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

doi:10.1007/s13659-020-00290-w

应用天然产物 ›› 2021, Vol. 11 ›› Issue (3): 315-324.DOI: 10.1007/s13659-020-00290-w

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

收稿日期:2020-08-23 修回日期:2020-11-23 出版日期:2021-06-24 发布日期:2021-06-04
通讯作者: Hajira Banu Haroon

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

Received:2020-08-23 Revised:2020-11-23 Online:2021-06-24 Published:2021-06-04
Contact: Hajira Banu Haroon

摘要/Abstract

摘要： 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.

关键词: Hemidesmus indicus var. pubescens, Aldose reductase, Polyol pathway, Diabetic cataract

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.

Key words: Hemidesmus indicus var. pubescens, Aldose reductase, Polyol pathway, Diabetic cataract

Hajira Banu Haroon, Vijaybhanu Perumalsamy, Gouri Nair, Dhanusha Koppal Anand, Rajitha Kolli, Joel Monichen, Kanchan Prabha. 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[J]. 应用天然产物, 2021, 11(3): 315-324.

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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

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

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