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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Septicemia | Research article

Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1cells and improves survival in sepsis

Authors: Sheena Philip, Greeshma Tom, Padmaja Balakrishnan Nair, Sankar Sundaram, Asha Velikkakathu Vasumathy

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Tinospora cordifolia (Willd).Miers is a perennial climbing medicinal shrub that has been traditionally used for the treatment of chronic inflammatory ailments. Our previous pre- clinical studies on anti-inflammatory effects, proved that the chloroform extract of T. cordifolia (CETC) suppressed the LPS induced up-regulation of pro-inflammatory biomarkers, hence, further follow up study was carried out to evaluate whether CETC can exhibit a protective effect against LPS induced lethal endotoxemia in vivo and also to analyze the impact of CETC pre-treatment on the secretion of pro-inflammatory cytokines in vitro by THP-1 cells.

Methods

To corroborate our previous preclinical studies on inflammation, we investigated the mechanism of the anti-inflammatory effect of T. cordifolia on THP-cells which were pre-incubated with CETC (30 min) and stimulated subsequently with LPS (1 μg/ml) for 20 h. Levels as well as gene expressions of various cytokines were compared with that of LPS alone incubated cells. Alongside, in vivo oral anti-inflammatory efficacy against LPS induced endotoxemia study was effectuated, wherein rats were administered with CETC 48, 24, 12 and 1 h prior to the injection of LPS and the survival of rats were monitored upto 10 days. Cytokine levels were quantified by ELISA. Nitrite levels were measured using Griess reagent. Expression of pro-inflammatory proteins was inspected in rat tissues by histochemical and immuno -histochemical examinations.

Results

CETC was able to down-regulate the up-regulation of pro-inflammatory biomarkers in THP-1 macrophages though blockade of NF-κB nuclear translocation and could improve the survival rate during endotoxemic episodes with a marked suppression of the tissue expression of pro-inflammatory proteins.

Conclusion

These findings concomitantly reveal the anti-inflammatory mechanism of CETC and support us to move forward for the development of drugs against disorders resulting from deregulated immune reactions.

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Adedapo AA, Sofidiya MO, Maphosa V, Moyo B, Masika P, Afolayan AJ. Anti-inflammatory and analgesic activities of the aqueous extract of Cussonia paniculata stem bark. ACG Pub. 2008;2:46–53.

Drayton DL, Liao S, Mounzer RH, Ruddle NH. Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol. 2006;7:344–53.CrossRef

Wang Q, Kuang H, Su Y, Sun Y, Feng J, Guo R, Chan K. Naturally derived anti-inflammatory compounds from Chinese medicinal plants. J Ethnopharmacol. 2013;146:9–39.CrossRef

Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA. Possible new role for NF-κB in the resolution of inflammation. Nat Med. 2001;7:1291–7.CrossRef

Sheu MJ, Deng JS, Huang MH, Wu CH, Huang SS, Huang GJ. Antioxidant and anti-inflammatory properties of Dichondra repens Forst. and its reference compounds. Food Chem. 2012;132:1010–18.

Jung WK, Choi I, Lee DY, Yea SS, Choi YH, Kim MM, Park SG, Seo SK, Lee CM, Lee SW, Park YM, Choi IW. Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW264.7 macrophages via the p38/ERK and NF-κB pathways. Int J Biochem Cell Biol. 2008;40:2572–82.CrossRef

Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E. Serum cytokine levels in human septic shock: Relation to multiple-system organ failure and mortality. Chest. 1993;103:565–75.

Marzocco S, Paola RD, Ribecco MT, Sorrentino R, Domenico B, Genesio M, Pinto A, Autore G, Cuzzocrea S. Effect of methyl guanidine in a model of septic shock induced by LPS. Free Radic Res. 2004;38:1143–53.

Shaheen N, Ahmed S, Azhar I, Hasan MM. Analgesic, anti-inflammatory and antiemetic activities of Cleome scaposa DC. Phytopharmacol. 2013;4:106–13.

10.

Titheradge MA. The enzymatic measurement of nitrate and nitrite. In: Nitric Oxide Protocols, edited by Titheradge MA. Totowa: Humana, 1998;83–93.

11.

