IN VITRO MECHANISTIC APPROACH AND EVALUATION OF ANTIDIABETIC ACTIVITY OF ATROPA ACUMINATA

Main Article Content

Priyanka Thakur
Vinay Pandit

Keywords

Diabetes, Atropa acuminata, antioxidant, HPTLC, Lipid peroxidation, alphaamylase

Abstract

Objective: The purpose of this study was to look into the antidiabetic and antioxidant properties of hydroethanolicextract of Atropa acuminata (HEEAA). Experimental research was conducted to furnish the scientific evidence of antioxidant activity against various stable free radicals like nitric oxide, superoxide, and lipid peroxidation (measures the radical scavenging activity of antioxidants) and ant diabetic potential against different enzymes like alpha-amylase, alphaglycosidase, dipeptidyl peptidase IV (DPP-IV), pancreatic lipase,etc. of Atropa plant (Atropa acuminata)and also evaluate their maximum inhibitory value (IC50 values).


Methods: Shade-dried root material was pulverized, homogenous material was passed through sieve number 40, using solvent ethanol: water in a ratio of 50:50 soxhletextraction was performed. Thick semi-solid material was vacuum dried using a rotary vacuum flash evaporator and then concentrated in a desiccator, stored in a refrigerator at 40°C for evaluating maximum inhibitory concentration (IC50 values) in both activities (free radical scavenging and enzyme inhibitory antidiabetic activity).


 


Results: High-performance thin layer chromatography (HPTLC) results confirmed the presence of atropine in the extract withan RF valueof 0.37 and the percentage yield calculated as per standard calculation for atropine was 0.553 % w/v respectively. Among the different antioxidant studies, the maximum inhibitory concentration value in lipid peroxidation assay for plant extract was greater (170.3±0.6 and 152.4±0.5) in comparison to other antioxidant assays performed. Although,the extract showed no or very weak significant inhibition against dipeptidyl peptidase IV and pancreatic lipase.The extract displayed an appreciable effect on alpha-amylase and alphaglycosidase enzyme inhibition at the highest investigated concentration (200 µg/ml).


Conclusion: The results showed that A. acuminata hydroethanolic extract has anti-oxidant activity and appears to exert a hypoglycemic impact.

