Withanolides isolated from Nicandra physaloides protect liver cells against oxidative stress-induced damage

Natural withanolides, an update

“…223 Nic-2 isolated from the calyxes and fruits of Nicandra physaloides was found to markedly increase cellular survival and the activities of two antioxidant enzymes (CAT and SOD) and a non-enzymatic antioxidant (GSH), and reduce the accumulation of ROS in H 2 O 2 -induced human normal hepatocyte (LO2) cells via activating Nrf2 nuclear translocation and enhancing the expression of target gene HO-1. 107 4β-Hydroxywithanolide E, a novel and potent activator of Nrf2, inhibited oxidative stress in normal human lung epithelial Beas-2B cells, wild-type AB zebrafish, and a cigarette smoke-induced mice lung injury model. 224 In addition, the antioxidant factor levels of SOD, CAT, and GPx were increased after treatment with physalin A in LPS-induced RAW 264.7 cells, indicating the anti-oxidative activity of physalin A.…”

“…Withanolides 471–482 (ref. 105, 107 and 142) were isolated from the aerial parts of Nicandra physalodes . Compounds 477 and 478 are a pair of C-26 epimers.…”

“…Withanolides 465 and 479–482 (ref. 107) were obtained as non-resolvable epimeric mixtures at C-26. It is notable that 480 , different from other withanolides with a 24,25:22,26-diepoxy-22,26-lactrol side chain, was also isolated as an unresolvable epimeric isomer.…”

“…Withanolides showed anti-oxidative activities in different models, and several pharmacological effects of withanolides, including anti-pancreatitis 223 and hepatoprotection, 107 were mediated partly by enhanced anti-oxidative activity. Withaferin A lowered MDA levels by about 2.5 fold and increased GSH expression by about 2 fold in the pancreatic tissue of Cerulein-treated mice.…”

Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights

“…Further mechanistic studies showed that WA markedly inhibited the mitogen-activated protein kinase (MAPKs) including ERK, JNK and p38 as well as NFκB activation, whereas withanone regulated only ERK and JNK signaling pathways (Purushotham et al, 2017). One withanolide protected liver cells from oxidative stress-induced damage by increasing cellular survival rate and activities of superoxide dismutase, glutathione and catalase, and reducing the accumulation of reactive oxygen species via activating nuclear translocation of NRF2 and increasing expression of the NRF2 target gene heme oxygenase 1 (Hmox1) (Wang et al, 2018). Six withanolides showed anti-inflammatory activities through inhibition of nitric oxide production in murine macrophage RAW 264.7 cells stimulated by LPS (Wu et al, 2018).…”