Deciphering the Mechanism of Siwu Decoction Inhibiting Liver Metastasis by Integrating Network Pharmacology and In Vivo Experimental Validation.

BACKGROUND: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. OBJECTIVE: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. MATERIALS AND METHODS: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein-protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. RESULTS: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. CONCLUSION: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.

Chinese patent herbal medicine (Shufeng Jiedu capsule) for acute upper respiratory tract infections: A systematic review and meta-analysis.

BACKGROUND: Shufeng Jiedu capsule has been widely used in China for acute upper respiratory tract infections (AURTIs). The aim of this study was to evaluate its effectiveness and safety for AURTIs. METHODS: Randomized controlled trials comparing SFJD with conventional drug for patients with AURTIs were included. Eight databases were searched from their inceptions to February 2021. Data was synthesized using risk ration (RR) or mean difference (MD) with their 95% confidence interval (CI). The primary outcome was resolution time of typical symptoms. RESULTS: Twenty-five RCTs involving 3410 patients were included. SFJD in combination with conventional drug was associated with; in common cold shortening the duration of fever (MD -1.54 days, 95% CI [-2.15,-0.92], I 2 = 80%, n = 385, 3 trials) and cough (MD -1.22 days, 95% CI [-1.52, -0.93]); in herpangina, shortening the duration of fever (MD -0.68 days, 95% CI [-1.15, -0.21], I2  = 68%, n = 140, 2 trials) and blistering (MD -0.99 days, 95% CI [-1.23, -0.76], n = 386, 3 trials); in acute tonsillitis and acute pharyngitis shortening the duration of fever (MD -1.13 days, 95% CI [-1.36, -0.90], I 2 = 33%, n = 688, 7 trials) and sore throat (MD -1.13 days, 95% CI [-1.40, -0.86], I 2 = 84.1%, n = 1194, 10 trials). SFJD also improving their cure rate with a range (1-5 days). No serious adverse events were reported. CONCLUSION: Low certainty evidence suggests that SFJD appears to shorten the duration of symptoms in AURTIs, improve cure rate and seems safe for application. However, high quality placebo controlled trials are warranted to confirm its benefit.