Abstract 51 | pdf Downloads 35

References

1. Shrivastava U, Misra A, Mohan V, Unnikrishnan R, Bachani D. Obesity, diabetes and cardiovascular diseases in India: public health challenges. Curr Diabetes Rev. 2017 Feb 1;13(1):65-80. doi:10.2174/1573399812666160805153328.
2. Fang EF, Xie C, Schenkel JA, Wu C, Long Q, Cui H, Aman Y, Frank J, Liao J, Zou H, Wang NY. A research agenda for aging in China in the 21st century: Focusing on basic and translational research, long-term care, policy, and social networks. Ageing Res Rev. 2020 Dec 1;64:101174. doi:10.1016/j.arr.2020.101174.
3. Zhang Y, Cui Y, Shen M, Zhang J, Liu B, Dai M, Chen L, Han D, Fan Y, Zeng Y, Li W, Lin F, Li S, Chen X, Pan P; medical team from Xiangya Hospital to support Hubei, China. Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study. Diabetes Res Clin Pract. 2020 Jul;165:108227. doi: 10.1016/j.diabres.2020.108227. Epub 2020 May 22. PMID: 32446795; PMCID: PMC7242190.
4. Domján BA, Ferencz V, Tänczer T, Szili-Janicsek Z, Barkai L, Hidvégi T, Jermendy G, Kempler P, Winkler G, Gerő L, Tabák AG. Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary. Prim Care Diabetes. 2017 Apr;11(2):107-111. doi: 10.1016/j.pcd.2016.09.001. Epub 2016 Sep 24. PMID: 27669637.
5. Ting DS, Cheung GC, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016 May;44(4):260-77. doi: 10.1111/ceo.12696. Epub 2016 Feb 17. PMID: 26716602.
6. Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL. Oxidative Stress in Atherosclerosis. Curr Atheroscler Rep. 2017 Sep 18;19(11):42. doi: 10.1007/s11883-017-0678-6. PMID: 28921056.
7. Valko M, Jomova K, Rhodes CJ, Kuča K, Musílek K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. 2016 Jan;90(1):1-37. doi: 10.1007/s00204-015-1579-5. Epub 2015 Sep 7. PMID: 26343967.
8. Yun B, King M, Draz MS, Kline T, Rodriguez-Palacios A. Oxidative reactivity across kingdoms in the gut: Host immunity, stressed microbiota and oxidized foods. Free Radic Biol Med. 2022 Jan;178:97-110. doi: 10.1016/j.freeradbiomed.2021.11.009. Epub 2021 Nov 26. PMID: 34843918.
9. Lee WY, Lee CY, Kim YS, Kim CE. The Methodological Trends of Traditional Herbal Medicine Employing Network Pharmacology. Biomolecules. 2019 Aug 13;9(8):362. doi: 10.3390/biom9080362. PMID: 31412658; PMCID: PMC6723118.
10. Chen J, Shi Q, Wang Y, Li Z, Wang S. Dereplication of known nucleobase and nucleoside compounds in natural product extracts by capillary electrophoresis-high resolution mass spectrometry. Molecules. 2015 Mar 26;20(4):5423-37. doi: 10.3390/molecules20045423. PMID: 25822081; PMCID: PMC6272742.
11. Kibiti CM, Afolayan AJ. Preliminary Phytochemical Screening and Biological Activities of Bulbine abyssinica Used in the Folk Medicine in the Eastern Cape Province, South Africa. Evid Based Complement Alternat Med. 2015;2015:617607. doi: 10.1155/2015/617607. Epub 2015 Oct 12. PMID: 26579202; PMCID: PMC4633689.
12. Valko M, Jomova K, Rhodes CJ, Kuča K, Musílek K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. 2016 Jan;90(1):1-37. doi: 10.1007/s00204-015-1579-5. Epub 2015 Sep 7. PMID: 26343967.
13. Sirivibulkovit K, Nouanthavong S, Sameenoi Y. Paper-based DPPH Assay for Antioxidant Activity Analysis. Anal Sci. 2018;34(7):795-800. doi: 10.2116/analsci.18P014. PMID: 29998961.
14. Kamal Z, Ullah F, Ayaz M, Sadiq A, Ahmad S, Zeb A, Hussain A, Imran M. Anticholinesterase and antioxidant investigations of crude extracts, subsequent fractions, saponins and flavonoids of atriplex laciniata L.: potential effectiveness in Alzheimer's and other neurological disorders. Biol Res. 2015 Apr 1;48(1):21. doi: 10.1186/s40659-015-0011-1. PMID: 25889712; PMCID: PMC4393635.
