title: Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure.
abstract: Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance, oxidative stress, and cytokine imbalance. Boswellic acids, a series of pentacyclic triterpene molecules that are produced by plants in the genus Boswellia, has been traditionally used for the treatment of a variety of diseases. This study aimed at evaluating the protective effect of boswellic acids in a model of diet-induced NAFLD in rats in comparison to the standard insulin sensitizer, pioglitazone. Rats were fed with a high-fat diet (HFD) for 12 weeks to induce NAFLD. Starting from week 5, rats received boswellic acids (125 or 250 mg/kg) or pioglitazone parallel to the HFD. Feeding with HFD induced hepatic steatosis and inflammation in rats. In addition, liver index, insulin resistance index, activities of liver enzymes, and serum lipids deviated from normal. Further, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase 2 were elevated; this was associated with an increase in hepatic expression of inducible nitric oxide synthase (iNOS) and formation of 4-hydroxy-2-nonenal (HNE). Rats treated with boswellic acids (125 or 250 mg/kg) or pioglitazone showed improved insulin sensitivity and a reduction in liver index, activities of liver enzymes, serum TNF-α and IL-6 as well as hepatic iNOS expression and HNE formation compared to HFD group. Furthermore, at the cellular level, boswellic acids (250 mg/kg) ameliorated the expression of thermogenesis-related mitochondrial uncoupling protein-1 and carnitine palmitoyl transferase-1 in white adipose tissues. Data from this study indicated that boswellic acids might be a promising therapy in the clinical management of NAFLD if appropriate safety and efficacy data are available.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.forename: Bassant M
authors.initials: BM
authors.lastname: Barakat
authors.forename: Shymaa E
authors.initials: SE
authors.lastname: Bilasy
authors.forename: Manal S
authors.initials: MS
authors.lastname: Fawzy
authors.forename: Eman Z
authors.initials: EZ
authors.lastname: Abdelaziz
authors.forename: Noha E
authors.initials: NE
authors.lastname: Farag
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2 / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D007473:Ion Channels / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077205:Pioglitazone; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000071256:Uncoupling Protein 1
chemical_list: D000447:Aldehydes; D015850:Interleukin-6; D007473:Ion Channels; D024101:Mitochondrial Proteins; D020011:Protective Agents; D045162:Thiazolidinediones; D014280:Triglycerides; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C462359:tert-4-hydroxy-2-nonenal; C054625:boswellic acid; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D002334:Carnitine O-Palmitoyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000077205:Pioglitazone