No abstract

Resveratrol is one of the most well-known drugs used in the treatment of aging. However, the potential mechanisms of resveratrol on intestinal aging have not yet been fully investigated. Herein, we aimed to further explore the pharmacological mechanisms of resveratrol as a therapy for intestinal aging. We performed network construction and enrichment analysis via network pharmacology. Then a further animal experimental validation containing 20 female C57BL/6J (wild type, WT) and 16 female ATF4 +/-(knock down, KD) naturally aging mice and oral supplementary resveratrol (44 mg/kg/ day) for 30 days were conducted. The expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), linear alkylethoxylate (AE), and malondialdehyde (MDA) were measured by ELISA, the observation of pathological changes and apoptosis in intestinal tissue were performed by HE, PAS, and TUNEL staining, the ATF4/Chop/Bcl-2/Bax signaling pathway-related proteins and mRNAs expression were measured by western blotting and real-time PCR. The network pharmacology showed 132 targets of resveratrol on aging. The enrichment analysis showed resveratrol antiaging involved mainly included protein heterodimerization activity, apoptosis, etc. Then ATF4/Chop/Bcl-2/Bax signaling pathway in biological process of apoptosis was selected to verify the potential mechanisms. Animal studies showed resveratrol upregulated the relative expression of SOD, GSH-Px, CAT, AE, whereas it downregulated the relative expression of MDA in intestine compared with the control group. There was also higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice. Moreover, there was higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice after resveratrol treatment. Decreased ATF4, Chop, Bax but increased Bcl-2 proteins and mRNAs expression were determined after resveratrol treatment compared with the control group; lower ATF4, Chop, Bax but higher Bcl-2 proteins and mRNAs expression were found in KD mice than that in WT mice. Additionally,

Vitamin K2 (VK2), found to act to treat hypertension, has been widely used in the food and pharmaceutical industries nowadays. However, the potential targets and molecular mechanisms of VK2 for salt-sensitive hypertension have not been fully investigated. Therefore, the study aimed to investigate the potential molecular mechanisms of VK2 for salt-sensitive hypertension using network pharmacology and 16S rRNA sequencing strategy. The network pharmacology-based findings from KEGG enrichment analysis revealed that VK2-treated salt-sensitive hypertension was mechanically associated with the complement and coagulation cascades, calcium signaling pathway, renin–angiotensin system, etc. A total of 29 different bacteria in an animal experiment after VK2 supplementation were screened and functionally enriched using PICRUSt2. Additionally, 10 signaling pathways were identified in which the renin–angiotensin system was found to be the potential molecular mechanisms with the greatest change in multiple and statistical significance. Moreover, the results of the renin–angiotensin system-related protein expression exhibited VK2-inhibited renin–angiotensin system in salt-induced hypertensive mice, which significantly verified the previous biological and functional prediction analysis. Finally, spearman correlation analysis showed the different bacteria such as Dubosiella, Ileibacterium, etc., had a positive or negative correlation with renin–angiotensin system-related proteins in salt-induced mice. In conclusion, the potential molecular mechanisms of VK2 for salt-sensitive hypertension may be beneficially achieved by the specific inhibition of the renin–angiotensin system, contributing to the development for a new preventive strategy of salt-sensitive hypertension.

Background: Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension.Objective: This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension.Methods: According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This metaanalysis used RevMan 5.4 to evaluate the articles.Results: This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16-1.37, P < .00001), which could effectively reduce the systolic BP (MD = −15.28 mm Hg; 95% CI: −20.17 to −10.40, P < .00001=, diastolic BP (MD = −9.70 mm Hg; 95% CI: −12.66 to −6.73, P < .00001), Triglycerides (MD = −1.48, 95%CI: −2.09 to −0.87, P < .00001), total cholesterol (MD = −1.43, 95% CI: −1.63 to −1.24, P < .00001) and low density lipoprotein cholesterol (MD = −0.93, 95% CI: −1.07 to −0.80, P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum highdensity lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46, P < .00001).Conclusion: THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference.