The Potential Chemopreventive Effect of Andrographis paniculata on 1,2-Dimethylhydrazine and High-Fat-Diet-Induced Colorectal Cancer in Sprague Dawley Rats.

Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.

Mechanisms of Natural Extracts of Andrographis paniculata That Target Lipid-Dependent Cancer Pathways: A View from the Signaling Pathway.

Andrographis paniculata is a local medicinal plant that is widely cultivated in Malaysia. It is comprised of numerous bioactive compounds that can be isolated using water, ethanol or methanol. Among these compounds, andrographolide has been found to be the major compound and it exhibits varieties of pharmacological activities, including anti-cancer properties, particularly in the lipid-dependent cancer pathway. Lipids act as crucial membrane-building elements, fuel for energy-demanding activities, signaling molecules, and regulators of several cellular functions. Studies have shown that alterations in lipid composition assist cancer cells in changing microenvironments. Thus, compounds that target the lipid pathway might serve as potential anti-cancer therapeutic agents. The purpose of this review is to provide an overview of the medicinal chemistry and pharmacology of A. paniculata and its active compounds in terms of anti-cancer activity, primary mechanism of action, and cellular targets, particularly in the lipid-dependent cancer pathway.

Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats.

BACKGROUND: This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA. METHODS: The chloroform fraction of VA (200 mg/kg and 400 mg/kg body weight) was administered to SDRs for 7 and 14 days. Thereafter, the expression (transcription) of key carbohydrate regulatory genes was evaluated in selected tissues - adipose, muscle and liver. Also, the body weight and blood glucose changes were monitored. RESULTS: A 14-day administration of 200 mg and 400 mg of the extract and metformin (500 mg/kg) showed a striking decrease (P <0.05) in the expression of the gluconeogenic enzymes - fructose 1,6-bisphosphatase, phosphoenol pyruvate carboxykinase and glucose 6-phosphatase in the liver and muscle compared to the diabetic control. These genes were highly expressed in tissues of untreated diabetic rats (P <0.05) indicating severe gluconeogenesis. Furthermore, the extract as well as metformin significantly increased glucose oxidation via the pentose phosphate pathway (PPP) i.e. increased expression of the glucose 6-phosphate dehydrogenase (G6PDH) gene (P <0.05) in the liver. Conversely, the expression of the G6PDH in the muscle and adipose tissues significantly decreased (P <0.05), suggesting enhanced utilization of NADPH and ribose in the clearance of reactive oxygen species and for expression of other relevant genes respectively. Also, transcription of the cell proliferation regulatory enzyme, phosphatidylinositol 3-kinase increased in the liver, but decreased in the muscle and adipose tissues (P <0.05) upon treatment with the extract or metformin, implying that the liver responded to the VA and metformin treatments more than other organs. The extract administration also caused a decrease in the expression of key enzymes of glycolysis namely hexokinase and phosphofructokinase, suggestive of a glucose sparing for ribose and NADPH production in PPP. CONCLUSION: Overall, data obtained in this study suggest that VA exerts little or no effect on glycolysis; rather, it may achieve its anti-diabetic action by a simultaneous suppression of gluconeogenesis and potentiation of glucose oxidation via PPP pathway, almost exclusively in the liver.

Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines.

Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 µg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.