Current Drug Targets - Volume 18, Issue 13, 2017

Background: Diabetic retinopathy is one of the serious complications of diabetes and the leading cause of decreased vision and blindness worldwide. Neurodegeneration has been recognized as initiating factor in causing the retinal damage, which leads to micro-vascular damage in diabetic retinopathy. Diabetes-induced oxidative stress is believed to be the key factor that damages neurons in the diabetic retina. Various therapeutic approaches for effective attenuation of increased oxidative stress by antioxidants have emerged. One such approach is to utilize dietary flavonoids, which have been found to possess powerful antioxidant activity. Some of the naturally occurring flavones possess anti-diabetic effects by enhancing insulin sensitivity and reducing plasma glucose levels in diabetic animal models. Objective: Considering the importance of developing new antioxidant compounds and the relevance of their applications in the treatment of diabetes and its complications, in this review article, we discuss and highlight various neuroprotective mechanisms of flavonoids in the diabetic retina. Results: Dietary supplementation of flavonoids to diabetics may reduce oxidative stress, which in turn might ameliorate apoptosis and the levels of neurotrophic factors in the diabetic retina. Conclusion: This approach will elucidate a novel strategy for preventing and treating diabetic retinoneuropathy the leading cause of low vision and blindness.

Background: The Mediterranean diet includes olive oil as its primary source of fat. This diet is frequently associated to longevity and a lower incidence of chronic diseases due to its biological activities and health effects. Apart from oleic acid, olive oil contains many bioactive components including polyphenols that have been reported to exert antioxidant and anti-inflammatory activities. Polyphenols may almost in part be responsible for the protective effects against cardiovascular diseases associated with olive oil. Objective: To review and discuss the available literature on hydroxytyrosol effects as a cardioprotective agent. Moreover, we also discuss the chemistry, nutritional aspects and bioavailability of hydroxytyrosol. Results: Hydroxytyrosol is one of the major phenolic compounds in olive oil and has demonstrated strong radical-scavenging properties. Several studies have been performed in order to look further into the effects of the polyphenol hydroxytyrosol in relation to cardiovascular events and illnesses in animal trials and in vitro. However, no clinical trials have focused on the specific action of hydroxytyrosol and cardiovascular diseases, although some are being undertaken to look at olive oil or olive leaf extract properties. Conclusion: Hydroxytyrosol from olive oil exerts antioxidant, anti-inflammatory, anti-platelet aggregation and ati-atherogenic activities in in vitro and animal models. However, its possible therapeutic use in humans requires additional clinical trials.

Background: Alzheimer's disease (AD) is the most widespread age-related neurodegenerative disease. Recently, a growing body of evidence suggested the phytochemical use to slow down AD onset and progression. Objective: To review the phytochemical role potentially involved in AD treatment. Method: A systematic review from existing literature on phytochemicals used in the treatment of AD patients was conducted. Selection criteria included: 1) age≥60 years; 2) AD diagnosis in agreement with the criteria of National Institute on Aging-Alzheimer's Association (NIAAA), and 3) suitable measures to asses cognitive, functional and clinical status. Results: Ninety-seven articles were involved in the present study. Several phytochemicals seem to slow down AD onset, delay disease progression and let recovery through targeting multiple pathological causes by anti-cholinergic, antioxidant and anti-inflammatory features. Conclusion: Deeper knowledge on phytochemicals and their specific molecular targets is essential to guarantee safe use of these compounds as an option for AD treatment.

Background: The evolution of the Green movement in western society has changed attitudes in the general population who now perceive natural compounds as being inherently harmless and more desirable than artificial chemical products. Objective: Considering the growing interest towards introducing naturally emerged medicines, the purpose of this review was to overview the ongoing research into prevention and treatment of multiple sclerosis (MS) lesions. Method: This review was carried out by searching bibliographic databases such as PubMed and Scopus for studies reported between 1st January 2008 to 30th January 2016 on MS patients or animal models of MS, investigating the beneficial effects of natural compounds in MS treatment. In this updated systematic review, the search terms were “multiple sclerosis” or “neurodegeneration” and (“natural compounds” or “medicinal plants”, “traditional medicine” or “native medicine”). Results: Studies with vitamins (A, B12, D, H), minerals (selenium and lithium), n-3 PUFAs, lipoic acid, statins, resveratrol, marijuana, EGCG and some probiotics have shown significant helpful effects in MS by preventing or delaying the onset of disease. Other natural compounds such as xanthines, anthocyanins, glucosinolates, isoflavones, organosulfurs, steroid glycosides, and alkaloids have also shown protective effects in the treatment of MS in animal models. Adverse effects were also reported in some of the experiments. Conclusion: Further studies with a focus on the molecular mechanisms of the protective natural compounds are needed to decrease possible side effects and to develop new medicines for MS. Apigenin, chrysin, baicalein, cyanidin, flavone glycoside, daidzein, coumestrol, sulforaphane, bee venom and huperzine A are the candidates for more prospective investigations.

