Kaempferol and Chrysin Synergies to Improve Septic Mice Survival

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2017 Jan 10

PMID 28067837

Citations 10

Authors

Omar A Harasstani

Chau Ling Tham

Daud A Israf

Affiliations

Soon will be listed here.

Abstract

Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as -alpha (TNF-α), , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple pathophysiological factors involved during sepsis. Although the kaempferol/chrysin combination did not exhibit significant antibacterial effects, it did exhibit anti-inflammatory and antioxidant activities, which translate to significant improvement in the survival rate of septic animals. These findings suggest the potential application of this combination treatment as a beneficial adjuvant supplement strategy in sepsis control.

Citing Articles

Pharmacological Potential of Kaempferol, a Flavonoid in the Management of Pathogenesis via Modulation of Inflammation and Other Biological Activities.

Alrumaihi F, Almatroodi S, Alharbi H, Alwanian W, Alharbi F, Almatroudi A Molecules. 2024; 29(9).

PMID: 38731498 PMC: 11085411. DOI: 10.3390/molecules29092007.

Kaempferol improves acute kidney injury via inhibition of macrophage infiltration in septic mice.

Xu Z, Wang X, Kuang W, Wang S, Zhao Y Biosci Rep. 2023; 43(7).

PMID: 37440431 PMC: 10372469. DOI: 10.1042/BSR20230873.

Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols-Polyphenols as an Element of Diet Therapy in Depressive Disorders.

Winiarska-Mieczan A, Kwiecien M, Jachimowicz-Rogowska K, Donaldson J, Tomaszewska E, Baranowska-Wojcik E Int J Mol Sci. 2023; 24(3).

PMID: 36768580 PMC: 9916817. DOI: 10.3390/ijms24032258.

Plants' bioactive secondary metabolites in the management of sepsis: Recent findings on their mechanism of action.

Mahomoodally M, Aumeeruddy M, Legoabe L, DallAcqua S, Zengin G Front Pharmacol. 2023; 13:1046523.

PMID: 36588685 PMC: 9800845. DOI: 10.3389/fphar.2022.1046523.

Optimization of Flavonoid Extraction from Buds, and the Antioxidant and Antibacterial Activities of the Extract.

Zhang P, Song Y, Wang H, Fu Y, Zhang Y, irina pavlovna K Molecules. 2022; 27(17).

PMID: 36080462 PMC: 9457869. DOI: 10.3390/molecules27175695.

References

Hillegass L, Griswold D, Brickson B . Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990; 24(4):285-95. DOI: 10.1016/0160-5402(90)90013-b. View

Wu B, Walker J, Spur B, Rodriguez A, Yin K . Effects of Lipoxin A4 on antimicrobial actions of neutrophils in sepsis. Prostaglandins Leukot Essent Fatty Acids. 2014; 94:55-64. DOI: 10.1016/j.plefa.2014.11.005. View

Pichichero E, Cicconi R, Mattei M, Canini A . Chrysin-induced apoptosis is mediated through p38 and Bax activation in B16-F1 and A375 melanoma cells. Int J Oncol. 2010; 38(2):473-83. DOI: 10.3892/ijo.2010.876. View

Rittirsch D, Huber-Lang M, Flierl M, Ward P . Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009; 4(1):31-6. PMC: 2754226. DOI: 10.1038/nprot.2008.214. View

Yamaguchi R, Kawata J, Yamamoto T, Ishimaru Y, Sakamoto A, Ono T . Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps. Blood Cells Mol Dis. 2015; 55(2):127-33. DOI: 10.1016/j.bcmd.2015.05.012. View

Torres M, De Maio A . An exaggerated inflammatory response after CLP correlates with a negative outcome. J Surg Res. 2005; 125(1):88-93. DOI: 10.1016/j.jss.2004.11.025. View

Devi K, Malar D, Nabavi S, Sureda A, Xiao J, Nabavi S . Kaempferol and inflammation: From chemistry to medicine. Pharmacol Res. 2015; 99:1-10. DOI: 10.1016/j.phrs.2015.05.002. View

Guo T, Chi R, Karrow N, Zhang L, Pruett S, Germolec D . Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice. Toxicol Appl Pharmacol. 2005; 209(3):244-54. DOI: 10.1016/j.taap.2005.04.014. View

Chou T . Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3):621-81. DOI: 10.1124/pr.58.3.10. View

10.

Liu L, Gong L, Wang H, Xiao Y, Wu X, Zhang Y . Baicalin inhibits macrophage activation by lipopolysaccharide and protects mice from endotoxin shock. Biochem Pharmacol. 2008; 75(4):914-22. DOI: 10.1016/j.bcp.2007.10.009. View

11.

Girbes A, Beishuizen A, Strack van Schijndel R . Pharmacological treatment of sepsis. Fundam Clin Pharmacol. 2008; 22(4):355-61. DOI: 10.1111/j.1472-8206.2008.00606.x. View

12.

Lomas-Neira J, Chung C, Grutkoski P, Dunican A, Simms H, Cioffi W . Divergent roles of murine neutrophil chemokines in hemorrhage induced priming for acute lung injury. Cytokine. 2005; 31(3):169-79. DOI: 10.1016/j.cyto.2005.04.005. View

13.

Cuzzocrea S . Shock, inflammation and PARP. Pharmacol Res. 2005; 52(1):72-82. DOI: 10.1016/j.phrs.2005.02.016. View

14.

Feng X, Yan W, Liu X, Duan M, Zhang X, Xu J . Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and cytokines production and NF-kappaB activation in CLP-induced sepsis in rats. J Surg Res. 2006; 135(1):129-36. DOI: 10.1016/j.jss.2006.02.028. View

15.

Seam N, Suffredini A . Mechanisms of sepsis and insights from clinical trials. Drug Discov Today Dis Mech. 2008; 4(2):83-93. PMC: 2516940. DOI: 10.1016/j.ddmec.2007.10.004. View

16.

Lin S, Chung F, Kuo C, Chou P, Wang T, Chang P . Circulating angiopopietin-1 correlates with the clinical course of multiple organ dysfunction syndrome and mortality in patients with severe sepsis. Medicine (Baltimore). 2015; 94(20):e878. PMC: 4602874. DOI: 10.1097/MD.0000000000000878. View

17.

Xie X, Shinozawa Y, Sasaki J, Takuma K, Akaishi S, Yamanouchi S . The effects of arginine and selective inducible nitric oxide synthase inhibitor on pathophysiology of sepsis in a CLP model. J Surg Res. 2007; 146(2):298-303. DOI: 10.1016/j.jss.2007.07.016. View

18.

Lee Y, Choi H, Seo M, Jeon H, Kim K, Lee B . Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish. Food Funct. 2015; 6(8):2824-33. DOI: 10.1039/c5fo00481k. View

19.

Fernandez-Cancio M, Centelles J, Imperial S . Sources of interference in the use of 2,3-diaminonaphthalene for the fluorimetric determination of nitric oxide synthase activity in biological samples. Clin Chim Acta. 2001; 312(1-2):205-12. DOI: 10.1016/s0009-8981(01)00625-8. View

20.

Tsikas D . Circulating and excretory nitrite and nitrate: their value as measures of nitric oxide synthesis, bioavailability and activity is inherently limited. Nitric Oxide. 2015; 45:1-3. DOI: 10.1016/j.niox.2015.01.001. View