Supplementary MaterialsImage_1. for 14 and 28 times before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor- (TNF-), interleukin (IL)-1, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg Agnuside for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly ( 0.05) decreased the release of proteins like TNF-, IL-1, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin Rabbit polyclonal to Vang-like protein 1 immunoreactivity were also reduced as compared with those in the LPS-challenged group. Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to recognize the bioactive phytochemicals and the complete underlying systems. Schumah & Thonn. (PA) is one of the Euphorbiaceae family members and is typically useful for kidney health conditions, diabetes, discomfort, jaundice, gonorrhea, chronic dysentery, pores and skin ulcer, and hepatitis B. Lately, the vegetable has received raising attention and continues to be studied for different pharmacological properties such as for example immunomodulatory, antinociceptive, anti-inflammatory, antioxidant, antibacterial, anticancer, antiulcer, gastroprotective, antifungal, antiplasmodic, antiviral, aphrodisiac, contraceptive, hepatoprotective, antihyperglycemic, antilipidemic, nephroprotective, and anti-amnesic actions (Parle and Joshi, 2007; Patel et al., 2011). Though it demonstrates a broad spectral range of pharmacological activities, the unifying top features of each one of these actions are directed on the antioxidant and anti-inflammatory properties from the plant. PA contains different phytoconstituents such as for example Agnuside lignans, alkaloids, phenolics, terpenes, tannins, flavonoids, sterols, and volatile natural oils (Patel et al., 2011). Of most these phytochemicals, phyllanthin, hypophyllanthin, corilagin, and geraniin are located by the bucket load and potentially in charge of the reported anti-inflammatory activities of PA (Patel et al., 2011; Jantan et al., 2014). A lot of the anti-inflammatory research had been performed in types of inflammation either or at doses of 100 to 500 mg/kg for 14 days revealed nontoxic effect with no abnormalities in general behavior and physiology of rats (Ilangkovan et al., 2015). Additionally, a single or daily repeated doses administration of Agnuside PA for 28 days revealed no morphological changes in histopathological observation of the kidney, liver, and pancreas (Lawson-Evi et al., 2008; Kushwaha et al., 2013). Lack of study for assessment of neurotoxicity of PA has led us to examine the effects of this plant extract on neurobehavior and brain histopathological changes in rats. Although the anti-inflammatory activities of PA have been documented (Ilangkovan et al., 2015; Harikrishnan et al., 2018), there is a lack of evidence to substantiate similar effects in the CNS. Treatment with PA extract and phyllanthin was found to improve memory impairment and exhibited anticholinesterase activity in young and older mice (Joshi and Parle, 2006; Joshi and Parle, 2007). These are important early findings that demonstrated the plant activity in the brain suggestive of its potential value in the prevention and treatment of neurodegenerative diseases. Similarly, other species such as (Ambali et al., 2012) and (Ashwlayan and Singh, 2011) have also been reported to reverse memory deficits induced by scopolamine, sodium nitrite, or chlorpyrifos in different animal models of cognitive behavior, which further support a notion of their neuroprotective role. Therefore, the present study sought to examine the neuroprotective effects of PA extract as compared with IBF, a widely studied nonsteroidal anti-inflammatory drug, for its neuroprotective effects against LPS-induced memory impairment and inflammation in rodents. Materials and Methods Animals Adult male Wistar rats weighing 190C200 g (5 weeks old) were obtained from the Laboratory Animal Resource Unit (LARU), Universiti Kebangsaan Malaysia (UKM), Malaysia. The rats were housed in a temperature-controlled room (22C25C) and exposed to 12 h dark/light cycles. Experiments were carried out on the basis of procedures approved by UKM Animal Ethics Committee. Animals were allowed to acclimatize for 7?days before the initiation of treatment. The animal laboratory was maintained under standard conditions. The studies were performed according to procedures for the usage of pets in study as authorized by the UKM Pet Ethics Committee using the approval quantity FF/2017/NORAZRINA/24-Might/850-JUNE-2017-JULY-2018 for the toxicity.