Kaempferide improves oxidative stress and inflammation by inhibiting the TLR4/IκBα/NF-κB pathway in obese mice

Document Type : Original Article

Authors

1 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China

2 Department of vascular surgery, The Second Affiliated Hospital of Nanchang University

3 Guangdong Online Hospital Clinic, Guangdong Second Provincial People’s Hospital, Guangzhou 510317, PR China

4 Taihe Hospital Shiyan, Hubei, PR China

Abstract

Objective(s): Kaempferide (Ka), a major natural active component of Tagetes erecta L, has numerous pharmacological effects such as anti-obesity, anticancer, and anti-hypertension. However, there is no clear evidence that Ka is directly related to inflammation and oxidative stress in obese mice. We aimed to explore the effects of Ka on inflammation and oxidative stress and its mechanism.
Materials and Methods: The obese mice were induced by a high-fat diet (HFD). The anti-obesity effect was tested by liver and body weight, liver and adiposity index, and white adipose tissue. Blood sample analysis was used to detect the hypolipidemic and hypoglycemic effects. The anti-oxidation effect was assessed using GSH, SOD, MDA, CAT, T-AOC, and other indicators. The anti-inflammatory effect was assessed using TNF-α, MCP-1, and Adiponectin. Western blot and Real-Time PCR were used to evaluate the related signaling pathways.
Results: Obesity, glycolipid metabolism disorder, inflammation, and oxidative stress developed in HFD mice. These changes can be effectively alleviated by Ka treatment for 16 weeks. Further studies have suggested that these beneficial effects of Ka may be associated with inhibition of the TLR4/IκBα/NF-κB signaling pathways.
Conclusion: Ka possesses important anti-obesity, hypoglycemic, and hypolipidemic effects. The mechanism may be causally associated with the TLR4/IκBα/NF-κB signaling pathway, which improves inflammation and oxidative stress.

