Modulation of IR as a therapeutic target to prevent NASH using NRF from Diceratella elliptica (DC.) jonsell. Strong Nrf2 and leptin inducer as well as NF-kB inhibitor.

BACKGROUND: Insulin resistance (IR) and lipotoxicity were evidenced as the major nonalcoholic steatohepatitis (NASH) initiators. However, absence of the effective treatment against NASH progression raised our aim to discover a new promising insulin modulator and NSH preventer. PURPOSE: Our study aimed to extract and prepare a nitriles rich fraction (NRF) from Diceratella elliptica (DC.) Jonsell, investigate its insulin-sensitizing & anti-NASH potentialities and address its molecular targets in IR-NASH pathogenesis. STUDY DESIGN: NRF was prepared using natural autolysis method and compounds were identified. Then, seventy male Wistar rats were feed high fat diet (HFD) or normal pellets for 35 days. In day 14th, HFD rats were injected by Streptozotocin (STZ) once and treatment was started in day 21st with either NRF (30, 60 and 120 mg/kg; orally) or pioglitazone (PioG) (10 mg/kg; i.p) beside HFD. While, NRF-alone rats were treated with NRF (120 mg/kg; orally) beside the normal pellets. Body weight, glucose homeostasis, hepatopathological examinations were performed. METHODS: Gas liquid chromatography-mass spectrophotometry (GLC/MS) was used for compounds' identification while spectrophotometer was used for total glucosinolates (GLS) quantification. Also, the biochemical and molecular investigations concerned with liver lipotoxicity, oxidative stress, inflammation and insulin signaling pathway were investigated and confirmed with the computational prediction of the major compounds' targets. RESULTS: Butenyl and benzyl GLS were the major along with other volatile compounds. NRF had significantly increased the insulin sensitivity and improved NASH-hisptopathology showing hepatoprotective effect. While, the fraction's anti-NASH potentiality was evidenced in the normalized hepatic steatosis markers, inflammation and oxidative stress key transcriptional factors resulting in induction of insulin receptor substrates (IRSs) phosphorylation and its downstream effectors. CONCLUSION: NRF has reversed IR, stimulated leptin secretion and prevented NASH initiation showing promising anti-NASH and anti-fibrotic effects.

Anti-fibrotic potential of a Matthiola arabica isothiocyanates rich fraction: impact on oxidative stress, inflammatory and fibrosis markers.

The present study is the first one to investigate the glucosinolates (GLS) profile and anti-fibrotic effect of isothiocyanates (ITCs) rich fraction of Matthiola arabica (Brassicaceae) using an experimental model of liver fibrosis in rats. Five GLS (ethyl glucosinolate, gluconapin, glucodehydroerucin, glucoerucin and glucoraphanin) were identified by gas liquid chromatography-mass spectrometric (GLC-MS) analysis of their hydrolysis products, produced by the natural autolysis and exogenous myrosinase hydrolysis using one and two units of the enzyme. Spectrophotometric determination of the total intact GLS revealed that content in the fresh sample was 1.8 times higher than in the dry one. ITCs rich fraction was prepared by natural autolysis of the fresh aerial part. Male albino rats were given carbon tetrachloride (CCl4) (0.5 ml/kg, twice a week) and/or ITCs -rich fraction (30 mg/ kg, three times a week) for six weeks. Liver function, different oxidative stress, inflammatory and fibrosis markers were investigated. Treatment of animals with ITCs rich fraction significantly counteracted the changes in liver function induced by CCl4. Histopathological examination under both light and electron microscope showed the anti-fibrotic effect of ITCs rich fraction. This finding was confirmed with the markedly improved liver fibrosis markers with ITCs rich fraction co-treatment. In elucidation of anti-fibrotic mechanisms of ITCs rich fraction, the significant glutathione depletion and lipid peroxidation caused by CCl4 intoxication was restored by ITCs rich fraction co-treatment. Besides, ITCs rich fraction showed an anti-inflammatory effect through its ability to counteract the significant increase in nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) expression, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in liver tissue that caused by CCl4 intoxication. These findings indicate that ITCs-rich fraction of M. arabica possesses a promising anti-fibrotic effect which can be attributed to its antioxidant and anti-inflammatory properties.

Production of glucosinolate hydrolysis products in Farsetia aegyptia suspension cultures following elicitation.

Levels of glucosinolates in Farsetia aegyptia var. ovalis suspension cultures were monitored after treatment with yeast extract, chitosan, methyl jasmonate, ampicillin, and Phytophthora infestans autoclaved mycelia as elicitors. Glucosinolates were identified, and an estimation of their levels obtained from their hydrolysis products. Yeast extract improved glucotropaeolin (benzyl-glucosinolate) and glucocheirolin [3-(methylsulfonyl)propyl-glucosinolate] accumulation, and production of sec-butyl, isobutylglucosinolate and gluconasturtiin (2-phenylethyl-glucosinolate) was only detected in yeast elicited cultures. Increases were shown in glucotropaeolin levels in cultures elicited using methyljasmonate, and chitosan and methyljasmonate in combination.

Verrucae treated by levamisole.

To assess the role of levamisole in treatment of different types of warts, a double-blind study was conducted on 40 patients with different types of warts. Patients were divided into two equal groups, A and B. Group A received levamisole 5 mg/kg body weight on 3 consecutive days every 2 weeks for a period up to 5 months, while patients of group B received placebo for the same period. In group A, 12 patients showed complete cure (60%), two showed partial cure (10%), and the remaining six patients showed no response (30%). In group B, complete cure was achieved only in one case. The higher cure rate was observed in plane and common warts, while plantar warts showed no improvement with levamisole treatment.