Neuronal Alterations and Antioxidant Status of Lipopolysaccharide Induced Neuronal damage in Mice: Eff icacy of Three Medicinal Plants

Background: Several factors including neuroinflammation and oxidative stress formation contribute to the progression and development of cognitive impairment. Lipopolysaccharide (LPS) injection has been used as non - transgenic mouse models for Alzheimer’s diseases (AD). Plant medicine has been proposed to be the prospect in treatment/ management of neurodegenerative disease. Aim: The present study sought to evaluate the effect of three medicinal plants ( Bacopa floribunda (R.Br)Wettst , Scoparia dulcis L and Cordia millenii Bak . ) locally used for memory enhancement on neuronal histology and antioxidant status against L ipopolysaccharide induced neuronal damage in mice . Methods: Forty - nine (49) BALB/c male mice were randomly grouped into seven (7) groups of 7 mice each. All animals except in group I control (vehicle), were injected intraperitoneally (I.P.) with LPS (250 μg/kg) once, after oral pre - treatment with plant extracts an d control drugs for 7 days. Group II (untreated) received LPS only (250 μg/kg) , group III received LPS + Sulindac Sulfide (SS, 4 mg/kg), group IV received LPS + Donepezil (DPZ, 1 mg/kg) group V, VI, and VII received LPS + 200 mg/kg of plant extracts [ Sco paria dulcis (SD), Bacopa floribunda (BF), and Cordia millenii (CM)] respectively. After the experiment, histological analysis of the hippocampus from the whole brain was carried out while the other brain tissue s comprising frontal cortex and cerebellum we re used for determination of biomarkers of antioxidant status such as catalase (CAT); superoxide dismutase (SOD); malondialdehyde (MDA) and reduced glutathione (GSH). Results: Oral administration of LPS induced neuronal damage through cell death as eviden ced by the histological analysis and altered brain antioxidant status in mice. However, the plant extracts were able to prevent such neuronal alterations and restored the antioxidant status when compared to the LPS induced neuronal damage in mice. Conclusi on: LPS induced neuroinflammation was prevented by the extracts of; B. floribunda, S. dulcis and C. millenni. Neural damage was also prevented by the extracts. This activity could be attributed to their antioxidant potential as evidenced from their inhibit ory effect on MDA and increased CAT activity and GSH. Nevertheless, other possible mechanisms of action against neuronal damage need to be assessed to further justify their use traditionally in the treatment/management of neurodegenerative disease

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

Original Article - ANALGESIC AND ANTI-INFLAMMATORY EFFECTS OF KOLAVIRON (A GARCINIA KOLA SEED EXTRACT)

Kolaviron is a defatted ethanol extract from the seeds of Garcinia Kola. In the present study, the analgesic and anti-inflammatory properties of Kolaviron is investigated using both thermal and chemical models of pain assessment in mice and rats. Varying doses of Kolaviron were given 30 minutes prior to the induction of abdominal constrictions in mice and the determination of the mean tail immersion duration at water bath temperature of 50.0 ± 10°C in mice. Kolaviron exhibited dose-related anti-nociceptive properties against acetic acid induced abdominal constrictions in mice: at 50mg/kg, it gave 28.92% inhibition (P > 0.05) and at 200mg/kg it gave 55.49% inhibition (P < 0.01). The compound also increased the mean tail immersion duration at water bath temperature of 50.0 ± 1°C in mice