Background: Neurodegenerative diseases are increasingly inevitable as the population gets older, with enormous socio-economic costs. The World Health Organization (WHO) has reported that by 2040, neurodegenerative diseases will overtake cancer to become the second leading cause of death, after cardiovascular disease. Objective: Herein, this review outlines the neuroprotective effects and clinical implications of ellagitannins, a class of hydrolysable tannins, for the management and treatment of neurodegenerative disorders. Results: Recent investigations suggest that the combination of genes and environmental toxins may contribute to the risk of developing neurodegenerative disorders. Thus, intervention strategies aimed at reducing exposure to risk factors such as life style, smoking, diet, vitamin deficiencies, chemical exposure and pollution are warranted. Modulation of dietary components including ellagitannins, as a therapeutic strategy to slow down or attenuate the progression of neuronal degeneration has become a focus of interest in the last few decades. Conclusion: Polyphenolic plant phytochemicals and ellagitannins in particular, contain an array of neuroprotective properties useful to improve human health and protect against neurodegeneration.

Background: The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such as Alzheimer's and Parkinson's disease and cerebral ischemia for over 2000 years. Objective: In this article we review the neuroprotective effects of silymarin against various neurological dysfunctions. Results: The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis. The ease of availability, comparative low cost and safety profile provide additional advantages for the use of this compound as a potent drug with immense clinical benefit. However, there is a growing need for improvements in the bioavailability of silymarin and related products, and more consistent and reliable human trials are required to accurately validate the neuroprotective efficacy of this natural compound. Conclusion: The promising outcomes of the studies mentioned in this review provide renewed insight into the clinical relevance of silymarin in a variety of neurodegenerative disorders where neuroinflammation and oxidative stress are pathologically relevant to disease progression.

Background: Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. Literature review: The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds to α7 nicotinic acetylcholine receptors (nAChRs) with very high affinity. This discovery has led to extensive exploration of the possible outcomes of this binding, ranging from the subcellular signaling pathways to its effects on behavioral and cognitive functions. Intriguingly, there are conflicting reports about the effects of this Aβ and α7 nAChR interaction; a few studies report a neuroprotective role of this interaction while others claim that it is neurotoxic. Conclusion: This review focuses on the neurotoxic and neuroprotective effects of Aβ and α7 nAChR interaction and its implications on different cell signaling pathways and other physiological functions. Moreover, the implications this interaction might have on Alzheimer's disease therapy are also discussed.

Abstract: Background: Stress is involved in memory impairment through multiple mechanisms, including activation of hypothalamic-pituitary axis, which in turn activates release of corticosterone in blood. Cholinergic system blockade by the muscarinic antagonist, scopolamine, also impairs memory. Objective: This study aimed to investigate the effect of turmeric (20mg/kg) on learning and memory and cholinergic system in a mouse model of stress along with cholinergic blockade. Methods: Restrained stress was induced and cholinergic receptors were blocked using scopolamine in mice. Animals were treated with turmeric (turmeric rhizome powder which was also subjected to NMR analyses) and learning and social behavior was examined. Effect of turmeric on cholinergic muscarinic receptors (mAChR; M1, M3 and M5) gene expression was assessed by RT-PCR in both pre-frontal cortex and hippocampus. Results: Ar-turmerone, curcuminoids and α-linolenic acid were the lead compounds present in turmeric extract. Increased serum corticosterone levels were observed in stressed mice when compared to the control group, while turmeric treatment significantly reduced serum corticosterone level. Turmeric treatment caused an improved learning and memory in Morris water maze test in stressed animals. Social novelty preference was also restored in turmeric treated animals. Following turmeric treatment, M5 expression was improved in the cortex and M3 expression was improved in the hippocampus of stress + scopolamine + turmeric treated group. Conclusions: These findings highlight the therapeutic role of turmeric by increasing the expression of M3, M5 and improving learning and memory. Turmeric can be an effective candidate for the treatment of amnesia caused by the stress.

Immune-based inflammatory diseases involve immune related dysregulation in different sites of body, which includes rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular research have facilitated investigation of their pathogenesis that is involved in inflammatory cytokines cells and several genes. The available drug therapy provides suboptimal therapeutic effects and higher adverse effects. Emergence of liposomal systems of the drugs meant for the above mentioned disease has gained broader importance due to their high treatment efficacy by means of optimal therapeutic drug delivery. Beyond the conventional liposomal formulations, evolution of second generation liposomes including stealth liposomes, cationic liposomes, immuno-liposomes, etc. has gained tremendous attention owing to their drug target potential, diagnostic importance and imaging in treatment of above mentioned immune mediated inflammatory disorders.

Background & Objective: The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. Results and Conclusion: In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function.