Phytochemical profiling and in vitro screening for anticholinesterase, antioxidant, antiglucosidase and neuroprotective effect of three traditional medicinal plants for Alzheimer’s Disease and Diabetes Mellitus dual therapy

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.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2140-x) contains supplementary material, which is available to authorized users.

Evaluation of neuroprotective potential of methanolic extract of Hemidesmus indicus extract in Aβ (1-42) induced rats

“…Hence, we can convey that methanol extract of H. indicus has considerable AChE inhibitory potential against Aβ (1-42) infused AD model and dose-dependently inhibited the intracellular AChE activity in the rat brain. Our results are inconsistent with the previous indings by researchers, which reported that different extracts of H. indicus have successfully inhibited AChE activity (Kundu and Mitra, 2013;Penumala et al, 2018).…”

Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice

“…In this assay, the test samples were performed spectrophotometrically for AChE and BuChE inhibition potential using AChEI and BuChEI as substrates following the method of Ellman et al with minor changes [16, 43]. The test sample stock solution was prepared in the concentration of 1.0 mg/mL and then diluted into 500, 250, 125, 62.5, 31.05, and 15.625 μ g/mL solutions in order to select the appropriate concentration range of IC 50 .…”

“…Acetylcholine (ACh), closely associated with AD, was a neurotransmitter responsible for the cognitive function, learning, and memory. According to the “cholinergic hypothesis,” acetylcholinesterase (AChE), a key enzyme in biological nerve conduction, was mainly associated with the degradation of ACh [15, 16]. In addition, there were some studies on neurotransmitter dysfunction such as dopamine and 5-hydroxytryptamine, but not much as ACh in AD [17].…”

Neuroprotective, antidiabetic and antioxidant effect of Hedera nepalensis and lupeol against STZ + AlCl3 induced rats model

“…Symptoms of AD syndrome in the elderly stage include the social and occupational activities hindrance. It is known to cause dementia in about 80% of individuals, according to recent findings [ 2 – 5 ] . Diagnosis of AD comprises of two well-known abnormalities, that is memory loss and defects in normal function of speaking, attention, thought, sense of judgement or problem solving [ 6 ].…”