Main active components of Si-Miao-Yong-An decoction (SMYAD) attenuate autophagy and apoptosis via the PDE5A-AKT and TLR4-NOX4 pathways in isoproterenol (ISO)-induced heart failure models.

Heart failure (HF), the main cause of death in patients with many cardiovascular diseases, has been reported to be closely related to the complicated pathogenesis of autophagy, apoptosis, and inflammation. Notably, Si-Miao-Yong-An decoction (SMYAD) is a traditional Chinese medicine (TCM) used to treat cardiovascular disease; however, the main active components and their relevant mechanisms remain to be discovered. Based on our previous ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) results, we identified angoriside C (AC) and 3,5-dicaffeoylquinic acid (3,5-DiCQA) as the main active components of SMYAD. In vivo results showed that AC and 3,5-DiCQA effectively improved cardiac function, reduced the fibrotic area, and alleviated isoproterenol (ISO)-induced myocarditis in rats. Moreover, AC and 3,5-DiCQA inhibited ISO-induced autophagic cell death by inhibiting the PDE5A/AKT/mTOR/ULK1 pathway and inhibited ISO-induced apoptosis by inhibiting the TLR4/NOX4/BAX pathway. In addition, the autophagy inhibitor 3-MA was shown to reduce ISO-induced apoptosis, indicating that ISO-induced autophagic cell death leads to excess apoptosis. Taken together, the main active components AC and 3,5-DiCQA of SMYAD inhibit the excessive autophagic cell death and apoptosis induced by ISO by inhibiting the PDE5A-AKT and TLR4-NOX4 pathways, thereby reducing myocardial inflammation and improving heart function to alleviate and treat a rat ISO-induced heart failure model and cell heart failure models. More importantly, the main active components of SMYAD will provide new insights into a promising strategy that will promote the discovery of more main active components of SMYAD for therapeutic purposes in the future.

Diarylheptanoid: A privileged structure in drug discovery.

Privileged structures are widely used in the process of drug design, and provide an effective template in medicinal chemistry. Diarylheptanoids are a class of structurally distinctive compounds with a wide variety of bioactivity, raising keenly interest in the past decades. Turmeric is a golden spice from the rhizome of the plant Curcuma longa, used for food preparations and giving color since ancient times. Curcumin, obtained from turmeric, has showed widely biological abilities with low toxicity in recent studied. Thus, a spice originally common in the kitchen has recently broadened its application to the clinic. This review aims to highlight diarylheptanoid as a privileged scaffold in drug discovery. In this review, we summarized diverse biological and pharmacological effects of diarylheptanoids and explored the therapeutic application and development of diet based on their structure.

Five novel diarylheptanoids from green walnut husks (Juglans regia L.).

A ethanol extract of green walnut husks (Juglans regia L.) was isolated by various chromatographic techniques yielding 5 previously unknown diarylheptanoids, namely Juglanin F (1), Juglanin G (2), Juglanin H (3), Juglanin I (4) and Juglanin J (5), respectively, together with 12 known diarylheptanoids. The structures of these 17 compounds were elucidation on the basis of spectroscopic analysis. Upon evaluation of compounds 1-5 on the human hepatoma cells HepG2, compound 3 exhibited moderate inhibitory activity with IC50 27.72 µM.