Ameliorative effect of ferulic acid on thyroid dysfunction against propyl-thiouracil induced hypothyroid rats.

PURPOSE: Hypothyroidism is an endocrine disorder characterised by decreased T3, T4 and increased TSH levels. This study aims to examine the potential effects of Ferulic acid (FA) on rats with hypothyroidism induced by propylthiouracil through the estimation of biochemical parameters and histopathological studies. METHODS: Twenty-five female wistar rats were allocated into five groups: Control group [1% CMC, p.o.], Disease group [PTU-50 mg/kg, p.o.], [Levothyroxine (LT4) group - 20 µg/kg, p.o. + PTU-50 mg/kg, p.o.], [FA -25 mg/kg, p.o. + PTU-50 mg/kg, p.o.] and [FA 50 mg/kg, p.o. + PTU-50 mg/kg, p.o.]. On 15th day blood was collected and serum was separated for estimation of biochemical parameters, liver and kidney homogenate was utilised for the estimation of oxidative stress markers and the thyroid gland was dissected to examine histological features. RESULTS: PTU administration for 14 days showed a substantial decline in T3 and T4 and increases in TSH levels. PTU-administered rats significantly increased TC, TG and LDL levels, and decreased HDL levels. AST, ALT, urea, creatinine, and IL-6 were determined and these levels were significantly altered in PTU-induced hypothyroid group. In hypothyroid rats MDA, NO, GSH and SOD levels were significantly altered. However, treatment with FA for 14 days attenuated PTU-induced alterations. Furthermore, FA improves the histological changes of the thyroid gland. CONCLUSION: In conclusion, FA treatment showed a protective effect against hypothyroidism by stimulating the thyroid hormones through the activation of thyroid peroxidase enzyme and improving thyroid function. In addition, FA diminished the increase in lipids, liver and kidney markers, oxidative stress and inflammation.

Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF.

BACKGROUND: Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of ß-amyloid (Aß) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders. OBJECTIVE: This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation. METHODS: Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect. RESULTS: Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-ß levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-ß levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05) Conclusion: Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-ß levels, neuroinflammatory mediators and enhanced BDNF levels.

Neuroprotective Effect of Saroglitazar on Scopolamine-Induced Alzheimer's in Rats: Insights into the Underlying Mechanisms.

Alzheimer's disease (AD) is one of the most prevalent and progressive neurodegenerative disorders, hallmarked by increased amyloid-ß deposition and enhanced oxidative load in the brain, ensuing cognitive decline. The present study is aimed at elucidating the neuroprotective effect of saroglitazar, a dual peroxisome-proliferator-activated receptor (PPARα/γ) agonist used in the treatment of diabetic dyslipidemia, against memory impairment induced by intraperitoneal scopolamine injection. 30 male Wistar rats were randomly divided into the following five groups: (A) Veh + Veh, (B) SGZ + Veh, (C) Veh + SCOP, (D) DPZ + SCOP, and (E) SGZ + SCOP. Rats of the respective groups were pretreated with saroglitazar (10 mg/kg, p.o.) and donepezil (3 mg/kg, p.o.) once daily for 16 days. During the final 9 days of the study, a daily injection of scopolamine (3 mg/kg, i.p.) was administered to the respective groups. Adjacent to the scopolamine injection, behavioral tests such as the open field, Y maze, novel object recognition test, and Morris water maze were conducted to assess learning and memory. Additionally, biochemical parameters such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), nitric oxide (NO), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), brain-derived neurotrophic factor (BDNF), ß-amyloid levels, and NF-κB were measured in the hippocampus. The rats that received scopolamine injections showed significantly impaired short-term spatial and learning memory. This was associated with an increase in ß-amyloid, iNOS, nitric oxide (NO), malondialdehyde, NF-κB, and TNF-α levels in the hippocampus of AD rats. On the other hand, saroglitazar has provided promising data on its protective role in cognition by protecting the BDNF, SOD, and GSH decline. As a result, saroglitazar was found to be a promising therapy in AD by upregulating the antioxidant status and cholinergic activity and preventing memory loss. Collectively, findings in the present study revealed that saroglitazar protected AD by suppressing scopolamine-mediated learning and memory deficits, oxidative stress, and cholinergic damage. Studying these mechanisms may conclude the protective role of saroglitazar against AD. However, further studies in transgenic animals will provide numerous insights into treatment mechanisms and contribute to developing a therapeutic intervention for AD.

Advancing health care via artificial intelligence: From concept to clinic.

Ever Since, pharmaceutical companies are facing challenges to develop new drug products faster and economical with good quality, safety and efficacy. The advent of Artificial intelligence (AI) with computational technology empowers scientists, impacts society at a great scale by developing new drugs at rapid pace. Artificial intelligence is the science and engineering of creating intelligent machines using personified knowledge. There are many opportunities to apply AI tools to the drug discovery pipeline. Examples include target identification, identification of biomarkers, molecular modelling, synthesis of molecules, predicting toxicity and picking up leads. Further, this technology also helps the clinical scientists in clinical trial design, execution and real-time analysis. Altogether it facilitates the process of drug discovery, development and also provides better therapy to the patients. Apart from drug discovery and development, AI also has applications in the area of diagnosis, drug delivery, patient adherence and better monitoring of safety. There are many instances where AI can perform tasks better than humans and aid healthcare providers in treating patients. In this article, we have provided discussion on how AI is advancing the health care field to achieve greater success.