15. Mat Yusuf SNA, Che Mood CNA, Ahmad NH, Sandai D, Lee CK, Lim V. Optimization of biogenic synthesis of silver nanoparticles from flavonoid-rich Clinacanthus nutans leaf and stem aqueous extracts. R Soc Open Sci. 2020 Jul 22;7(7):200065. doi: 10.1098/rsos.200065.
PMID: 32874618; PMCID: PMC7428249.
16. Kang CH, Kim JS, Kim H, Park HM, Paek NS. Heat-Killed Lactic Acid Bacteria Inhibit Nitric Oxide Production via Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in RAW 264.7 Cells. Probiotics Antimicrob Proteins. 2021 Dec;13(6):1530-1538. doi: 10.1007/s12602021- 09781-9. Epub 2021 Apr 5. PMID: 33818712; PMCID: PMC8578100.
17. Naguib M, Gogotsi Y. Synthesis of two-dimensional materials by selective extraction. Acc Chem Res. 2015 Jan 20;48(1):128-35. doi: 10.1021/ar500346b. Epub 2014 Dec 9. PMID: 25489991.
18. Kalyanaraman B, Hardy M, Podsiadly R, Cheng G, Zielonka J. Recent developments in detection of superoxide radical anion and hydrogen peroxide: Opportunities, challenges, and implications in redox signaling. Arch Biochem Biophys. 2017 Mar 1;617:38-47.
doi: 10.1016/j.abb.2016.08.021. Epub 2016 Aug 30. PMID: 27590268; PMCID: PMC5318280.
19. Yuan H, Li X, Zhang X, Kang R, Tang D. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun. 2016 Sep 16;478(2):838-44. doi: 10.1016/j.bbrc.2016.08.034. Epub 2016 Aug 7. PMID: 27510639.
20. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem. 2017 May 1;524:13- 30. doi: 10.1016/j.ab.2016.10.021. Epub 2016 Oct 24. PMID: 27789233.
21. Wickramaratne MN, Punchihewa JC, Wickramaratne DB. In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina. BMC Complement Altern Med. 2016 Nov 15;16(1):466. doi: 10.1186/s12906-016-1452-y. PMID: 27846876; PMCID: PMC5109804.
22. Bashary R, Vyas M, Nayak SK, Suttee A, Verma S, Narang R, Khatik GL. An Insight of Alpha- amylase Inhibitors as a Valuable Tool in the Management of Type 2 Diabetes Mellitus. Curr Diabetes Rev. 2020;16(2):117-136. doi: 10.2174/1573399815666190618093315. PMID: 31237215.
23. Assefa ST, Yang EY, Chae SY, Song M, Lee J, Cho MC, Jang S. Alpha Glucosidase Inhibitory Activities of Plants with Focus on Common Vegetables. Plants (Basel). 2019 Dec 18;9(1):2. doi: 10.3390/plants9010002. PMID: 31861279; PMCID: PMC7020213.
24. Li N, Wang LJ, Jiang B, Guo SJ, Li XQ, Chen XC, Luo J, Li C, Wang Y, Shi DY. Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors. Bioorg Med Chem Lett. 2018 Jul 1;28(12):2131-2135. doi: 10.1016/j.bmcl.2018.05.022. Epub 2018 May 16. PMID: 29773502.
25. Zheng Y, Tian J, Yang W, Chen S, Liu D, Fang H, Zhang H, Ye X. Inhibition mechanism of ferulic acid against α-amylase and α-glucosidase. Food Chem. 2020 Jul 1;317:126346. doi: 10.1016/j.foodchem.2020.126346. Epub 2020 Feb 3. PMID: 32070843.
26. Schrenk D, Gao L, Lin G, Mahony C, Mulder PPJ, Peijnenburg A, Pfuhler S, Rietjens IMCM, Rutz L, Steinhoff B, These A. Pyrrolizidine alkaloids in food and phytomedicine: Occurrence, exposure, toxicity, mechanisms, and risk assessment - A review. Food Chem Toxicol. 2020 Feb;136:111107. doi: 10.1016/j.fct.2019.111107. Epub 2020 Jan 3. PMID: 31904473.
27. Butala MA, Kukkupuni SK, Vishnuprasad CN. Ayurvedic anti-diabetic formulation Lodhrasavam inhibits alpha-amylase, alpha-glucosidase and suppresses adipogenic activity in vitro. J Ayurveda Integr Med. 2017 Jul-Sep;8(3):145-151. doi: 10.1016/j.jaim.2017.03.005. Epub 2017 Jun 28. PMID: 28668259; PMCID: PMC5607396.
28. Ampomah IG, Malau-Aduli BS, Seidu AA, Malau-Aduli AEO, Emeto TI. Integrating traditional medicine into the Ghanaian health system: perceptions and experiences of traditional medicine practitioners in the Ashanti region. Int Health. 2023 Jul 4;15(4):414-427. doi: 10.1093/inthealth/ihac059. PMID: 36063112; PMCID: PMC10318977.
