Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT

Abstract

Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon. Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis. Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner. The knockdown of heme oxygenase-1 partially reversed the curcumin-inhibited HCV protein expression. In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin. Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication. Inhibition of ERK and NF-κB was likely to promote HCV protein expression. In summary, curcumin inhibited HCV replication by heme oxygenase-1 induction and AKT pathway inhibition. Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression. This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy.

Grape Seed Extract Attenuates Hepatitis C Virus Replication and Virus-Induced Inflammation

“…In addition, many natural products show significant cytoprotective effects in various diseases as well as that GSE have been studied and showed significant effects in many disease, including cancer, inflammation, and even infectious diseases. Comparable with present study, there are several compounds which have significant antioxidant activity against HCV infection, such as curcumin, silymarin, silibinin, and epigallocatechin-3-gallate (EGCG) (Chen C. et al, 2012; Chen M.H. et al, 2012; Polyak et al, 2013).…”

Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection

“…In human cells, HO1 can inhibit the replication of viruses such as HIV (40), Ebola (59) and HCV (60). However, a direct role for HO1 in human macrophages infected with Mtb infection has not previously been established.…”

Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells

“…Viral entry into both hepatoma cell lines as well as PHHs was inhibited by the presence of the compound without affecting the viability of the cells. Using reporter replicon, it has been reported that curcumin can inhibit HCV subgenomic RNA replication 38 39. However, the activity of the reporter gene was inhibited by only 50% at 15 µM, and RNA levels reduced to only ∼55% at 20 µM.…”