Early use of AHCC during hepatitis stages shows potential to reduce the risk of cirrhosis, according to new research
A recent report in Gastrointestinal and Liver Physiology presents the effect of a functional food called active hexose correlated compound (AHCC) on liver fibrosis.
What is AHCC?
A Japanese firm, Amino Up Co., Ltd., produces a standardized extract of the mycelia of the cultured mushroom Lentinula edodes. AHCC has shown the ability to increase dendritic cell numbers in the blood, enhance virus elimination, increase influenza antibody titers post-vaccination, and reduce cancer recurrences after liver tumor resection.
In the last case, its use was also associated with a reduction in cirrhosis odds compared to the group that did not take this agent. This prompted the current study, where AHCC was examined for its potential to prevent the progression of liver fibrosis by inhibiting hepatic stellate cell (HSC) activation.
About the study
The study used eight-week-old male mice who were injected intraperitoneally with carbon tetrachloride to induce liver fibrosis. They were also given 3% AHCC by mouth to examine its effect on the fibrotic process.
In vitro studies were also performed on activated HSCs to understand the expression profile of other molecules in relation to their activation.
Suppression of liver fibrosis with AHCC
AHCC ingestion reduced the elevation in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) following CCl4 injections, compared to the control group. Inflammatory cytokines were comparable in both groups, indicating the action of CCl4.
However, fibrosis markers like collagen1a, α smooth muscle actin (αSMA), and heat shock protein 47 (HSP47), were lower in the AHCC group vs controls. AHCC also prevented the upregulation of the genes encoding these protein products.
Suppression of HSC activation
Following AHCC administration, HSCs were not activated. Gene activation markers like ACTA2 (encoding αSMA), SERPINH1 (encoding HSP47), COL1A1 (encoding collagen1A), and COL1A2 were suppressed, with the corresponding suppression of collagen1a, α smooth muscle actin (αSMA), and HSP 47 expression.
Conversely, quiescence markers like CYGB and MMP1 were enhanced, and cytoglobin expression increased. CYGB encodes Cytoglobin and has been shown to inhibit fibrosis in multiple models.
The scientists then turned to uncovering the mechanism of action of AHCC.
Alterations in protein expression
AHCC action on HSC activation was twofold. One, it activated Toll-like receptor (TLR) 2 and enhanced the expression of the stress-activated protein kinase/Jun NH2-terminal kinase (SAPK/JNK) pathway. This induces cytoglobin expression during liver injury.
Cytoglobin prevents oxidative damage to nearby hepatocytes by inhibiting reactive oxygen species (ROS) production during liver injury. ROS are known to activate HSCs.
Secondly, AHCC inhibited the production of collagen1 α via the TLR4-NF-κβ pathway. AHCC also increases MMP1 expression, thus enhancing the degradation of already produced ECM collagen. This may contribute to AHCC’s preventive effect.
Other mechanisms
Prior research has reported that cytoglobin suppresses TGFβ expression. TGFβ is the primary cytokine in fibrosis, preventing MMP1 expression and increasing αSMA production. During hepatitis, it is primarily produced by the hepatocyte, which is, in turn, activated by it. Cytoglobin may thus act in this way to regulate fibrosis.
Additionally, AHCC is hepatoprotective and thus indirectly reduces HSC activator production by preventing hepatocyte damage.
Conclusion
The findings indicate that AHCC may prevent the progression of liver fibrosis by preventing HSC activation. Multiple mechanisms have been elucidated, suggesting that “Daily intake of AHCC from mild fibrotic stages may have the potential to prevent the progression of liver fibrosis.”
Further work is required to identify the effects of AHCC on the TLR receptors TLR2 and TLR4 in each of the liver cell types.
Conflict of interest
H. Urushima received a research grant from Amino Up Co., Ltd. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.
