Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

In Vitro α-glucosidase Inhibition and Computational Studies of Kaempferol Derivatives from Dryopteris cycanida

Author(s): Surriya Amin, Barkat Ullah, Mumtaz Ali*, Haroon Khan*, Abdur Rauf, Sher A. Khan and Eduardo Sobarzo-Sánchez*

Volume 20, Issue 9, 2020

Page: [731 - 737] Pages: 7

DOI: 10.2174/1568026620666200130161033

Price: $65


Background: Dryopteris cycadina has diverse traditional uses in the treatment of various human disorders which are supported by pharmacological studies. Similarly, the phytochemical studies of this plant led to the isolation of numerous compounds.

Methodology: The present study deals with α-glucosidase inhibition of various kaempferol derivates including kaempferol-3, 4/-di-O-α- L-rhamnopyranoside 1, kaempferol-3, 5-di-O-α-L-rhamnoside 2 and kaempferol-3,7-di-O-α- L-rhamnopyranoside 3.

Results: The results showed marked concentration-dependent inhibition of the enzyme when assayed at different concentrations and the IC50 values of compounds 1-3 were 137±9.01, 110±7.33, and 136±1.10 mM, respectively far better than standard compound, acarbose 290±0.54 mM. The computational studies revealed strong docking scores of these compounds and augmented the in vitro assay.

Conclusion: In conclusion, the isolated kaempferol derivatives 1-3 from D. cycadina exhibited potent α- glucosidase inhibition.

Keywords: Dryopteris cycadina, Kaempferol derivatives, α-glucosidase inhibition, Molecular docking studies, Isolated kaempferol derivatives, epithelial cells.

