Evaluation of cholinesterase inhibitory activity of six Indonesian Cassia species
Evaluation of cholinesterase inhibitory activity of six Indonesian Cassia species
Alzheimer’s disease (AD) is a neurodegenerative disorder, which is the most common cause of dementia. The aging population means that the number of people suffering from AD is expected to increase each year if there is no effective treatment found. One of the strategies for the treatment of AD is the use of cholinesterase inhibitors. Plants have been the source of many bioactive metabolites, including cholinesterase inhibitors. The objective of this study is to investigate the potency of several plant extracts from the genus Cassia as cholinesterase inhibitors. The cholinesterase inhibitory screening was carried out against two enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), according to the modified Ellman’s method. The chemistry of the active fractions was studied by LC-MS/MS method. The results suggested that amongst six plant extracts from the genus Cassia investigated, the ethanolic extract of Cassia spectabilis showed the strongest inhibition against both AChE and BChE enzymes, with IC50 values of 39.5 and 36.9 µg/mL, respectively. Investigation on the n-hexane, ethyl acetate, and nbutanol fractions obtained from the C. spectabilis extract showed that the ethyl acetate and the n-butanol fractions gavebetter inhibitory activity compared to the n-hexane fraction. Based on the LC-MS/MS data, the two active fractionsgave similar profile. Both fractions contained alkaloid cassine and spectaline, which may responsible for thecholinesterase inhibitory activity
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- [1] Bird TD. Genetic Aspects of Alzheimer Disease. Genet Med. 2008; 10(4): 231-239. [CrossRef]
- [2] Murray AP, Faraoni MB, Castro MJ, Alza NP, Cavallaro V. Natural AChE Inhibitors from Plants and Their Contribution to Alzheimer’s Disease Therapy. Curr Neuropharmacol. 2013; 11(4): 388-413. [CrossRef]
- [3] Mathew M, Subramanian S. In Vitro Screening for Anti-cholinesterase and Antioxidant Activity of Methanolic Extracts of Ayurvedic Medicinal Plants Used for Cognitive Disorders. Plos one. 2014; 9(1): e86804. [CrossRef]
- [4] Hostettmann K, Borloz A, Urbain A, Marston A. Natural Product Inhibitors of Acetylcholinesterase. Curr Org Chem. 2006; 10(8): 825-847. [CrossRef]
- [5] Lleo A, Greenberg SM, Growdon JH. Current Pharmacotherapy for Alzheimer’s Disease. Annu Rev Med. 2006; 57: 513-533. [CrossRef]
- [6] Chopra K, Misra S, Kuhad A. Current Perspectives on Pharmacotherapy of Alzheimer’s Disease. Expert Opin Pharmacother. 2011; 12(3): 335-350. [CrossRef]
- [7] Suciati, Rabgay K, Fachrunniza Y, Saesong T, Hadi TA, Wahyuni TS, Widyawaruyanti A, Ingkaninan K. Enzyme Inhibitory Activities of Marine Sponges against Cholinesterase and 5α-Reductase. Malays Appl Biol. 2019; 48(3): 77-83.
- [8] Ganapaty S, Thomas PS, Ramana KV, Vidyadhar KN, Chakradhar V. A Review of Phytochemical Studies of Cassia Species. Journal of Natural Remedies. 2002; 2(2): 102-120.
- [9] Dave H, Ledwani L. A Review on Anthraquinones Isolated from Cassia Species and Their Applications. Indian J Nat Prod Resour. 2012; 3(3): 291-319.
- [10] Sundaramoorthy S, Gunasekaran S, Arunachalam S, Sathiavelu M. A Phytopharmacologucal Review on Cassia Species. J Pharm Sci Res. 2016; 8(5): 260-264.
- [11] Jothy SL, Torey A, Darah I, Choong YS, Saravanan D, Chen Y, Latha LY, Deivanai S, Sasidharan S. Cassia spectabilis (DC) Irwin et Barn: A Promising Traditional Herb in Health Improvement. Molecules. 2012; 17(9): 10292-10305. [CrossRef]
- [12] Torey A, Sasidharan S, Yeng C, Latha LY. Standardization of Cassia spectabilis with Respect to Authenticity, Assay and Chemical Constituents Analysis. Molecules. 2010; 15(5): 3411-3420. [CrossRef]
- [13] Deshpande HA, Bhalsing SR. Recent Advances in the Phytochemistry of Some medicinally important Cassia species: A Review. Int J Pharm Med Bio Sc. 2013; 2(3): 60-78.
- [14] Ekasari W, Wahyuni TS, Arwaty H, Putri NT. Determination of Effective Dose of Antimalarial from Cassia spectabilis Leaf Ethanol Extract in Plasmodium berghei-Infected Mice. Aft J Infect Dis. 2018; 12(1 Suppl): 110-115.
