1α, 25-dihydroxy vitamin D3 containing leaf aqueous extract of Catharanthus roseus (L.) G. Don inhibits pro-inflammatory signaling in adipocytes-macrophage co-culture and improves glucose homeostasis in adipocytes and muscle cells

Increase in the number of adipocytes and fat load in adipocytes cause stress in adipose tissue leading to proinflammatory signalling and insulin resistance. Previously, aqueous extract of Catharanthus roseus (L.) G. Don leaf (CRACE) was shown to be effective in inhibiting adipocyte differentiation and reduction of lipid load in mature adipocytes. Further, bioactivity-guided fractionation of the phytoextract following reverse phase HPLC and HR-LCMS analysis revealed that 1a, 25-dihydroxy vitamin D3 is the bioactive moiety in CRACE. The current study investigated the effect of 1a, 25-dihydroxy vitamin D3 containing phytoextract, CRACE, on inflammatory signalling in adipocytes-macrophage co-culture. CRACE treatment increased the secreted levels of key pro-inflammatory and pro-lipolytic cytokines TNFa and IL6 but reduced the secreted levels of other adipose-related pro-inflammatory cytokines- resistin, lipocalin2, and serpin E1. CRACE increased the secretion of important anti-inflammatory adipokines IGFBP3 and LIF1 while reducing the secreted levels of chemo-attractants MCP1, MCSF, VEGF, and IGFBP6. A significant reduction in RAW 264.7 macrophage migration towards mature 3T3 -L1 adipocytes was observed in the presence of CRACE. While fatty acid uptake was increased in adipocytes and decreased in muscle cells in the presence of CRACE, glucose uptake was increased in both cells. In conclusion, 1a, 25-dihydroxy vitamin D3 containing phytoextract, CRACE, is a potent inhibitor of pro-inflammatory signaling in adipocytes-macrophage cross talk. It also promotes glucose homeostasis in adipocytes and muscle cells. Thus, it has the potential to improve two conditions simultaneously: obesity and obesity-associated type -2 diabetes. (c) 2024 SAAB. Published by Elsevier B.V. All rights reserved.