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

AMPK, in particular, reduces glucose output and lowers antigens pass through the liver through arterial blood
blood glucose levels by increasing AMP and decreasing flow, the liver’s optimal function requires maintaining a
ATP concentrations. AMPK is also believed to regulate delicate equilibrium between immunity and tolerance
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lipogenesis and activate SREBP 1. In addition, curcumin to these antigens. Liver inflammation can occur due to
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has been found to suppress the effects of specific protein-1, chronic infection, autoimmunity, alcohol abuse, and
which attenuates the expression of SREBP2, reduces the malignancy. Various immune and non-hematopoietic
gene expression of LOX1, and suppresses LDL receptor cell populations generate persistent inflammatory signals
expression, thereby reducing HSC activation. 113,114 that maintain hepatic myofibroblasts in a constant state
Furthermore, curcumin plays a role in other stages of of activation, preventing their programmed death. This
fibrogenesis by regulating the deposition of extracellular chronic activation impairs the effectiveness of NK cells in
proteins in the liver’s extracellular space, a process promoting apoptosis. In diseased livers, this exacerbated
controlled by MMPs and their inhibitors (TIMPs). inflammation disrupts the mechanisms that normally
Fibrosis occurs when there is an imbalance caused by the promote tolerance, further intensifying the inflammatory
hyperactivation of HSCs. Studies have shown that curcumin response. These pathways encompass various mechanisms
has an impact on the regulation of TIMP-1 and TIMP-2 that contribute to tumor growth, such as the expansion
in vivo and in vitro, leading to the upregulation of MMP- of immunoregulatory cell populations, alterations in
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2, MMP-7, MMP-9, and MMP-13. This upregulation of epigenetic and metabolic processes that enhance immune
MMPs contributes to the inhibition of HSC activation by cell tolerance, and the activation of negative regulators that
degrading fibrillar collagens, a major component of the dampen pro-inflammatory signaling pathways. Targeting
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ECM. In addition, the reduction of PPARγ expression these immune regulatory pathways holds the potential to
in activated HSCs is another important mechanism in reduce the severity of liver diseases or induce the clearance
liver fibrosis. Curcumin interferes with liver fibrosis by of pathogens and tumors. Viewing liver disease as a
inducing PPARγ expression, which reduces the storage consequence of overlapping dysregulated inflammatory
capability of vitamin A and lipid droplets, promotes the processes opens new possibilities for developing therapies
deposition of ECM, and triggers the expression of α-SMA that specifically target inflammation and promote
and type I collagenα1. Furthermore, curcumin stimulates resolution within the liver.
cell proliferation and growth. The trans-activating activity The potential of medicinal herbs as valuable sources
of NF-κB is inhibited by curcumin’s activation of PPARγ, for a variety of medicines has been widely acknowledged.
whereas the utilization of a specific PPARγ antagonist Researchers across the globe have recognized the
promotes HSC proliferation. Adipokines, such as leptin diverse therapeutic properties exhibited by these herbs.
and adiponectin, play a crucial role in regulating adipocyte Interestingly, plant-based drugs may possess more
energy metabolism. In this regard, curcumin has shown favorable biochemical characteristics compared to
anti-diabetic effects by inhibiting NF-κB in adipocytes synthetic drugs, although modern medicine does not fully
and reducing NF-κB-regulated adipokines, making it a endorse the use of natural products for medicinal purposes.
promising target for the treatment of diabetes mellitus. In a Nevertheless, it is crucial to recognize that numerous
study conducted by Pickich et al., the effects of curcumin compounds, such as colchicines, vincristine, vinblastine,
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on cytokines and chemokines were evaluated in a rat model podophyllotoxin, and taxol, have been derived from
of non-alcoholic steatohepatitis induced by a Western diet nature and effectively utilized as therapeutic agents. Recent
and CCl . Curcumin’s potential to modulate cytokines, evidence suggests that it is possible to reverse the processes
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chemokines, and immune cells to exert protective effects of fibrosis and cirrhosis. The induction of apoptosis in
in the liver is a recurring theme in preclinical research and HSCs has been linked to fibrosis reversal, highlighting the
animal models. While animal studies have shown promise, potential of targeting HSC activation and proliferation
there is still a lack of studies on humans. Therefore, further for the prevention and reversal of fibrosis. Curcumin has
research and clinical trials are needed to fully understand demonstrated various beneficial effects on HSCs. Studies
curcumin’s ability to modify immune responses in the liver. have shown that curcumin can effectively reduce hepatic
fibrosis in rodent models by reducing oxidative stress,
5. Conclusion inhibiting HSC activation, and suppressing the expression
The liver is an essential organ in the human body, responsible of type I collagen α1 gene. Curcumin has also been found
for numerous vital functions, such as detoxifying the to modulate various intracellular signaling pathways in
blood, synthesizing and secreting all plasma proteins HSCs, including the ERK, JNK, AP-1, PPARγ, and NF-κB
except immunoglobulins, and storing important vitamins pathways. Previous studies have highlighted the activation
and minerals. However, since unprocessed dietary of the NRF2 pathway by curcumin in HSCs, which is

Volume 3 Issue 3 (2024) 13 doi: 10.36922/gpd.3186