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has been used as a folk remedy to treat several illnesses including
gastrointestinal disorders. However, its effects on intestinal inflammation and colorectal cancer (CRC) have not been clearly
We investigated the effects of an aqueous extract of Inonotus obliquus (IOAE) on HCT116 and DLD1 cells and in
three mice models, DSS-induce experimental colitis, AOM/DSS-induced colitis associated colon cancer (CACC) and adenoma
Cell cytotoxicity was assessed by MTT assay. Apoptosis induction and cell cycle arrest was analyzed by flow cytometry.
Immunohistochemical analysis of intestinal tissues was performed for inflammation scoring and expression of proteins.
Cytoplasmic and nuclear protein lysates were isolated for western blotting. Total RNA was isolated and reverse-transcribed to
cDNA for PCR amplification of inflammation related genes.
HCT116 and DLD1 cell lines:
IOAE suppressed cell proliferation by inducing mitochondrial intrinsic apoptosis,
autophagy, and S phase cell cycle arrest. IOAE suppressed
-catenin and its downstream targets cyclin D1 and c-Myc along with
CRC oncogene CDK8. IOAE also inhibited the nuclear and cytoplasmic levels of NF-κB.
DSS-induced colitis mice: IOAE ameliorates colonic inflammation by suppressing iNOS and Cox-2 and myeloperoxidase
accumulation. IOAE inhibited the mRNA expression of inflammation mediators (TNF-
, IL-6, IFN-
and iNOS) in colon.
induced CACC mice
: IOAE suppressed the number of colorectal tumor. IOAE diminished the expressions of iNOS,
Cox-2, Cyclin D1 and c-Myc, and dramatically inhibited the mRNA expression of pro-inflammatory cytokines in colon. These
results indicate potent anti-inflammatory and anti-proliferative effects of IOAE in CACC model of mice.
IOAE suppressed polyp formation in small intestine. IOAE inhibited the levels of
-catenin along with cyclin
D1, c-Myc and CDK8. IOAE triggered caspase-3 activation and PARP cleavage in intestinal tissues. IOAE inhibited the mRNA
expression of inflammation mediators also.
IOAE suppressed colorectal carcinoma in vitro and in vivo through anti-inflammation and downregulation of
-catenin/NF-κB pathway. Considering recent anticancer approaches involving natural products with least side effects, we
advocate that Chaga could be a beneficial supplement in prevention of colorectal cancer.
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