Total flavonoids of Abelmoschus manihot ameliorate lipid deposition in HK-2 cells by inhibiting fatty acid uptake mediated by CD36
DOI:
https://doi.org/10.3329/bjp.v19i3.77820Keywords:
Abelmoschus manihot , CD36, Fatty acid uptake , Flavonoid , HK-2 cell, Lipid deposition, Oil red O stainingAbstract
This study aimed to explore the mechanism by which total flavones of Abelmoschl manihot reduce intracellular lipid deposition in HK-2 cells (Human renal cortex proximal tubule epithelial cells) and thus reduce cell apoptosis. Palmitic acid was employed to induce intracellular lipid deposition. The cell proliferation activity was detected by the CCK-8 assay. The cell death status was evaluated by flow cytometry. The intracellular lipid deposition was observed by oil red O and BODIPY probe staining. The expression level of CD36 in HK-2 cells was determined by western blot. The results indicated that total flavones of A. manihot could inhibit the expression of CD36 in HK-2 cells in a dose-dependent manner and reduce lipid deposition. Consequently, total flavones of A. manihot protect HK-2 cells by reducing intracellular lipid deposition by inhibiting CD36-mediated fatty acid uptake.
Downloads
30
20
References
Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, Al-Majali KM, Trembling PM, Mann CJ, Shoulders CC, Graf D, St Lezin E, Kurtz TW, Kren V, Pravenec M, Ibrahimi A, Abumrad NA, Stanton LW, Scott J. Identification of Cd36 (fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet. 1999; 21: 76-83.
Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol. 2017; 13: 629-46.
Chen X, Lin B, Fang D. Qualitative and quantitative analysis of alkaloids in Eurycoma longifolia by HPLC-Q-TOF-MS combined with UPLC-QQQ-MS/MS. Chin J Chin Mater Med. 2021; 46: 6435-46.
Coburn CT, Hajri T, Ibrahimi A, Abumrad NA. Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues. J Mol Neurosci. 2001; 16: 117-21.
Feng L, Gu CW, Li YX, Huang JS. High glucose promotes CD36 expression by upregulating peroxisome proliferator-activated receptor γ levels to exacerbate lipid deposition in renal tubular cells. Biomed Res Int. 2017; 2017: 1414070.
Ge J, Miao JJ, Sun XY, Yu JY. Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. J Ethnopharmacol. 2016; 189: 238-49.
Griffin E, Re A, Hamel N, Fu C, Bush H, McCaffrey T, Asch AS. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med. 2001; 7: 840-46.
Hao JW, Wang J, Guo H, Zhao YY, Sun HH, Li YF, Lai XY, Zhao N, Wang X, Xie C, Hong L, Huang X, Wang HR, Li CB, Liang B, Chen S, Zhao TJ. CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis. Nat Commun. 2020; 11: 4765.
He J, Lee JH, Febbraio M, Xie W. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Exp Biol Med (Maywood). 2011; 236: 1116-21.
Heit B, Kim H, Cosío G, Castaño D, Collins R, Lowell CA, Kain KC, Trimble WS, Grinstein S. Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization. Dev Cell. 2013; 24: 372-83.
Herman-Edelstein M, Scherzer P, Tobar A, Levi M, Gafter U. Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res. 2014; 55: 561-72.
Huang GS, Zhu YY, Yong C, Tian F, Liu L, Wu QJ, Shu Y, Yao M, Tang CQ, Wang XF, Chen W, Zhou EC. Artemisia capillaris Thunb. water extract attenuates adriamycin-induced renal injury by regulating apoptosis through the ROS/MAPK axis. J Food Biochem. 2022; 46: e14065.
Kennedy DJ, Kashyap SR. Pathogenic role of scavenger receptor CD36 in the metabolic syndrome and diabetes. Metab Syndr Relat Disord. 2011; 9: 239-45.
Jiang XS. Activation of NRF2/ARE signaling pathway protects against palmitic acid-induced renal tubular epithelial cells damage via ameliorating mtros-mediated mitochondrial dysfunction and NLRP3 inflammasome activation. Chongqing Medical University. 2020.
