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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

In Silico and In Vivo Studies of Decursin Isolated From the Ethanolic Extract of Feronia elephantum Correa (Rutaceae) Bark as a Potential Antidiabetic and Antihyperlipidemic Agents in STZ-induced Diabetic Rats

Author(s): Sunayana Vikhe*, Rahul Kunkulol and Dipak Raut

Volume 20, Issue 5, 2023

Published on: 11 August, 2022

Page: [517 - 535] Pages: 19

DOI: 10.2174/1570180819666220512101855

Price: $65

Abstract

Background: Feronia elephantum (Rutaceae), frequently named wood apple, is a preferable medicinal plant. In Ayurveda, its bark has been recommended for treating diabetes. In addition, it is one of the active chemical constituents, decursin, shown in recent research to significantly impact colon cancer, breast cancer, Alzheimer's disease, inflammation, and ulcerative colitis.

Objective: The present study was carried out to investigate the traditional use of Feronia elephantum bark in streptozotocin-induced diabetes and lipid-lowering action in rats. Decursin has been isolated from the bark and tested for in vitro and in vivo biological activities.

Methods: The Soxhlet extraction method obtained the ethanolic extract, and fractionation was done with column chromatography and TLC. The structure of isolated decursin has been confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy.

Results: The decursin noticeably depletes increased blood glucose levels and positively affects altered lipid profiles after administering a dose of 150 mg/kg orally compared with the hypoglycemic drug metformin. In molecular docking simulations, decursin exhibited excellent inhibition of α-amylase, dipeptidyl peptidase-IV, and moderate activity against α-glucosidase and glucokinase. Furthermore, the enzymes 3- hydroxy-3-methylglutaryl coenzyme A and Niemann-Pick C1-Like 1 are ideal targets to control hyperlipidemia and have shown moderate inhibition by decursin.

Conclusion: From these results, it has been concluded that decursin is the perfect candidate for further optimization as a lead molecule to treat diabetes and hyperlipidemia.

Keywords: α-amylase, α-glucosidase, dipeptidyl peptidase-IV, glucokinase, HMG-CoA, NPC1L1.

