Exploring the HIF-1α signalling pathway and the mechanism of YiQiHuoXue decoction against Precancerous Lesions of Gastric Cancer based on Network Pharmacology and Molecular Docking.

Precancerous Lesions of Gastric Cancer (PLGC) are an essential step in the advancement of Gastric cancer (GC). Early intervention represents the most effective strategy to impede the development of PLGC. However, additional research is necessary to comprehend the molecular mechanism of PLGC. YQHXD is originated from Si Wu Decoction, has been utilized as an empirical formula for the treatment of PLGC for several years. In this study, we employed network pharmacology, molecular docking, and experimental validation to examine the inhibitory and ameliorative properties of YQHXD on PLGC. Multiple databases were utilized to gather genetic information on drugs in PLGC and YQHXD, in order to obtain cross-targets. We discovered 142 common targets between YQHXD and PLGC. GO and KEGG enrichment analyses indicate that YQHXD treatment of PLGC might be linked with cellular response to oxygen levels and the HIF-1α signaling pathway. Finally, we performed in vitro experiments, of which the results reveal that YQHXD mitigates gastric mucosal atrophy, intestinalization, and heterogeneous hyperplasia, and reduces the expression of inflammatory factors in rats. Therefore, we considered that YQHXD has the potential to delay the PLGC process by inhibiting the HIF-1α signaling pathway.

Integrating network pharmacology and experimental evidence to decipher the cardioprotective mechanism of Yiqihuoxue decoction in rats after myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency and blood stasis" syndrome is one of the most common syndromes treated with Traditional Chinese Medicine among ischemic heart disease (IHD) patients in clinic. As a Chinese herbal formula with the function of tonifying Qi and activating blood, Yiqihuoxue Decoction (YQHX) has been frequently proven to be effective in the clinical treatment of IHD. AIM OF THE STUDY: The cardioprotective mechanisms of YQHX in treating ischemic heart disease were investigated, with emphasis on the key targets and pathways. MATERIALS AND METHODS: In the present study, the potential targets of compounds identified in YQHX were predicted using PharmMapper, Symmap, and STITCH databases, and a "herb-compound-target" network was constructed using Cytoscape. Subsequently, the GO and KEGG functional enrichment analyses were analyzed using the DAVID database. Furthermore, a protein-protein interaction network was constructed using STRING to obtain the key target information. Besides, we used a myocardial ischemia rat model to investigate the cardioprotective effects of YQHX. Transmission electron microscopy and Western blotting were used to observe apoptotic bodies and confirm protein expressions of key candidate targets, respectively. RESULTS: Network pharmacology showed that a total of 141 potential targets were obtained from these databases. The functional analysis results revealed that the targets of YQHX were largely associated with apoptosis, and the PI3K-AKT and MAPK pathways might represent key functional pathways. The hub genes of network include ALB, TP53, AKT1, TNF, VEGFA, EGFR, MAPK1, CASP3, JUN, FN1, MMP9, and MAPK8. In vivo, YQHX significantly improved cardiac function and suppressed apoptosis in ischemic rat myocardium. Furthermore, YQHX could significantly upregulate Nrf2 and HO-1 expression, and inhibit JNK phosphorylation. CONCLUSIONS: Based on network pharmacology and experimental evidence, this study proves that the cardioprotective effects and mechanisms of YQHX depend on multi-component, multi-target, and multi-pathway. In particular, YQHX exerts anti-apoptotic effects potentially by regulating the Nrf2/HO-1 and JNK-MAPK pathways.

Yiqihuoxue decoction protects against post-myocardial infarction injury via activation of cardiomyocytes PGC-1α expression.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of ischemic heart disease, exacerbating cardiomyocytes injury in myocardial infarction (MI). Peroxisome proliferator-activated receptor gamma co-activator (PGC-1α) has been recognized as the key regulator of mitochondrial biogenesis and energy metabolism. Yiqihuoxue decoction (YQHX), a Traditional Chinese Medicine (TCM) prescription, can prevent and treat ischemic heart disease. However, the mechanisms of YQHX on PGC-1α expression in the ischemic heart have remained unclear. METHODS: Myocardial ischemia rat model and ischemia/hypoxia injury model in the cardiomyocytes were used to minic human cardiovascular disease. Rats were randomly assigned into 4 groups: Sham, Model, YQHX (8.2 g/kg) and Trimetazidine (10 mg/kg) group. 28 days after MI, cardiac functions and morphology were detected by echocardiography and HE staining, respectively. In vitro, the effects of YQHX on H9c2 cell viability, LDH and ROS were detected, respectively. PGC-1α relevant proteins were evaluated by Western blotting. RESULTS: In vivo, echocardiography and HE staining results showed that YQHX improved cardiac functions and modified pathological changes. YQHX enhanced PGC-1α expression and improved the mitochondrial ultrastructure and functions in rats MI model for 4 weeks. Further, we explored its potential mechanisms in cardiomyocytes. In vitro, YQHX significantly enhanced cell viability and reduced LDH release and ROS production induced by hypoxia in cardiomyocytes. Interestingly, exposure of cardiomyocytes to hypoxic conditions for 12 h induced the downregulation of PGC-1α expression, but the expression levels nearly returned to the normal state after hypoxia for 24 h. YQHX significantly enhanced PGC-1α expression between 12 h and 24 h induced by hypoxia through a mechanism associated with the activation of AMPK phosphorylation in H9c2 cells. In addition, YQHX upregulated the expression of Tfam and NRF-1, while NRF-1 expression was completely blocked by an AMPK inhibitor. YQHX largely restored the mitochondrial morphology and increased mitochondrial membrane potential in hypoxia-induced injury. Furthermore, the UHPLC-LTQ-Orbitrap-MSn analysis found that there were 87 chemical constituents in YQHX. CONCLUSIONS: These results suggest that the protective effect of YQHX on cardiomyocytes against hypoxia-induced injury may be attributed to activation of PGC-1α and maintenance of mitochondrial functions through a mechanism involving the activation of AMPK phosphorylation.

Clinical effects of Yiqihuoxue decoction on remnant stomach paralysis syndrome after subtotal gastrectomy / 国际中医中药杂志

Objective To approach effect of Yiqihuoxue decoction on remnant stomach paralysis syndrome after subtotal gastrectomy. Methods A total of 44 patient of remnant stomach paralysis syndrome were randomly recruited into a control group and a treatment group, with 22 patients in each group. The control group was treated with TPN parenteral alimentation. On this basis, the treatment group was treated with Yiqihuoxue decoction and mental intervention. The clinical effects were observed in both groups after the treatment. Results The total effective rate was 54.55% and 100% in the control group and the treatment group respectively, showing statistic difference(P=0.00625 ＜0.01).Conclusion It was effective to treat remnant stomach paralysis syndrome with Yiqihuoxue decoction, TPN parenteral nutrition and mental intervention.