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Gene & Protein in Disease Modulating immune response in liver by curcumin

and fibrosis, indicating that curcumin’s effects on these role of curcumin in a mouse model of LPS-induced acute
cells could have broader implications for tissue remodeling liver injury. They found that curcumin reduced pro-
in various organs. inflammatory cytokines and oxidative stress, increased
liver antioxidant enzymes, and decreased liver apoptosis by
Failure to prevent liver disease may lead to its
advancement from mild stages to more serious conditions, inhibiting the phosphoinositide 3-kinase/protein kinase B
such as hepatitis, fibrosis, and cirrhosis. The involvement signaling pathway.
of HSCs is a key factor in the development of liver fibrosis, Studies have demonstrated that curcumin facilitates
irrespective of the underlying cause. HSCs are responsible the replication of mitochondrial DNA through its
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for the production of collagens, which are the predominant action on cyclic adenosine monophosphate levels. By
proteins in the ECM of the liver. As previously mentioned, inhibiting leptin signaling, curcumin effectively hampers
fibrosis is characterized by the excessive accumulation the activation of HSCs by impeding leptin receptor
of collagen between hepatocytes and liver sinusoids. phosphorylation. Moreover, curcumin suppresses leptin
The activation of HSCs is triggered by chronic tissue receptor gene expression, stimulates PPARγ activity, and
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injury, ROS, inflammatory cytokines, and apoptotic reduces oxidative stress. It also exhibits inhibitory effects
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signals. TGF-β is another crucial factor in initiating and on HSC activation induced by hyperglycemia in vitro.
sustaining HSC phenotypic activity, which is further In HSCs, curcumin effectively hinders the movement and
amplified by oxidative stress. When the balance between genetic expression of glucose transporter-2, leading to a
collagen synthesis and degradation by membrane-bound decrease in intracellular glucose levels and consequently
metalloproteinase is disrupted, fibrosis progresses to reducing overall glucose levels within HSCs. Furthermore,
cirrhosis. Cirrhosis, the final stage of progressive fibrosis, curcumin possesses anti-glycation properties. 99
is characterized by the degradation of hepatic lobular Advanced glycation end-products (AGEs) are
structures and impaired blood flow. In vivo studies often compounds formed through reactions between proteins,
investigate the mechanisms of HSC activation using lipids, and carbohydrates through oxidative and non-
the fibrotic agent carbon tetrachloride (CCl ) in animal oxidative processes. Hyperglycemia increases the
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models. Curcumin has been found to significantly inhibit production of AGEs, whose accumulation in tissues and
HSC activation, reduce liver damage, and decrease the blood is accelerated by aging, chronic renal failure, and
expression of α-SMA in CCl -induced liver fibrosis models diabetes, resulting in inflammation and liver fibrogenesis.
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administered over 12 weeks. 90 The formation of AGEs involves intermediates called
Curcumin has demonstrated the ability to target Amadori products, which can be converted to AGEs
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multiple sites and pathways in various models. For through oxidative reactions. The deposition of AGEs in
instance, Bruck et al. found that curcumin inhibited TAA- tissues contributes to HSC activation; however, this process
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induced cirrhosis in rats, leading to a decrease in oxidative can be mitigated by antioxidant agents. Numerous studies
stress and hydroxyproline levels in rats. It also reduced have demonstrated that curcumin reduces HSC activation
the histopathological score in the liver and significantly due to its anti-glycation properties. 104,105 In addition,
affected changes in spleen weight between treatment curcumin has been found to inhibit lipid metabolism,
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groups. Similarly, Chenari et al. demonstrated that another factor involved in HSC activation. In vitro,
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curcumin treatment in the BDL fibrotic rat model resulted studies have shown that curcumin induces the expression
in significant reductions in low-density lipoprotein (LDL), of genes related to lipogenesis, such as SREBP1c, PPARγ,
total cholesterol, and triglyceride levels, as well as in the and C/EBPα, leading to intracellular lipid accumulation in
gene expressions of adenosine monophosphate-activated HSCs and ultimately inhibiting HSC activation. 106
protein kinase (AMPK), carnitine palmitoyltransferase 1A, Various scientific investigations have revealed that
isocitrate dehydrogenase 2, and manganese-dependent curcumin treatment delays the progression of hepatic
SOD. Curcumin has also shown effectiveness in treating fibrosis in rats and mice of steatohepatitis. 107,108 In vitro
chronic hepatic diseases, as evidenced by reduced levels of models have demonstrated that curcumin inhibits HSC
ALT, gamma-glutamyl transferase, and TGF-β expression activation by eliciting AMPK activity, which leads to the
in a rat model of BDL-induced liver cirrhosis. In addition, expression of genes associated with lipid accumulation,
a dosage of 100 mg/kg of curcumin was found to decrease thereby increasing intracellular triglyceride and fatty acid
oxidative stress by altering the levels of glutathione. A levels. The activation of HSC is facilitated by a decrease
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separate study confirmed curcumin’s efficacy in treating in lipid storage capacity, reduction of intracellular lipid
BDL-induced liver damage and oxidative stress. droplets, and suppression of various transcription factors
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Moreover, Zhong et al. investigated the hepatoprotective such as PPARγ, C/EBPa, and SREBP1. 109,110 Hepatic
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Volume 3 Issue 3 (2024) 12 doi: 10.36922/gpd.3186