Graphical Abstract
[1]
Pal, M. Medicinal chemistry approaches for glucokinase activation to treat type 2 diabetes. Curr. Med. Chem., 2009, 16(29), 3858-3874.
[http://dx.doi.org/10.2174/092986709789177993] [PMID: 19747136]
[2]
Zelent, D.; Najafi, H.; Odili, S.; Buettger, C.; Weik-Collins, H.; Li, C.; Doliba, N.; Grimsby, J.; Matschinsky, F.M. Glucokinase and glucose homeostasis: Proven concepts and new ideas. Biochem. Soc. Trans., 2005, 33(Pt 1), 306-310.
[http://dx.doi.org/10.1042/BST0330306] [PMID: 15667334]
[3]
Grewal, A.S.; Sekhon, B.S.; Lather, V. Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus. Mini Rev. Med. Chem., 2014, 14(7), 585-602.
[http://dx.doi.org/10.2174/1389557514666140722082713] [PMID: 25052034]
[4]
Singh, R.; Lather, V.; Pandita, D.; Judge, V.; Arumugam, K.; Grewal, A. Synthesis, docking and antidiabetic activity of some newer benzamide derivatives as potential glucokinase activators. Lett. Drug Des. Discov., 2016, 14(5), 540-553.
[http://dx.doi.org/10.2174/1570180813666160819125342]
[5]
Fyfe, M.C.T.; Procter, M.J. Glucokinase activators as potential antidiabetic agents possessing superior glucose-lowering efficacy. Drugs Future, 2009, 34(8), 641-653.
[http://dx.doi.org/10.1358/dof.2009.034.08.1394557]
[6]
Grewal, A.S.; Sharma, K.; Singh, S.; Singh, V.; Pandita, D.; Lather, V. Design, synthesis and antidiabetic activity of novel sulfamoyl benzamide derivatives as glucokinase activators. J. Pharm. Technol. Res. Manag., 2018, 6(2), 115-124.
[http://dx.doi.org/10.15415/jptrm.2018.62008]
[7]
Saranya, R.; Thirumalai, T.; Hemalatha, M.; Balaji, R.; David, E. Pharmacognosy of Enicostemma littorale: A review. Asian Pac. J. Trop. Biomed., 2013, 3(1), 79-84.
[http://dx.doi.org/10.1016/S2221-1691(13)60028-3] [PMID: 23570022]
[8]
Indumathi, C.; Durgadevi, G.; Nithyavani, S.; Gayathri, P.K. Estimation of terpenoid content and its antimicrobial property in enicostemma litorrale. Int. J. Chemtech Res., 2014, 6(9), 4264-4267.
[9]
Abirami, P.; Gomathinayagam, M.; Panneerselvam, R. Preliminary study on the antimicrobial activity of Enicostemma littorale using different solvents. Asian Pac. J. Trop. Med., 2012, 5(7), 552-555.
[http://dx.doi.org/10.1016/S1995-7645(12)60097-2] [PMID: 22647818]
[10]
Rajagopal, K.; Sasikala, K. Antihyperglycaemic and antihyperlipidaemic effects of Nymphaea stellata in alloxan-induced diabetic rats. Singapore Med. J., 2008, 49(2), 137-141.
[PMID: 18301841]
[11]
Valiathan, M.S. Healing Plants. Curr. Sci., 1998, 75(11), 1122-1127.
[http://dx.doi.org/10.1007/978-3-319-95681-7_300057]
[12]
Harborne, J.B. Indian Medicinal Plants. A Compendium of 500 Species. Vol.1; Edited by P. K. Warrier, V. P. K. Nambiar and C. Ramankutty. J. Pharm. Pharmacol., 2011, 46(11), 935.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb05722.x]
[13]
Hingwasia, N.; Khare, S.; Dubey, B.K.; Joshi, A.; Dhakad, S.; Jain, A. Evaluation on antidiabetic activity of hydroalcoholic extract of bark of Feronia limonia. Asian J. Pharm. Pharmacol., 2018, 4(2), 168-172.
[http://dx.doi.org/10.31024/ajpp.2018.4.2.11]
[14]
Kumar, A.S.; Venkatesalu, V.; Kannathasan, K.; Chandrasekaran, M. Chemical constituents and antibacterial activity of the leaf essential oil of Feronia limonia. Indian J. Microbiol., 2010, 50(S1)(Suppl. 1), 70-73.
[http://dx.doi.org/10.1007/s12088-010-0052-7] [PMID: 22815575]
[15]
Siridechakorn, I.; Laphookhieo, S. Chemical constituents from Feronia limonia roots. Chem. Nat. Compd., 2012, 48(2), 308-309.
[http://dx.doi.org/10.1007/s10600-012-0231-3]
[16]
MacLeod, J.K.; Moeller, P.D.R.; Bandara, B.M.R.; Leslie Gunatilaka, A.A.; Wijeratne, E.M.K. Acidissimin, a new limonoid from Limonia acidissima. J. Nat. Prod., 1989, 52(4), 882-885.
[http://dx.doi.org/10.1021/np50064a040]
[17]
