Antidiabetic and Antioxidant Effects of Bryonia multiflora Boiss. & Heldr. in a Rat Model of Streptozotocin-Induced Diabetes

Elif Ebru Alkan; İsmail Çelik; Bedia Bati

doi:10.46871/eams.1287621

Research Article

Antidiabetic and Antioxidant Effects of Bryonia multiflora Boiss. & Heldr. in a Rat Model of Streptozotocin-Induced Diabetes

Year 2023, Volume: 4 Issue: 1 - Experimental and Applied Medical Science Vol:4, Issue:1 [en] [en], 442 - 459

Elif Ebru Alkan İsmail Çelik Bedia Bati

https://doi.org/10.46871/eams.1287621

Abstract

Objective: This aim of this study is to investigate the antidiabetic, antioxidant and hypolipidemic potential of Bryonia multiflora Boiss. & Heldr. in streptozotocin (STZ) induced diabetes in rats. Material and Methods: During 21 days, control group (NC) and diabetes control (DC) were fed only with food and water, while diabetes acarbose group (DAC) was fed with 20 mg / kg of acarbose. The DB1, DB2, DB3 groups were fed with 100 mg / kg, 200 mg/kg and 400 mg / kg Bryonia multiflora plant extract, respectively. The body weight and biochemical parameters glucose level, insulin level, glycosylated hemoglobin, total cholesterol, triglyceride, aminotransferase (ALT), lactate dehydrogenase (LDH), C-peptide, LDL- cholesterol (LDL-c), HDL-cholesterol (HDL-c), creatinine (CRE), blood urea nitrogen (BUN), urea (Ure) and antioxidant parameters were examined for all treated groups and compared against diabetic control group and normal control group. Results: Bryonia multiflora (BM) plant extract (100 mg/kg, 200 mg/kg and 400 mg/kg) that administered in respective groups of diabetic animals for 21 days significantly reduced the blood glucose level and glycosylated hemoglobin ( HbA1c) levels in streptozotocin induced diabetic rats. While the levels of insulin and C-peptide of DC group were found significantly lower (p <0.05) compared to NC group, a significant increase (p < 0.05) in insulin and c- peptide level were determined in the groups treated with plant extracts compared to DC group. According to the results; significantly higher levels have been observed in DC group serum ALT, AST, BUN, and CRE compared to NC group (p<0.05), while declines have been observed in groups treated with BM extract (p<0.05). There has been decline in VLDL, cholesterol, and triglycerite levels in the plant extract applied groups (p<0.05), while HDL levels increased (p<0.05). On the other hand, MDA levels increased while GSH and SOD levels declined as DC group compared to the control group. MDA levels significantly declined (p<0.05) while SOD and GSH levels significantly increased in therapeutic groups treated with plant extracts. Conclusion: The results indicate that BM extract have antidiabetic effects by regulating antioxidant activities thereby improving the function of β-cells maintaining normal insulin and glucose levels. Thus the investigation results that Bryonia multiflora has significant antidiabetic, antioxidant activity.

Keywords

Antidiabetic, Antioxidant, Bryonia multiflora, Diabetes mellitus, Oxidative stress, Rats

