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Increasing the Sensitivity of Adipocytes and Skeletal Muscle Cells to Insulin
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Visceral-adipose tissues secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-6. Adipocytes and macrophages (in a paracrine manner) activate Jun-N-terminal kinase and nuclear factor-κB, which phosphorylate insulin receptor substrate and reduce the sensibility of insulin receptor to create a state of insulin resistance in adipocytes and neighboring skeletal muscle cells.1Physalis peruviana L. elaborates 4β-hydroxywithanolide E268 (Figure 4.18), which inhibited monocyte chemoattractant peptide-1 production with half maximal inhibitory concentrations of 1.5 μM in 3T3-L1/RAW264.7 macrophages coculture.269 In adipocytes, tumor necrosis factor-α induced the nuclear translocation of nuclear factor-κB and these effects were inhibited by 4β-hydroxywithanolide E at a concentration of 10 μM.269 This sterol inhibited the expression of monocyte chemoattractant peptide-1, tumor necrosis factor-α, and interleukin-6269 4β-Hydroxywithanolide E given orally to db/db mice for 2 weeks orally at a dose of 30 mg/kg/day lowered macrophages infiltration in epididymal adipose tissue and inhibited the expression of proinflammatory cytokines monocyte chemoattractant peptide-1, tumor necrosis factor-α and interleukin-6 expression.269 In addition, this regimen improve doral glucose tolerance with a 30 minutes decrease of postprandial glycemia by 20%.269 This sterol lowered basal glycemia by 40% and evoked a mild increase in insulinemia.269 4β-Hydroxywithanolide E lowered plasma monocyte chemoattractant peptide-1, free fatty acids and increased plasma adiponectin.269 Adiponectin inhibits the transformation of macrophages into foam cells and reduces intracellular cholesteryl ester by suppressing the expression of class A scavenger receptors in atheromas.270
Effects of Dietary Phytochemicals on DNA Damage in Cancer Cells
Published in Nutrition and Cancer, 2023
Yang Ye, Ying Ma, Mei Kong, Zhihua Wang, Kang Sun, Fang Li
4β-Hydroxywithanolide E is a natural compound isolated from Physalis peruviana that has anti-inflammatory and antitumor properties (147,148). This compound acts as an antagonist of Wnt signaling and activator of Nrf2 in various diseases (149,150). Tang et al. reported that 4β-hydroxywithanolide E upregulates the expression of DSB signaling proteins (γH2AX and MR complex), increases ROS levels, and enhances 8-OHDG-mediated oxidative DNA damage in human gingival carcinoma cells (58). Chiu et al. showed that 4β-hydroxywithanolide E interferes with the cell cycle of Ca9-22 cells by increasing the number of sub-G1 cells and G1 or inducing G2/M arrest (151). In MCF-7 human breast cancer cells, 4β-hydroxywithanolide E upregulates ATM autophosphorylation and γH2AX expression, thus initiating DNA damage and irreversibly inducing apoptosis (59). Additionally, 4β-hydroxywithanolide E induces DNA damage through the ATM-NBS1 pathway in human lung cancer, leading to cycle arrest and apoptosis (152).