Son, S.H.; Park, K.K.; Park, S.K.; Kim, Y.C.; Kim, Y.S.; Lee, S.K.; Chung, W.Y. Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytother. Res., 2011, 25(7), 959-964.
[http://dx.doi.org/10.1002/ptr.3372] [PMID: 21170925]
[18]
Kim, J.H.; Jung, J.H.; Kim, S.H.; Jeong, S.J. Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association. Phytother. Res., 2014, 28(2), 238-244.
[http://dx.doi.org/10.1002/ptr.4986] [PMID: 23580332]
[19]
Li, L.; Li, W.; Jung, S.W.; Lee, Y.W.; Kim, Y.H. Protective effects of decursin and decursinol angelate against amyloid β-protein-induced oxidative stress in the PC12 cell line: The role of Nrf2 and antioxidant enzymes. Biosci. Biotechnol. Biochem., 2011, 75(3), 434-442.
[http://dx.doi.org/10.1271/bbb.100606] [PMID: 21389625]
[20]
Shehzad, A.; Parveen, S.; Qureshi, M.; Subhan, F.; Lee, Y.S. Decursin and decursinol angelate: Molecular mechanism and therapeutic potential in inflammatory diseases. Inflamm. Res., 2018, 67(3), 209-218.
[http://dx.doi.org/10.1007/s00011-017-1114-7] [PMID: 29134229]
[21]
Oh, S.R.; Ok, S.; Jung, T.S.; Jeon, S.O.; Park, J.M.; Jung, J.W.; Ryu, D.S. Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis. Asian Pac. J. Trop. Med., 2017, 10(9), 864-870.
[http://dx.doi.org/10.1016/j.apjtm.2017.08.017] [PMID: 29080614]
[22]
Vikhe, S.; Nirmal, S. Antiallergic and antihistaminic actions of Ceasalpinia bonducella seeds: Possible role in treatment of asthma. J. Ethnopharmacol., 2018, 216, 251-258.
[http://dx.doi.org/10.1016/j.jep.2017.12.007] [PMID: 29247697]
[23]
Thorburn Burns, D. Plant drug analysis: A thin layer chromatography atlas. Anal. Chim. Acta, 1986, 181, 294-295.
[http://dx.doi.org/10.1016/S0003-2670(00)85252-6]
[24]
Ajibade, T.O.; Arowolo, R.; Olayemi, F.O. Phytochemical screening and toxicity studies on the methanol extract of the seeds of Moringa oleifera. J. Complement. Integr. Med., 2013, 10(1)
[http://dx.doi.org/10.1515/jcim-2012-0015] [PMID: 23652639]
[25]
Dallakyan, S.; Olson, A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol., 2015, 1263, 243-250.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19] [PMID: 25618350]
[26]
Miyata, T. Discovery studio modeling environment. Ensemble, 2015, 17(2), 98-104.
[27]
Rappé, A.K.; Casewit, C.J.; Colwell, K.S.; Goddard, W.A., III; Skiff, W.M. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J. Am. Chem. Soc., 1992, 114(25), 10024-10035.
[http://dx.doi.org/10.1021/ja00051a040]
[28]
Khan, S.L.; Siddiqui, F.A.; Jain, S.P.; Sonwane, G.M. Discovery of potential inhibitors of SARS-CoV-2 (COVID-19) Main Protease (Mpro) from Nigella Sativa (Black Seed) by molecular docking study. Coronaviruses, 2020, 2(3), 384-402.
[http://dx.doi.org/10.2174/2666796701999200921094103]
[29]
Khan, S.L.; Siddiui, F.A. Beta-sitosterol: As immunostimulant, antioxidant and inhibitor of SARS-CoV-2 spike glycoprotein. Arch. Pharmacol. Ther., 2020, 2(1)
[http://dx.doi.org/10.33696/Pharmacol.2.014]
[30]
Chaudhari, R.N.; Khan, S.L.; Chaudhary, R.S.; Jain, S.P.; Siddiqui, F.A. B-Sitosterol: Isolation from muntingia calabura linn bark extract, structural elucidation and molecular docking studies as potential inhibitor of SARS-CoV-2 Mpro (COVID-19). Asian J. Pharm. Clin. Res., 2020, 13(5), 204-209.
[http://dx.doi.org/10.22159/ajpcr.2020.v13i5.37909]
[31]
Khan, S.L.; Siddiqui, F.A.; Shaikh, M.S.; Nema, N.V.; Shaikh, A.A. Discovery of potential inhibitors of the receptor-binding Domain (RBD) of pandemic disease-causing SARS-CoV-2 spike glycoprotein from triphala through molecular docking. Curr. Chinese Chem, 2021, 01.
[http://dx.doi.org/10.2174/2666001601666210322121802]
[32]
Bhattaram, V.A.; Graefe, U.; Kohlert, C.; Veit, M.; Derendorf, H. Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine, 2002, 9(Suppl. 3), 1-33.
[http://dx.doi.org/10.1078/1433-187X-00210] [PMID: 12222652]