Project Number

2014-FBE-D151

References

1. Mahendran G, Thamotharan G, Sengottuvelu S et al. Anti-diabetic activity of Swertia corymbosa (griseb) Clarke aerial parts extract in streptozotocin induced diabetic rats. J. Ethnopharmacol. 2014; 151:1175–1183.
2. Niu CS, Chen W, Wu HT et al. Decrease of plasma glucose by allantoin, an active principle of yam (Dioscorea spp.), in streptozotocin-induced diabetic rats. J. Agric. Food Chem. 2010; 58:12031–12035.
3. Baynes JW. Role of oxidative stress in the development of complications in diabetes. Diabetes. 1991; 40:9-21.
4. Bhatti JS, Sehrawat A, Mishra J, Sidhu IS et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic. Biol. Med. 2022, 184, 114–134.
5. Toker G, Erdemoğlu N, Toker MC. High Performance Liquid Chromatographic Analysis of Cucurbitacins in Some Bryonia species. FABAD J. Pharm. Sci. 2000; 25: 153-156
6. Miro M. Cucurbitacins and their pharmacological effects. Phytother. Res.1995; 9159-168.
7. Aslan R, Dündar Y, Eryavuz A et al. Effects of Different Dietary Levels of Yucca Shidigera powder (deodorase) added to diets on performance, some hemotological and biochemical blood parameters and total antioxidant capacity of laying hens. Revue. Med. Vet. 2005; 156:350-355.
8. Tokgun O, Tokgun PE, Turel S et al. BM extract induces autophagy via regulating long non-coding RNAs in breast cancer cells. Nutr. Cancer 2021, 73, 1792–1803.
9. Dalar A, Konczak I. Phenolic contents, antioxidant capacities and inhibitory activities against key metabolic syndrome relevant enzymes of herbal teas from Eastern Anatolia. Ind. Crop. Prod. 2013; 44:383–390.
10. Lorke D. A new approach to practical acute toxicity. Arch. Toxicol. 1983; 53:275-289.
11. Ibeha BO, EzeaJa MI. Preliminary study of antidiabetic activity of the methanolic leaf extract of Axonopus compressus (P. Beauv) in alloxan-induced diabetic rats. J. Ethnopharmacol. 2011; 138: 713–716.
12. Yurt B, Celik I. Hepatoprotective effect and antioxidant role of sun, sulphited- dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats. Food Chem Toxicol. 2011;49(2):508-13. https://doi. org/10.1016/j.fct.2010.11.035 PMid:21115094.
13. Dogan A, Celik I. Hepatoprotective and antioxidant activities of grape seeds against ethanol-induced oxidative stress in rats. Br J Nutr. 2012;107:45-51. https://doi.org/10.1017/S0007114511002650 PMid:21733325.
14. Jain SK, McVie R, Duett J et al. Erythrocyte membrane lipid peroxidation and glycolylated hemoglobin in diabetes. Diabetes. 1989;38:1539-43. https://doi. org/10.2337/diab.38.12.1539 https://doi.org/10.2337/diabetes.38.12.1539 PMid:2583378.
15. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61(5):882-8 PMid:13967893.
16. Mannervik B, Guthenberg C. Glutathione S-transferase (Human Plasenta). Method Enzymol. 1981;77:231-5. https://doi.org/10.1016/S0076- 6879(81)77030-7.
17. Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat live. J Biol Chem. 1975;250:5475-80. PMid:237922.
18. Paglia DE, Valentine WN. Studies on quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70:158. PMid:6066618.
19. McCord JM, Fridovich I. Superoxide dismutase, An enzymatic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244:6049-53. PMid:5389100.
20. Aebi H. Catalase In Methods of Enzymatic Analysis (Bergemeyer, H U.,ed). Academic Press, New York-London. 1974; pp 673-84. https://doi. org/10.1016/B978-0-12-091302-2.50032-3.
21. Sridevi M, Kalaiarasi P, Pugalendi KV. Antihyperlipidemic activity of alcoholic leaf extract of Solanum surattense in streptozotocin-diabetic rats. Asian Pacific Journal of Tropical Biomedicine. 2011; 276-280.
22. Fidan AF, Dündar Y. Hypocholesterolemic and Antioxidant Effects of Phenolic Compounds with Yucca schidigera and Inhaled Saponins. Journal of Lalahan Livestock Research Institute. 2007; 47:31-39.
23. Mohan KG, Pallavi E, Ravi Kumar B et al. Hepatoprotective activity of Ficus carica Linn. leaf extract against carbon tetrachloride-induced hepatotoxicity in rats. DARU. 2007; 15:162-166.
24. Al-Adsani A, Memon A, Suresh A. Pattern and Determinants of Dyslipedemia in Type 2 Diabetes Mellitus patients in Kuwait. Acta. Diabetol.2004; 129-135.
25. Ramkumar KM, Vanitha P, Uma C et al. Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats. Food and Chemical Toxicology. 2011; 49:3390-3394.
26. Mooradian AD. Nature Clinical Practice Endocrinology and Metabolism. 2009; 5:150-159.
27. Whitehead CC, McNab JM, Griffin HD. The effects of low dietary concentrations of saponin on liver lipidaccumulation and performance in laying hens. Br. Poult. Sci. 1981; 22: 282-288.
28. Carl A, Burtis R, Edward R, Ashwood MD. Tietz Textbook of Clinical Chemistry. 2003; 790-796.
29. Seghrouchni I, Drai J, Bannier E et al. Oxidative stress parameters in type I, type II and insulin-treated type 2 diabetes mellitus; insulin treatment efficiency. Clin. Chim. Acta. 2002; 321:89-96.
30. Go HK, Mahbubur R, Kim GB et al. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes. Nutrients. 2015; 7: 8532-44.
31. Akkaya H, Çelik S. Fırat University Veterinary Journal of Health Sciences. 2010; 24:05 – 10.
32. Godin DV, Wohaieb SA, Garnett ME et al. Molecular and Cellular Biochemistry. 1998; 84:223-231.
33. Smith S, Lall AMA. Study on Lipid Profile Levels of Diabetics and Non-Diabetics Among Naini Region of Allahabad, India. Turk J. Bioche. 2008; 33:138–141.
34. Harwood HJ, Chandler CE, Pellarin LD et al. Pharmacological consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin B-tigogenin cellobioside (CP-88818;Tiqueside). J. Lipid. Res. 1993; 34:377-395.
35. JeNCins KJ, Atwal AS. Effect of dietary saponins on fecal bile acids and neutral sterols, and availability of vitamins A and E in the chick. J. Nutr. Biochem. 1994; 5:134-137.
36. Milgate J, Roberts DCK. The nutritional and biological significance of saponins. Nutr. Research, 1995; 15:1223-1249.
37. Kuçukkurt İ, Fidan AF. Saponinler ve Bazı Biyolojik Etkileri. Kocatepe Vet. J. 2008; 1: 89-96.
38. Karasu C. Increased activity of H2O2 in aorta isolated from chronically streptozotocin-diabetic rats: Effects of antioxidant enzymes and enzyme inhibitors. Free Radical Biology and Medicine, 1999; 27:16-27.
39. Haluzik M, NedviDCova J. The role of nitric oxide in the development of streptozotocine-induced diebetes mellitus: experimental and clinical implications. Physiol. Res. 2000; 49:37-42.
40. Abou-Seif MA, Youssef AA. Evaluation of some biochemical changes in diabetic patients. Clin. Chim. Acta. 2004; 346:161-170.
41. Özer Ç, Gönül B. The effects of ascorbic acid administration on the liver oxidant processes in diabetic rats. Gazi Medical Journal. 2006; 17:196-199.
42. Adachi Y, Honi K, Takahashi Y. Serum GST activity in liver disease. Clinica Chimica Act. 1990; 106:243-255.
43. Sacks DB. Tietz Textbook of Clinical Chemistry (Burtis CA, Ashwood ER, ed). Carbohydrates, Philadelphia. 1994; pp 928-1001.
44. Akkuş İ. Free Radicals and Physiopathologic Effects. Konya, Turkey. 1995; 38.
45. Ozkol H, Tuluce Y. Dilsiz N, Koyuncu I. Therapeutic potential of some plant extracts used in turkish traditional medicine on streptozocin-ınduced type 1 diabetes mellitus in rats. J. Membrane Biol. 2013; 246:47–55.
46. Alkan, E.E.; Celik, I. The therapeutics effects and toxic risk of Heracleum persicum Desf. extract on Streptozocin-induced diabetic rats. Toxicol. Rep. 2018, 5, 919–926.

