Cardiac hypertrophy is a response to the increased hemodynamic workload that arises from various physiological stimuli and pathological insults. Although it initially appears to be adaptive, the long-term cardiac hypertrophy is associated with a significantly increased risk of heart failure and ultimately leads to high rates of mortality and morbidity.   

Drug treatments can temporarily relieve the symptoms of patients by slowing the development of myocardial hypertrophy to heart failure, but cannot significantly prolong the survival of patients with moderate and severe heart failure. Also, drugs have different degrees of toxic side effects. Therefore, it is in urgent need to develop better pioneering compounds and anti-hypertrophy drugs.  

Millions of natural product hybrids (NPHs) as combinations of parts of different natural products severed as new leads for drug discovery. In a study published online in Acta Pharmacologica Sinica, research teams led by Prof. YANG Huangtian from Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences (CAS) and Prof. CHENG Yongxian from Kunming Institute of Botany of CAS reported a structurally novel natural product derivate with potent anti-hypertrophy effect and uncovered the molecular mechanism. 

The researchers screened 24 natural compounds from various plants and animals, such as agaricus chinensis, cricks, glucoderma lucidum, tripterygium wilfordii and acorus calamus, and their synthetic derivatives, and identified a new small molecule QF84139 with anti-cardiac hypertrophic effect. 

By using the in vitro and in vivo hypertrophic model, the researchers demonstrated for the first time that this small molecule can ameliorate the cardiac hypertrophy induced by phenylephrine and pressure overload through activating adenosine 5′- monophosphate-activated protein kinase (AMPK) signaling pathway that maintains cellular energy balance and regulates nutrient levels.   

These findings emphasize the value of natural product derivatives in the development pharmacological therapy for cardiac hypertrophy. The structurally novel compound QF84139 would provide a promising lead compound for developing effective agents for the treatment of cardiac hypertrophy. 

The novel structured small molecule QF84139 inhibits the pressure-overload induced cardiac hypertrophy by activating AMPK signaling. (Image by Prof. YANG's team)