Zingerone Suppresses Liver Inflammation Induced by Antibiotic Mediated Endotoxemia through Down Regulating Hepatic mRNA Expression of Inflammatory Markers in Pseudomonas aeruginosa Peritonitis Mouse Model

Abstract

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory phytomedicine against hepatic inflammation induced by antibiotic mediated endotoxemia. These results thus suggest that zingerone treatment can be used as a co-therapy with antibiotics to reduced endotoxin induced inflammation during treatment of severe P.aeruginosa infections.

Hepatoprotective potential of zingerone against nonalcoholic fatty liver disease in rats fed with fructose-enriched diet

“…Zingerone is a potent antiinflammatory phytomedicine by down regulating hepatic tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) of hepatic inflammation induced by antibiotic-mediated endotoxemia (Kumar et al 2014). Consistent with the previous finding by Kumar et al (2014) in our study, zingerone administration to fructose-enriched diet rats attenuated the activities of the serum hepatic function indicators enzymes. These evidences demonstrate that long-term administration of zingerone prevented the fructose-enriched diet induced hepatic damage.…”

“…Zingerone is a potent antioxidant (Hemalatha and Prince 2015), reduces oxidative stress and lipid peroxidation (Vinothkumar et al 2014; and also protects against reactive oxygen species mediated DNA damage (Rajan et al 2013). Zingerone is a potent antiinflammatory phytomedicine by down regulating hepatic tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) of hepatic inflammation induced by antibiotic-mediated endotoxemia (Kumar et al 2014). Consistent with the previous finding by Kumar et al (2014) in our study, zingerone administration to fructose-enriched diet rats attenuated the activities of the serum hepatic function indicators enzymes.…”

Design, synthesis, molecular docking, anti‐quorum sensing, and anti‐biofilm activity of pyochelin‐zingerone conjugate

“…Along with anti-virulence activity, zingerone is also known for its immunoprotective potential. In particular, zingerone inhibits both planktonic and biofilm growth of opportunistic pathogen P. aeruginosa and causes significant protection from P. aeruginosa infection in animal models based on prior work in our lab (Kumar et al, 2013;Kumar et al, 2014).…”

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“…World Health Organization (WHO) is recommending the use of complementary and alternative approaches in combating diabetes through the utilization of herbal remedies due to their natural origin and nontoxicity 10,11 . Ginger, the rhizome of the plant Zingiber officinale, is a herbal dietary spice indigenous to India and its use has spread to most of the inhabited world due to the potent anti-inflammatory, antioxidative, antiarthritic, antithrombotic, anticancer, hypolipidaemicand antidiabetic properties [12][13][14] . The herbal properties of ginger are similar to non-steroid antiinflammatory drugs (NSAIDs), and hence, it can regulate biochemical pathways which are activated with chronic inflammation such as diabetes 15 .…”

“…Besides, histopathological studies of multiple organs such as pancreas, liver, kidney, adipose, aorta and testis for substantiating the normal functioning of organs as well as nontoxicity of ginger or its phytochemicals while treating the diabetes induced animal models are scarce. Further, there is no report on the antidiabetic and hypolipidaemic effects of zingerone (4-(4-hydroxy-3-methoxy phenyl) butan-2-one), which is a stable active component of dry ginger rhizome and is known to have wide ranging pharmacological activities such as hepatoprotective 13 ,…”