A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms.

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.

Hepatoprotective effect of pinostrobin against thioacetamide-induced liver cirrhosis in rats.

The study in vivo assessed the effect of pinostrobin on the histology, immunohistochemistry, and biochemical parameters of thioacetamide (TAA) induced liver cirrhosis in Sprague Dawley rats. The rats were noticeably gavaged with two doses of pinostrobin (30 mg/kg and 60 mg/kg) with TAA and exhibited a substantial decrease in the liver index and hepatocyte propagation with much minor cell injury. These groups meaningfully down-regulated the proliferation of cellular nucleus antigen (PCNA) and alpha-smooth muscle actin (α-SMA). The liver homogenate displayed augmented antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) activities escorted with reducing in malondialdehyde (MDA) level. The serum level of bilirubin, total protein, albumin, and liver enzymes (ALP, ALT, and AST) returned to normal and was similar to that of normal control and silymarin with TAA-treated groups. pinostrobin-fed groups also decreased the level of Tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and increased the level of Interleukin-10 (IL-10). Acute toxicity with a higher dose of 500 mg/kg of pinostrobin did not manifest any toxicological signs in rats. The hepatoprotective effect of pinostrobin could be due to potentially inhibited the progression of liver cirrhosis, down-regulation of PCNA and α-SMA proliferation, prevented oxidation of hepatocytes, improved SOD and CAT enzymes, condensed MDA, repairs of liver biomarkers, reduced cellular inflammation and modulation of inflammatory cytokines.

Effect of nano silver on gastroprotective activity against ethanol-induced stomach ulcer in rats.

Silver nanoparticles (Ag NPs) have unique properties and display an important role in bioactivities such as antimicrobial, antiviral, antifungal, and anticancer. Stable Ag NPs were prepared by reaction of silver nitrate solution with extract of Melissa and characterized by UV-Vis spectroscopy, AFM, SEM, XRD, and Zeta potential. The resulted Ag NPs have a size range between 20 and 35 nm. The current study aims to evaluate the gastroprotective effect of Ag NPs against ethanol-induced gastric ulcers in rats. Thirty rats were randomly divided into five groups. The experimental groups were fed 175 and 350 ppm/p.o of Ag NPs orally. Ag NPs improved the adversative influence of ethanol-induced stomach damage as confirmed by declining ulcer index and raised the percentage of ulcer prevention. Significantly reduced ethanol-induced gastric lesions were evidenced by increased mucus secretion and pH of stomach content, decreased ulcer area, nonappearance of edema, and leucocyte penetration of the subcutaneous layer. In gastric homogenate, Ag NPs displayed a substantial upsurge in superoxide dismutase (SOD), catalase (CAT) activities, and significantly reduced malondialdehyde (MDA) levels., Ag NPs increased the intensity of periodic acid Schiff stained (PAS) and produced over-regulation of HSP-70 and down-regulation of Bax proteins. Ag NPs confirmed gastro-protection which might be attributed to its antioxidant effect, increased mucus secretion, increased SOD, and CAT, reduced MDA level, over-regulation of HSP-70 protein, and down-regulation of Bax protein.

Hepatoprotective effects of methanolic extract of green tea against Thioacetamide-Induced liver injury in Sprague Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, herbal medicines have been applied in the treatment of cancer. Tea, derivative from the dried leaves of Camellia sinensis (L.) Kuntze plant is the most popular beverage globally after water and is available in various forms. Green tea has been expansively investigated for its beneficial properties of cancer prevention and therapy. The goal of the research: The current study was conducted to evaluate the hepaprotective character of methanolic green tea extract and its mechanism of action contrary to thioacetamide (TAA)-produced liver fibrosis of Sprague Dawley rats. MATERIALS AND METHODS: Thirty rodents were equally placed in 5 clusters including normal control, TAA group as a positive control, silymarin as standard drug control, and treatment groups consisting of high dose and a low dose Camellia sinensis. Rats in experimental clusters by mouth fed with C. sinensis at 250 mg/kg or 500 mg/kg daily for 2 months. After 60 days, all rats were sacrificed. Blood specimens were gathered for liver biochemical examination. Livers of all groups were dissected out and subjected to histopathological examination through the Hematoxylin and Eosin stain, Masson trichrome, and immunohistochemistry stains (PCNA). Liver tissue homogenate was also analyzed for antioxidant activity parameters. RESULTS: Gross morphological examination showed a regular liver architecture in C. sinensis fed collections compared to the TAA sets. Histology of rat's liver fed with C. sinensis showed an important decrease in the liver index with hepatic cells propagation, mild cellular injury, and immunostaining showed significant down-expression of proliferating cell nuclear antigen (PCNA). TAA produced liver fibrosis through a significant increase in serum alanine transferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Total protein and albumin also decreased in the TAA group. Moreover, the reduction of antioxidant enzyme activity including superoxide dismutase and catalase as well as the increase in malondialdehyde was detected in the TAA control group. Meanwhile, an abnormal level of liver biochemical parameters was restored closer to the normal levels in serum of the C. sinensis-fed clusters. In addition, C. sinensis fed assemblies showed elevated antioxidative enzymes activity with a reduction in malondialdehyde level comparable to the levels in silymarin-treated rats. CONCLUSIONS: Green tea potentially inhibited the progression of liver cirrhosis, down -regulation of PCNA proliferation, prevented oxidation of hepatocytes, recovered SOD and CAT enzymes, condensed MDA and reduced cellular inflammation.