[33]
Biarnés, M.; Montolio, M.; Nacher, V.; Raurell, M.; Soler, J.; Montanya, E. Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes, 2002, 51(1), 66-72.
[http://dx.doi.org/10.2337/diabetes.51.1.66] [PMID: 11756324]
[34]
Giribabu, N.; Kumar, K.E.; Rekha, S.S.; Muniandy, S.; Salleh, N. Chlorophytum borivilianum root extract maintains near normal blood glucose, insulin and lipid profile levels and prevents oxidative stress in the pancreas of streptozotocin-induced adult male diabetic rats. Int. J. Med. Sci., 2014, 11(11), 1172-1184.
[http://dx.doi.org/10.7150/ijms.9056] [PMID: 25249786]
[35]
Prabu, D.; Nappinnai, M.; Ponnudurai, K.; Thirugnanasambanthan, A.; Srinivasan, S.; Ramvikas, M. Effects of Turnera ulmifolia (Linn.) leaves on blood glucose level in normal and alloxan-induced diabetic rats. Iran. J. Pharmacol. Ther., 2009, 8(2), 77-81.
[36]
Garber, A.J.; Attenuating, C.V. Attenuating CV risk factors in patients with diabetes: clinical evidence to clinical practice. Diabetes Obes. Metab., 2002, 4(s1)(Suppl. 1), S5-S12.
[http://dx.doi.org/10.1046/j.1462-8902.2001.00038.x] [PMID: 11843949]
[37]
Hwang, J.T.; Kim, S.H.; Hur, H.J.; Kim, H.J.; Park, J.H.; Sung, M.J.; Yang, H.J.; Ryu, S.Y.; Kim, Y.S.; Cha, M.R.; Kim, M.S.; Kwon, D.Y. Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet. Phytother. Res., 2012, 26(5), 633-638.
[http://dx.doi.org/10.1002/ptr.3612] [PMID: 21972114]
[38]
Lenzen, S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia, 2008, 51(2), 216-226.
[http://dx.doi.org/10.1007/s00125-007-0886-7] [PMID: 18087688]
[39]
Kang, S.Y.; Kim, Y.C. Decursinol and decursin protect primary cultured rat cortical cells from glutamate-induced neurotoxicity. J. Pharm. Pharmacol., 2007, 59(6), 863-870.
[http://dx.doi.org/10.1211/jpp.59.6.0013] [PMID: 17637179]
[40]
Kim, J.H.; Jeong, S.J.; Kwon, H.Y.; Park, S.Y.; Lee, H.J.; Lee, H.J.; Lieske, J.C.; Kim, S.H. Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells. Biol. Pharm. Bull., 2010, 33(8), 1279-1284.
[http://dx.doi.org/10.1248/bpb.33.1279] [PMID: 20686219]
[41]
Kim, W.J.; Lee, S.J.; Choi, Y.D.; Moon, S.K. Decursin inhibits growth of human bladder and colon cancer cells via apoptosis, G1-phase cell cycle arrest and extracellular signal-regulated kinase activation. Int. J. Mol. Med., 2010, 25(4), 635-641.
[http://dx.doi.org/10.3892/ijmm-00000386] [PMID: 20198313]
[42]
Tundis, R.; Loizzo, M.R.; Menichini, F. Natural Products as α-Amylase and α-Glucosidase Inhibitors and Their Hypoglycaemic Potential in the Treatment of Diabetes: An Update. Mini Rev. Med. Chem., 2010, 10(4), 315-331.
[http://dx.doi.org/10.2174/138955710791331007] [PMID: 20470247]
[43]
Gupta, R.; Walunj, S.S.; Tokala, R.K.; Parsa, K.V.; Singh, S.K.; Pal, M. Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr. Drug Targets, 2009, 10(1), 71-87.
[http://dx.doi.org/10.2174/138945009787122860] [PMID: 19149538]
[44]
Lacroix, I.M.E.; Li-Chan, E.C.Y. Food-derived dipeptidyl-peptidase IV inhibitors as a potential approach for glycemic regulation - current knowledge and future research considerations. Trends Food Sci. Technol., 2016, 54, 1-16.
[http://dx.doi.org/10.1016/j.tifs.2016.05.008]
[45]
Smelcerovic, A.; Miljkovic, F.; Kolarevic, A.; Lazarevic, J.; Djordjevic, A.; Kocic, G.; Anderluh, M. An overview of recent dipeptidyl peptidase-IV inhibitors: linking their structure and physico-chemical properties with sar, pharmacokinetics and toxicity. Curr. Top. Med. Chem., 2015, 15(23), 2342-2372.
[http://dx.doi.org/10.2174/1568026615666150619142731] [PMID: 26088350]
[46]
Salvatore, T.; Carbonara, O.; Cozzolino, D.; Torella, R.; Sasso, F.C. Adapting the GLP-1-signaling system to the treatment of type 2 diabetes. Curr. Diabetes Rev., 2007, 3(1), 15-23.
[http://dx.doi.org/10.2174/157339907779802076] [PMID: 18220652]
