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Plumbagin, a Vitamin K3 Analogue, abrogates Lipopolysaccharide-Induced Oxidative Stress, Inflammation and Endotoxic Shock via NF-κB Suppression

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Abstract

Plumbagin has been reported to modulate cellular redox status and suppress NF-κB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-α, IL-6 and prostaglandin-E2 production in a concentration-dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-κB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro-inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-κB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin.

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ACKNOWLEDGEMENTS

The authors would like to acknowledge the technical assistance provided by Mr. Deepak Kathole, Mr. Kashinath Munankar and Ms. Punitha Bhupati. The financial support from the Department of Atomic Energy, Government of India, is kindly acknowledged.

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Authors and Affiliations

  1. Radiation Biology and Health Sciences Division, Bio-Medical Group, Bhabha Atomic Research Centre, Trombay, Mumbai, India

    Rahul Checker, Raghavendra S. Patwardhan, Deepak Sharma, Jisha Menon, Maikho Thoh, Santosh K. Sandur, Krishna B. Sainis & T. B. Poduval

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  1. Rahul Checker
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Correspondence to Santosh K. Sandur.

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K.B.S, T.B.P and S.K.S conceived and designed the experiments; R.C., M.T., J.M. and R.S.P. performed the experiments; S.K.S., D.S. and R.C. analysed the data; S.K.S., D.S. and R.C. wrote the manuscript in consultation with the other authors.

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Checker, R., Patwardhan, R.S., Sharma, D. et al. Plumbagin, a Vitamin K3 Analogue, abrogates Lipopolysaccharide-Induced Oxidative Stress, Inflammation and Endotoxic Shock via NF-κB Suppression. Inflammation 37, 542–554 (2014). https://doi.org/10.1007/s10753-013-9768-y

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