG, which was in line with the clinical principle of TCM. It also established a useful method for TCM synergistic property research. [Copyright &y& Elsevier]