Year 2023, Volume: 4 Issue: 1 - Experimental and Applied Medical Science Vol:4, Issue:1 [en] [en], 442 - 459

Elif Ebru Alkan İsmail Çelik Bedia Bati

https://doi.org/10.46871/eams.1287621

Abstract

Supporting Institution

Van Yüzüncü Yıl Üniversitesi BAP

Project Number

2014-FBE-D151

Thanks

Dsteğinden ötürü Van Yüzüncü Yıl Üniversitesi BAP 'e teşekkürü borç biliriz.

References

1. Mahendran G, Thamotharan G, Sengottuvelu S et al. Anti-diabetic activity of Swertia corymbosa (griseb) Clarke aerial parts extract in streptozotocin induced diabetic rats. J. Ethnopharmacol. 2014; 151:1175–1183.
2. Niu CS, Chen W, Wu HT et al. Decrease of plasma glucose by allantoin, an active principle of yam (Dioscorea spp.), in streptozotocin-induced diabetic rats. J. Agric. Food Chem. 2010; 58:12031–12035.
3. Baynes JW. Role of oxidative stress in the development of complications in diabetes. Diabetes. 1991; 40:9-21.
4. Bhatti JS, Sehrawat A, Mishra J, Sidhu IS et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic. Biol. Med. 2022, 184, 114–134.
5. Toker G, Erdemoğlu N, Toker MC. High Performance Liquid Chromatographic Analysis of Cucurbitacins in Some Bryonia species. FABAD J. Pharm. Sci. 2000; 25: 153-156
6. Miro M. Cucurbitacins and their pharmacological effects. Phytother. Res.1995; 9159-168.
7. Aslan R, Dündar Y, Eryavuz A et al. Effects of Different Dietary Levels of Yucca Shidigera powder (deodorase) added to diets on performance, some hemotological and biochemical blood parameters and total antioxidant capacity of laying hens. Revue. Med. Vet. 2005; 156:350-355.
8. Tokgun O, Tokgun PE, Turel S et al. BM extract induces autophagy via regulating long non-coding RNAs in breast cancer cells. Nutr. Cancer 2021, 73, 1792–1803.
9. Dalar A, Konczak I. Phenolic contents, antioxidant capacities and inhibitory activities against key metabolic syndrome relevant enzymes of herbal teas from Eastern Anatolia. Ind. Crop. Prod. 2013; 44:383–390.
10. Lorke D. A new approach to practical acute toxicity. Arch. Toxicol. 1983; 53:275-289.
11. Ibeha BO, EzeaJa MI. Preliminary study of antidiabetic activity of the methanolic leaf extract of Axonopus compressus (P. Beauv) in alloxan-induced diabetic rats. J. Ethnopharmacol. 2011; 138: 713–716.
12. Yurt B, Celik I. Hepatoprotective effect and antioxidant role of sun, sulphited- dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats. Food Chem Toxicol. 2011;49(2):508-13. https://doi. org/10.1016/j.fct.2010.11.035 PMid:21115094.
13. Dogan A, Celik I. Hepatoprotective and antioxidant activities of grape seeds against ethanol-induced oxidative stress in rats. Br J Nutr. 2012;107:45-51. https://doi.org/10.1017/S0007114511002650 PMid:21733325.
14. Jain SK, McVie R, Duett J et al. Erythrocyte membrane lipid peroxidation and glycolylated hemoglobin in diabetes. Diabetes. 1989;38:1539-43. https://doi. org/10.2337/diab.38.12.1539 https://doi.org/10.2337/diabetes.38.12.1539 PMid:2583378.
15. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61(5):882-8 PMid:13967893.
16. Mannervik B, Guthenberg C. Glutathione S-transferase (Human Plasenta). Method Enzymol. 1981;77:231-5. https://doi.org/10.1016/S0076- 6879(81)77030-7.
17. Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat live. J Biol Chem. 1975;250:5475-80. PMid:237922.
18. Paglia DE, Valentine WN. Studies on quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70:158. PMid:6066618.
19. McCord JM, Fridovich I. Superoxide dismutase, An enzymatic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244:6049-53. PMid:5389100.
20. Aebi H. Catalase In Methods of Enzymatic Analysis (Bergemeyer, H U.,ed). Academic Press, New York-London. 1974; pp 673-84. https://doi. org/10.1016/B978-0-12-091302-2.50032-3.
21. Sridevi M, Kalaiarasi P, Pugalendi KV. Antihyperlipidemic activity of alcoholic leaf extract of Solanum surattense in streptozotocin-diabetic rats. Asian Pacific Journal of Tropical Biomedicine. 2011; 276-280.
22. Fidan AF, Dündar Y. Hypocholesterolemic and Antioxidant Effects of Phenolic Compounds with Yucca schidigera and Inhaled Saponins. Journal of Lalahan Livestock Research Institute. 2007; 47:31-39.
