Capsiate-rich fraction of Capsicum annuum induces muscular glucose uptake, ameliorates rosiglitazone-induced adipogenesis, and exhibits activation of NRs regulating multiple signaling pathways

Authors: CHAE, HEE-SUNG - University Of Mississippi; Cantrell, Charles; KHAN, IKHLAS - University Of Mississippi; Jarret, Robert - Bob; KHAN, SHABANA - University Of Mississippi

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2023
Publication Date: 11/16/2023
Citation: Chae, H., Cantrell, C.L., Khan, I.A., Jarret, R.L., Khan, S.I. 2023. Capsiate-rich fraction of Capsicum annuum induces muscular glucose uptake, ameliorates rosiglitazone-induced adipogenesis, and exhibits activation of NRs regulating multiple signaling pathways. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.3c06148?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as.
DOI: https://doi.org/10.1021/acs.jafc.3c06148?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as

Interpretive Summary: Chili pepper extract and its constituents, capsaicinoids and capsinoids, are reported to have a variety of pharmacological effects, such as antibacterial, antioxidant, pain-relieving, and anti-inflammatory effects. Capsaicinoids are secondary metabolites that confer Capsicum (‘chili’ peppers) fruits their appealing pungency (‘heat’) and have multiple proven health benefits and industrial applications. However, the main ingredient of chili peppers, capsaicin, remains controversial. Otherwise, capsinoids, the non-pungent analogs of capsaicinoids, were first identified in fruit of Capsicum annuum. Recent studies have reported that various biological activity characteristics of capsaicinoids are also characteristic of capsinoids albeit with less of the adverse effects associated with pungency. We investigated the effects of a C. annuum extracts and pure capsiate on metabolic disorder important receptors. The findings from this study suggest that capsiate will enhance glucose uptake effect and prevent lipid accumulation. Additionally, capsiate could inhibit the adverse effect of blood glucose lowering drugs belonging to thiazolidinediones class without compromising their main effects.

Technical Abstract: Capsiate has been found to be a key ingredient in the fruits of a nonpungent cultivar of Capsicum annuum. We investigated the effects of a C. annuum pentane extract (CE), a capsiate rich fraction (CR), and pure capsiate (Ca) on nuclear factor erythroid 2–related factor 2 (NRF2), peroxisome prolifera-tor-activated receptors alpha and gamma (PPARa and PPAR'), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of NRF2, PPARa, PPAR' and LXR was determined in hepatic (HepG2) cells by reporter gene assays. CE (500 µg/mL), CR (100 µg/mL) and Ca (100 µM) caused 1.30-, 2.94-, and 2.89-fold activation of NRF2, 3.01-, 4.16-, and 2.35-fold activation of PPARa and 2.85-,3.01-, and 3.20-fold activation of PPAR', while the activation of LXR was only 1.45-, 1.94-, and 1.67-fold compared to control. To further explore the potential of capsiate and enriched preparations against obesity and metabolic disorder, their effect on adipogenesis and glucose uptake was deter-mined in adipocytes (3T3-L1 cells) and myocytes (C2C12 cells). CR (200 µg/mL) and Ca (100 µM) in-hibited (28.4%, and 32.5%) the lipid accumulation in adipocytes and increased glucose uptake (44.7%, and 30.1%) in muscle cells. Futhermore, capsiate inhibited (27.8%) the adipogenic effect induced by rosiglitazone without compromising its glucose uptake enhancing effect. This is the first report to reveal the multiple nuclear receptors agonistic action and glucose uptake enhancing property of capsiate from C. annuum along with its antiadipogenic effect indicating its potential in preventing the undesired adipogenic effects of full PPAR' agonists such as the glitazone class of antidiabetic drugs.