Research Article
Abstract
Alzheimer’s disease (AD) is a progressive loss of neurons, caused by impaired activity of many enzymes involved in normal brain physiology. Active research has shown promising counter effects on AD symptoms by medicinal plant extracts. Our current study investigates the disease-modifying potential of Chlorogenic acid against multiple targets involved in AD by inhibiting the key enzymes in AD pathophysiology, such as acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), β-APP cleaving enzyme 1 (BACE1) and monoaminoxidase-B (MAO-B). UPLC-QTOF analysis of the hydroalcoholic root extract of Nardostachys jatamansi showed the presence of polyphenols mainly. The most abundant m/z 359.03 corresponds to the peak of chlorogenic acid. It was further validated and quantified using novel RP-HPLC method. The chlorogenic acid inhibited AChE and BuChE to 58% and 40% respectively in concentration dependent manner. The percentage inhibition for BACE1 was reported to be 41% at 50μM whereas, chlorogenic acid inhibited MAO-B enzyme very strongly and significantly at 40μM (88%). The in vitro experimentation showed complementarity with in silico results, where strong molecular interactions of chlorogenic acid with target proteins- AChE, BuChE, BACE1, MAO-B and Aβ 42 was observed. Thus chlorogenic acid could be developed as MTDL candidate against factors implicated in AD.
Keywords
Chlorogenic acid; Nardostachys jatamansi; Alzheimer’s disease; BACE1;
Neuroprotection; MAO-B; Molecular docking
Abstract
Alzheimer’s disease (AD) is a progressive loss of neurons, caused by impaired activity of many enzymes involved in normal brain physiology. Active research has shown promising counter effects on AD symptoms by medicinal plant extracts. Our current study investigates the disease-modifying potential of Chlorogenic acid against multiple targets involved in AD by inhibiting the key enzymes in AD pathophysiology, such as acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), β-APP cleaving enzyme 1 (BACE1) and monoaminoxidase-B (MAO-B). UPLC-QTOF analysis of the hydroalcoholic root extract of Nardostachys jatamansi showed the presence of polyphenols mainly. The most abundant m/z 359.03 corresponds to the peak of chlorogenic acid. It was further validated and quantified using novel RP-HPLC method. The chlorogenic acid inhibited AChE and BuChE to 58% and 40% respectively in concentration dependent manner. The percentage inhibition for BACE1 was reported to be 41% at 50μM whereas, chlorogenic acid inhibited MAO-B enzyme very strongly and significantly at 40μM (88%). The in vitro experimentation showed complementarity with in silico results, where strong molecular interactions of chlorogenic acid with target proteins- AChE, BuChE, BACE1, MAO-B and Aβ 42 was observed. Thus chlorogenic acid could be developed as MTDL candidate against factors implicated in AD.
Keywords
Chlorogenic acid; Nardostachys jatamansi; Alzheimer’s disease; BACE1;
Neuroprotection; MAO-B; Molecular docking
References
1. Thies, W.; Bleiler, L. Alzheimer’s association- Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2013; 9, 208-245
2. Hardy, J. Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J. Alzheimer's Dis. 2006, 9, 151-153
3. Merlini, G.; Bellotti, V. Molecular mechanisms of amyloidosis. N. Engl. J. Med. 2003, 349, 583-596
4. Floyd, R.A.; Hensley, K. Oxidative stress in brain aging: implications for therapeutics of neurodegenerative diseases. Neurobiol. Aging. 2002, 23, 795-807
5. Jomova, K.; Vondrakova, D.; Lawson, M.; Valko, M. Metals, oxidative stress and neurodegenerative disorders. Mol. Cell. Biochem. 2010, 345, 91-104
6. Purnima, B.M.; Kothiyal, P. A review article on phytochemistry and pharmacological profiles of Nardostachys jatamansi DC-medicinal herb. J. Pharmacogn. Phytochem. 2015, 3, 102-106
7. Saroya, A.S.; Singh, J. Pharmacotherapeutic Potential of Natural Products in Neurological Disorders, 1st ed.; Springer: Singapore, 2018
8. Kwon, S.H.; Lee, H.K.; Kim, J.A.; Hong, S.I.; Kim, H.C.; Jo, T.H.; Park, Y.I.; Lee, C.K.; Kim, Y.B.; Lee, S.Y.; Jang, C.G. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur. J. Pharmacol. 2010, 649, 210-217
9. Anggreani, E; Lee, C.Y. Neuroprotective effect of chlorogenic acids against Alzheimer’s disease. Int. J. Food Sci. Nutr. Diet. 2017, 6, 330-337
10. International conference on harmonization. Guideline IH, Validation of analytical procedures: text and methodology Q2 (R1): Geneva, Switzerland, 2005.
