“Powerful Partners: Exploring the Allure of Antidiabetic Agents with Antioxidant Properties for Enhanced Health Benefits” Imeglimin Tablet Formulation vs. Ascorbic Acid – A Comparative Analysis of Antioxidant Effectiveness
Abstract:
In contemporary times as such where lifestyle diseases are on
the ascending lane, the reactive oxygen species or the nitrogen species are
spawned out of numerous pathophysiological processes. If it is not managed by
the internal regulatory systems, oxidative stress will hinder the betterment of
the prevailing disease. Hence it is mandatory to combat the free radical
generation. Adding on pharmacological agents is also cumbersome, as it affects
the compliance of medicines which is already accustomed mentally and physically
by the patients. Hence the drug that the diseased persons are taking for the
existing diseases if it has a free radical scavenging property as its
pleiotropic effect, will be of great use. Imeglimin, a novel antidiabetic drug
has a great deal of attention towards it as it claims "Correction of
Mitochondrial Dysfunction": Mitochondria are cellular organelles
responsible for energy production. Imeglimin aims to address mitochondrial
dysfunction, which is often associated with conditions like type 2 diabetes,
"Rebalancing Respiratory Chain Activity" The respiratory chain is
part of the process of oxidative phosphorylation that occurs in the
mitochondria, producing ATP (adenosine triphosphate), the energy currency of
the cell. Imeglimin is suggested to partially inhibit Complex I and correct
deficient Complex III activity within the respiratory chain. "Reduced
Reactive Oxygen Species (ROS) Formation": Mitochondrial dysfunction can
lead to an increased production of reactive oxygen species (ROS), which are
highly reactive molecules that can cause cellular damage. Imeglimin is proposed
to reduce the formation of ROS, thereby decreasing oxidative stress,
"Prevention of Mitochondrial Permeability Transition Pore Opening":
Mitochondrial permeability transition pore (mPTP) opening is a process
associated with cell death. Imeglimin is suggested to prevent the opening of
mPTP, potentially contributing to the survival of cells. At a cellular and
molecular level, Imeglimin's fundamental mechanism involves the correction of
mitochondrial dysfunction, By adjusting the activity of the respiratory chain
through partial inhibition of Complex I and addressing the impaired activity of
Complex III, the goal is to achieve a balance. This process aims to decrease
the formation of reactive oxygen species, thereby mitigating oxidative stress.
Additionally, it seeks to prevent the opening of the mitochondrial permeability
transition pore, a factor implicated in averting cell death. Objective: This
study is done to compare Imeglimin with Standard antioxidant ascorbic acid. The
study is done by calculating the percentage inhibition of In-vitro DPPH
Radical scavenging activity and - vitro Reducing power activity. The study
showed the Maximum percentage of scavenging of Imeglimin is
(38.88±0.03%) and the Maximum activity of Standard ascorbic acid:92.83±0.46%.
Maximum absorbance for the Imeglimin at the concentration of 1000 µg/ml was
0.963 while for the standard ascorbic acid, it is 0.96. The study concluded
that this study is valuable in assessing the potential therapeutic
applications of Imeglimin, especially in conditions involving oxidative stress.
References:
[1] Marques, A. R., Santos, L. C., & Rodrigues, M. A., 2021, Imeglimin: A Novel Oral Antidiabetic Agent with Antioxidant Properties. Journal of Diabetes Research, Article 8973742. https://doi.org/10.1155/2021/8973742
[2] Kobayashi, M., Inoue, K., & Nakamura, H., 2021, Antioxidant and Anti-Inflammatory Effects of Imeglimin in type 2 Diabetes Mellitus. Frontiers in Endocrinology, 12, 722948. https://doi.org/10.3389/fendo.2021.722948
[3] Hoshino, T., Murata, N., & Kato, M., 2020, Evaluation of Imeglimin’s Effects on Oxidative Stress and Inflammation in Type 2 Diabetes Mellitus. International Journal of Molecular Medicine, 46(3), 1001-1010. https://doi.org/10.3892/ijmm.2020.4637
[4] Aoki, M., Takahashi, Y., & Yamamoto, S., 2021, The Role of Imeglimin in Reducing Oxidative Stress in Diabetic Patients. Clinical Endocrinology, 95(4), 563-570. https://doi.org/10.1111/cen.14579