23. Mohan KG, Pallavi E, Ravi Kumar B et al. Hepatoprotective activity of Ficus carica Linn. leaf extract against carbon tetrachloride-induced hepatotoxicity in rats. DARU. 2007; 15:162-166.
24. Al-Adsani A, Memon A, Suresh A. Pattern and Determinants of Dyslipedemia in Type 2 Diabetes Mellitus patients in Kuwait. Acta. Diabetol.2004; 129-135.
25. Ramkumar KM, Vanitha P, Uma C et al. Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats. Food and Chemical Toxicology. 2011; 49:3390-3394.
26. Mooradian AD. Nature Clinical Practice Endocrinology and Metabolism. 2009; 5:150-159.
27. Whitehead CC, McNab JM, Griffin HD. The effects of low dietary concentrations of saponin on liver lipidaccumulation and performance in laying hens. Br. Poult. Sci. 1981; 22: 282-288.
28. Carl A, Burtis R, Edward R, Ashwood MD. Tietz Textbook of Clinical Chemistry. 2003; 790-796.
29. Seghrouchni I, Drai J, Bannier E et al. Oxidative stress parameters in type I, type II and insulin-treated type 2 diabetes mellitus; insulin treatment efficiency. Clin. Chim. Acta. 2002; 321:89-96.
30. Go HK, Mahbubur R, Kim GB et al. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes. Nutrients. 2015; 7: 8532-44.
31. Akkaya H, Çelik S. Fırat University Veterinary Journal of Health Sciences. 2010; 24:05 – 10.
32. Godin DV, Wohaieb SA, Garnett ME et al. Molecular and Cellular Biochemistry. 1998; 84:223-231.
33. Smith S, Lall AMA. Study on Lipid Profile Levels of Diabetics and Non-Diabetics Among Naini Region of Allahabad, India. Turk J. Bioche. 2008; 33:138–141.
34. Harwood HJ, Chandler CE, Pellarin LD et al. Pharmacological consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin B-tigogenin cellobioside (CP-88818;Tiqueside). J. Lipid. Res. 1993; 34:377-395.
35. JeNCins KJ, Atwal AS. Effect of dietary saponins on fecal bile acids and neutral sterols, and availability of vitamins A and E in the chick. J. Nutr. Biochem. 1994; 5:134-137.
36. Milgate J, Roberts DCK. The nutritional and biological significance of saponins. Nutr. Research, 1995; 15:1223-1249.
37. Kuçukkurt İ, Fidan AF. Saponinler ve Bazı Biyolojik Etkileri. Kocatepe Vet. J. 2008; 1: 89-96.
38. Karasu C. Increased activity of H2O2 in aorta isolated from chronically streptozotocin-diabetic rats: Effects of antioxidant enzymes and enzyme inhibitors. Free Radical Biology and Medicine, 1999; 27:16-27.
39. Haluzik M, NedviDCova J. The role of nitric oxide in the development of streptozotocine-induced diebetes mellitus: experimental and clinical implications. Physiol. Res. 2000; 49:37-42.
40. Abou-Seif MA, Youssef AA. Evaluation of some biochemical changes in diabetic patients. Clin. Chim. Acta. 2004; 346:161-170.
41. Özer Ç, Gönül B. The effects of ascorbic acid administration on the liver oxidant processes in diabetic rats. Gazi Medical Journal. 2006; 17:196-199.
42. Adachi Y, Honi K, Takahashi Y. Serum GST activity in liver disease. Clinica Chimica Act. 1990; 106:243-255.
43. Sacks DB. Tietz Textbook of Clinical Chemistry (Burtis CA, Ashwood ER, ed). Carbohydrates, Philadelphia. 1994; pp 928-1001.
44. Akkuş İ. Free Radicals and Physiopathologic Effects. Konya, Turkey. 1995; 38.
45. Ozkol H, Tuluce Y. Dilsiz N, Koyuncu I. Therapeutic potential of some plant extracts used in turkish traditional medicine on streptozocin-ınduced type 1 diabetes mellitus in rats. J. Membrane Biol. 2013; 246:47–55.
46. Alkan, E.E.; Celik, I. The therapeutics effects and toxic risk of Heracleum persicum Desf. extract on Streptozocin-induced diabetic rats. Toxicol. Rep. 2018, 5, 919–926.

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Details

Primary Language	English
Journal Section	Research Articles
Authors	Elif Ebru Alkan 0000-0003-1980-3383 İsmail Çelik 0000-0003-2199-6348 Bedia Bati
Project Number	2014-FBE-D151
Early Pub Date	August 2, 2023
Publication Date
Published in Issue	Year 2023 Volume: 4 Issue: 1 - Experimental and Applied Medical Science Vol:4, Issue:1 [en] [en]

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Vancouver	Alkan EE, Çelik İ, Bati B. Antidiabetic and Antioxidant Effects of Bryonia multiflora Boiss. & Heldr. in a Rat Model of Streptozotocin-Induced Diabetes. Exp Appl Med Sci. 2023;4(1):442-59.

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