EFFECTS OF KOLAVIRON AND THE BIFLAVANONES OF (garcinikola on acetic acid-incuced coltis in wistar rats)

Abstract

Ulcerative colitis, a chronic inflammatory bowel disease, is characterized by inflammation, ulceration and increased colonic production of reactive oxygen species. Agents with anti-inflammatory property may be administered to ameliorate the symptoms. Kolaviron, a complex biflavonoid from Garcinia kola seeds, is known to possesses anti inflammatory and free radical scavenging properties. Previous reports have shown that kolaviron possess anti-colitis effects, with little information on its mechanism of action. The study was designed to investigate the possible mechanisms of action of kolaviron and its constituents- Garcinia biflavonone-1 (GB1), Garcinia biflavonone-2 (GB2) and kolaflavanone, on acetic acid-induced colitis in wistar rats. Thirty male Wistar rats (160 -200g) were assigned to six groups of five rats each and treated as follows: Distilled Warier (DW) (0.5 mL100g). Kolaviron (100 mg/kg), GBI (100 mg/kg),GB2 (100 mg/kg) and Kolaflavanone (100 mg/kg). The sixth group served as normal control. After seven days of treatment, colitis was induced by intra-rectal administration of 7% acetic acid (1mL/200g) in it the rats except normal control and assessed 48-hours thereafter, based on symptoms of colitis such as weight loss and stool consistency using a diarrhoea store scale. Colonic lipid peroxidation, mycloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNF-a). Leukotriene B (LTB4), Prostaglandin E₂ (PGE₂) and Nitric Oxide (NO) were measured spectrophotometricarlly. Colonic total Protein (TP), Catalase (CAT), reduced glutathione (GSH) and Paraoxonase (PON) were measured using pathologically and scored microscopically. Data were analysed using descriptive statistics, ANOVA and Student t test at p⁼0.05. The diarrhoea scores in DW group (2.7±0.2) was significantly higher than the kolaviron (0.3±0.2) GBI (1.0±0.4) and GB2 (1.2±0.4) treated group. Kolaviron, GB1 and GB2 significantly reduced the weight loss. The gross (84.±4.2%) and microscopic (3.6±0.2) colonic damages assessed in Dwgroup were significaantly reduced by kolaviron (29.6±9.6%, 2.0±0.5), GB1 (16.8±11%, 1.5±0.5) and GB2 (16.4±3.5%, 1.3±0.6). Kolaflavanone showed no significant effect on diarrhoea, weight loss and tissue damage. Lipid peroxidaiion level in the kolaviron (40.1±11.6 nmol/mg), GB1 (20.8±2.4 nmol/mg), GB2 (24.4±1.1 nmol/mg) were significantly lower than the DW group (94.9±6..9 nmol/mg). When compared to DW group, levels of MPO, TNF-a and NO were reduced in the order GB2 > kolaviron >GB1 . The TP was significantly increased by GB I and GB2 while kolaflavanone showed insignificant effect on lipid peroxidation, TP, MPO and TNF-a. The LTB₄ and PGE₂ levels in DW group (154.5±17.4 and 630±27.7 pg/mL)were significantly higher than in kolaviron (85.3±15.9, 212.2±41.5 pg/ml). GB I (8.8±18.5), 274.3±77.7 pg/ml), GB2 (12.3±2.4, 49.8± 11.4 pg/mL) and kolaflavanone (25.9±I2.9, 62.9±20.5 pg/ml) groups. Histology showed that severe epithelial damage evidenced by destruction of crypt architecture and loss of goblet cells in DW group were completely absent in GB2 and minimal in kolaviron and GB1 groups. Kolavirori and its constituents inhibited the acetic acid-induced inflammatory responses in colitis via oxidative stress-dependent mechanism by suppression of mycloperoxidase, tumor necrosis factor-alpha, leukotriene B, prostaglandin E₂ and nitric Oxide. Garcinia biflavanones-1 and -2 appear to be active constituents of Garcinia kola responsible for its anti-colitis efrfects. Keywords: Acetic acid-induced colitis, Garcinia kola, Pro-inflammaiory mediators. Garciniaflavanones word count: 499