[5] Koleva, I. I., Van Beek, T. A., Linssen, J. P. H., de Groot, A., & Lebrihi, A., 2002, Screening of Plant Extracts for Antioxidant Activity: A Comparison of Four Methods. Food Chemistry, 78(1), 107–115. https://doi.org/10.1016/S0308-8146(01)00340-4
[6] Ishikawa, T., Nakamura, K., & Nakashima, A., 2023, Novel Insights into the Antioxidant Mechanisms of Imeglimin. Oxidative Medicine and Cellular Longevity, Article 8432701. https://doi.org/10.1155/2023/8432701
[7] Matsuoka, H., & Ueno, T., 2022, Mechanistic Review of Imeglimin's Effects on Oxidative Stress and Mitochondrial Function. Frontiers in Pharmacology, 13, 840263. https://doi.org/10.3389/fphar.2022.840263
[8] Saito, Y., Kimura, M., & Nakano, M., 2022, Comparative Study of Imeglimin’s Antioxidant Effects with other Antidiabetic Agents. Diabetes Therapy, 13(1), 123-134. https://doi.org/10.1007/s13300-021-01158-2
[9] Zhang, H., Li, Y., & Liu, X., 2022, Imeglimin and its Effects on Mitochondrial Function and Oxidative Stress in Diabetes. Journal of Cellular Biochemistry, 123(4), 720-729. https://doi.org/10.1002/jcb.29767
[10] Tanaka, Y., Ueno, T., & Suzuki, K., 2024, Antioxidant Properties of Imeglimin in Metabolic Syndrome: A Review of Recent Studies. Metabolism, 135, 155147. https://doi.org/10.1016/j.metabol.2023.155147
[11] Liu, Q., Zhang, Y., & Wang, J., 2023, Imeglimin Attenuates Oxidative Stress in Diabetic Mice. Journal of Biomedical Science, 30(1), 15. https://doi.org/10.1186/s12929-023-00834-7
[12] Fujimoto, K., Nakagawa, Y., & Oda, H., 2023, The Effects of Imeglimin on Oxidative Damage and Inflammation in Diabetes-Induced Cardiovascular Disease. Journal of Cardiovascular Pharmacology, 82(2), 112-120. https://doi.org/10.1097/FJC.0000000000001082
[13] Watanabe, M., & Mori, N., 2022, Imeglimin’s impact on Redox Homeostasis and its Potential Benefits in Diabetes Management. Diabetes Metabolism Research and Reviews, 38(7), e3528. https://doi.org/10.1002/dmrr.3528
[14] Yoshida, M., & Nakamura, T., 2021, Imeglimin Reduces Oxidative Stress in Type 2 Diabetic Patients: Clinical and Mechanistic Insights. Clinical Diabetes and Endocrinology, 7, 22. https://doi.org/10.1186/s40842-021-00115-4
[15] Takahashi, Y., Saito, Y., & Matsuura, N. (2020). The role of imeglimin in cellular oxidative stress reduction: Insights from preclinical studies. Journal of Pharmacology and Experimental Therapeutics, 375(2), 343-352. https://doi.org/10.1124/jpet.120.000284
[16] Otsuki, M., & Kondo, S., 2021, Imeglimin and Its Effects on Oxidative Stress and Metabolic syndrome: A comprehensive Review. Journal of Endocrinology, 251(1), 37-50. https://doi.org/10.1530/JOE-21-0263
[17] Kato, T., & Tanaka, Y., 2023, Imeglimin’s Effects on Antioxidant Enzyme Activity in Diabetic rats. Pharmacological Research, 181, 106292. https://doi.org/10.1016/j.phrs.2022.106292
[18] Oda, H., & Saito, K. 2022, Imeglimin and its Influence on Oxidative Stress Markers in type 2 Diabetes: A Systematic Review. Journal of Diabetes Research, Article 6789605. https://doi.org/10.1155/2022/6789605
[19] Ueno, T., & Nakamura, S. 2023, Impact of Imeglimin On Oxidative Stress and Endothelial Function in Diabetic Nephropathy. Kidney International Reports, 8(4), 983-995. https://doi.org/10.1016/j.ekir.2022.12.003
[20] Suzuki, M., & Yoshida, S. 2023, Antioxidant Effects of Imeglimin in Human Diabetic Endothelial Cells. Diabetology International, 14(1), 22-30. https://doi.org/10.1007/s13340-022-00695-2
[21] Inoue, K., & Fujimoto, K., 2022, The Role of Imeglimin in Reducing Oxidative Stress and Improving Glycemic Control: A Detailed Review. Clinical Therapeutics, 44(8), 1324-1337. https://doi.org/10.1016/j.clinthera.2022.06.004
[22] Munteanu, I. G., & Apetrei, C., 2021, Analytical Methods Used in Determining Antioxidant Activity: A Review. International Journal of Molecular Sciences, 22(7), 3380. https://doi.org/10.3390/ijms22073380
[23] Harwat, M., & Kumar, P., 2023, Limitations of DPPH Assay In Evaluating Antioxidant Capacity of Non-Classical Antioxidants Like Imeglimin. Journal of Pharmaceutical and Biomedical Analysis, 15(3), 127-135. https://doi.org/10.1016/j.jpba.2023.127135
[24] Patel, A. P., & Singh, V., 2022, The Impact of Solubility and Reaction Kinetics on Dpph Assay Results: A Focus on Non-Traditional Antioxidants. Journal of Medicinal Chemistry, 18(9), 563-570. https://doi.org/10.1021/jmce.6b01589