Current Research on Therapy in Alzheimer’s Disease Experimental Model: Beta-Amyloid1-42 Induction (original) (raw)
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2015
The current study aimed to evaluate the anti-inflammatory and anti-apoptotic efficacy of Salvia triloba and Piper nigrum total extract in modulation of neuroinflammation insults characteristic for Alzheimer's disease in experimental rat model. Male Sprague Dawley rats were classified into five groups: (1), control group; (2), ADinduced group which was orally administered with aluminum chloride (AlCl3) in a dose of 17 mg/kg b. wt. daily for one month; (3), AD-induced group which was treated orally with rivastigmine in a dose of 0.3 mg/kg b. wt. daily for three months; (4), AD-induced group divided into two subgroups each subgroup was treated orally with one of the selected medicinal plants extract in a dose of 750 mg/kg b. wt. for Salvia triloba L. and 187.5 mg/kg b. wt. for Piper nigrum daily for three months and (5), AD-induced group was divided into two subgroups each subgroup was treated orally with one of the selected medicinal plants extract in a dose of 375 mg/kg b. wt. fo...
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Alzheimer's disease (AD) is a destructive neurodegenerative disorder characterized by progressive memory defeat and impairment in behavior, language, and visuospatial skills. Neuropsychiatric symptoms such as apathy, depression, aggression, agitation, sleep disruption, and psychosis are now recognized as core symptoms of AD that are expressed to varying degrees throughout the course of disease. The neuro pathological features of AD comprise extracellular senile plaques constituted of β-amyloid (Aβ) pledges, intracellular neurofibrillary tangles (NFTs), and cerebral atrophy; others include apolipoprotein E, oxidative stress, mitochondrial dysfunction and cholinergic hypothesis. Anti-amyloid therapy is available for the treatment of Alzheimer's disease, others are anticholinergic therapy, and therapy for mitochondrial dysfunction, γ-secretase inhibitors (GSI) and modulators (GSM),-secretase (BACE1) inhibitors, Glial modulating drugs includes RAGE receptor antagonists, TNF-α antagonists, neuroprotective drugs such as antioxidants, phosphodiesterase inhibitors, PPARγ agonists, and anti-tau or tau modulators like microtubule stabilizers, kinase inhibitors. This review includes discussion on neurobiological mechanisms and newly developed compounds which have lesser side effects and are proving more efficient for treatment of Alzheimer's disease.
Therapeutic Potential of Different Natural Products for the Treatment of Alzheimer’s Disease
Oxidative Medicine and Cellular Longevity
A high incidence of dementia (60–80%) and a high rate of memory loss are two of the most common symptoms of Alzheimer’s disease (AD), which affects the elderly. Researchers have recommended that traditional Chinese medicine (TCM) and Indian medicines can be used to prevent and cure AD. Several studies have linked neuroinflammation linked to amyloid-β (Aβ) deposition in the brain to the pathophysiology of neurodegenerative disorders. As a result, more research is needed to determine the role of inflammation in neurodegeneration. Increased microglial activation, cytokine production, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) all play a role in the inflammatory process of AD. This review focuses on the role of neuroinflammation in neuroprotection and the molecular processes used by diverse natural substances, phytochemicals, and herbal formulations in distinct signaling pathways. Currently, researchers are focusing on pharmacologically active natural compounds wi...
Natural Therapeutics for Alzheimer’s Disease
Functional Food and Human Health, 2018
Alzheimer's disease (AD) is a neurodegenerative disease which is serious, persistent and progressive and is linked with deterioration of memory and cognition. Commonly, Alzheimer's is the reason to cause dementia in aged people. The pathogenesis of this disease is linked with the buildup of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in brain tissues, and also the tau protein gets hyper-phosphorylated in neurons. The generation of reactive oxygen species (ROS) as a result of oxidative stress is regarded as the main cause of AD. The present treatment offers only symptomatic relief which turns down the rate of cognitive destruction related with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is believed as one of the key therapeutic approach contributing only symptomatic relief and modest disease modifying result. None of the drugs currently available could delay or halt the progression of AD. Several compounds showed positive results in preclinical studies but failed in clinical trials as they had limited targeting because of their inability to cross blood-brain barrier (BBB). Several problems exist in the development of new therapeutics. Medicinal plants have been reported for promising anti-AD action in many preclinical and clinical trials. Natural compounds provide various structural characteristics and biological activities and therefore are an attractive source for developing compounds against AD. Advance in extraction and separation method leads to the generation of natural products as potential therapeutics. Various medicinal plants also in their basic structure or as secluded compounds have demonstrated to lessen the pathological characteristics related with AD. In this chapter an effort has been made to focus on natural substances having role in anti-Alzheimer's therapy with their source, mechanism of action and limitations.
