Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats.

OBJECTIVES: Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. METHODS: Ninety male Wistar rats (80-100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. RESULTS: Higher percentage of CAD significantly (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu Ammonis 3 (CA3) region. CONCLUSIONS: The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.

Exposure to prolonged unpredictable light impairs spatial memory via induction of oxidative stress and tumor necrosis factor-alpha in rats.

OBJECTIVES: The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats. METHODS: Artificial lighting was provided using an array of white light-emitting diodes coupled to a microcontroller that switches them on or off at unpredictable times and duration (light intensity = 200 ± 20 lx). Within the last eight days of 40 days exposure, animals were subjected to open field test, Morris water maze, and novel object recognition behavioral paradigms. Brain levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione S-transferase (GST), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were assayed. RESULTS: Exposed rats showed impaired spatial learning and memory (p<0.05), but no changes in object recognition memory or locomotor activity. Oxidative stress analyses also revealed significant changes in the concentrations of MDA, SOD, catalase, and GSH levels (p<0.05), not GST. Similarly, there was an increased TNF-α expression (p<0.05), not VEGF. CONCLUSIONS: We conclude that oxidative stress is involved in memory impairment in rats exposed to prolonged unpredictable lights, which again suggests the detrimental effects of extended light exposure on the nervous system.

Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats.

OBJECTIVES: Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. METHODS: Ninety male Wistar rats (80-100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. RESULTS: Higher percentage of CAD significantly (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu Ammonis 3 (CA3) region. CONCLUSIONS: The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.

Flavonoid-Rich Fraction of Ocimum gratissimum Attenuates Lipopolysaccharide-Induced Sickness Behavior, Inflammatory and Oxidative Stress in Mice.

PURPOSE: Ocimum gratissimum L. leaves has been traditionally used for management of febrile illnesses and symptoms typified of sickness behavior. In this work we investigated the modulatory effect of flavonoid-rich fraction of O. gratissimum leaves (EAFOg) on sickness behavior, inflammatory and oxidative stress responses in LPS-challenged mice. METHOD: O. gratissimum leaf was first extracted with n-hexane, chloroform and methanol, and EAFOg was obtained by ethylacetate partitioning of a sequentially resultant methanol extract. The effect of EAFOg (25-100 mg/kg) on acute LPS-induced neurobehavioral impairment in an open field test (OFT) and depressive-like behavior in forced swimming test (FST) was investigated. Serum nitrite and TNF-α, as well as myeloperoxidase (MPO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in liver and brain tissues. RESULT: EAFOg prevented the reduction in locomotor and rearing activity in OFT and the increase in immobility time in FST. The fraction significantly attenuated the elevation of serum TNF- α and nitrite levels. EAFOg reversed LPS-induced increase in MDA, MPO, and nitrite levels and attenuated GSH depletion in liver and brain tissues of mice. CONCLUSION: Flavonoid-rich fraction of O. gratissimum leaf demonstrated significant modulation of LPS-induced sickness behavior, inflammatory and oxidative stress response in mice. This suggests an important therapeutic strategy in slowing down LPS-mediated hepatic and neuronal disease processes.

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

Kolaviron is a mixture of biflavonoids 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-κB and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assays and reporter assays. 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 pro-inflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IκB/NF-κB signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/antioxidant response element pathway. RNAi experiments revealed that Nrf2 is needed for the anti-inflammatory effects 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.

Antinociceptive and anti-inflammatory potentials of kolaviron: mechanisms of action.

BACKGROUND: Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron. METHODS: The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation. RESULTS: In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron groups. The result of the study also shows a highly significant inhibition of paw edema in the carrageenan-induced receiving kolaviron when compared with the vehicle carrageenan-induced groups. Histological staining also showed that kolaviron significantly reduced the infiltration of inflammatory cells in the paw tissues. CONCLUSIONS: Kolaviron possesses antinociceptive and anti-inflammatory activity, both centrally and peripherally, which justifies its folkloric use to relieve pain and inflammation. It may be exerting its effects through mechanisms that involve opioidergic and adrenergic systems, and may not involve the cholinergic system.

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents.

Anti-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 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 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound.

Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice.

