Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Kolaviron is a mixture of bioflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-B and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assay, and reporter assay. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the proinflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IB/NF-B signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/ antioxidant response element (ARE) pathway. RNAi experiments revealed that Nrf2 is need for the anti-inflammatory effect of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders

Anti-ulcerogenic and proton pump (H⁺, K⁺ ATPase) inhibitory activity of <i style="">Kolaviron </i>from<i style=""> Garcinia kola</i> Heckel in rodents

461-468Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess&nbsp; anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 g/ml compared with omeprazole with IC50 of 32.3 g/ml. KV showed both cyto-protective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound

Ameliorative effects of Musa sapientum peel extract on acetic acid-induced colitis in rats

Ameliorative effects of Musa sapientum peel extract (MSPE) were studied on Acetic Acid (AA)-induced colitis in rats. From a dose response study, the effective and yet, safe for the treatment of AA-induced colitis in rats was determined, and also, a further study was carried out to determine the effective fraction(s) of MSPE that will be useful in the treatment of AA induced colitis in rats. Colitis was induced with 0.2 ml of 6% acetic acid through a lower abdominal laparotomy. Treatment with graded doses of methanolic extract of dried peel of Musa sapientum (MS) (50, 100 and 200 mg/kg) for 7 days in AA induced colitis in rats showed 50 mg/kg as an optimal effective dose for the healing of AA induced colitis in rats. This dose (50 mg/kg) was further studied with fractions of MSPE in comparison to a standard drug (sulfasalazine) of the same dose (50 mg/kg) on AA induced colitis in rats for 18 days. Colitis was assessed using stool consistency, macroscopic gross score and histological studies. Normal stool consistency was seen early in treated animals as compared with control; MS peel (crude extracts and fractions) significantly reduced macroscopic and histologic colon tissue damage in a manner similar to that of sulfasalazine. The results from these findings suggests that MSPE fractions of ethyl acetate and methanol may be effective in reducing both macroscopic and histological damage in a manner similar to sulfasalazine, and that it may be helpful in the treatment of colitis

Chronic intermittent oxygen deprivation alters hippocampal cholinergic and glutamatergic system via oxido-inflammatory burden and HIF-1a/Bcl-2 activity in hypothyroid mice: Ameliorative role of Ginkgo biloba supplement

Background: Several investigations in recent years have reported a relationship between hypothyroidism or ischemia and central nervous system (CNS) beginning from fetal to adult life, but the effect of ischemia and hypothyroidism comorbidity on CNS and whether phytotherapeutic approach would attenuate this pathology remains unknown. Thus, the study investigated the role of ginkgo biloba supplement (GBS), a potent anti-oxido-inflammatory and neurorestorative plant-based product on hypoxic stress-induced neurobehavioral and neurophysiological alterations in hypothyroid mice, and the underpinning molecular mechanisms Methodology: Mice were orally pre-treated with Carbimazole (1.2 mg/kg) for 14 days to develop hypothyroidism. Post-hypothyroid induction, mice were treated orally with GBS (20 mg/kg) and levothyroxine (10 µg/kg) 1 hr before 20 min exposure to hypoxia (5 times daily) for 14 consecutive days. Symptoms of behavioral deficit and neuropsychiatry were evaluated in using different models. Thereafter, brain hippocampi were sectioned for biochemical assays, immunohistochemistry and histoarchitectural studies. Results: Herein, treatment with GBS suppressed spatial memory deficit and neuropsychiatric phenotypes and attenuated hippocampal cholinergic excitotoxicity by enhancing acetylcholinesterase enzyme and glutamatergic release in the hypothyroid mice following hypoxic stress exposure. The hippocampal endogenous antioxidant system was also upregulated with concomitant downregulation of inflammatory mediators. GBS treatment consequently regulated the hypothalamic-pituitary-adrenal axis to reduce corticosterone release. Additionally, our data showed that the suppressive impact of GBS on oxido-inflammatory mainstream decreases immunoexpression of hypoxic inducible factor-1alpha (HIF-1α) and loss of hippocampal pyramidal neurons in the CA3 region with marked increase in viable neuronal cells and upregulated immunoexpression of B-cell lymphoma-2 (Bcl-2) anti-apoptotic marker. Conclusion: Herein, we deduced that prolonged intermittent exposure to hypoxia in hypothyroidism may provoke further the psychological and physiological status in the hippocampal brain region. Meanwhile, reversal of these provocative effects by the GBS treatment might be playing an important effect to suppress the hypoxic/ischemic triggered neurobehavioral and neurophysiological alterations