Pharmacological and Neuroprotective Natural Products in the Treatment of Alzheimer's Disease
https://ijshr.com/IJSHR\_Vol.6\_Issue.3\_July2021/IJSHR-Abstract.062.html, 2021
Alzheimer's illness (AD) is a progressive, neurodegenerative issue and has become an incredible medical condition especially among the old individuals, for the most part happens after the age of 55 years and expansion in frequency with propelling age, however its therapy alternatives are generally not many and inadequate. The reason for AD isn't actually known, yet is thought to incorporate both hereditary and natural elements (multifactorial). There is no known remedy for Alzheimer's sickness, since it is beyond the realm of imagination to expect to invert the demise of synapses however the indications can be overseen by some pharmacological specialists and Neuroprotective Natural Products. In spite of the improvement of various pharmacological methodologies throughout the years pointed toward treating Alzheimer's Disease (AD) without a doubt, not many have been supported for clinical use in patients. To date there still exists no illness adjusting treatment that could forestall or protect the intellectual debilitation, especially of memory aquisition, that is normal for AD. One of the opportunities for this situation may be that most of medication disclosure endeavors centers around result proportions of diminished neuropathological biomarkers normal for AD, without taking into acount neuronal cycles fundamental for the age and support of memory measures. In endeavors to find new methodologies for AD treatment, regular items have stirred interest in the examination local area and in the drug business for their neuroprotective movement, focusing on various obsessive instruments related with AD. A wide assortment of normal items from various beginnings have been assessed preclinically and clinically for their neuroprotective instruments in forestalling and lessening the multifactorial pathologies of AD. It is accepted that normal item blends or concentrates containing different bioactive mixtures that can work additively or synergistically to display various neuroprotective systems may be a compelling methodology in AD drug discovery.
Exploring the efficacy of natural products in alleviating Alzheimer’s disease
Neural Regeneration Research, 2019
Alzheimer's disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD.
Pharmacological and Herbal remedies in the Management of Neurodegenerative Disorder (Alzheimer’s)
International Journal of Pharmacognosy and Life Sciences, 2021
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder and has become a great health problem particularly among the elderly people, generally occurs after the age of 55 years and increase in incidence with advancing age, affecting nearly 25 million people worldwide. Alzheimer's disease (AD) was first identified by the German psychiatrist, Alois Alzheimer, in 1907. People with this disease may exhibit symptoms of short-term memory loss, diminished motor skills, inefficient coordination and impaired intellectual capabilities. The cause of AD is not exactly known, but is thought to include both genetic and environmental factors (multifactorial). There is no known cure for Alzheimer's disease, since it is not possible to reverse the death of brain cells but the symptoms can be managed by some pharmacological agents and herbal remedies. The herbal remedies are becoming more popular in the recent years and providing very promising benefits to the patients suffering from AD. Several clinical trials using herbal mixtures are also going on and will hopefully show positive results for treating AD in the future. This paper reviews the Pathophysiology of AD along with the synthetic drugs and herbal medicines which are used for the Management of AD.
Pathophysiology of Alzheimer Disease: Current Drug Therapy
Alzheimer's disease (AD) is a neurodegenerative age related disease in which patients of age 65 or more suffer from memory impairment problems. This disease is related to the nervous system degradation and various pathophysiological conditions have been identified such as formation of β-amyloid and plaques, nerve degeneration, neurotransmitter depletion, accumulation of toxins, oxidative stress and inflammation. Local RAS system in the brain is different from vascular RAS and play an important role in pathophysiology of AD. RAS system modulates inflammatory processes, neurotransmitter activity and amyloid and plaque formation. Angiotensin II, a vasoconstriction peptide of RAS system also induces neuronal cell loss by the process of cell senescence. Genetic polymorphism is also an important factor for pathophysiology and treatment of AD. No treatment is available which can eradicate AD completely; only prophylactic treatments are available which gives only prophylactic relief. Treatments are given which improve the pathophysiological condition of the disease and restore the brain cells activity. Treatment approach includes prevention of β amyloid and plaque formation, restoration of neurotransmitter system, prevention of oxidative stress and inflammation. Other than allopathic medicines, traditional system of medicines also have number of herbs and plants which have the property of learning and memory improvement via different mechanism of actions.
Alzheimer Disease: Various Therapeutic Interventions and Alternative under Clinical Trial
Alzheimer Disease (AD) is an incurable progressive neurodegenerative disorder. It is the most common cause of dementia and is increasing worldwide. Various mechanism of pathogenesis of AD is given and is still under study. Despite of its etiology, the disease is characterized by presence of senile plaques which is deposition of Amyloid Beta protein and other is intracellular neurofibrillary tangles. Several other factors like Hypertension, diabetes, obesity and inflammation, hormonal imbalance are associated with increased risk of AD. This article summarizes various interventions which have impact on slowing the progression of disease therefore any intervention which delays the onset of moderate to severe symptoms will have significant effect on patient and their families. Also it includes various drugs and agents which are currently under clinical trial studies. These agents mainly act upon Beta Amyloid, cholinergic system,various vaccines, antibodies, γ and ß Secretase inhibitors and modulators, Agent affecting phosphorylation and blocking of tau protein along with agents which have indirect effect on neurotransmission like serotonergic 5HT₆, Histaminergic H₃, modulation of acetylcholine response of α-7 nicotinic acetylcholine receptors. Development of new drugs is very time consuming process and had very less chance of success. The drug which passes the phase 2 clinical trials with positive results generally fails in phase 3 trial because of serious adverse effect and lack of drug safety profile.