Abstract
BackgroundExtensive epidemiological and clinical studies revealed that Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis have been used extensively in popular medicine. The present study was aimed at phytochemical profiling and evaluating multifunctional ability of titled plants in the AD and T2D dual therapy.MethodsMethanolic extracts and their derived fractions were evaluated for their inhibitory capacities against acetylcholinesterase (AChE) & butyrylcholinesterase (BuChE), and α– & β–glucosidase besides kinetic analysis of inhibition using methods of Elmann and Shibano, respectively. Antioxidant potency of active fractions was assessed by their DPPH and ABTS radical scavenging activities. Active fractions were tested by the MTT assay to verify cytotoxicity and neuroprotective ability in human nueroblastoma cell lines. Phytochemical screening was done with the aid of spectrophotometric methods.ResultsAll the methanolic extracts of test plants (BAM, HIM, RMM) showed concentration dependent inhibitory activities against AChE, BuChE, α– and β–glucosidase enzymes. Subsequent fractionation and evaluation revealed that chloroform fractions BAC, HIC and RMC with IC50 values of 12.29±2.14, 9.94±2.14, 16.65±1.99 and 27.38±1.24; 28.14±0.9, 5.16±0.22, 11.03±0.5 and 87.64±15.41; 41.35±1.6, 15.86±7.3, 26.04±0.37 and 25.33±0.3 were most prominent with regard to inhibition potential against AChE, BuChE, α– and β–glucosidase, respectively. Kinetic analysis of these active fractions proved that they disclosed mixed-type inhibition against AChE, BuChE, α– and β–glucosidase enzymes. In the MTT assay, active fractions BAC, HIC, RMC showed significant cell viability at high concentrations (400 μg). Moreover, in MTT assay, the active fractions displayed excellent neuroprotective effects against oxidative stress induced cell death and significant cell viability in SK N SH cells at all concentrations.ConclusionThe strong anticholinesterase, antiglucosidase, antioxidant and neuroprotective activities of methanolic extracts and their derived chloroform fractions indicate the potential of Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis as multifunctional therapeutic remedies for the dual therapy of T2D and AD.
Highlights
Extensive epidemiological and clinical studies revealed that Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD
Alzheimer’s disease (AD) is a chronic neurodegenerative irreversible brain disorder that affects daily living through memory loss and cognitive impairment [1, 2]
Biological evaluations of extracts and fractions against various targets related to AD and T2D were made to prove B. axillaris (BA), HI and RM as multifunctional agents for dual therapy for the first time
Summary
Extensive epidemiological and clinical studies revealed that Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. AD is affecting 46.8 million people throughout the world and this number is likely to get doubled by 2030 due to lack of effective treatment [3]. Type 2 Diabetes Mellitus (T2D) is an age-related metabolic disorder with complex etiology and affecting 10% population across the world [9]. T2D causes abnormal absorption of glucose into the blood that creates a condition called hyperglycemia and results in serious complications in various organ systems like liver, heart, kidney, retina and brain [12, 13]. One of the therapeutic approaches to decrease postprandial hyperglycemia is the inhibition of carbohydrate hydrolyzing enzymes, α– and β–glucosidases (α– and β–Glu), thereby delaying glucose digestion in the digestive tract [14]
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