Keywords

References

1. Keys A. Overweight, obesity, coronary heart disease and mortality. Nut Rev 1980; 38:297-307.
2. Jain SS, Ashokkumar M, Bird RP. Differential expression of TNF-α signaling molecules and ERK1 in distal and proximal colonic tumors associated with obesity. Tumor Biol 2011; 32:1005-1012.
3. Peairs AD, Rankin JW, Yong WL. Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults. Nutr J 2011; 10:122-123.
4. Peng Y, Rideout D, Rakita S, Lee J, Murr M. Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver. Surg Obes Relat Dis 2012; 8:73-81.
5. Park H-K, Ahima RS. Endocrine Disorders Associated with Obesity. In: Ahima RS, editor. Metabolic Syndrome: A Comprehensive Textbook. Cham: Springer International Publishing; 2014. p. 1-18.
6. Feng R, Sun G, Zhang Y, Sun Q, Ju L, Sun C, et al. Short-term high-fat diet exacerbates insulin resistance and glycolipid metabolism disorders in young obese men with hyperlipemia by metabolomics analysis using UPLCQ-TOF MS. J Diabetes 2018; 11:148-160.
7. Dong W, Zhang X, Li D, Hao W, Meng F, Bo W, et al. Kaempferide protects against myocardial ischemia/reperfusion injury through activation of the PI3K/Akt/GSK-3β pathway. Mediators Inflamm 2017:5278218-5278230.
8. Dumon MF, Freneix-Clerc M, Carbonneau MA, Thomas MJ, Clerc M. Demonstration of the anti-lipid peroxidation effect of 3’,5,7-trihydroxy-4’-methoxy flavone rutinoside: in vitro study. Ann Biol Clin 1994; 52:265-270.
9. Freneix-Clerc M, Dumon MF, Carbonneau MA, Thomas MJ, Clerc M. In vivo study of the antilipoperoxidant effect of 3’,5,7-trihydroxy-4’-methoxy flavone 7 rutinoside. Ann Biol Clin 1994, 52:171-177.
10. Kyung-Ah K, Gu W, In-Ah L, Eun-Ha J, Dong-Hyun K, Mathias C. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PloS One 2012; 7:47713-74424.
11. Lin Y, Ren N, Li S, Chen M, Pu P. Novel anti-obesity effect of scutellarein and potential underlying mechanism of actions. Biomed Pharmacother 2019; 117:109042-109050.
12. Ouchi N, Murohara T, Shibata R, Yuasa D, Ohashi k. Adiponectin as a target in obesity-related inflammatory state. Endocr Metab Immune Disord Drug Targets 2015; 15:145-150.
13. Wolowczuk I. Obesity – an inflammatory state. Acta Vet Scand 2015; 57:1-1.
14. Escoubetlozach L, Benner C, Kaikkonen MU, Lozach J, Heinz S, Spann N, et al. Mechanisms establishing TLR4-responsive activation states of inflammatory response genes. PLoS Genet 2011; 7:1002401-1002415.
15. Stefanie Z, Ulmer AJ, Shoichi K, Katus HA, Holger H. TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS. Cardiovasc Res 2002; 56:126-134.
16. Lee J, Burckart GJ. Nuclear factor kappa B: Important transcription factor and therapeutic target. J Clin Pharmacol 1998; 38:981-993.
17. Verma IM, Stevenson JK, Schwarz EM, Antwerp DV, Miyamoto S. Rel/NF-κB/IκB family: Intimate tales of association and dissociation. Genes Dev 1995; 9:2723-2735.
18. Wang R, Yu XY, Guo ZY, Wang YJ, Wu Y, Yuan YF. Inhibitory effects of salvianolic acid B on CCl4-induced hepatic fibrosis through regulating NF-κB/IκBα signaling. J Ethnopharmacol 2012; 144:592-598.
19. Lentsch AB, Ward PA. The NFκB/IκB system in acute inflammation. Arch Immunol Ther Exp 2000; 48:59-63.
20. Kim SR, Bae YH, Bae SK, Choi KS, Yoon KH, Koo TH, et al. Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. Mol Cell Res 2008; 1783:886-895.
21. Wang C, Ha X, Li W, Xu P, Zhang J. Correlation of TLR4 and KLF7 in inflammation induced by obesity. Inflammation 2016; 40:1-10.
22. Yajun WU, Jie SU, Huang P, Chen G, Chen S, Guiyuan L. Buddleoside prevents TNF-α-induced human aortic endothelial cells inflammatory injury through inhibiting TLR4/IκBα/NF-κB signaling pathway. Chin J Mod Appl Pharm 2017; 34:637-643.
23. Ko MK, Sindhu S, Parikh JG, Rao NA. The role of TLR4 activation in photoreceptor mitochondrial oxidative stress. Invest Ophthalmol Vis 2011; 52:5824-5835.
24. Wang L, Liu XH, Chen H, Chen ZY, Weng XD, Qiu T, et al. Picroside II protects rat kidney against ischemia/reperfusion-induced oxidative stress and inflammation by the TLR4/NF-κB pathway. Exp Ther Med 2015; 9:1253-1258.
25. Helmut S. Oxidative stress: a concept in redox biology and medicine. Redox Biol 2015; 4:180-183.
26. Djordjevic A, Spasic S, Jovanovic-Galovic A, Djordjevic R, Grubor-Lajsic G Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products. J Matern Fetal Med 2004; 16:367-372.
27. Lamichhane A, Prasad S, Bhaskar N, Singh J, Pandey R. Malondialdehyde (MDA): an oxidative stress marker in type II Diabetes mellitus with and without complications. Curr Trends Biotechnol Chem Res 2013; 2:112-123.
28. Liang Q, Sheng Y, Jiang P, Ji L, Wang Z. The gender-dependent difference of liver GSH antioxidant system in mice and its influence on isoline-induced liver injury. Toxicology 2011; 280:61-69.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 4
April 2021
Pages 493-498

Files

Share

How to cite

Statistics