Li M, Song CQ, Wang S, Xue Y, Ma YK. Effects of total flavone of Abelmoschl manihot combined with glipizide on model rats of diabetic nephropathy. Chin J Pharmacovigilance. 2018; 15: 12-15.
Li J, Zhang J, Wang M. Extraction of flavonoids from the flowers of Abelmoschus manihot (L.) medic by modified supercritical CO₂ extraction and determination of antioxidant and anti-adipogenic activity. Molecules 2016; 21: 810.
Liang CP, Han S, Okamoto H, Carnemolla R, Tabas I, Accili D, Tall AR. Increased CD36 protein as a response to defective insulin signaling in macrophages. J Clin Invest. 2004; 113: 764-73.
Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: An overview. Biomarkers 2005; 10 Suppl 1: S10-23.
Morrow JD. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol. 2005; 25: 279-86.
Sampson MJ, Davies IR, Braschi S, Ivory K, Hughes DA. Increased expression of a scavenger receptor (CD36) in monocytes from subjects with Type 2 diabetes. Atherosclerosis 2003; 167: 129-34.
Stadler K, Bonini MG, Dallas S, Jiang J, Radi R, Mason RP, Kadiiska MB. Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes. Free Radic Biol Med. 2008; 45: 866-74.
Stadler K, Goldberg IJ, Susztak K. The evolving understanding of the contribution of lipid metabolism to diabetic kidney disease. Curr Diab Rep. 2015; 15: 40.
Sun Y, Ge X, Li X, He J, Wei X, Du J, Sun J, Li X, Xun Z, Liu SW, Zhang H, Wang ZY, Li YC. High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction. Cell Death Dis. 2020; 11: 914.
Susztak K, Ciccone E, McCue P, Sharma K, Bottinger EP. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy. PLoS Med. 2005; 2: e45.
Wang MT, Chen HX, Wu Q, Huang Y, Zhou YZ. Berberine triggers necroptosis of cervical H8 cells by activating receptor-interacting protein kinase 1. Bangladesh J Pharmacol. 2024; 19: 13-22
Weinberg JM. Lipotoxicity. Kidney Int. 2006; 70: 1560-66.
Xue C, Guo J, Qian D, Duan JA, Shang E, Shu Y, Lu Y. Identification of the potential active components of Abelmoschus manihot in rat blood and kidney tissue by microdialysis combined with ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011; 879: 317-25.
Yang WX, Luo Y, Yang SK, Zeng MR, Zhang SM, Liu JL, Han YZ, Liu Y, Zhu XJ, Wu H, Liu FY, Sun L, Xiao L. Ectopic lipid accumulation: Potential role in tubular injury and inflammation in diabetic kidney disease. Clin Sci (Lond). 2018; 132: 2407-22.
Zeng Y, He Y, Wang L, Xu H, Zhang Q, Wang Y, Zhang J, Wang L. Dihydroquercetin improves experimental acute liver failure by targeting ferroptosis and mitochondria-mediated apoptosis through the SIRT1/p53 axis. Phytomedicine 2024; 128: 155533.
Zhao J, Tostivint I, Xu L, Huang J, Gambotti L, Boffa JJ, Yang M, Wang L, Sun Z, Chen X, Liou-Schischmanoff A, Baumelou A, Ma T, Lu G, Li L, Chen D, Piéroni L, Liu B, Qin X, He W, Wang Y, Gu HF, Sun W. Efficacy of combined Abelmoschus manihot and irbesartan for reduction of albuminuria in patients with Type 2 diabetes and diabetic kidney disease: A multicenter randomized double-blind parallel controlled clinical trial. Diabetes Care. 2022; 45: e113-e15.
Zhong DD, Chen JS, Qiao RR, Song C, Hao C, Zou YY, Bai M, Su W, Yang BX, Sun D, Jia ZJ, Sun Y. Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling. Cell Rep. 2024; 43: 114075.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Xiaofang Wang, Chenquan Tang, Yi Jiang, Yi Xue, Enchao Zhou
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).