[47]
Kushwaha, R.N.; Haq, W.; Katti, S.B. Sixteen-years of clinically relevant dipeptidyl peptidase-IV (DPP-IV) inhibitors for treatment of type-2 diabetes: a perspective. Curr. Med. Chem., 2014, 21(35), 4013-4045.
[http://dx.doi.org/10.2174/0929867321666140915143309] [PMID: 25245373]
[48]
Liu, Y.; Hu, Y.; Liu, T. Recent advances in non-peptidomimetic dipeptidyl peptidase 4 inhibitors: medicinal chemistry and preclinical aspects. Curr. Med. Chem., 2012, 19(23), 3982-3999.
[http://dx.doi.org/10.2174/092986712802002491] [PMID: 22709010]
[49]
Salvo, F.; Moore, N.; Arnaud, M.; Robinson, P.; Raschi, E.; De Ponti, F.; Bégaud, B.; Pariente, A. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ, 2016, 353, i2231.
[http://dx.doi.org/10.1136/bmj.i2231] [PMID: 27142267]
[50]
Scheen, A.J. Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes. Expert Opin. Drug Saf., 2015, 14(4), 505-524.
[http://dx.doi.org/10.1517/14740338.2015.1006625] [PMID: 25630605]
[51]
Tella, S.H.; Rendell, M.S. DPP-4 inhibitors: focus on safety. Expert Opin. Drug Saf., 2015, 14(1), 127-140.
[http://dx.doi.org/10.1517/14740338.2015.977863] [PMID: 25488788]
[52]
Gallwitz, B. Clinical Use of DPP-4 Inhibitors. Front. Endocrinol. (Lausanne), 2019, 10, 389.
[http://dx.doi.org/10.3389/fendo.2019.00389] [PMID: 31275246]
[53]
Kamata, K.; Mitsuya, M.; Nishimura, T.; Eiki, J.; Nagata, Y. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure, 2004, 12(3), 429-438.
[http://dx.doi.org/10.1016/j.str.2004.02.005] [PMID: 15016359]
[54]
Agius, L. Glucokinase and molecular aspects of liver glycogen metabolism. Biochem. J., 2008, 414(1), 1-18.
[http://dx.doi.org/10.1042/BJ20080595] [PMID: 18651836]
[55]
Iynedjian, P.B. Molecular physiology of mammalian glucokinase. Cell. Mol. Life Sci., 2009, 66(1), 27-42.
[http://dx.doi.org/10.1007/s00018-008-8322-9] [PMID: 18726182]
[56]
Irwin, D.M.; Tan, H. Evolution of glucose utilization: glucokinase and glucokinase regulator protein. Mol. Phylogenet. Evol., 2014, 70, 195-203.
[http://dx.doi.org/10.1016/j.ympev.2013.09.016] [PMID: 24075984]
[57]
Coghlan, M.; Leighton, B. Glucokinase activators in diabetes management. Expert Opin. Investig. Drugs, 2008, 17(2), 145-167.
[http://dx.doi.org/10.1517/13543784.17.2.145] [PMID: 18230050]
[58]
Pal, M. Recent advances in glucokinase activators for the treatment of type 2 diabetes. Drug Discov. Today, 2009, 14(15-16), 784-792.
[http://dx.doi.org/10.1016/j.drudis.2009.05.013] [PMID: 19520181]
[59]
Matschinsky, F.M.; Zelent, B.; Doliba, N.; Li, C.; Vanderkooi, J.M.; Naji, A.; Sarabu, R.; Grimsby, J. Glucokinase activators for diabetes therapy: May 2010 status report. Diabetes Care, 2011, 34(Suppl. 2), S236-S243.
[http://dx.doi.org/10.2337/dc11-s236] [PMID: 21525462]
[60]
Matschinsky, F.M.; Porte, D. Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics. F1000 Med. Rep., 2010, 2(1), 43.
[http://dx.doi.org/10.3410/M2-43] [PMID: 20948841]
[61]
Filipski, K.J.; Futatsugi, K.; Pfefferkorn, J.A.; Stevens, B.D. Glucokinase activators. Pharm. Pat. Anal., 2012, 1(3), 301-311.
[http://dx.doi.org/10.4155/ppa.12.26] [PMID: 24236843]
[62]
Friesen, J.A.; Rodwell, V.W. The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases. Genome Biol., 2004, 5(11), 248.
[http://dx.doi.org/10.1186/gb-2004-5-11-248] [PMID: 15535874]
[63]
Wu, N.; Sarna, L.K.; Hwang, S.Y.; Zhu, Q.; Wang, P.; Siow, Y.L. O, K. Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during high fat diet feeding. Biochim. Biophys. Acta, 2013, 1832(10), 1560-1568.
[http://dx.doi.org/10.1016/j.bbadis.2013.04.024] [PMID: 23651731]
[64]
Betters, J.L.; Yu, L. NPC1L1 and cholesterol transport. FEBS Lett., 2010, 584(13), 2740-2747.
[http://dx.doi.org/10.1016/j.febslet.2010.03.030] [PMID: 20307540]

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