Apocynum venetum leaf extract alleviated doxorubicin-induced cardiotoxicity by regulating organic acid metabolism in gut microbiota.

Apocynum venetum leaf is commonly utilized for its beneficial effects in reducing blood pressure, inducing sedation, promoting diuresis, anti-aging, and cardioprotection, which also exhibit positive effects on the gut microbiota. The gut microbiota plays a role as an endocrine organ by producing bioactive metabolites that can directly or indirectly impact host physiology, specifically cardiovascular diseases. In this study, main chemical components of A. venetum leaf extract (AVLE) were identified by LC-MS, and an orally administered AVLE was employed to treat mice with doxorubicin (Dox)-induced cardiotoxicity. The results showed that AVLE contained hyperoside and oganic acids. The pharmacological findings revealed that AVLE regulated the gut microbiota, resulting in a significant increase in the levels of two organic acids, indole-3-propionic acid (IPA) and acetic acid (AA). Both IPA and AA exhibited the ability to reduce BNP, CK, and LDH levels in mice with Dox-induced cardiotoxicity. Moreover, IPA demonstrated an improvement in Dox-induced cardiac injury by inhibiting apoptosis, while AA promoted increased secretion of ghrelin through the parasympathetic nervous system, subsequently reducing cardiac fibrosis by decreasing collagen I, collagen III, and activin A. Hence, our study demonstrates that AVLE exerts a beneficial cardioprotective effect by modulating the gut microbiota, providing a potential novel target for the treatment and prevention of Dox-induced cardiotoxicity.

Exploring the Latent Mechanism of Huanglian Jiedu Decoction Formula for Anti-atopic Dermatitis by Systems Pharmacology.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease, which does not have a specific drug presently. Huanglian jiedu decoction (HJD) is one of the effective traditional Chinese medicine prescriptions. The real material and mechanisms of HJD for AD are not clear. OBJECTIVE: Network pharmacology and in vivo experiments were used to explore the real material and mechanisms of HJD for AD. METHODS: A systems' pharmacology approach that provides a comprehensive analysis of bioactive compounds, targets, and pathway interactions was employed to elucidate the molecular pathogenesis of HJD for AD. First, the compound databases were constructed for HJD, and compound targets were predicted. Then, the hub targets of HJD were selected by degree centrality analysis and validated using the molecular docking method. Finally, Compound-Target and Target-Pathway networks were constructed to explore the latent mechanism of HJD for AD. Then, animal models of AD were established, the pathology of the skin lesions was observed, and RT-PCR and ELISA methods were used to verify the key targets in the serum of AD mice. RESULTS: The results showed that 60 bioactive compounds (palmatine, wogonin, cavidine, etc.) of HJD interacting with 169 related hub targets (PTGS2, HSP90AA1, etc.) were authenticated. HJD potentially participates in response to stimuli, biological regulation, and reproduction through the PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and Fc epsilon RI signaling pathway, which are interrelated to the pathogenesis of AD. Compared with the control group, the thickening of the epidermis in the model group was obvious with inflammatory cells infiltrating, the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α were up-regulated; and 6.4g/kg and 12.8g/kg HJD could significantly reduce the thickening of the epidermis and infiltration of inflammatory cells, down-regulate the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α in the AD mice. HJD might exert its anti-AD effects by downregulating key indicators (PI3K, AKT, JNK, ERK, IL-4, and TNF-α) in the PI3K/AKT and MAPK pathways. CONCLUSIONS: Our study could help us understand the compound and mechanism of HJD for AD. Moreover, it had a guidance function to change the traditional arrangement of formula for HJD.

Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours.

Digestive system tumours, including stomach, colon, esophagus, liver and pancreatic tumours, are serious diseases affecting human health. Although surgical treatment and postoperative chemoradiotherapy effectively improve patient survival, current diagnostic and therapeutic strategies for digestive system tumours lack sensitivity and specificity. Moreover, the tumour's tolerance to drug therapy is enhanced owing to tumour cell heterogeneity. Thus, primary or acquired treatment resistance is currently the main hindrance to chemotherapy efficiency. N6-methyladenosine (m6A) has various biological functions in RNA modification. m6A modification, a key regulator of transcription expression, regulates RNA metabolism and biological processes through the interaction of m6A methyltransferase ("writers") and demethylase ("erasers") with the binding protein decoding m6A methylation ("readers"). Additionally, m6A modification regulates the occurrence and development of tumours and is a potential driving factor of tumour drug resistance. This review systematically summarises the regulatory mechanisms of m6A modification in the drug therapy of digestive system malignancies. Furthermore, it clarifies the related mechanisms and therapeutic prospects of m6A modification in the resistence of digestive system malignancies to drug therapy.

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy: A systematic review and meta-analysis (PRISMA-compliant article).

BACKGROUND: To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy. METHODS: Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model. RESULTS: A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = -3.51, 95% CI: -4.20 to -2.83, P < .001) and vitamin B12 (WMD = -62.23, 95% CI: -83.27 to -41.19, P < .001) were decreased significantly compared with the control group. CONCLUSIONS: Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.