Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q exactive focus mass spectrometry, network pharmacology, and molecular docking.

OBJECTIVE: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG). METHODS: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]. RESULTS: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways. CONCLUSIONS: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.

Effect of Yangxue Rougan pills on the TGF-β1/Smad signaling pathway in a rat model of liver fibrosis induced by multiple factors / 临床肝胆病杂志

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

The effects of Xinjia-Liangfu formula combined 5-Fu on survivin and caspase-3 expression of gastric cancer xenografts in nude mice / 国际中医中药杂志

Objective To observe the effect of Xinjia-Liangfu(XJLF)formula on human gastric cancer(SGC-7901)tumor growth in nude mice and its impact on survivinand Caspase-3 expression in tumor tissue. Methods The animal model of SGC-7901 xenografted nude mice was established, and all the mice were randomly divided into 6 groups, namely model control group, 5-Fu group, XJLF formula high-dose group, XJLF formula medium-dose group , XJLF formula low-dose group and drug combination group(XJLFformula medium-dose and 5-Fu). After 10 days of continuous treatment, tumor inhibition rate was calculated and the expression of Survivin and Caspase-3 was detected by immunohistochemistry techniques. Results The tumor inhibition rates of 5-Fu group, XJLF formula high-dose group, XJLF formula medium-dose group, XJLF formula low-dose group and drug combination group were 55.03%, 56.38%, 41.23%, 23.09%and 60.28%respectively, and the tumor inhibition rate of drug combination group was significantly increased compared to the model control group(P<0.05), 5-Fu group(P<0.05)and XJLF high-dose group(P<0.05) Meanwhile, the Caspase-3 expression was significantly up-regulated and the Survivin expression was significantly down-regulated in drug combination group(Caspase-3 was 77 539.74±50 912.5, Suvivin was 35 709.1±10404.4)compared to the model control group(Caspase-3 was 18 464.71±7 537.01,Suvivin was 63 449.4±50 498.8), P<0.05 or 0.01, 5-Fu groupCaspase-3 was (47 198.89±10 751.2), Suvivin was(37 016.8±6 024.4), P<0.05 or 0.01and XJLF formula high-dose groupCaspase-3was (44213.57±7041.6), Suvivin was (38811.1±7313.0)respectively. Conclusion The tumor inhibition rate of drug combination group was higher than XJLF formula high-dose group and 5-Fu group. Also combination group hadstronger effect compared to model control group in terms of down-regulation of Caspase-3 expression and up-regulation of Survivin expression, which indicates a benefit ofXJLF and 5-Fu combination treatment.