Graphical Abstract
Ichiki, H.; Miura, T.; Kubo, M.; Ishihara, E.; Komatsu, Y.; Tanigawa, K.; Okada, M. New antidiabetic compounds, mangiferin and its glucoside. Biol. Pharm. Bull., 1998, 21(12), 1389-1390.
[] [PMID: 9881663]
Ikeda, K.; Takahashi, M.; Nishida, M.; Miyauchi, M.; Kizu, H.; Kameda, Y.; Arisawa, M.; Watson, A.A.; Nash, R.J.; Fleet, G.W.; Asano, N. Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae). Carbohydr. Res., 2000, 323(1-4), 73-80.
[] [PMID: 10782288]
Khattak, S.; Khan, H. Phyto-glycosides as therapeutic target in the treatment of diabetes. Mini Rev. Med. Chem., 2018, 18(3), 208-215.
[] [PMID: 27629995]
Hakamata, W.; Kurihara, M.; Okuda, H.; Nishio, T.; Oku, T. Design and screening strategies for α-glucosidase inhibitors based on enzymological information. Curr. Top. Med. Chem., 2009, 9(1), 3-12.
[] [PMID: 19199993]
Samoshin, A.V.; Dotsenko, I.A.; Samoshina, N.M.; Franz, A.H.; Samoshin, V.V. Thio-beta-D-glucosides: Synthesis and evaluation as glycosidase inhibitors and activators. Int. J. Carbohyd. Chem., 2014, 2014(3).
Abbas, G. Al-Harrasi, A.S.; Hussain, H. Discovery and development of antidiabetic agents from natural products; Elsevier: Amsterdam, 2017, pp. 251-269.
Azam, S.S.; Uddin, R.; Wadood, A. Structure and dynamics of alpha-glucosidase through molecular dynamics simulation studies. J. Mol. Liq., 2012, 174, 58-62.
Chang, J.; Block, T.M.; Guo, J-T. Antiviral therapies targeting host ER alpha-glucosidases: current status and future directions. Antiviral Res., 2013, 99(3), 251-260.
[] [PMID: 23816430]
Taha, M.; Ismail, N.H.; Imran, S.; Wadood, A.; Rahim, F.; Saad, S.M.; Khan, K.M.; Nasir, A. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles. Bioorg. Chem., 2016, 66, 117-123.
[] [PMID: 27149363]
Holman, R.R.; Bethel, M.A.; Mentz, R.J.; Thompson, V.P.; Lokhnygina, Y.; Buse, J.B.; Chan, J.C.; Choi, J.; Gustavson, S.M.; Iqbal, N.; Maggioni, A.P.; Marso, S.P.; Öhman, P.; Pagidipati, N.J.; Poulter, N.; Ramachandran, A.; Zinman, B.; Hernandez, A.F. Effects of once-weekly exenatide on cardiovascular outcomes in Type 2 diabetes. N. Engl. J. Med., 2017, 377(13), 1228-1239.
[] [PMID: 28910237]
Papandréou, M-J.; Barbouche, R.; Guieu, R.; Kieny, M.P.; Fenouillet, E. The α-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoproteinmediated membrane fusion at the CXCR4 binding step. Mol. Pharmacol., 2002, 61(1), 186-193.
[] [PMID: 11752220]
Hua, J.; Qi, J.; Yu, B-Y. Iridoid and phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl. and their α-glucosidase inhibitory activities. Fitoterapia, 2014, 93, 67-73.
[] [PMID: 24321577]
Hirschhorn, R.; Reuser, A.J. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. Metabolic and Molecular Bases of Inherited Disease, 2001, 3, 3389-3420.
Poovitha, S.; Parani, M. In vitro and in vivo α-amylase and α-glucosidase inhibiting activities of the protein extracts from two varieties of bitter gourd (Momordica charantia L.). BMC Complement. Altern. Med., 2016, 16(1)(Suppl. 1), 185.
[] [PMID: 27454418]
Kim, Y.M.; Wang, M.H.; Rhee, H.I. A novel α-glucosidase inhibitor from pine bark. Carbohydr. Res., 2004, 339(3), 715-717.
[] [PMID: 15013410]
Gomathi, D. KALAISELVI, M.; UMA, C. In vitro α-amylase and α-glucosidase inhibitory effects of ethanolic extract of evolvulus alsinoides (L.). Intl. Res. J. Pharm., 2012, 3, 226-229.
Somsák, L.; Bokor, É.; Czifrák, K.; Juhász, L.; Tóth, M. Carbohydrate derivatives and glycomimetic compounds in established and investigational therapies of type 2 diabetes mellitus. ntech Open Access Publisher: Londom, 2011.,
Lin, A.H-M.; Lee, B-H.; Chang, W-J. Small intestine mucosal α-glucosidase: A missing feature of in vitro starch digestibility. Food Hydrocoll., 2016, 53, 163-171.
Derosa, G.; Sibilla, S. Optimizing combination treatment in the management of type 2 diabetes. Vasc. Health Risk Manag., 2007, 3(5), 665-671.
[PMID: 18078018]
Kim, S.D. Α-glucosidase inhibitor isolated from coffee. J. Microbiol. Biotechnol., 2015, 25(2), 174-177.
[] [PMID: 25502825]
Marya, ; Khan, H.; Nabavi, S.M.; Habtemariam, S. Anti-diabetic potential of peptides: Future prospects as therapeutic agents. Life Sci., 2018, 193, 153-158.
[] [PMID: 29055800]
Mink, J.N.; Singhurst, J.R.; Holmes, W.C. Dryopteris marginalis (Dryopteridaceae): new to Texas. Phytoneuron, 2010, 53, 1-6.
Vasudeva, S. Economic importance of pteridophytes. Indian Fern J, 1999, 16(1-2), 130-152.
