Mechanism of Action of Capsaicin and Quercitrin in Regulating Lipid Metabolism in HepG2 Cells through EGFR/PI3K/Akt Signaling Pathway
, Si MI1 (
)Abstract
The objective of this study was to investigate the molecular mechanism behind the regulatory effect of capsaicin combined with quercitrin on liver lipid metabolism. The effects of capsaicin alone or in combination with quercitrin on the survival rate of HepG2 cells with oleic acid-induced lipid accumulation were investigated. Oil red O staining was used to observe lipid accumulation in HepG2 cells. Meanwhile, the levels of total triglyceride (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total bile acid (TBA) were determined. Moreover, the expression levels of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), farnesoid X receptor 1 (FXR1), cholesterol 7α-hydroxylase (CYP7A1) and fibroblast growth factor 19 (FGF19) were determined by Western blotting. The results showed that the proliferation rate of HepG2 cells in each treatment group was greater than 75%, demonstrating no significant cytotoxicity. The results of oil red O staining showed a reduction in lipid accumulation in both single and combined treatment groups. The application of capsaicin alone or combined with quercitrin reduced the contents of TG, TC and LDL-C, increased the contents of HDL-C and TBA, and up-regulated the protein expression levels of EGFR, PI3K, Akt, FXR1 and FGF19. In summary, capsaicin combined with quercitrin exerted a synergistic regulatory effect on lipid metabolism in HepG2 cells, with the most pronounced effect being observed at a 3:1 ratio.
References
DING L, XU Y, WANG L M, et al. The cardiometabolic risk profile of Chinese adults with diabetes: a nationwide cross-sectional survey[J]. Journal of Diabetes and Its Complications, 2017, 31(1): 43-52. DOI:10.1016/j.jdiacomp.2016.10.023.
BONACCIO M, CASTELNUOVO D A, COSTANZO S, et al. Chili pepper consumption and mortality in Italian adults[J]. Journal of the American College of Cardiology, 2019, 74(25): 3139-3149. DOI:10.1016/j.jacc.2019.09.068.
LI R, LAN Y Q, CHEN C Y, et al. Anti-obesity effects of capsaicin and the underlying mechanisms: a review[J]. Food & Function, 2020, 11(9): 7356-7370. DOI:10.1039/d0fo01467b.
ZHANG D, SUN X X, BATTINO M, et al. A comparative overview on chili pepper (Capsicum genus) and sichuan pepper (Zanthoxylum genus): from pungent spices to pharma-foods[J]. Trends in Food Science & Technology, 2021, 117: 148-162. DOI:10.1016/J.TIFS.2021.03.004.
LI W F, YANG H Y, LU Y L. Capsaicin alleviates lipid metabolism disorder in high beef fat-fed mice[J]. Journal of Functional Foods, 2019, 60: 103444. DOI:10.1016/j.jff.2019.103444.
SHIN M K, YANG S M, HAN I S. Capsaicin suppresses liver fat accumulation in high-fat diet-induced NAFLD mice[J]. Animal Cells and Systems, 2020, 24(4): 214-219. DOI:10.1080/19768354.2020.1810771.
YANG S Y, LIU L, MENG L K, et al. Capsaicin is beneficial to hyperlipidemia, oxidative stress, endothelial dysfunction, and atherosclerosis in Guinea pigs fed on a high-fat diet[J]. Chemico-Biological Interactions, 2019, 297: 1-7. DOI:10.1016/j.cbi.2018.10.006.
ZUO C C, ZHANG H J, LIANG S, et al. The alleviation of lipid deposition in steatosis hepatocytes by capsaicin-loaded α-lactalbumin nanomicelles via promoted endocytosis and synergetic multiple signaling pathways[J]. Journal of Functional Foods, 2021, 79: 104396. DOI:10.1016/j.jff.2021.104396.
LI R, XIAO J, CAO Y, et al. Capsaicin attenuates oleic acid-induced lipid accumulation via the regulation of circadian clock genes in HepG2 cells[J]. Journal of Agricultural and Food Chemistry, 2021, 70(3): 794-803. DOI:10.1021/ACS.JAFC.1C06437.
MI S, ZHANG X N, WANG Y H, et al. Effect of different genotypes on the fruit volatile profiles, flavonoid composition and antioxidant activities of chilli peppers[J]. Food Chemistry, 2022, 374: 131751. DOI:10.1016/J.FOODCHEM.2021.131751.
MI S, YU W L, LI J, et al. Characterization and discrimination of chilli peppers based on multi-element and non-targeted metabolomics analysis[J]. LWT-Food Science and Technology, 2020, 131: 109742. DOI:10.1016/j.lwt.2020.109742.
YAO Y J, LI Z F, QIN B W, et al. Evaluation of the intracellular lipidlowering effect of polyphenols extract from highland barley in HepG2 cells[J]. Food Science and Human Wellness, 2023, 13(1): 454-461. DOI:10.26599/FSHW.2022.9250039.
JIAO W Y, MI S, SANG Y X, et al. Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol[J]. Food Chemistry, 2021, 374: 131755. DOI:10.1016/j.foodchem.2021.131755.
MI S, ZHU W X, ZHANG X N, et al. Enhanced hypoglycemic bioactivity via RAS/Raf-1/MEK/ERK signaling pathway by combining capsaicin and QUERCETIN from chili peppers[J]. Molecular Nutrition & Food Research, 2023, 67(10): 2200577. DOI:10.1002/MNFR.202200577.
XIONG W F, LI Y, YAO Y J, et al. Antioxidant mechanism of a newly found phenolic compound from adlay (NDPS) in HepG2 cells via Nrf2 signalling[J]. Food Chemistry, 2022, 378: 132034. DOI:10.1016/j.foodchem.2021.132034.
CERMENO M, FITZGERALD R J, OBRIEN N M. In vitro antioxidant and immunomodulatory activity of transglutaminase-treated sodium caseinate hydrolysates[J]. International Dairy Journal, 2016, 63: 107-114. DOI:10.1016/j.idairyj.2016.08.007.
LI T T, LI Y C, WU H, et al. Extracellular cell matrix stiffness-driven drug resistance of breast cancer cells via EGFR activation[J]. Mechanobiology in Medicine, 2023, 1(2): 100023. DOI:10.1016/j.mbm.2023.100023.
SUN R Y, LI D, SUN M B, et al. Bacillus natto ameliorates obesity by regulating PI3K/AKT pathways in rats[J]. Biochemical and Biophysical Research Communications, 2022, 603: 160-166. DOI:10.1016/j.bbrc.2022.03.012.
LIM W D, WALES W P, MI S, et al. Glucagon-like peptide-2 alters bile acid metabolism in parenteral nutrition-associated liver disease[J]. Journal of Parenteral and Enteral Nutrition, 2016, 40(1): 22-35. DOI:10.1177/0148607115595596.
YANG H, SUN Y J, ZHANG J L, et al. Resveratrol ameliorates triglyceride accumulation through FXR deacetylation in high glucose-treated HepG2 cells[J]. Journal of Functional Foods, 2023, 107: 105679. DOI:10.1016/j.jff.2023.105679.
CLIFFORD B L, SEDGEMAN L R, WILLIAMS K J, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption[J]. Cell Metabolism, 2021, 33(8): 1671-1684. DOI:10.1016/j.cmet.2021.06.012.
ANTONELLIS J P, DROZ A B, COSGROVE R, et al. The anti-obesity effect of FGF19 does not require UCP1-dependent thermogenesis[J]. Molecular Metabolism, 2019, 30: 131-139. DOI:10.1016/j.molmet.2019.09.006.
京公网安备11010802044758号