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Schematic diagram depicting the protective effect of NX on oxidative stress -induced mitochondrial dependent apoptosis via activation of AMPK/JNK pathway. NX, Nuanxin capsule; ROS, reactive oxygen species; p, phosphor; AMPK, AMP-activated protein kinase; JNK, c-Jun N-terminal Kinase; ΔΨm, mitochondrial membrane potential. • NX is a mitochondrial-targeted antioxidant against HF that improves cardiac function. • NX acts on mitochondrial-related targets by reducing exogenous and endogenous ROS production. • NX improves oxidative stress-induced mitochondrial function by increasing mitochondrial ATP production, maximal respiration and spare respiratory capacity. Oxidative stress and apoptosis play critical roles in the pathogenesis of heart failure (HF).Nuanxin capsule (NX) is a Chinese medicine that has outstanding protective effects on HF. The present study aimed to elucidate whether NX could protect HF against oxidative stress-induced apoptosis through intrinsic mitochondrial pathway. In vivo , HF was induced by transverse aortic constriction. NX and Compound C (Comp C) were administered to C57BL/6 J mice for over a 4-week period. Cardiac function was assessed with echocardiography. In vitro , H9c2 cells were exposed to H 2 O 2 in the presence or absence of NX and Compound C. Cell viability, cytotoxicity, reactive oxygen species (ROS) production, apoptosis, mitochondrial membrane potential (ΔΨm) and mitochondrial function by oxygen consumption rate (OCR) were detected. The expressions of cytochrome c, BAX, Bcl-2, cleaved caspase-3, AMPK and JNK were evaluated by western blotting. The results indicated that NX significantly improved cardiac function and enhanced the cell viability, ΔΨm and mitochondrial respiration. Also NX treatment reduced cell cytotoxicity and ROS production. Moreover, NX inhibited mitochondrial-mediated apoptosis by upregulating AMPK and downregulating JNK both in vivo and in vitro. The protective effects of NX on cardiac function by reducing oxidative stress-induced mitochondrial dependent apoptosis were reversed by Compound C treatment. These findings demonstrated that NX effectively improved cardiac function in TAC mice by reducing oxidative stress-induced mitochondrial dependent apoptosis by activating AMPK/JNK signaling pathway. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Osmanthus fragrans var. thunbergii ( O. fragrans ) flower has been consumed as folk medicine for thousands of years. O. fragrans flower extract is a well-characterized phenylethanoid glycoside-rich extract, which has been used as a natural anti-oxidant. The aim of this study was to evaluate the safety of O. fragrans flower phenylethanoid glycoside-rich extract (OFFE). Materials and methods The OFFE was extracted by 80% (v/v) aqueous ethanol with 0.01% sodium isoascorbate (w/v) from the O. fragrans flower and purified on HPD300 resins. The total phenylethanoid glycosides content and individual phenylethanoid glycosides was determined by photocolorimetric method and reversed phase UPLC respectively. An acute oral toxicity study, reverse mutation test, bone marrow cell micronucleus test, and sperm abnormality test as well as a 90-day oral toxicity study were performed on experimental animals. Results The total content of phenylethanoid glycosides in OFFE was 73.4 g acteoside equivalent per 100 g of extract, include acteoside (52.5 g per 100 g of extract), salidroside (13.8 g per 100 g of extract), and isoacteoside (2.6 g per 100 g of extract) and so on. No acute lethal effect at the maximal tested OFFE dose of 10 g/kg body weight (bw) in either rats or mice was observed, suggesting that OFFE can be considered nontoxic. No evidence for mutagenicity was detected in any of the three mutagenic tests. Administration at levels of 0.50, 1.00, and 2.00 g/kg bw to rats for 90 days failed to induce any significant hematological, clinical, chemical, or histopathological changes. The no-observed adverse-effect-level for OFFE was >2.00 g/kg bw for the study on subchronic toxicity. Conclusion The results showed that consuming OFFE has no adverse effects and poses no health risk in the acute oral toxicity study, subchronic oral toxicity study, and in the micronucleus test, which may provide supportive evidence for the safety of OFFE powder that has been used in medicine as well as in functional foods, and dietary supplements. [ABSTRACT FROM AUTHOR]