Joshi, K.; Joshi, A.R. Ethnobotanical studies on some lower plants of the central development region, nepal. Ethnobotanical Leaflets, 2008, 2008(1), 113.
Gao, Z.; Ali, Z.; Zhao, J.; Qiao, L.; Lei, H.; Lu, Y.; Khan, I.A. Phytochemical investigation of the rhizomes of Dryopteris crassirhizoma. Phytochem. Lett., 2008, 1(4), 188-190.
Pal Singh, I.; Bharate, S.B. Phloroglucinol compounds of natural origin. Nat. Prod. Rep., 2006, 23(4), 558-591.
[] [PMID: 16874390]
Lin, Y-S.; Lee, S-S. Flavonol glycosides with α-glucosidase inhibitory activities and new flavone C-Diosides from the leaves of Machilus konishii. Helv. Chim. Acta, 2014, 97(12), 1672-1682.
Han, X.; Li, Z.; Li, C.Y.; Jia, W.N.; Wang, H.T.; Wang, C.H. Phytochemical constituents and biological activities of plants from the genus dryopteris. Chem. Biodivers., 2015, 12(8), 1131-1162.
[] [PMID: 26265567]
Liu, Q.; Hu, H-J.; Li, P-F.; Yang, Y-B.; Wu, L-H.; Chou, G-X.; Wang, Z-T. Diterpenoids and phenylethanoid glycosides from the roots of Clerodendrum bungei and their inhibitory effects against angiotensin converting enzyme and α-glucosidase. Phytochemistry, 2014, 103, 196-202.
[] [PMID: 24726372]
Ali, M.; Khan, S.A.; Rauf, A.; Khan, H.; Shah, M.R.; Ahmad, M.; Mubarak, M.S.; Hadda, T.B. Characterization and antinociceptive activity (in vivo) of kempferol-3, 4′-di-O-α-L-rhamnopyranoside isolated from Dryopteris cycadina. Med. Chem. Res., 2015, 24(8), 3218-3229.
Ali, M.; Rauf, A.; Hadda, T.B.; Bawazeer, S.; Abu-Izneid, T.; Khan, H.; Raza, M.; Khan, S.A.; Shah, S.U.; Pervez, S.; Patel, S.; Orhan, I.E.S.; Pervez, S. Mechanisms underlying anti-hyperalgesic properties of Kaempferol-3, 7-di-O-α-L-rhamnopyranoside isolated from Dryopteris cycadina. Curr. Top. Med. Chem., 2017, 17(4), 383-390.
[] [PMID: 27558683]
Peng, X.; Zhang, G.; Liao, Y.; Gong, D. Inhibitory kinetics and mechanism of kaempferol on α-glucosidase. Food Chem., 2016, 190, 207-215.
[] [PMID: 26212963]
Dewi, R.T.; Maryani, F. Antioxidant and α-Glucosidase inhibitory compounds of Centella Asiatica. Procedia Chem., 2015, 17, 147-152.
Habtemariam, S. A-glucosidase inhibitory activity of kaempferol-3-O-rutinoside. Nat. Prod. Commun., 2011, 6(2), 201-203.
[] [PMID: 21425674]
Hua, F.; Zhou, P.; Wu, H-Y.; Chu, G-X.; Xie, Z-W.; Bao, G-H. Inhibition of α-glucosidase and α-amylase by flavonoid glycosides from Lu’an GuaPian tea: molecular docking and interaction mechanism. Food Funct., 2018, 9(8), 4173-4183.
[] [PMID: 29989631]
Nabavi, S.F.; Khan, H.; D’onofrio, G.; Šamec, D.; Shirooie, S.; Dehpour, A.R.; Argüelles, S.; Habtemariam, S.; Sobarzo-Sanchez, E. Apigenin as neuroprotective agent: Of mice and men. Pharmacol. Res., 2018, 128, 359-365.
[] [PMID: 29055745]
Rauf, A.; Khan, R.; Raza, M.; Khan, H.; Pervez, S.; De Feo, V.; Maione, F.; Mascolo, N. Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect. Fitoterapia, 2015, 103, 129-135.
[] [PMID: 25819005]
Khan, H.; Marya, ; Amin, S.; Kamal, M.A.; Patel, S. Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects. Biomed. Pharmacother., 2018, 101, 860-870.
[] [PMID: 29635895]
Rauf, A.; Uddin, G.; Siddiqui, B.S.; Khan, H.; Shah, S.U.A.; Ben Hadda, T.; Mabkhot, Y.N.; Farooq, U.; Khan, A. Antinociceptive and anti-inflammatory activities of flavonoids isolated from Pistacia integerrima galls. Complement. Ther. Med., 2016, 25, 132-138.
[] [PMID: 27062961]
Khan, H.; Jawad, M.; Kamal, M.A.; Baldi, A.; Xiao, J.; Nabavi, S.M.; Daglia, M. Evidence and prospective of plant derived flavonoids as antiplatelet agents: Strong candidates to be drugs of future. Food Chem. Toxicol., 2018, 119, 355-367.
[] [PMID: 29448091]
Taukoorah, U.; Mahomoodally, M.F. Crude aloe vera gel shows antioxidant propensities and inhibits pancreatic lipase and glucose movement in vitro. Adv. Pharmacol. Sci., 2016, 2016(1), 1-9.
[] [PMID: 26880905]
Taha, M.; Ismail, N.H.; Imran, S.; Wadood, A.; Rahim, F.; Ali, M.; Rehman, A.U. Novel quinoline derivatives as potent In vitro α-glucosidase inhibitors: In silico studies and SAR predictions. MedChemComm, 2015, 6, 1826-1836.
Taha, M.; Ismail, N.H.; Imran, S.; Wadood, A.; Ali, M.; Rahim, F.; Khan, A.A.; Riaz, M. Novel thiosemicarbazide–oxadiazole hybrids as unprecedented inhibitors of yeast α-glucosidase and in silico binding analysis. RSC Advances, 2016, 6(40), 33733-33742.

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy