METHODS AND RESULTS: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels.
CONCLUSION: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.
AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.
MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.
RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.
CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats.
MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon.
RESULTS: APME or APAE pretreatment significantly (p
AIM: The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats.
MATERIALS AND METHODS: The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue.
RESULTS: Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties.
CONCLUSION: Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent.