Anti-diabetic Potential Mechanisms of Phytomedicines – A Review
Abstract:
Diabetic mellitus is an endocrine disorder characterized by hyperglycemia, polyphagia, polyuria, and polydipsia. In this condition, the cells and tissues are unable to utilize glucose for energy due to inadequate insulin secretion. The complications of the disease include diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy that affect the eyes, nerves, kidneys and stroke, renal failure, and heart attacks are other serious consequences of diabetes. The conventional modern medicines for treatment are oral hypoglycemic drugs, sulfonylureas and glinides, metformin and thiazolidinedione, dipeptidyl peptidase-4 (DPP4) inhibitors, and injections such as GLP-1 agonists. Due to the presence of a lot of side effects, the modern world is now turning to bioactive chemical components synthesized from plants. Today, drugs derived from herbs or plants are widely used because of the exploitation of specific compounds and their therapeutic actions. Various phytochemicals have notable and significant mechanisms for reducing the blood glucose level. These natural agents can have a protective and therapeutic effect on diabetes mellitus through cellular mechanisms such as the regeneration of pancreatic β cells, antioxidative stress, and intracellular signalling transduction pathways. The present study aims to review the mechanisms of various phytochemicals that play a role in antidiabetic activity. The possible mechanisms by which the antidiabetic herbs act are α-glucosidase inhibitors, PPAR activators, free radical scavengers, HMG Co suppressors, regenerators of beta cells, and cause an increase in insulin secretion and glycogen synthesis in glycemic control.References:
[1] American Diabetes Association, 2012, Diagnosis
and Classification of Diabetes Mellitus. Diabetes Care, 36(Supplement_1),
S67–S74. https://doi.org/10.2337/dc13-S067
[2] International Diabetes Federation, 2021, IDF
Diabetes Atlas, 10th edition. Brussels, Belgium: https://www.diabetesatlas.org/.
[3]
Kakkar, R., 2016, Rising
burden of Diabetes-Public Health Challenges & way out. Nepal Journal of
Epidemiology, 6(2), 557–559. https://doi.org/10.3126/nje.v6i2.15160
[4]
Ali, M. K., Narayan, K. M.,
& Tandon, N. 2010, Diabetes & coronary heart disease: current
perspectives. The Indian journal of
medical research, 132(5), 584–597.
[5]
Singh, N., Armstrong, D.
G., & Lipsky, B. A., 2005, Preventing foot ulcers in patients with
diabetes. JAMA, 293(2), 217. https://doi.org/10.1001/jama.293.2.217
[6]
Levetan, C., 2007, Oral
antidiabetic agents in type 2 diabetes. Current Medical Research and Opinion,
23(4), 945–952. https://doi.org/10.1185/030079907x178766
[7]
Inzucchi, S. E., 2002, Oral
antihyperglycemic therapy for type 2 diabetes. JAMA, 287(3), 360.
https://doi.org/10.1001/jama.287.3.360
[8]
Mendoza, N., & Silva,
E. M. E., 2018, Introduction to
phytochemicals: Secondary metabolites from plants with active principles for
pharmacological importance. In Phytochemicals - Source of Antioxidants and
Role in Disease Prevention. InTech.http://dx.doi.org/10.5772/intechopen.78226
[9]
Vinayagam, R., Xiao, J.,
& Xu, B., 2017, An insight into anti-diabetic properties of dietary
phytochemicals. Phytochemistry Reviews, 16(3), 535–553. https://doi.org/10.1007/s11101-017-9496-2
[10]
Singh, V. K., Umar, S.,
Ansari, S. A., & Iqbal, M., 2008, Gymnema sylvestre for Diabetics. Journal
of Herbs, Spices & Medicinal Plants, 14(1–2), 88–106. https://doi.org/10.1080/10496470802341508
[11]
Gulab S. Thakur., 2012,
Gymnema sylvestre: An Alternative Therapeutic Agent for Management of Diabetes.
Journal of Applied Pharmaceutical Science, 2(12), 001-006. https://doi.org/10.7324/japs.2012.21201
[12]
Persaud, S., Al-Majed, H.,
Raman, A., & Jones, P., 1999, Gymnema sylvestre stimulates insulin release
in vitro by increased membrane permeability. Journal of Endocrinology, 163(2), 207-212. https://doi.org/10.1677/joe.0.1630207
[13]
AlAttas, S. A., Zahran, F.
M., & Turkistany, S. A., 2016, Nigella sativa and its active constituent
thymoquinone in oral health. Saudi Medical Journal, 37(3),
235–244. https://doi.org/10.15537/smj.2016.3.13006
[14]
Varghese, R. M., Kumar, S.
A., & Selvaraj, Y., 2023, Assessment of Soft Tissue, Airway Dimension and
Hyoid Bone Position in Class II Patients Treated by PowerScope Class 2
Corrector. The Journal of Contemporary Dental Practice, 24(5), 308–313.
https://doi.org/10.5005/jp-journals-10024-3485
[15]
Atangwho, I. J., Ebong, P.
E., Eyong, E. U., Williams, I. O., Eteng, M. U., & Egbung, G. E., 2009, Comparative
chemical composition of leaves of some antidiabetic medicinal plants:
Azadirachta indica, Vernonia amygdalina and Gongronema latifolium. African Journal of Biotechnology, 8(18),
4685-4689.
[16]
Djeujo, F. M., Stablum, V.,
Pangrazzi, E., Ragazzi, E., & Froldi, G., 2023, Luteolin and Vernodalol as
Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on
α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters. Pharmaceutics,
15(5), 1541. https://doi.org/10.3390/pharmaceutics15051541
[17]
Baquer, N. Z., Kumar, P.,
Taha, A., Kale, R., Cowsik, S., & McLean, P., 2011, Metabolic and molecular
action of Trigonella foenum-graecum (fenugreek) and trace metals in
experimental diabetic tissues. Journal of Biosciences, 36(2),
383–396. https://doi.org/10.1007/s12038-011-9042-0
[18]
Sowmithra Devi, S.,
Sundari, S.,2023, Occlusal Contact Changes With Traumatic Occlusion After
Orthodontic Treatment: A Prospective Study. Journal of Advanced Oral Research.
14(2):134-142. doi:10.1177/23202068231190202
[19]
Kahramanoğlu, İ., Chen, C.,
Chen, J., & Wan, C., 2019, Chemical Constituents, Antimicrobial Activity,
and Food Preservative Characteristics of Aloe vera Gel. Agronomy, 9(12),
831. https://doi.org/10.3390/agronomy9120831
[20]
Tanaka, M., Misawa, E.,
Ito, Y., Habara, N., Nomaguchi, K., Yamada, M., … Higuchi, R., 2006, Identification
of five phytosterols from aloe vera gel as anti-diabetic compounds. Biological
and Pharmaceutical Bulletin, 29(7), 1418–1422. https://doi.org/10.1248/bpb.29.1418
[21]
Kumar, D., Mitra, A., &
M, M., 2011, Azadirachtolide: An anti-diabetic and hypolipidemic effects from
Azadirachta indica leaves. Pharmacognosy Communications, 1(1),
78–84. https://doi.org/10.5530/pc.2011.1.5
[22]
Ponnusamy, S., Haldar, S.,
Mulani, F., Zinjarde, S., Thulasiram, H., & RaviKumar, A., 2015. Gedunin
and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem
(Azadirachta indica) as Anti-Diabetic Agents. PLOS ONE, 10(10),
e0140113. https://doi.org/10.1371/journal.pone.0140113
[23]
Aabideen, Z. U., Mumtaz, M.
W., Akhtar, M. T., Raza, M. A., Mukhtar, H., Irfan, A., Saari, N., 2021, Cassia
fistula Leaves; UHPLC-QTOF-MS/MS Based Metabolite Profiling and Molecular
Docking Insights to Explore Bioactives Role towards Inhibition of Pancreatic
Lipase. Plants, 10(7), 1334. https://doi.org/10.3390/plants10071334
[24]
Adisakwattana, S., 2017, Cinnamic
acid and its derivatives: Mechanisms for prevention and management of diabetes
and its complications. Nutrients, 9(2), 163. https://doi.org/10.3390/nu9020163
[25]
Roy, J. R., Janaki, C. S.,
Jayaraman, S., Periyasamy, V., Balaji, T., Vijayamalathi, M., &
Veeraraghavan, V. P., 2022, Carica papaya Reduces Muscle Insulin Resistance via
IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and
Streptozotocin-Induced Type-2 Diabetic Rats. Antioxidants, 11(10),
2081. https://doi.org/10.3390/antiox11102081
[26]
Ansari, P., Flatt, P. R.,
Harriott, P., Hannan, J. M. A., & Abdel-Wahab, Y. H. A., 2021, Identification
of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the
Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and
Isolation of Active Phytoconstituents. Plants, 10(6), 1190. https://doi.org/10.3390/plants10061190
[27]
Srinivasan, S., Sathish,
G., Jayanthi, M., Muthukumaran, J., Muruganathan, U., & Ramachandran, V., 2013,
Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes
of glucose metabolism in streptozotocin-induced diabetic rats. Molecular and
Cellular Biochemistry, 385(1–2), 159–168. https://doi.org/10.1007/s11010-013-1824-2
[28]
Adebanke, O., Babatunde,
A., Franklyn, I., Keleeko, A., Joseph, O., & Olubanke, O., 2023, Free
radical scavenging activity, pancreatic lipase and a-amylase inhibitory
assessment of ethanolic leaf extract of Phyllanthus amarus. Plant Science Today,
10(2), 20–26. https://doi.org/10.14719/pst.1809
[29]
Ahmad, N., Hasan, N.,
Ahmad, Z., Zishan, M., & Zohrameena, S., 2016, MOMORDICA CHARANTIA: FOR TRADITIONAL USES AND
PHARMACOLOGICAL ACTIONS. Journal of Drug
Delivery and Therapeutics, 6(2), 40-44. https://doi.org/10.22270/jddt.v6i2.1202
[30]
Yan, L., Vaghari-Tabari,
M., Malakoti, F., Moein, S., Qujeq, D., Yousefi, B., & Asemi, Z., 2022, Quercetin:
An effective polyphenol in alleviating diabetes and diabetic complications. Critical
Reviews in Food Science and Nutrition, 63(28), 9163–9186. https://doi.org/10.1080/10408398.2022.2067825
[31]
Varghese, R.M.,
Subramanian, A.K., Maliael, M.T., 2023, PowerScope™ for Class II Malocclusions:
A Systematic Review and Meta-analysis. World Journal of Dentistry,14(7):639–647
[32]
Bozkurt, O., Kocaadam-Bozkurt,
B., & Yildiran, H., 2022, Effects of curcumin, a bioactive component of
turmeric, on type 2 diabetes mellitus and its complications: An updated review.
Food & Function, 13(23), 11999–12010. https://doi.org/10.1039/d2fo02625b
[33]
Majeed, M., Mundkur, L., Paulose,
S., & Nagabhushanam, K., 2022, Novel Emblica officinalis extract containing
β-glucogallin vs. metformin: A randomized, open-label, comparative efficacy
study in newly diagnosed type 2 diabetes mellitus patients with dyslipidemia. Food
& Function, 13(18),9523–9531. https://doi.org/10.1039/d2fo01862d
[34]
Mathiyazhagan, J., &
Kodiveri Muthukaliannan, G., 2020, The role of mTOR and oral intervention of
combined Zingiberofficinale Terminalia chebula extract in type
2 diabetes rat models. Journal of Food Biochemistry, 44(7). https://doi.org/10.1111/jfbc.13250
[35]
Mahindrakar, K. V., &
Rathod, V. K., 2020, Antidiabetic potential evaluation of aqueous extract of
wasteSyzygium cuminiseed kernel’s byin vitroα-amylase and α-glucosidase
inhibition. Preparative Biochemistry & Biotechnology, 51(6),
589–598. https://doi.org/10.1080/10826068.2020.1839908
[36]
Rasool, S., Al Meslmani,
B., & Alajlani, M., 2023, Determination of hypoglycemic, hypolipidemic and
nephroprotective effects of berberis calliobotrys in alloxan-induced diabetic
rats. Molecules, 28(8), 3533. https://doi.org/10.3390/molecules2808353
[37]
Etsassala, N. G. E. R.,
Badmus, J. A., Marnewick, J. L., Egieyeh, S., Iwuoha, Emmanuel. I., Nchu, F.,
& Hussein, A. A., 2022, Alpha-Glucosidase and Alpha-Amylase Inhibitory
Activities, Molecular Docking, and Antioxidant Capacities of Plectranthus
ecklonii Constituents. Antioxidants, 11(2), 378. https://doi.org/10.3390/antiox11020378
[38]
Maher, S., Choudhary, M.
I., Saleem, F., Rasheed, S., Waheed, I., Halim, S. A., … Ahmad, S., 2020, Isolation
of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro
and In Silico Validation. Biology, 9(8), 197. https://doi.org/10.3390/biology9080197
[39]
Hsu, J.-H., Yang, C.-S.,
& Chen, J.-J., 2022, Antioxidant, Anti-α-Glucosidase, Antityrosinase, and
Anti-Inflammatory Activities of Bioactive Components from Morus alba. Antioxidants,
11(11), 2222. https://doi.org/10.3390/antiox11112222
[40]
Kumar, R., Sood, P., Rana,
Dr. V., & Prajapati, A. K., 2023, Combine therapy of gallic acid and
allicin in management of diabetes. Journal for Research in Applied Sciences
and Biotechnology, 2(3), 91–99. https://doi.org/10.55544/jrasb.2.3.12