Sreejith PS, Mascarenhas RR, Praseeja RJ, Asha VV. The apoptosis inducing effect of Glycosmis pentaphylla (Retz.) Correa and its influence on gene expression in hepatocellular carcinoma cell line, Hep3 B. J Ethnopharmacol. 2012;139:359–65.

12.

Shalini V, Bhaskar S, Kumar KS, Mohanlal S, Jayalekshmy A, Helen A. Molecular mechanisms of anti-inflammatory action of the flavonoid, tricin from Njavara rice (Oryza sativa L.) in human peripheral blood mononuclear cells: possible role in the inflammatory signaling. Int Immunopharmacol. 2012;14:32–8.

13.

Bellini MF, Angeli JPF, Matuao R, Terezan AP, Ribeiro LR, Mantovani MS. Antigenotoxicity of Agaricus blazei mushroom organic and aqueous extracts in chromosomal aberration and cytokinesis block micronucleus assays in CHO-k1 and HTC cells. Toxicol Vitro. 2006;20:355–60.

14.

Aldini R, Micucci M, Cevenini M, et al. Antiinflammatory effect of phytosterols in experimental murine colitis model: prevention, induction, remission study. PLoS One. 2014;9(9):e108112.CrossRef

15.

Kwon OK, Lee MY, Yuk JE, Oh SR, Chin YW, Lee HK, Ahn KS. Anti-inflammatory effects of methanol extract of the root of Lilium lancifolium on LPS-stimulated RAW264.7 cells. J Ethnopharmacol. 2010;130:28–34.

16.

Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM. Docosahexaenoic acid induces an anti- inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem. 2007;18:250–8.CrossRef

17.

Philip S, Tom G, Vasumathi AV. Evaluation of the anti-inflammatory activity of Tinospora cordifolia (Willd.) Miers chloroform extract – a preclinical study. J Pharm Pharmacol. 2018;70:1113–25.

18.

Nakanishi M, Rosenberg DW. Multifaceted roles of PGE₂ in inflammation and cancer. Semin Immunopathol. 2013;35:123–37.CrossRef

19.

Salvemini D. Regulation of cyclooxygenase enzymes by nitric oxide. Cell Mol Life Sci. 1997;53:576–82.CrossRef

20.

Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 2003;54:469–87.PubMed

21.

Ishihara K, Hirano T. Survey: IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev. 2002;13:357–68.CrossRef

22.

Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Ann Rev Immunol. 1994;12:141–79.

23.

Standiford TJ. Anti-inflammatory cytokines and cytokine antagonists. Curr Pharm Des. 2000;6:633–49.CrossRef

24.

Opal SM. The host response to endotoxin, antilipopolysaccharide strategies and the management of severe sepsis. Int J Med Microbiol. 2007;297:365–77.CrossRef

25.

Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, Patriotis C, Jenkins NA, Copeland NG, Kollias G, Tsichlis PN. TNF-α induction by LPS is regulated post transcriptionally via a Tpl2/ERK-dependent pathway. Cell. 2000;103:1071–83.CrossRef

26.

Heinzel FP, Rerko RM, Ling P, Hakimi J, Schoenhaut DS. Interleukin 12 is produced in vivo during endotoxemia and stimulates synthesis of gamma interferon. Infect Immun. 1994;62:4244–9.

27.

Enomoto N, Takei Y, Hirose M, Konno A, Shibuya T, Matsuyama S, Suzuki S, Kitamura KI, Sato N. Prevention of ethanol-induced liver injury in rats by an agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone. J Pharmacol Exp Ther. 2003;306:846–54.CrossRef

28.

Kang JS, Jeon YJ, Park SK, Yang KH, Kim HM. Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol. 2004;67:175–81.CrossRef

29.

Ishihara T, Kohno K, Ushio S, Iwaki K, Ikeda M, Kurimoto M. Tryptanthrin inhibits nitric oxide and prostaglandin E2 synthesis by murine macrophages. Eur J Pharmacol. 2000;407:197–204.CrossRef

Title: Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1cells and improves survival in sepsis
Authors: Sheena Philip
Greeshma Tom
Padmaja Balakrishnan Nair
Sankar Sundaram
Asha Velikkakathu Vasumathy
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Septicemia
Septicemia
Cytokines
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03244-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1cells and improves survival in sepsis

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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