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Vol 25, No. 07, July 2021   |   Issue PDF view/purchase
A Plant-Based Remedy for Big, Broken Hearts
A cross-disciplinary research from the Chinese Academy of Sciences (CAS) has discovered a novel natural product derivative with anti-hypertrophic effects, paving way for future developments of therapeutic agents for cardiac hypertrophy.

Cardiac hypertrophy refers to the abnormal enlargement or thickening of the heart muscle. At first, having a big heart may not seem so bad, and some would even argue that it is merely an adaptive response to sustain cardiac output in the face of stressful situations. However, enlarged hearts are linked to elevated risks of heart failure, mortality, and morbidity.

To alleviate the symptoms of myocardial or cardiac hypertrophy, a range of drug treatments have been explored to inhibit the abnormal growth of cardiac muscles. But many of these drugs have not been effective to improve the survival outcomes of patients suffering from moderate and severe heart failure. In fact, these moderately-performing medications also pose risks of toxicity, thus cueing the quest for safer and more effective alternative drugs.

A group of researchers, led by Professor Yang Huangtian from Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences (CAS) and Professor Cheng Yongxian from Kunming Institute of Botany of CAS, has discovered a promising plant-based, natural product derivative with anti-hypertrophic effects and uncovered the molecular mechanisms behind its action.

After extensively investigating 24 natural compounds from several plants and animals like Agaricus chinensis, cricks, Glucoderma lucidum, Tripterygium wilfordii, Acorus calamus, and their synthetic derivatives, the scientists identified a small molecule called QF84139, a newly synthesized pyrazine derivative with anti-hypertrophic effects.

It had been previously established that cardiac hypertrophy can occur as a result of pressure overload or consuming phenylephrine, a class of medications used as nasal decongestants.

Using in vitro and in vivo hypertrophic models, the study demonstrated that QF84139 was able to inhibit hypertrophy by activating the adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway that is responsible for maintaining cellular energy balance and regulating nutrient levels.

Their valuable findings have underscored the underrated merits of natural product derivatives in pharmacology and opened a new door for researchers to explore alternative therapeutics. The discovery of QF84139 would provide a promising lead compound for developing effective treatment of cardiac hypertrophy, and pave the way for the development of new drugs and treatments.

Source: Li et al. (2021). Small molecule QF84139 ameliorates cardiac hypertrophy via activating the AMPK signaling pathway. Acta Pharmacologica Sinica, 1-14.

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