Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), a natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, particularly in relation to senescence, remain elusive. Thus, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of AS-IV in treating ISO-induced MF in mice, employing transcriptomics, proteomics, in vitro, and in vivo experiments. We assessed the positive effects of AS-IV on ISO-induced MF using HE staining, Masson staining, ELISA, immunohistochemical staining, transthoracic echocardiography, transmission electron microscopy, and DHE fluorescence staining. Additionally, we elucidated the regulatory role of AS-IV in MF through comprehensive transcriptomics and proteomics analyses, complemented by Western blotting and RT-qPCR validation of pertinent molecular pathways. Our findings demonstrated that AS-IV treatment markedly attenuated ISO-induced myocardial injury and oxidative stress, concomitantly inhibiting the release of SASPs. Furthermore, integrated transcriptomics and proteomics analyses revealed that the anti-MF mechanism of AS-IV was associated with regulating cellular senescence and the p53 signaling pathway. These results highlight AS-IV exerts its anti-MF effects not only by inhibiting oxidative stress but also by modulating senescence through the p53 signaling pathway.

Background: Diabetes is one of the most common chronic diseases in the world. In recent years, with the continuous improvement of people's living standards and changes in dietary structure, the incidence of diabetes is gradually increasing. Studies have shown that ascorbic acid supplementation can reduce blood glucose, increase insulin synthesis and secretion, improve insulin resistance, and reduce the occurrence and development of complications of type 2 diabetes mellitus (T2DM). However, relevant studies have common problems such as the lack of large sample studies and low quality of included studies. Therefore, it is needed that we meta-analyze the clinical trials with high quality to elucidate the efficacy and safety of ascorbic acid supplementation in patients with T2DM. Methods: We will search randomized controlled trials published by PubMed, Embase, the Cochrane Library, Web of Science, and the Clinical Trials.gov website from inception to August 2020 on the effects of ascorbic acid supplementation on blood glucose, glycosylated hemoglobin, serum insulin, insulin resistance and other variables in T2DM patients with no language restrictions. The retrieval adopts the combination of medical subject headings and random words, and traces the references of the included literature to supplement the acquisition of relevant literature. Two researchers will independently screen the retrieved literature, extract the data and cross-check, and the Review Manage software V5.3.0 will be utilized for meta-analysis. Results: Our study will provide a high-quality and in-depth comprehensive analysis of the effects of ascorbic acid supplementation on blood glucose control, glycosylated hemoglobin and insulin resistance in type 2 diabetic patients. Conclusion: This systematic review and meta-analysis concerning randomized controlled trials of ascorbic acid supplementation for type 2 diabetic patients will provide a new direction and strong evidence to evaluate whether ascorbic acid supplementation is of benefit to glucose control and insulin resistance in T2DM. PROSPERO registration number: CRD 42019146826

Background: Heart failure with reduced ejection fraction (HFrEF) is a prevalent cardiovascular disease globally, posing a significant burden on healthcare and society. Left ventricular remodelling is the primary pathology responsible for HFrEF development and progression, leading to increased morbidity and mortality. Pueraria, a traditional Chinese herbal medicine and food, is commonly used in China to treat HFrEF. Accumulating evidence suggests that pueraria can effectively reverse left ventricular remodelling in HFrEF patients. This meta-analysis aims to assess the impact of pueraria on left ventricular remodelling in HFrEF patients. Methods: Eight electronic databases, including PubMed, EMBASE, Clinicaltrials.gov, Cochrane Library, Wanfang, CNKI, CQVIP, and CBM were searched for literature from inception to June 2023. All randomized controlled trials (RCTs) using pueraria in the treatment of HFrEF were included. The Cochrane Risk of Bias tool was utilized for RCTs’ methodological evaluation, while Review Manager 5.4.1 was used to analyze the data. Results: Nineteen RCTs with a total of 1,911 patients (1,077 males and 834 females) were identified. Meta-analysis indicated that combination medication of pueraria and conventional medicine (CM) was superior to the CM alone in raising left ventricular ejection fraction (LVEF; MD = 6.46, 95% CI, 4.88 to 8.04, P < 0.00001), and decreasing left ventricular end-diastolic diameter (LVEDD; MD = -4.78, 95% CI, -6.55 to -3.01, P < 0.00001), left ventricular end-Systolic diameter (LVESD; MD = -3.98, 95% CI, -5.98 to -1.99, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP; MD = -126.16, 95% CI, -185.30 to -67.03, P < 0.0001). Besides, combination medication improved clinical efficacy rate (RR = 3.42, 95% CI, 2.54 to 4.59, P < 0.00001), 6-min walk test (6-MWT; MD = 65.54, 95% CI, 41.77 to 89.31, P < 0.00001), and TCM syndrome score efficacy (RR = 3.03, 95% CI, 1.57 to 5.83, P = 0.0009). Regarding safety, no difference was observed for adverse events (RR = 0.59, 95% CI, 0.22 to 1.54, P = 0.28). Conclusion: The use of pueraria combined with conventional medicine in HFrEF patients has superiority over conventional medicine alone in ameliorating cardiac function and reversing left ventricular remodeling. Moreover, combination medication has no increase in adverse drug events. Given some limitations, more prudence and high-quality clinical trials are needed in the future to verify the conclusions.

Guizhi Wuling Decoction (GWD), a combined prescription consisting of the classical formulas Wuling San and Guizhi Fuling Wan without modification, has been clinically applied for cardiovascular diseases. Previous studies have reported its cardioprotective and anti-fibrotic effects; however, the underlying molecular mechanisms remain incompletely understood. To investigate whether restoration of mitochondrial homeostasis contributes to the anti-fibrotic effects of GWD and to explore the involvement of AMPK/PGC-1α signaling. Myocardial fibrosis (MF) was induced in C57BL/6 J mice by isoproterenol (ISO) administration. Cardiac function, myocardial fibrosis, mitochondrial ultrastructure, mitochondrial membrane potential, ATP production, and NAD+/NADH ratio were evaluated. Absorbed constituents in GWD-containing serum were characterized using UHPLC-MS/MS. Integrated transcriptomic-proteomic analysis highlighted AMPK signaling as one of the important pathways associated with GWD treatment. Molecular docking and molecular dynamics simulations were conducted to evaluate the interactions between representative absorbed compounds and candidate targets. The involvement of AMPK signaling was further validated by pharmacological inhibition using Compound C. GWD significantly improved cardiac function, attenuated myocardial fibrosis, and restored mitochondrial homeostasis, as evidenced by improved mitochondrial ultrastructure, increased mitochondrial membrane potential, ATP production, and NAD+/NADH ratio. Integrated transcriptomic and proteomic analyses identified AMPK signaling as an important pathway associated with the protective effects of GWD. Mechanistically, GWD activated the AMPK/PGC-1α signaling pathway and upregulated mitochondrial biogenesis- and quality control-related proteins, including NRF1, TFAM, and MFN2. Pharmacological inhibition of AMPK by Compound C significantly attenuated GWD-associated improvement of mitochondrial homeostasis and anti-fibrotic effects. GWD alleviates ISO-induced MF, at least in part, by restoring mitochondrial homeostasis. Integrated multi-omics analyses and pharmacological validation suggest that AMPK/PGC-1α signaling may contribute to the anti-fibrotic effects of GWD. These findings provide experimental evidence suggesting the involvement of mitochondrial homeostasis in MF and offer new insights into the anti-fibrotic effects of GWD.