Atypical sulfur-containing physalin from Physalis minima and protective effect against ischemia-reperfusion injury

Four previously undescribed physalins (1-4), along with six known ones (5-10) were isolated and identified from the whole plants of Physalis minima L., a medicinal and edible plant traditionally used in southwest China. Their structures were established through comprehensive spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry and 1D/2D nuclear magnetic resonance spectroscopy. Moreover, the absolute configurations of 1-3, 5 and 7 were examined by X-ray diffraction analyses. Compound 1, an undescribed sulfur-containing physalin, exhibited the most protective effect against oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated ischemia-reperfusion (I/R) injury in PC12 cells. Meanwhile, compound 1 was found to reduce the inflammatory response, with mechanistic studies indicating that it decreased pyroptosis-associated proteins, such as cleaved-caspase1, NLRP3, and GSDMD N-terminus. Importantly, GSDMD knockdown significantly reversed the protective effects of compound 1, highlighting the involvement of pyroptosis in the compound's protective mechanism against OGD/R-induced I/R injury in PC12 cells in vitro.