Mercury chloride causes cognitive impairment, oxidative stress and neuroinflammation in male Wistar rats: The potential protective effect of 6-gingerol-rich fraction of Zingiber officinale via regulation of antioxidant defence system and reversal of pro-inflammatory markers increase.

This study investigated the effects of 6-gingerol-rich fraction of Zingiber officinale (6-GIRIFZO) on mercury chloride (HgCl2)-induced neurotoxicity in Wistar rats. Thirty -five male Wistar rats weighing between (150-200 g) were divided randomly into five groups (n = 7): group 1: control, received 0.5 mL of normal saline, group 2: received HgCl2 (5 mg/kg), group 3: received N-acetylcysteine (NAC) (50 mg/kg) as well as HgCl2 (5 mg/kg), group 4: received 6-GIRIFZO (100 mg/kg) and HgCl2 (5 mg/kg), group 5: had 6-GIRIFZO (200 mg/kg) and HgCl2 (5 mg/kg), consecutively for 14 days. On the day14, the rats were subjected to behavioural tests using a Morris water maze and novel object recognition tests. The rats were then euthanized to obtain brain samples for the determination of biochemical parameters (acetylcholinesterase (AchE), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione (GSH), tumor necrosis factor- alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6)) using standard methods. The result revealed a significant increase in escape latency and a significant decrease in recognition ratio in the rats that were exposed to HgCl2 only. However, 6-GIRIFZO produced a significant reduction in the escape latency and (p < 0.05) increase in the recognition ratio. Similarly, HgCl2 exposure caused a significant (p < 0.05) decrease in the brain SOD, GPx, CAT, GSH with increased brain levels of MDA, NO, AchE, TNF-α, NF-κB, IL-1ß and IL-6. Similarly to the standard drug, NAC, 6-GIRIFZO (100 and 200 mg/kg) significantly (p < 0.05) increased brain SOD, GPx, CAT, and GSH levels with decreased concentrations of MDA, NO, AchE, TNF-α, NF-κB, IL-1ß and IL-6. Also, pre-treatment with 6-GIRIFZO prevented the HgCl2-induced morphological aberrations in the rats. This study concludes that 6-GIRIFZO prevents HgCl2-induced cognitive deficit via reduction of brain inflammation as well as oxidative stress in rats.

Synergistic Action of Virgin Coconut Oil and Clomiphene in Reversing Endocrine Dysregulation in Letrozole-Model of Polycystic Ovarian Syndrome in Rats: Role of Nrf2/HMOX-1 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder in women's reproductive age. Currently, the pathophysiology of PCOS is unclear, and the limited treatment options are unsatisfactory. Virgin coconut oil (VCO) is functional food oil associated with pharmacological effects in reproductive disorders. Therefore, we aimed to evaluate whether VCO could enhance clomiphene (CLO) therapy against PCOS in female rats. Rats were randomly divided: (1) Control, (2) PCOS model, (3) PCOS + CLO, (4) PCOS + VCO, and (5) PCOS + CLO + VCO. The PCOS was induced via daily letrozole (1 mg/kg, orally) administration for 21 days. After the PCOS induction, CLO, VCO, and CLO + VCO were administered from days 22 to 36. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estrogen, progesterone, and prolactin were estimated. Polymerase chain reaction gene expression for nuclear factor-erythroid-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), catalase (CAT), glutathione reductase (GSR), LH receptor (LHr), androgen receptor (AR), tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and caspase-3 were analyzed. The letrozole-induced PCOS caused considerable increases in GnRH, LH, prolactin, estrogen, and testosterone, whereas FSH decreased significantly compared to the control. The gene expression of Nrf2, HO-1, CAT, and GSR were markedly diminished, while IL-1ß, TNF-α, caspase-3, AR, and LHr prominently increased compared to control. Interestingly, the CLO and VCO separately exerted anti-inflammatory and endocrine balance effects. However, VCO-enhanced CLO effect in LH, prolactin and testosterone, Nrf2, HO-1, CAT, GSR, and AR. VCO may synergize with CLO to depress hyperandrogenism and oxidative inflammation in PCOS.

Neuroprotective Effects of Virgin Coconut Oil Supplemented Diet against Sodium Benzoate-induced Acetylcholinesterase Dysfunction and Cognitive Impairment: Role of Nrf2/NfKb Signaling Pathway.

The effect of virgin coconut oil (VCO) supplemented diet on sodium benzoate (SB) - induced neurotoxicity in male Wistar rats was investigated. Twenty (20) male Wistar rats weighing 160-180g were divided into four (4) groups: Control which received 1ml of normal saline, SB-treated; received 200 mg/kg b.w, SB + Low Dose VCO-treated (SB + 5% VCO mixed with 95g of rat chow), and SB + High Dose VCO-treated (SB+ 15% VCO mixed with 85g of rat chow). The brain was processed for NRF-2, NF-kB, and acetylcholine esterase (AchE) gene expression levels. Also, the blood sample was processed for assessment of superoxide dismutase (SOD), catalase (CAT), and IL1B levels. One-way ANOVA and Tukey post hoc tests were used to analyze data. SB-treated rats with no intervention showed anxiety-like behavior and impaired memory as depicted by a significant (p<0.0001) increase in anxiety index, increase in brain NF-KB, increase in serum IL1B and increase in AchE gene expression level, reduction in the recognition ratio, decreased spontaneous alternation performance, decreased CAT and SOD levels and decreased NRF-2 expression level when compared to other groups (especially control and SB + 5% VCO). VCO supplemented diet (both 5% and 15%) significantly (p<0.0001) increased the CAT and SOD levels, increased the NRF-2 gene expression level, and significantly (p <0.0001) decreased the IL1-B level. Moreover, 5% VCO significantly (p<0.0001) decreased the anxiety index, decreased AchE and NFkB gene expression levels, increased spontaneous alternation performance, and increased recognition ratio compared to 15% VCO. VCO shows a neuroprotective effect in attenuating cognitive impairment and anxiety-like behavior in SB-induced model by modulating oxidative stress and inflammatory pathways, and also enhancing cholinergic neurotransmission. Keywords: Virgin coconut oil; sodium benzoate; acetylcholinesterase; catalase; superoxide dismutase; oxidative stress.