Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy.

Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n = 1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.

Evaluation of Trace Element Contamination and Health Risks of Medicinal Herbs Collected from Unpolluted and Polluted Areas in Sichuan Province, China.

Trace element contamination in Chinese herbal medicines has been recognized as a potential health concern for consumers. To assess the health risk to the herb-consuming population, nine trace elements (Cu, Cd, Cr, Mo, Ni, Pb, Sr, Zn, and As) were investigated based on their concentrations in three common medicinal plants (Astragalus membranaceus, Codonopsis tangshen, and Paris polyphylla var. chinensis) and soils from unpolluted and polluted areas in the Sichuan Province, China. The results showed that the metal content differed significantly in medicinal plants and soils from unpolluted versus polluted areas. No significant differences in metal accumulation were observed for these CHMs grown in either unpolluted or polluted areas. Evaluation of the health risk index suggested that soil ingestion and medicated diet represented the dominant exposure routes, indicating that trace metal(loids) in local soil might pose potential risks through soil-food chain transfer. Hazard quotient values for AM (1.473) and CT (1.357) were higher than the standard value (HQ > 1), whereas the hazard indices for PC, AM, and CT were 13.18, 14.33, and 14.01 times higher than the safe limit (HI > 1) in the polluted area, indicating non-cancer-related health hazards. Ingestion of soil was responsible for 36.39 to 91.06% of the total cancer risk and medicated diet accounted for 6.35 to 62.71%, compared with inhalation and dermal contact, suggesting carcinogenic health risks in herbs from polluted soils. In this study, Pb showed relatively higher non-carcinogenic risks, while Cr and Ni posed the highest cancer risks. Therefore, we propose more effective measures, which should be considered for Cr, Ni, and Pb remediation in soil to reduce their pollution in the studied areas.

Identification and evaluation of Lonicera japonica flos introduced to the Hailuogou area based on ITS sequences and active compounds.

Lonicera japonica flos (LJF), the dried flower buds of L. japonica Thunb., have been used in traditional Chinese herbal medicine for thousands of years. Recent studies have reported that LJF has many medicinal properties because of its antioxidative, hypoglycemic, hypolipidemic, anti-allergic, anti-inflammatory, and antibacterial effects. LJF is widely used in China in foods and healthcare products, and is contained in more than 30% of current traditional Chinese medicine prescriptions. Because of this, many Chinese villages cultivate LJF instead of traditional crops due to its high commercial value in the herbal medicine market. Since 2005, the flower buds of L. japonica are the only original LJF parts considered according to the Chinese Pharmacopoeia of the People's Republic of China. However, for historical and commercial reasons, some closely related species of Lonicera Linn. continue to be mislabeled and used as LJF. Currently, there are hundreds of commercial varieties of LJF on the market and it is difficult to choose fine LJF varieties to cultivate. In this study, a total of 21 varieties labeled as LJF on the market were planted in the Hailuogou area. In order to choose the optimum variety, internal transcribed spacer (ITS) sequence alignment analysis was used to test whether the 21 varieties were genuine LJF or not. Cluster analysis of active components based on the content of chlorogenic acid and luteoloside in flower buds, stems and leaves was used to evaluate the quality of the varieties. Results demonstrated that four of the varieties were L. macranthoides Hand.-Mazz., while the other 17 varieties were L. japonica, and genuine LJF. The ITS sequence analysis was proven to be highly effective in identifying LJF and Lonicerae flos. Among the 17 L. japonica varieties, the amounts of chlorogenic acid and luteoloside in flower buds, stems and leaves were significantly different. Based on the cluster analysis method, the variety H11 was observed to have the highest level of active components, and is therefore recommended for large-scale planting in the Hailuogou area.