- [15] Kim DH, Yoon BH, Kim YW, Lee S, Shin BY, Jung JW, Kim HJ, Lee YS, Choi JS, Kim SY, Lee KT, Ryu JH. The Seed Extract of Cassia obtusifolia Ameliorates Learning and Memory Impairments Induced by Scopolamine or Transient Cerebral Hypoperfusion in Mice. J Pharmacol Sci. 2007; 105(1): 82-93. [CrossRef]
- [16] Yi JH, Park HJ, Lee S, Jung JW, Kim BC, Lee YC, Ryu JH, Kim DH. Cassia obtusifolia Seed Ameliorates Amyloid βInduced Synaptic Dysfunction through Anti-inflammatory and Akt/GSK-3β Pathways. J Ethnopharmacol. 2016; 178: 50-57. [CrossRef]
- [17] Jung HA, Ali MY, Jung HJ, Jeong HO, Chung HY, Choi JS. Inhibitory Activities of Major Anthraquinones and Other Constituents from Cassia obtusifolia against β-Secretase and Cholinesterases. J Ethnopharmacol. 2016; 191: 152-160. [CrossRef]
- [18] Shresta S, Seong SH, Paudel P, Jung HA, Choi JS. Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occuring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia. Molecules. 2017; 23(1): 69-86. [CrossRef]
- [19] Feitosa CM, Freitas RM, Luz NN, Bezerra MZ, Trevisan MT. Acetylcholinesterase Inhibition by Somes Promising Brazilian Medicinal Plants. Braz J Biol. 2011; 71(3): 783-789. [CrossRef]
- [20] Pivatto M, Crotti AEM, Castro-Gamboa I, de Rezende A, Viegas C Jr, Young MCM, Furlan M, Bolzani VS. Electrospray Ionization Mass Spectrometry Screening of Piperidine Alkaloids from Senna spectabilis (Fabaceae) Extracts: Fast Identification of New Constituents and Co-metabolites. J Braz Chem Soc. 2005; 16(n-6b): 1431-1438. [CrossRef]
- [21] Freitas TR, Danuello A, Viegas C Jr. Bolzani VS, Pivatto M. Mass Spectrometry for Characterization of Homologous Piperidine Alkaloids and Their Activity as Acetylcholinesterase Inhibitors. Rapid Commun Mass Spectrom. 2018; 32(15): 1303-1310. [CrossRef]
- [22] Christofidis I, Welter A, Jadot J. Spectaline and Iso-6-cassine, Two New Piperidin 3-ol Alkaloids from The Leaves of Cassia spectabilis. Tetrahedron. 1977; 33(9): 977-979. [CrossRef]
- [23] Viegas C Jr, Bolzani VS, Furlan M, Berreiro EJ, Young CM, Tomazela D, Eberlin MN. Further Bioactive Piperidine Alkaloids from the Flower and Green Fruits of Cassia spectabilis. J Nat Prod. 2004; 67(5): 908-910. [CrossRef]
- [24] Pereira RM, Ferreira-Silva GÁ, Pivatto M, Santos LÁ, Bolzani VS, Chagas de Paula DA, Oliveira JC, Viegas C Jr, Ionta M. Alkaloids Derived from Flowers of Senna spectabilis, (-)-Cassine and (-)-Spectaline, Have Antiproliferative Activity on HepG2 Cells for Inducing Cell Cycle Arrest in G1/S Transition through ERK Inactivation and Downregulation of Cyclin D1 Expression. Toxicol in Vitro. 2016; 31: 86-92. [CrossRef]
- [25] Silva FO, Silva MGV, Cerqueira GS, Sabino EB, Almeida AAC, Costa JP, Freitas RM. Iso-6-Spectaline Effects on Convulsions Induced in Epilepsy Models. J Young Pharm. 2011; 3(3): 232-236. [CrossRef]
- [26] Silva FO, Silva MGV, Feng D, Freitas RM. Evaluation of Central Nervous System Effects of Iso-6-Cassine Isolated from Senna spectabilis var. excelsa (Schrad) in Mice. Fitoterapia. 2011; 82(2): 255-259. [CrossRef]
- [27] Viegas C Jr, Bolzani VS, Pimentel LS, Castro NG, Cabral RF, Costa RS, Floyd C, Rocha MS, Young MC, Barreiro EJ, Fraga CA. New Selective Acetylcholinesterase Inhibitors Designed from Natural Piperidine Alkaloids. Bioorg Med Chem. 2005; 13(13): 4184-4190. [CrossRef]
- [28] Castro NG, Costa RS, Pimentel LS, Danuello A, Romeiro NC, Viegas C Jr, Barreiro EJ, Fraga CA, Bolzani VS, Rocha MS. CNS-Selective Noncompetitive Cholinesterase Inhibitors Derived from The Natural Piperidine Alkaloid (-)- Spectaline. Eur J Pharmacol. 2008; 580(3): 339-349. [CrossRef]
- [29] Ellman GL, Courtney KD, Andres V Jr, Featherstone RM. A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity. Biochem Pharmacol. 1961; 7(2): 88-95. [CrossRef]
- [30] Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W. Screening for Acetylcholinesterase Inhibitory Activity in Plants Used in Thai Traditional Rejuvenating and Neurotonic Remedies. J Ethnopharmacol. 2003; 89(2-3): 261-264. [CrossRef]
- [31] Sirimangkalakitti N, Olatunji OJ, Changwichit K, Saesong T, Chamni S, Chanvorachote P, Ingkaninan K, Plubrukarn A, Suwanborirux K. Bromotyrosine Alkaloids with Acetylcholinesterase Inhibitory Activity from the Thai Sponge Acanthodendrilla sp. Nat Prod Commun. 2015; 10(11): 1945-1949. [CrossRef]