29. Duan X, He C, Kron SJ, Lin W. Nanoparticle formulations of cisplatin for cancer therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Sep;8(5):776-91. doi: 10.1002/wnan.1390. Epub 2016 Feb 5. PMID: 26848041; PMCID: PMC4975677.
30. Poonia A, Upadhayay A. Chenopodium album Linn: review of nutritive value and biological properties. J Food Sci Technol. 2015 Jul;52(7):3977-85. doi: 10.1007/s13197-014-1553-x. Epub 2015 Apr 7. PMID: 26139865; PMCID: PMC4486584.
31. Habtemariam S, Lentini G. The therapeutic potential of rutin for diabetes: an update. Mini Rev Med Chem. 2015;15(7):524-8. doi: 10.2174/138955751507150424103721. PMID: 25934979.
32. Fierascu RC, Sieniawska E, Ortan A, Fierascu I, Xiao J. Fruits By-Products - A Source of Valuable Active Principles. A Short Review. Front Bioeng Biotechnol. 2020 Apr 15;8:319. doi: 10.3389/fbioe.2020.00319. PMID: 32351951; PMCID: PMC7174504.
33. Hamidpour R, Hamidpour M, Hamidpour S, Shahlari M. Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer's disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and repellent activities. J Tradit Complement Med. 2015 Jan 16;5(2):66-70. doi: 10.1016/j.jtcme.2014.11.008. PMID: 26151013; PMCID: PMC4488098.
34. Griffiths K, Aggarwal BB, Singh RB, Buttar HS, Wilson D, De Meester F. Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention. Diseases. 2016 Aug 1;4(3):28. doi: 10.3390/diseases4030028. PMID: 28933408; PMCID: PMC5456284.
35. Altmann C, Schmidt MHH. The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration. Int J Mol Sci. 2018 Jan 1;19(1):110. doi: 10.3390/ijms19010110. PMID: 29301251; PMCID: PMC5796059.
36. Behl T, Kotwani A. Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacol Res. 2015 Sep;99:137-48. doi: 10.1016/j.phrs.2015.05.013. Epub 2015 Jun 6. PMID: 26054568.
37. Bhatti JS, Sehrawat A, Mishra J, Sidhu IS, Navik U, Khullar N, Kumar S, Bhatti GK, Reddy PH. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic Biol Med. 2022 May 1;184:114-134. doi: 10.1016/j.freeradbiomed.2022.03.019. Epub 2022 Apr 7. PMID: 35398495.
38. Mazumder K, Aktar A, Roy P, Biswas B, Hossain ME, Sarkar KK, Bachar SC, Ahmed F, Monjur- Al-Hossain ASM, Fukase K. A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship. Molecules. 2022 May 9;27(9):3036. doi: 10.3390/molecules27093036. PMID: 35566385; PMCID: PMC9102595.
39. Kidane Y, Bokrezion T, Mebrahtu J, Mehari M, Gebreab YB, Fessehaye N, Achila OO. In Vitro Inhibition of α-Amylase and α-Glucosidase by Extracts from Psiadia punctulata and Meriandra bengalensis. Evid Based Complement Alternat Med. 2018 Jul 16;2018:2164345. doi: 10.1155/2018/2164345. PMID: 30108648; PMCID: PMC6077584.
40. Kidane Y, Bokrezion T, Mebrahtu J, Mehari M, Gebreab YB, Fessehaye N, Achila OO. In Vitro Inhibition of α-Amylase and α-Glucosidase by Extracts from Psiadia punctulata and Meriandra bengalensis. Evid Based Complement Alternat Med. 2018 Jul 16;2018:2164345. doi: 10.1155/2018/2164345. PMID: 30108648; PMCID: PMC6077584.
41. Rasouli H, Yarani R, Pociot F, Popović-Djordjević J. Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives. Pharmacol Res. 2020 May;155:104723. doi: 10.1016/j.phrs.2020.104723. Epub 2020 Feb 24. PMID: 32105756.
42. Halim M, Halim A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes Metab Syndr. 2019 MarApr;13(2):1165-1172. doi: 10.1016/j.dsx.2019.01.040. Epub 2019 Jan 24. PMID: 31336460.
43. Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A, Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene. 2015 Jul;34(27):3605-16. doi: 10.1038/onc.2014.296. Epub 2014 Sep 29. PMID: 25263447.