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    Conflicts of interest
    Acknowledgements This study was financially supported by The Science and Engineering Research Board (SERB), Department of Science & Technology (DST), Government of India under the Fast Track Scheme for Young Scientist to Dr. V. Dhananjayan (No: SB/FT/LS-140/2012 Dated 26th April 2013). We are thankful to the Director, National Institute of Occupational Health, Ahmedabad and the Deputy Director, Health Services, Coimbatore for their support. Authors are also thankful to Mrs. Fathima, Village Health Nurse, and other staff of Primary Health Centre, Valparai, Tamil Nadu for their support in biological sample collection.
    Alzheimer’s disease (AD) is an irreversible and neurodegenerative SJB2-043 disorder, which is the most common form of dementia among the elderly. Over 46 million people live with dementia worldwide and the number of patients increases greatly every year, highlighting AD is one of the biggest global public health and social care challenges facing people in present and future., Four acetylcholinesterase (AChE) inhibitors, i.e. tacrine, donepezil, rivastigmine, and galantamine, have been used to enhance cholinergic function to alleviate cognitive impairment in AD patients for the past several decades. Compared with AChE, butyrylcholinesterase (BChE) plays only a supportive role in cholinergic neurotransmission, but it has been regarded as a promising drug target as its enzymatic activity and expression level significantly increase in the late stages of AD., Thus, the BChE-selective or dual-action cholinesterase inhibitors may be an effective therapeutic strategy for the ongoing management of AD. In addition, the amyloid cascade hypothesis declares that the accumulation of aggregated β-amyloid peptide (Aβ) in the brain plays a key role in the neuropathology of AD through triggering neuro-inflammation, progressive synaptic loss, and ultimately cognitive decline. As a result, the prevention of Aβ production or aggregation has currently attracted considerable attention for AD treatment. Natural SJB2-043 products are promising therapeutic agents for neurodegenerative diseases due to their various biological activities as well as minimal side effects. Several AChE inhibitors currently used in clinical, such as galanthamine and huperzine A, have natural origins. Therefore, extensive research has been conducted focusing on plant-derived inhibitors as potential sources of either new or more effective drug candidates for AD treatment. Benth (Leguminosae), a perennial climbing shrub, is mainly distributed in Sichuan, Yunnan and Guizhou provinces in China. Its seeds ( in Chinese) are widely used as anthelminthic drugs as well as external medicine for pain and bruises., Previous chemical studies revealed the presence of large amounts of flavonoids in this species, which exhibited anti-tumor, anti-allergic, anti-inflammatory and antimicrobial effects., , , However, the potential of this species on AD treatment is largely unknown. In our continuing effort to search for natural cholinesterase (ChE) inhibitors from plant kingdom, the ethanol extract of showed potent inhibitory activities against two cholinesterases (IC = 21.46 μg/mL, IC = 11.75 μg/mL) and Aβ aggregation (61.38% at 100 μg/mL). Then the successively solvent-partitioned extracts, i.e. petroleum ether (PE), ethyl acetate (EtOAc), and -butanol (-BuOH) and water extract, were obtained and their anticholinesterase activities were determined. As shown in , the BuOH extract was found to be the most active against both enzymes but was significantly selective for AChE (IC = 4.65 μg/mL, IC = 11.61 μg/mL). In our previous study, a new flavonol glycoside and a known alkaloid with significant anticholinesterase activities have been isolated from BuOH extract. Besides, the EtOAc extract showed significant inhibitory activity against two ChEs (IC = 40.45 μg/mL, IC = 12.75 μg/mL) and more selectivity towards BChE. Flavonoids, which have been revealed to be active constituents response for its various bioactivities, were mainly obtained from the middle polarity part of this species previously., Therefore, in order to find the active flavonoids with selective BChE or AChE-BChE inhibition, the EtOAc extract of was chosen for further bioassay-guided isolation ().