Pueraria tuberosa as Dipeptidyl-Peptidase-IV Inhibitor Prevents Streptozotocin-Induced Intestinal Stress

Shivani Srivastava; Harsh Pandey; Surya Kumar  Singh; Yamini Bhusan Tripathi

doi:10.3889/oamjms.2021.4830

Authors

Shivani Srivastava Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, India
Harsh Pandey Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, India
Surya Kumar Singh Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, India
Yamini Bhusan Tripathi Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, India

DOI:

https://doi.org/10.3889/oamjms.2021.4830

Keywords:

Pueraria tuberosa, Diabetic Complications, Dipeptidyl-Peptidase-IV, Streptozotocin, Intestine, Apoptosis

Abstract

BACKGROUND: Enhanced expression of PTY-2 dipeptidyl-peptidase-IV (DPP-IV) has been found to improve has been found in various intestinal diseases. Pueraria tuberosa tuber water extract-2 (PTY-2) is already known to have DPP-IV inhibitory potential. At the mRNA level, this inhibition has not yet been investigated. Increased incretin secretion due to inhibition of DPP-IV could lead to the suppression of stress and apoptosis of intestinal cells.

AIM: In this research, we tried to study the antioxidant, anti-apoptotic, and DPP-IV inhibitory effect of PTY 2 against intestinal damage induced by STZ.

METHODS: We found morphological damage to the intestine following streptozotocin (STZ) injection (65 mg/kg bw) in male Charles foster rats through histological examination. Superoxide dismutase (SOD) and DPP-IV mRNA expressions were analyzed by polymerase chain reaction and cell apoptosis was examined by tunnel assay and Bcl 2 immunoexpression.

RESULTS: In STZ-induced diabetic control, the number and length of villi were decreased, but these damages were reversed by 10 days of PTY-2 treatment. SOD expression was found to be decreased whereas DPP-IV expression was enhanced with significant intestinal cell apoptosis in the diabetic control group. Treatment with PTY-2 decreases stress by upregulating SOD expression and by downregulating the expression of DPP-IV. These PTY-2 recoveries contribute to the suppression of apoptosis in the intestinal cells.

CONCLUSION: The protective action of PTY-2 against STZ mediated intestinal damage is demonstrated by these short studies. Therefore, PTY-2 may be taken as a herbal remedy for diabetes-induced intestinal damages.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Akinola OB, Zatta L, Dosumu OO, Akinola OS, Adelaja AA, Dini L, et al. Intestinal lesions of streptozotocin-induced diabetes and the effects of Azadirachta indica treatment. Pharmacologyonline. 2009;3:872-81.

Karaca T, Uslu S, Yörük M. Effects of green tea and ginseng on villus length and crypt depth and on the distribution of mast and goblet cells in the small intestine of rats with streptozotocin (stz)-induced diabetes. Philipp J Vet Med. 2011;48(2):86-94.

Lambeir AM, Durinx C, Scharpé S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: An update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003;40(3):209-94. https://doi.org/10.1080/713609354 PMid:12892317

Burcelin R. The gut-brain axis: A major glucoregulatory player. Diabetes Metab. 2010;36(3):S54-8. https://doi.org/10.1016/ s1262-3636(10)70468-7 PMid:21211737

Yusta B, Holland D, Waschek JA, Drucker DJ. Intestinotrophic glucagon-like peptide-2 (GLP-2) activates intestinal gene expression and growth factor-dependent pathways independent of the vasoactive intestinal peptide gene in mice. Endocrinology. 2012;153(6):2623-32. https://doi.org/10.1210/en.2012-1069 PMid:22535770

Brubaker PL, Izzo A, Hill M, Drucker DJ. Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol. 1997;272(6):E1050-8. PMid:9227451

Hartmann B, Thulesen J, Kissow H, Thulesen S, Orskov C, Ropke C, et al. Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. Endocrinology. 2000;141(11):4013-20. https://doi.org/10.1210/endo.141.11.7752 PMid:11089531

Darmoul D, Rouyer-Fessard C, Blais A, Voisin T, Sapin C, Baricault L, et al. Dipeptidyl peptidase IV expression in rat jejunal crypt-villus axis is controlled at mRNA level. Am J Physiol. 1991;261(5):G763-9. https://doi.org/10.1152/ajpgi.1991.261.5.g763 PMid:1683165

Inoue T, Higashiyama M, Kaji I, Rudenkyy S, Higuchi K, Guth PH, et al. Dipeptidyl peptidase IV inhibition prevents the formation and promotes the healing of indomethacin-induced intestinal ulcers in rats. Dig Dis Sci. 2014;59(6):1286-95. https://doi.org/10.1007/s10620-013-3001-6 PMid:24379150

Srivastava S, Koley TK, Singh SK, Tripathi YB. The tuber extract of Pueraria tuberosa Linn. competitively inhibits DPP-IV activity in normoglycemic rats. Int J Pharm Pharm Sci. 2015;7(9):227-31.