BACKGROUND: Ethanolic leaf extract of Cnidoscolus aconitifolius was evaluated for analgesic and anti-inflammatory activities. METHODS: The analgesic activity of the extract was assayed by the formalin-induced paw licking test, acetic acid-induced abdominal writhing and hot plate test, whereas its anti-inflammatory activity was determined by its effects on carrageenan-induced paw edema. RESULTS: The extract of C. aconitifolius prolonged the reaction time of mice to pain in a dose-dependent manner. The optimal analgesic effect of the extract was obtained when the extract was administered 90 min before pain stimulation in the hot plate test. The extract of C. aconitifolius (100 or 200 mg/kg b.w.) inhibited acetic acid-induced irritation of paws of rats comparably with that of indomethacin (10 mg/kg b.w.) and had significantly lower mean number of lickings of paws than the control rats (p<0.05). Carrageenan-induced edema was markedly inhibited (p<0.05) by the extracts (100 and 200 mg/kg b.w.) when compared with control rats. Inhibition of writhing movement in rats administered with the extract was lower (p<0.05) than rats administered with indomethacin but its effect was dose-dependent. CONCLUSIONS: Our investigations show that C. aconitifolius possesses significant anti-inflammatory and analgesic activities that should be explored.

Anti-ulcer & antioxidant activities of Hedranthera barteri {(Hook F.) Pichon} with possible involvement of H+, K+ ATPase inhibitory activity.

BACKGROUND & OBJECTIVE: Hedranthera barteri (HB) is used in folk medicine as a vermifuge, laxative and an anti-inflammatory agent. The aim of this study was to evaluate the anti-ulcer and antioxidant properties of the dichloromethane fraction of HB root (DMHBR). METHODS: Anti-ulcerogenic activity was assessed in cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models in rats and histamine-induced duodenal ulcer (HST) in guinea pigs. The effect of DMHBR (100 mg/kg) on gastric juice for free and total acidity, peptic activity and mucin secretion, using the pylorus ligated model, were evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. The in vitro anti-oxidant assays were explored through DPPH, nitric oxide, hydroxyl radical, superoxide anion scavenging assays. RESULTS: DMHBR reduced the incidence of ulcers in CRU (63.3%), PL (58.5%), ASP (52.7%), HST (75.0%) and AL (53.87%). Also, reductions were observed in the free acidity (49.4%), total acidity (45.8%) and peptic activity (32.9%) with increase in the mucin secretion by 81.6 per cent. DMHBR (60-100 µg/ml) inhibited the H+,K+-ATPase activity with IC50 of 89.64 µg/ml compared with omeprazole (10-50 µg/ml ) with IC50 of 32.26 µg/ml. DMHBR showed antioxidant activity with IC50 values of DPPH (397.69 µg/ml), nitric oxide (475.88 µg/ml), hydroxyl radical (244.22 µg/ml) and superoxide anion radical (285.20 µg/ml). INTERPRETATION & CONCLUSION: DMHBR showed anti-ulcer activity against experimentally-induced peptic ulcer models and exhibited both cytoprotective and anti-secretory property. It exhibited a proton pump inhibition activity and its anti-ulcer properties may be partly ascribed to its antioxidant activities.

Analgesic and anti-inflammatory effects of aqueous extract of Zea mays husk in male Wistar rats.

The analgesic and anti-inflammatory activities of Zea mays husk extract (25, 50, 100, and 200 mg/kg of body weight) were investigated in rats. The hot plate and formalin-induced paw licking models were used to assess analgesic effects of the extract, whereas the carrageenan and cotton pellet models were used for the evaluation of anti-inflammatory activity. The extract at 25, 50, 100, and 200 mg/kg body weight significantly (P < .05) reduced pain stimuli and inflammatory activity when compared with the control group. The reductions in paw licking time and granuloma weight in the formalin and cotton pellet models were both dose dependent. Also, the 200 mg/kg doses of the extract produced higher effects compared with indomethacin (5 mg/kg body of weight) in all the tests. These observations suggest that Z. mays husk extract may have analgesic and anti-inflammatory effects that may be due to its tannins and polyphenolic constituents. These results provide scientific validation for the use of Z. mays husk decoction for the treatment of pain and inflammatory conditions in Nigerian folk medicine.