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Repression of Polyol Pathway Activity by Hemidesmus indicus var. pubescens R.Br. Linn Root Extract, an Aldose Reductase Inhibitor: An In Silico and Ex Vivo Study |
| Hajira Banu Haroon1, Vijaybhanu Perumalsamy2, Gouri Nair1, Dhanusha Koppal Anand1, Rajitha Kolli1, Joel Monichen2, Kanchan Prabha3 |
1 Department of Pharmacology, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, Bengaluru, Karnataka 560054, India;
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, Bengaluru, Karnataka 560054, India;
3 Department of Pharmaceutics, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, Bengaluru, Karnataka 560054, India |
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Abstract Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of Hemidesmus indicus var. pubescens root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between β-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that β-sitosterol (-10.2 kcal/mol) and hemidesmin-2 (-8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate-100 μg/mL (standard) and test extract (500 and 1000 μg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that H. indicus var. pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.
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| Keywords
Hemidesmus indicus var. pubescens
Aldose reductase
Polyol pathway
Diabetic cataract
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Corresponding Authors:
Hajira Banu Haroon
E-mail: hajirabanu.pg.ph@msruas.ac.in,hajirabanu.banu@gmail.com
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Issue Date: 04 June 2021
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1. M.S. Moghaddam, P.A. Kumar, G.B. Reddy, V.S. Ghole, Effect of Diabecon on sugar-induced lens opacity in organ culture:mechanism of action. J. Ethnopharmacol. 97(2), 397-403 (2005)
2. F. Giacco, M. Brownlee, Oxidative stress and diabetic complications. Circ. Res. 107(9), 1058-1070 (2010)
3. H. Kiziltoprak, K. Tekin, M. Inanc, Y.S. Goker, Cataract in diabetes mellitus. World. J. Diabetes. 10(3), 140-153 (2019)
4. T. Lakshmi, R. Rajendran, Hemidesmus indicus commonly known as Indian Sarasaparilla:an update. Int. J. Pharm. Bio. Sci. 4(4), 397-404 (2013)
5. R.N. Chopra, S.L. Nayar, I.C. Chopra, Glossary of Indian Medicinal Plants (CSIR, New Delhi, 1980).
6. M.I. Alam, B. Auddy, A. Gomes, Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and Plucheaindica) root extracts. J. Phytother Res. 10(1), 58-61 (1996)
7. S. Nandy, A. Mukherjee, D.K. Pandey, P. Ray, A. Dey, Indian Sarsaparilla (Hemidesmus indicus):recent progress in research on ethnobotany, phytochemistry and pharmacology. J. Ethnopharmacol. 254, 112609 (2020)
8. N.K. Mary, C.R. Achuthan, In vitro antioxidant and antithrombotic activity of Hemidesmus indicus (L.) R.Br. J. Ethnopharmacol. 87, 187-191 (2003)
9. M. Murali, G.K. Puneetha, M.C. Thriveni, M.H. Niranjan, G.R. Shivamurthy, S.R. Niranjana, H.S. Prakash, K.N. Amruthesh, Phytochemical screening and antioxidant activity of hemi-parasitic Indian mistletoe Viscum nepalense Sprengel. J. Pharm. Res. 4(10), 3348-3350 (2011)
10. S. Darbari, A. Agrawal, P. Verma, T.P. Rai, R. Garg, S.B. Chaudhary, Antimicrobial activity of root extracts of the medicinal plant Hemidesmus indicus (L.) R. Br. Var. Pubescens (w & a) H. K. F. World J. Pharm. Pharm. Sci. 5(4), 1556-1562 (2016)
11. S. Darbari, V. Madhavan, E. Maheswari, S.N. Yoganarasimhan, Antipyretic and antiepileptic activity studies on the roots of Hemidesmus indicus (L.) R. BR. VAR. Pubescens (WT & ARN) HOOK F. World J Pharm Res 4, 1267-1272 (2015)
12. A. Murali, P. Ashok, V. Madhavan, Hepatoprotective effect of Hemidesmus indicus var pubescens leaf extract on paracetamol induced hepatic damage. Med. Chem. Drug Dis. 3(2), 103-115 (2012)
