Identification of Potential Plant-Derived Pancreatic Beta-Cell-Directed Agents Using New Custom-Designed Screening Method: As an Example

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Jan 11

PMID 38202777

Authors

Altaf Al-Romaiyan

Shanta J Persaud

Peter M Jones

Affiliations

Soon will be listed here.

Abstract

Background: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore β-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on β-cells islets of Langerhans. Currently, there are no defined criteria for screening of β-cell-directed plant-based remedies as potential antidiabetic agents.

Summary: In this review, we have identified certain criteria/characteristics that can be used to generate a "screening portfolio" to identify plant extracts as potential β-cell-directed agents for the treatment of T2DM. To validate our screening method, we studied the potential therapeutic efficacy of a (GS) extract using the screening criteria detailed in the review. Six criteria have been identified and validated using OSA, a GS extract. By using this screening method, we show that OSA fulfilled most of the criteria identified for an effective β-cell-directed antidiabetic therapy, being an effective insulin-releasing agent at nontoxic concentrations; maintaining β-cell insulin content by stimulating a concomitant increase in insulin gene transcription; maintaining β-cell mass by protecting against apoptosis; and being effective at maintaining normoglycemia in vivo in a mouse model and a human cohort with T2DM.

Key Messages: The present review has highlighted the importance of having a screening portfolio for plant extracts that have potential antidiabetic effects in the treatment of T2DM. We propose that this screening method should be adopted for future studies to identify new β-cell-directed antidiabetic plant derived agents.

Citing Articles

Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

Al-Romaiyan A, Barakat A, Marafie S, Masocha W Front Pharmacol. 2024; 15:1478917.

PMID: 39399466 PMC: 11466869. DOI: 10.3389/fphar.2024.1478917.

References

Schulz I . Permeabilizing cells: some methods and applications for the study of intracellular processes. Methods Enzymol. 1990; 192:280-300. DOI: 10.1016/0076-6879(90)92077-q. View

Al-Romaiyan A, Huang G, Jones P, Persaud S . Commiphora myrrha stimulates insulin secretion from mouse and human islets of Langerhans. J Ethnopharmacol. 2020; 264:113075. DOI: 10.1016/j.jep.2020.113075. View

Frayling T . Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet. 2007; 8(9):657-62. DOI: 10.1038/nrg2178. View

Gaytan Martinez L, Sanchez-Ruiz L, Zuniga L, Gonzalez-Ortiz M, Martinez-Abundis E . Effect of Administration on Glycemic Control, Insulin Secretion, and Insulin Sensitivity in Patients with Impaired Glucose Tolerance. J Med Food. 2020; 24(1):28-32. DOI: 10.1089/jmf.2020.0024. View

Poitout V, Robertson R . Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2007; 29(3):351-66. PMC: 2528858. DOI: 10.1210/er.2007-0023. View

Liu B, Asare-Anane H, Al-Romaiyan A, Huang G, Amiel S, Jones P . Characterisation of the insulinotropic activity of an aqueous extract of Gymnema sylvestre in mouse beta-cells and human islets of Langerhans. Cell Physiol Biochem. 2009; 23(1-3):125-32. DOI: 10.1159/000204101. View

Al-Romaiyan A, King A, Persaud S, Jones P . A novel extract of Gymnema sylvestre improves glucose tolerance in vivo and stimulates insulin secretion and synthesis in vitro. Phytother Res. 2012; 27(7):1006-11. DOI: 10.1002/ptr.4815. View

Ramkumar K, Vanitha P, Uma C, Suganya N, Bhakkiyalakshmi E, Sujatha J . Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats. Food Chem Toxicol. 2011; 49(12):3390-4. DOI: 10.1016/j.fct.2011.09.027. View

Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram E . Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol. 1990; 30(3):295-300. DOI: 10.1016/0378-8741(90)90108-6. View

10.

Hauge-Evans A, Squires P, Persaud S, Jones P . Pancreatic beta-cell-to-beta-cell interactions are required for integrated responses to nutrient stimuli: enhanced Ca2+ and insulin secretory responses of MIN6 pseudoislets. Diabetes. 1999; 48(7):1402-8. DOI: 10.2337/diabetes.48.7.1402. View

11.

Sathya S, Kokilavani R, Gurusamy K . Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats. Anc Sci Life. 2012; 28(2):12-4. PMC: 3336356. View

12.

Gupta S . Inhibitory effect of Gymnema sylvestre (Gurmar) on adrenaline-induced hyperglycemia in rats. Indian J Med Sci. 1961; 15:883-7. View

13.

Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T . Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008; 40(5):638-45. PMC: 2672416. DOI: 10.1038/ng.120. View

14.

Ramkumar K, Rajaguru P, Latha M, Ananthan R . Effect of Gymnema montanum leaves on red blood cell resistance to oxidative stress in experimental diabetes. Cell Biol Toxicol. 2007; 24(3):233-41. DOI: 10.1007/s10565-007-9032-z. View

15.

Xu G, Stoffers D, Habener J, Bonner-Weir S . Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999; 48(12):2270-6. DOI: 10.2337/diabetes.48.12.2270. View

16.

Ananthan R, Latha M, Pari L, Ramkumar K, Baskar C, Bai V . Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate metabolic enzymes in alloxan-induced diabetic rats. J Med Food. 2003; 6(1):43-9. DOI: 10.1089/109662003765184732. View

17.

Eizirik D, Mandrup-Poulsen T . A choice of death--the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia. 2002; 44(12):2115-33. DOI: 10.1007/s001250100021. View

18.

Ahnert-Hilger G, Gratzl M . Controlled manipulation of the cell interior by pore-forming proteins. Trends Pharmacol Sci. 1988; 9(6):195-7. DOI: 10.1016/0165-6147(88)90081-8. View

19.

Shanmugasundaram E, Gopinath K, Radha Shanmugasundaram K, Rajendran V . Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. J Ethnopharmacol. 1990; 30(3):265-79. DOI: 10.1016/0378-8741(90)90106-4. View

20.

Ananthan R, Latha M, Ramkumar K, Pari L, Baskar C, Narmatha Bai V . Effect of Gymnema montanum leaves on serum and tissue lipids in alloxan diabetic rats. Exp Diabesity Res. 2004; 4(3):183-9. PMC: 2478603. DOI: 10.1155/EDR.2003.183. View