DHA-rich fish oil and Tualang honey reduce chronic stress-induced oxidative damage in the brain of rat model.

Background: Exposure to chronic stress induces oxidative damage which alters the dynamic balance between antioxidant and pro-oxidant activities in the brain. Tualang honey (TH) is a Malaysian wild multifloral honey which has been shown to contain high amount antioxidants. DHA-rich fish oil is a form of omega-3 fatty acids found in fish which also possesses some antioxidant activity. This study aimed to evaluate anti-stress activity of DHA-rich fish oil, TH and their combination on several parameters of oxidative stress in chronic stress rat model. Methods: Fifty male Sprague Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stress-exposed and treated with TH (1 g/kg body weight twice daily), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. Results: DHA-rich fish oil and TH significantly (p < 0.05) supressed stress-induced elevation of serum corticosterone and lipid peroxidation, and caused a significant increase in total antioxidant capacity. For glutathione status, only TH significantly reduced stress-induced elevation of oxidised glutathione (GSSG) and normalised GSH/GSSG ratio. Conclusion: Both DHA-rich fish oil and TH have protective effects against brain oxidative stress but consuming these substances together does not seem to provide an additional benefit compared to consuming them separately.

Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after Kainic Acid-Induced Status Epilepticus.

The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1ß, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.

Effect of tualang honey against KA-induced oxidative stress and neurodegeneration in the cortex of rats.

BACKGROUND: Administration of KA on rodents has resulted in seizures, behavioral changes, oxidative stress, and neuronal degeneration on selective population of neurons in the brain. The present study was undertaken to investigate the extent of neuroprotective effect conferred by Malaysian Tualang Honey (TH), an antioxidant agent, in the cerebral cortex of rats against KA-induced oxidative stress and neurodegeneration in an animal model of KA-induced excitotoxicity. METHODS: Male Sprague-Dawley rats were randomly divided into five groups: Control, KA-treated group, TH + KA-treated group, aspirin (ASP; anti-inflammatory agent) + KA-treated group and topiramate (TPM; antiepileptic agent) + KA-treated group. The animals were pretreated orally with drinking water, TH (1.0g/kg BW), ASP (7.5mg/kg BW) or TPM (40mg/kg BW), respectively, five times at 12 h intervals. KA (15mg/kg BW) was injected subcutaneously 30 min after last treatment to all groups except the control group (normal saline). Behavioral change was observed using an open field test (OFT) to assess the locomotor activity of the animals. Animals were sacrificed after 2 h, 24 h and 48 h of KA administration. RESULTS: KA significantly inflicted more neuronal degeneration in the piriform cortex and heightened the predilection to seizures as compared with the control animals. Pretreatment with TH reduced the KA-induced neuronal degeneration in the piriform cortex but failed to prevent the occurrence of KA-induced seizures. In the OFT, KA-induced animals showed an increased in locomotor activity and hyperactivity and these were attenuated by TH pretreatment. Furthermore, TH pretreatment significantly attenuated an increase of thiobarbituric acid reactive substances level and a decrease of total antioxidant status level enhanced by KA in the cerebral cortex. CONCLUSION: These results suggest that pretreatment with TH has a therapeutic potential against KA-induced oxidative stress and neurodegeneration through its antioxidant effect.

Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts.

Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

Exposure to chronic restraint stress has been shown to cause a number of morphological changes in the hippocampal formation of rats. Tocotrienol, an isoform of vitamin E, exhibits numerous health benefits, different from those of tocopherol. Recent studies have demonstrated that tocotrienol prevents stress-induced changes in the gastric mucosa, thus indicating that it may also protect other organs such as the brain from the damaging effects of stress. Therefore, the aim of the present study was to investigate the protective effect of tocotrienol-rich fraction (TRF) extracted from palm oil on the dentate gyrus of rats following exposure to chronic restraint stress. Thirty-six male Sprague Dawley rats were divided into four groups: control, stress, tocotrienol and combination of stress and tocotrienol. Animals were stressed by restraining them for 5 hours every day for 21 consecutive days. TRF was administered via oral gavage at a dose of 200 mg/kg body weight. Our results showed that the plasma corticosterone level was significantly increased in response to stress, compared to the control. The results confirmed previous findings that chronic restraint stress suppresses cellular proliferation and reduces granule cell number in the dentate gyrus. However, TRF supplementation failed to prevent or minimize these stress-induced changes. Therefore, we conclude that TRF at the current dosage is not effective in preventing the morphological changes in the dentate gyrus induced by chronic restraint stress.

A exposição crônica ao estresse por restrição causa série de alterações morfológicas na formação do hipocampo de ratos. Tocotrienol, uma isoforma da vitamina E, apresenta inúmeros benefícios para a saúde, diferente do tocoferol. Estudos recentes demonstraram que o tocotrienol impediu alterações induzidas por estresse na mucosa gástrica, indicando, assim, a possibilidade de que ele pode, também, proteger outros órgãos, como o cérebro, dos efeitos nocivos do estresse. Dessa forma, o objetivo do presente estudo foi investigar o efeito protetor da fração rica em tocotrienol (TRF), extraída do óleo de palma, no giro denteado após exposição crônica ao estresse por restrição. Trinta e seis ratos machos Sprague Dawley foram divididos em quatro grupos: controle, estresse, tocotrienol e combinação de estresse e tocotrienol. Os animais foram estressados por restrição, 5 horas por dia, durante 21 dias consecutivos. TRF foi administrado por gavagem oral na dose de 200 mg/kg de peso corporal. Nossos resultados mostraram que o nível de corticosterona plasmática foi significativamente aumentado em resposta ao estresse em comparação ao controle. Os resultados confirmam os achados anteriores de que o estresse por restrição suprime a proliferação celular e reduz o número de células granulares do giro denteado. No entanto, a suplementação de TRF foi ineficaz para evitar ou minimizar as alterações induzidas por estresse. Assim, concluímos que TRF na dose corrente não é efetiva para prevenir as alterações morfológicas no giro denteado induzida por estresse crônico por restrição.