11. Sharma, O.P.; Bhat, T.K. DPPH antioxidant assay revisited. Food Chem. 2009, 113, 1202-1205
12. Banerjee, S.; Kar, P.; Sarkar, I.; Chhetri, A.; Mishra, D.K.; Dutta, A.; Kumar, A.; Sinha, B.; Sen, A. Structural elucidation and chemical characterization of underutilized fruit silverberry (Elaeagnus pyriformis) silver nanoparticles playing a dual role as anti-cancer agent by promoting apoptosis and inhibiting ABC transporters. S. Afr. J. Bot. 2022, 145, 243-257
13. Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009, 30, 2785-2791
14. DeLano, W.L. Pymol: An open-source molecular graphics tool. CCP4. Prot. Crystallog. 2002, 40, 82-92
15. Roberds, S.L.; Anderson, J.; Basi, G.; Bienkowski, M.J.; Branstetter, D.G.; Chen, K.S.; Freedman, S.; Frigon, N.L.; Games, D.; Hu, K.; Johnson-Wood, K. BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain: implications for Alzheimer’s disease therapeutics. Hum. Mol. Genet. 2001, 10, 1317-1324
16. Lan, J.S.; Xie, S.S.; Li, S.Y.; Pan, L.F.; Wang, X.B.; Kong, L.Y. Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. 2014, 22, 6089-6104
This work is licensed under the
Creative Commons Attribution
4.0
License (CC BY-NC 4.0).
Abstract
Alzheimer’s disease (AD) is a progressive loss of neurons, caused by impaired activity of many enzymes involved in normal brain physiology. Active research has shown promising counter effects on AD symptoms by medicinal plant extracts. Our current study investigates the disease-modifying potential of Chlorogenic acid against multiple targets involved in AD by inhibiting the key enzymes in AD pathophysiology, such as acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), β-APP cleaving enzyme 1 (BACE1) and monoaminoxidase-B (MAO-B). UPLC-QTOF analysis of the hydroalcoholic root extract of Nardostachys jatamansi showed the presence of polyphenols mainly. The most abundant m/z 359.03 corresponds to the peak of chlorogenic acid. It was further validated and quantified using novel RP-HPLC method. The chlorogenic acid inhibited AChE and BuChE to 58% and 40% respectively in concentration dependent manner. The percentage inhibition for BACE1 was reported to be 41% at 50μM whereas, chlorogenic acid inhibited MAO-B enzyme very strongly and significantly at 40μM (88%). The in vitro experimentation showed complementarity with in silico results, where strong molecular interactions of chlorogenic acid with target proteins- AChE, BuChE, BACE1, MAO-B and Aβ 42 was observed. Thus chlorogenic acid could be developed as MTDL candidate against factors implicated in AD.
Abstract Keywords
Chlorogenic acid; Nardostachys jatamansi; Alzheimer’s disease; BACE1;
Neuroprotection; MAO-B; Molecular docking
This work is licensed under the
Creative Commons Attribution
4.0
License (CC BY-NC 4.0).
This work is licensed under the
Creative Commons Attribution 4.0
License.(CC BY-NC 4.0).