The cytotoxicity of 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan isolated from Swietenia macrophylla King seed extract on 3T3-L1 and RAW 264.7 cells

The exploration of natural products as anti-obesity candidates needs to be performed urgently since obesity has become a worldwide epidemic and many drugs for this health condition were withdrawn due to their serious adverse events such as psychiatric disorders and drug dependence. The 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan, a saponin isolated from Indonesian Swietenia macrophylla seeds extract has the potential to modulate obesity because it acts as a potent PPAR-γ agonist in silico and the seeds’ hypolipidemic effect has been proven. The cytotoxicity study is a crucial part of the early pharmaceutical development stage, whilst, the exploration of 1,4-bis(3,4,5trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan to ensure the compound’s safety in preadipocytes and macrophage cells which play a crucial role in obesity pathogenesis is still limited. This study aims to explore the cytotoxicity of saponin isolate on 3T3-L1 (preadipocytes) and RAW 264.7 (macrophages) cell lines to ensure its safety profile in vitro. Both cell lines were exposed to various concentrations of the isolate (3.125-200 µg/mL), then metformin was used as the standard drug and DMSO as solvent control for 24 hrs. The cytotoxicity test was conducted by MTT assay and IC50 was determined by probit analysis. Most of the 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan did not affect the viability of 3T3-L1 and RAW 264.7 with the IC50 148.90±12.22 and 84.78±1.69 µg/mL, respectively. Metformin and DMSO also did not alter the viability of both cells. These results were promising as a basis for further development since the isolates’ IC50 value was more than the cytotoxic threshold of NCI guidelines. © 2024 The Authors.