HYPOTHESIS/PURPOSE: We hypothesized that LPva extracts can modulate the lipid profiles and serum antioxidant status of hypercholesterolemic rats. In the present study, we investigated the effects of aqueous and 80% ethanol extracts of LPva on atherogenic and serum antioxidant parameters as well as changes in abdominal aorta of high-cholesterol diet rats.
METHODS: The major components of the extracts, gallic acid, flavonoids and alkyl resorcinols were analyzed by using a validated reversed phase HPLC method. The rats were induced to hypercholesterolemic status with daily intake of 2% cholesterol for a duration of 8 weeks. Three different doses (100, 200 and 400mg/kg) of the extracts were administered daily on the 4th week onwards. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugation for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination.
RESULTS: The serum of LPva treated rats showed significant reduction in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels and the abdominal aorta showed a significant decrease of atheroma lesions in treated rats. Serum lipid profiles of treated rats showed a decrease in total cholesterol, total triglycerides and low-density lipoprotein (LDL) levels as compared to control group. The atherogenic indices in treated rats were significantly improved along with an increasing level of serum high-density lipoprotein (HDL). The extracts also exhibited significant increase of antioxidant enzymes and decrease of MDA as a product of lipid peroxidation.
CONCLUSION: LPva extracts can reduce the risk of dyslipidemia by improving the serum lipid profiles and modulating serum antioxidants.
METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.
RESULTS: Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p
METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.
RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P
METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba.
RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways.
CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.
MATERIALS AND METHODS: A total of 30 CF-1 albino mice obtained from the animal house of faculty of Medicine, Benghazi University, Benghazi, Libya were included in the study. These mice were fed with high cholesterol diet and divided into 2 groups. Twenty mice were administered piperine at a dose of 5mg/kg body weight. Piperine was isolated in Department of Pharmacognosy, Faculty of Pharmacy, Benghazi University, Benghazi and 10 mice were not administered piperine but fed with high fat diet. These mice were anesthetized with ketamine and halothane and blood was drawn from each mouse before the study and after three weeks by cardiocentesis. Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase and total protein were measured by authenticated methods.
RESULTS: Serum alanine amino transferase was significantly elevated (p=0.0002) in group A mice after the administration of Piperine extract for three weeks compared to those of group B mice. Serum aspartate amino transferase was elevated significantly (p=0.046) and alkaline phosphatase (p= 0.0001) also was significantly increased after the administration of piperine. Serum total protein (p= 0.011) values were significantly decreased after the use of piperine for three weeks in group A mice.
CONCLUSION: This study showed that there might have been a considerable damage to liver with piperine extract. Further research may be required to prove this damage to liver function.