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: In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs which are under development and their respective mechanisms of actions.

Oxidative stress plays a significant role in the pathophysiology of numerous kidney diseases, generally mediated by reactive oxygen species (ROS). Arsenic (Ar) is known to exert its toxicity through the generation of ROS and inflammation. The current study investigates the protective effects of sulforaphane (SFN) against arsenic-induced renal damage via PI3K/Akt-mediated Nrf2 pathway signaling. Thirty-two male albino Wistar rats were randomly divided into four groups of eight animals each, designated as control, arsenic (Ar), sulforaphane plus Ar (SFN+Ar), and sulforaphane alone (SFN), with oral administration of Ar (5 mg/kg BW) and SFN (80 mg/kg BW) daily for 28 days. Ar administration significantly ( P < 0.05) increased the levels of ROS, OHdG, Ar accumulation, and lipid peroxidation, and decreased levels of enzymatic and nonenzymatic antioxidants. Notably, a significant ( P < 0.05) increase was observed in markers of apoptosis, DNA damage, TUNEL-positive cells, and dark staining of ICAM-1 in renal tissue with decreased PI3K/Akt/Nrf2 gene expression. The biochemical findings were supported by histopathological and electron microscopy evaluation, which showed severe renal damage in rats treated with Ar. Pretreatment with SFN significantly ( P < 0.05) attenuated renal ROS, OHdG, lipid peroxidation, and DNA damage, and increased phase II antioxidants via PI3K/Akt-mediated Nrf2 activation in renal tissue. These results show that dietary supplementation with SFN protects against Ar-induced nephrotoxicity via the PI3K/Akt-mediated Nrf2 signaling pathway in the rat kidney.

Environmental exposure to sodium fluoride (NaF) compounds is a worldwide health concern. Epigallocatechin gallate (EGCG) is a green tea catechin found in a variety of green tea preparations. The intention of this study was to investigate the hepatoprotective role of EGCG in NaF-intoxicated rats. Rats were orally treated with NaF alone (25 mg·(kg body mass)(-1)·day(-1)) or plus EGCG at different doses (20, 40, and 80 mg·(kg body mass)(-1)·day(-1)) for 4 weeks. Hepatotoxicity of NaF was determined by increased levels of serum hepatospecific markers and total bilirubin, along with increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides, protein carbonyl content, and conjugated dienes. The hepatotoxic nature of NaF was further evidenced by the decreased activity of enzymatic and nonenzymatic antioxidant levels in liver. NaF-treated rats also showed increased DNA damage and fragmentation in hepatocytes. Administration of EGCG (40 mg·(kg body mass)(-1)) to NaF-intoxicated rats significantly recuperated the distorted biochemical indices, DNA damage, and pathological changes in the liver tissue. Thus, the results of the present study clearly demonstrate that EGCG has strong free radical scavenging, antioxidant, and antigenotoxic properties that protect against NaF-induced oxidative hepatic injury in rats.

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