13. C. Abad-Zapatero, Expert Opin Drug Discov. 2, 469 (2007)
14. A. Snow, B. Shieh, K.C. Chang, A. Pal, P. Lenhart, D. Ammar, P. Ruzycki, S. Palla, G.B. Reddy, J.M. Petrash, Aldose reductase expression as a risk factor for cataract. Chem. Biol. Interact. 234, 247-253 (2015)
15. F. Alwadani, The role and prevalence of polyol pathway and oxidative stress markers as risk factors for diabetic cataract in adult type-I diabetic and diabetic cataract Saudi patients. J. Clin. Exp. Ophthalmol. 7, 558 (2016)
16. M. Umamaheswari, T. Dhinesh, V. Sivashanmugam, J. Subhadradev, A. Madeswaran, Anticataract and antioxidant activities of Achyranthes aspera Linn against glucose-induced cataractogenesis using goat lenses. J. Nat. Prod. Plant Resour. 2, 153-161 (2012)
17. Q. Lu, M. Hao, W. Wu, N. Zhang, A.T. Isaac, J. Yin, X. Zhu, L. Du, X. Yin, Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway. Acta. Biochem. Pol. 65, 35-41 (2018)
18. L.T. Chylack, J.H. Kinashita, A biochemical evaluation of a cataract induced in a high glucose medium. Invest. Opthalmol. 8, 401-412 (1969)
19. R. Thiagarajan, R. Manikandan, Antioxidants and cataract. Free Radical Res. 47(5), 337-345 (2013)
20. M. Ghamali, S. Chtita, R. Hmamouchi, A. Adad, M. Bouachrine, T. Lakhlifi, The inhibitory activity of aldose reductase of flavonoid compounds:combining DFT and QSAR calculations. J. Taibah. Univ. Sci. 10, 534-542 (2016)
21. C.K. Kokate (ed.), Practical Pharmacognosy (Vallabh Prakashan, New Delhi, 1999).
22. A.S. Grewal, N. Sharma, S. Singh, S. Arora, Molecular docking evaluation of some natural phenolic compounds as aldose reductase inhibitors for diabetic complications. JPTRM. 5, 135-148 (2017)
23. R. Thiagarajan, M.K.N.S. Varsha, V. Srinivasan, R. Ravichandran, K. Saraboji, Vitamin K1 prevents diabetic cataract by inhibiting lens aldose reductase 2 (ALR2) activity. Sci Rep. 9, 14684 (2019)
24. M. Kumar, T. Singh, J. Ali, L.K. Tyagi, In vitro anticataract activity of Zingiber officinale on goat lenses. Int J Pharm. Biol. Archives. 2(5), 1430-1433 (2011)
25. A. Ramesh, K.P. Praveen, R.D. Karthik, K. Prasad, Preclinical evaluation of anticataract activity of different fractions isolated from methanolic extract of whole plant of Hygrophila auriculata on isolated goat lens:by in-vitro model. J. Chem. Pharm. Res. 5(11), 322 (2013)
26. G. Somani, S. Sathaye, Bioactive fraction of Saraca indica prevents diabetes induced cataractogenesis:an aldose reductase inhibitory activity. Pharmacogn. Mag. 11, 102-110 (2015)
27. S.P. Patil, P.D. Jain, J.S. Sancheti, P.J. Ghumatkar, R. Tambe, S. Sathaye, Neuroprotective and neurotrophic effects of apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology 86, 192-202 (2014)
28. M. Sumanth, R. Ahmed, Antihepatotoxic and antioxidant activity of root of Taxacum officinale in CCL4 intoxicated rats. Phcog Mag. 4, 13 (2008)
29. H.J. Gitelmen, Ann. Biochem. 18, 521 (1967)
30. E.S. Berthelot, A standard method for calcium estimation. Clin. Chem. Acta 46, 46 (1973)
31. U. Grelach, W. Hiby, H.U. Bergmeyer (eds.), Methods of Enzymatic Analysis:Sorbitol Dehydrogenase (Academic Press, New York, 1974).
32. H.B. Haroon, A. Murali, Alcohol extract of Wattakaka volubilis (L.F) stapf root inhibits aldose reductase to prevent diabetes associated cataract formation in rats. Indian J. Pharm. Educ. Res. 53(2), 261-267 (2019)
33. G. Schumann, R. Bonora, F. Ceriotti, G. Ferard, IFFC primary reference procedure for the measurement of catalytic activity concentrations of enzymes at 37℃. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase. Clin. Chem. Lab Med. 40, 643-648 (2002) |
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