Curcumin can protect and treat liver diseases and alter different cellular pathways.
For instance,
curcumin induces the expression of heme oxygenase-1 which cleaves heme and produces CO, biliverdin
and bilirubin, and other antioxidant molecules [149]. Regarding the reported effects on cellular responses,
curcumin inhibits activation and proliferation of HSC, leading to a decrease in the production of
extracellular matrix collagen and protecting the liver from fibrogenesis. This effect on HSC was found to
be through the down-regulation of PDGF-βR, EGFR, and TGF-β coupled with the reduction of mRNA
level of PPAR-γ [150,151]. Curcumin induced the synthesis of reduced glutathione [152] leading to a
marked decrease in lipid peroxidation products such as lipid hydroperoxide and MDA [83,84]. The
increase in GSH level is due to the ability of curcumin in elevating the gene expression of the rate-
limiting enzyme in glutathione synthesis and glutamate cysteine ligase (GCL) [83]. Curcumin treatment
leads to a marked decrease in the level of proinflammatory cytokines such as TNF-α, INF-γ, IL-1β, and
IL-6 [84,153]. The decrease in proinflammatory cytokines was due to the inhibition of NF-κB
translocation to the nucleus and decreasing its DNA binding activity [84].
Curcumin increased the expression of SIRT3, an NAD+ -dependent deacetylase and ADP-ribosyl
transferase. SIRT3 activation by curcumin led to a decrease in lipid deposition through AMPK and the
mitochondrial CPT-1A. Moreover, SIRT3 caused a decrease in ROS levels by upregulating the
expression of MnSOD and the mitochondrial IDH2 [118]. Another signaling cellular pathway attenuated
in the liver by curcumin treatment is PI3K/Akt. Hence, curcumin inhibited and decreased the level of
apoptotic markers such as Bad, Bcl-xL, cytochrome c, Apaf-1, and cleaved caspase-9, -3, and -6. p38
mitogen-activated protein kinase/JUN was also downregulated and protected the liver cells from death
[121]. Also, curcumin downregulated the expression of ACE [108].
A wide variety of preclinical studies support dietary curcumin's effectiveness in managing
oxidative-associated liver diseases. However, there are few RCTs assessing the efficacy of curcumin in
liver disorders. Table 2 shows curcumin’s evidence in the prevention and treatment of oxidative-
associated liver diseases in humans. Further well-designed RCTs are therefore required to confirm the
dietary and adjunctive role of curcumin as promising protective or curative agents in the management of
oxidative-associated liver diseases.
To conclude, the results obtained from the present review revealed that curcumin can be effective
in various types of oxidative-associated liver disorders. This potentiality attributes to curcumin’s effects
on hepatotoxicity, non-alcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, and cirrhosis as
well as hepatic injury. Experimental evidence indicates that curcumin exhibits its preventive and curative
effect against oxidative-associated liver diseases through various cellular signaling pathways. Those
pathways include ERK/p38/MAPK pathway, hepatic Nrf2/ARE/Keap1 signaling, up-regulation of
detoxifying genes expression, TIMP signaling, AMPK pathway, and lipid metabolism, as well as down-
regulation of Rac1, NOX1, and Rac1-GTP transduction. Regarding the above-mentioned biological
activities of curcumin in either protecting or treating the liver, it is highly recommended to consider
curcumin as a safe and effective natural product for oxidative-associated liver diseases. Among the
studies that were conducted in various oxidative models associated with liver disease, some investigated
the protective effects of curcumin [83–86,97,98,105–107]. According to these articles, curcumin as a
dietary supplement has a protective role against the onset of liver diseases. The intake of a significant
content of curcumin in the daily regimen or as dietary supplementation along with restricted therapeutic
options can provide perfect prevention and treatment for liver disorders. The present review revealed that
further in vitro and preclinical studies are encouraged to recognize the exact bioavailability, bio-efficacy,
and cellular transduction signaling pathways of curcumin in managing oxidative-associated liver diseases.
