Key result
Several compounds from Vitis gracilis leaf extract exhibited high binding affinities to SIRT1 and AMPK in silico, with some outperforming the standard drug resveratrol.
Why the study?
Doxorubicin causes cardiotoxicity via inhibition of SIRT1 and AMPK activity in cardiomyocytes, prompting exploration of Vitis gracilis leaf compounds to counteract this toxicity.
Do compounds from Vitis gracilis leaf extract show potential to counteract doxorubicin-induced cardiotoxicity via SIRT1 and AMPK activation in silico?
Do compounds from Vitis gracilis leaf extract show potential to counteract doxorubicin-induced cardiotoxicity via SIRT1 and AMPK activation in silico?
In silico screening identifies several compounds from Vitis gracilis leaf extract as potential candidates to counteract doxorubicin-induced cardiotoxicity via SIRT1 and AMPK activation.
Provides in silico leads for doxorubicin cardiotoxicity; hypothesis-generating and requires experimental validation before clinical consideration.
Doxorubicin is a potent chemotherapy drug. However, it is known to cause cardiotoxicity via inhibition of sirtuin 1 (SIRT1) and adenosine monophosphate protein kinase (AMPK) activity in the cardiomyocytes. This research aimed to explore the pharmacokinetics, safety, and bioactivity of compounds from Vitis gracilis leaves in their interaction with SIRT1 and AMPK to counteract doxorubicin-induced cardiotoxicity. A total of 13 selected compounds from V. gracilis leaf extract were screened for their pharmacokinetics, toxicity, and interactions with SIRT1 and AMPK using in silico approach. It was found that the majority of the compounds are easily absorbed by the human intestine, mostly avoiding liver enzyme CYP2D6 interaction and kidney protein OCT2 inhibition. They span nontoxic to harmful, some posing hepatoxic, carcinogenic, and immunotoxic risks, while 12 meet drug-likeness criteria. Finally, molecular docking revealed that several compounds exhibit high binding affinities to the proteins SIRT1 and AMPK, with some even outperforming the standard drug resveratrol such as 3’,4’-dimethoxy-alpha-naphthoflavone, 5-[6-hydroxy-5-(3-methylbut-2-enyl)-1-benzofuran-2-yl]benzene-1,3-diol, 4,4-dimethyl-5alpha-cholesta-8,14,24- trien-3beta-ol, and norethindrone acetate. Therefore, the compounds could be considered candidates of drugs to counteract doxorubicin-induced cardiotoxicity via SIRT1 and AMPK activation.
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Santoso et al. (2024) studied Doxorubicin-induced cardiotoxicity. Vitis gracilis leaf extract compounds vs. Resveratrol was evaluated on Binding affinity to SIRT1 and AMPK proteins. Several compounds from Vitis gracilis leaf extract exhibited high binding affinities to SIRT1 and AMPK in silico, with some outperforming the standard drug resveratrol.
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