Srivastava S, Shree P, Tripathi YB. Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: In silico and experimental approach. J Diabetes Metab Disord. 2017;16(1):46. PMid:29201861

Srivastava S, Yadav D, Tripathi Y. DPP-IV inhibitory potential of methanolic extract of Pueraria tuberosa in liver of alloxan induced diabetic model. Biosci Biotechnol Res Asia. 2018;15(1):1-4.

Srivastava S, Pandey H, Singh SK, Tripathi YB. Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets. Biosci Trends. 2019;13(5):382-93. PMid:31597821

Pandey N, Tripathi YB. Antioxidant activity of tuberosin isolated from Pueraria tuberose Linn. J Inflamm (Lond). 2010;7:47. https://doi.org/10.1186/s40200-017-0328-0 PMid:20836891

Pandey N, Yadav D, Pandey V, Tripathi YB. Anti-inflammatory effect of Pueraria tuberosa extracts through improvement in activity of red blood cell anti-oxidant enzymes. Ayu. 2013;34(3):297-301. https://doi.org/10.4103/0974-8520.123131 PMid:24501527

Srivastava S, Shree P, Pandey H, Tripathi YB. Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis. Biomed Pharmacother. 2018;97:330-8. https://doi.org/10.1016/j.biopha.2017.10.071 PMid:29091882

Tripathi YB, Shukla R, Pandey N, Pandey V, Kumar M. An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats. J Diabetes. 2017;9(2):123-32. https://doi.org/10.1111/1753-0407.12393 PMid:26924185

Pramanik SS, Sur TK, Debnath PK, Bhattacharyya D. Effect of Pueraria tuberosa tuber extract on chronic foot shock stress in Wistar rats. Nepal Med Coll J. 2010;12(4):234-8. PMid:21744765

Verma SK, Jain V, Singh DP. Effect of Pueraria tuberosa DC. (Indian Kudzu) on blood pressure, fibrinolysis and oxidative stress in patients with stage 1 hypertension. Pak J Biol Sci. 2012;15(15):742-7. https://doi.org/10.3923/pjbs.2012.742.747 PMid:24171260

Asthana S, Agarwal T, Singothu S, Samal A, Banerjee I, Pal K, et al. Molecular Docking and Interactions of Pueraria tuberosa with vascular endothelial growth factor receptors. Indian J Pharm Sci. 2015;77(4):439-45. https://doi.org/10.4103/0250-474x.164780 PMid:26664060

Tripathi AK, Kohli S. Anti-diabetic activity and phytochemical screening of crude extracts of Pueraria tuberosa DC. (FABACEAE) grown in India on STZ-induced diabetic rats. Asian J Med Pharm Res. 2013;3(3):66-73.

Bhor VM, Raghuram N, Sivakami S. Oxidative damage and altered antioxidant enzyme activities in the small intestine of streptozotocin-induced diabetic rats. Int J Biochem Cell Biol. 2004;36(1):89-97. https://doi.org/10.1016/ s1357-2725(03)00142-0

PMid:14592535

Yang J, Campitelli J, Hu G, Lin Y, Luo J, Xue C. Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin. Life Sci. 2007;81(4):272-9. https://doi.org/10.1016/j.lfs.2007.04.040 PMid:17583752

Drucker DJ. Gut adaptation and the glucagon-like peptides. Gut. 2002;50(3):428-35. https://doi.org/10.1136/gut.50.3.428 Mid:11839727

Hytting-Andreasen R, Balk-Møller E, Hartmann B, Pedersen J, Windeløv JA, Holst JJ, et al. Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice. PLoS One. 2018;13(6):e0198046. https://doi.org/10.1371/journal.pone.0198046 PMid:29864142

Koehler JA, Baggio LL, Yusta B, Longuet C, Rowland KJ, Cao X, et al. GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7. Cell Metab. 2015;21(3):379-91. PMid:25738454

Tsai CH, Hill M, Asa SL, Brubaker PL, Drucker DJ. Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am J Physiol. 1997;273(1):E77-84. https://doi.org/10.1016/j.cmet.2015.02.005 PMid:9252482

Patterson E, Stanton C, Cryan JF, Fitzgerald GF, Ross RP, Dinan TG, et al. Streptozotocin-induced Type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity. Microbiology. 2015;161(1):182-93. https://doi.org/10.1099/mic.0.082610-0 PMid:25370749