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Review
. 2021 Jul 14:2021:2920530.
doi: 10.1155/2021/2920530. eCollection 2021.

Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus

Akurange Sujeevi Dammadinna Wickramasinghe  1 , Pabasara Kalansuriya  2 , Anoja Priyadarshani Attanayake  2
Affiliations
Review

Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus

Akurange Sujeevi Dammadinna Wickramasinghe et al. Evid Based Complement Alternat Med. .

Abstract

There is an increasing trend of investigating natural bioactive compounds targeting pancreatic β-cells for the prevention/treatment of diabetes mellitus (DM). With the exploration of multiple mechanisms by which β-cells involve in the pathogenesis of DM, herbal medicines are gaining attention due to their multitasking ability as evidenced by traditional medicine practices. This review attempts to summarize herbal medicines with the potential for improvement of β-cell functions and regeneration as scientifically proven by in vivo/in vitro investigations. Furthermore, attempts have been made to identify the mechanisms of improving the function and regeneration of β-cells by herbal medicines. Relevant data published from January 2009 to March 2020 were collected by searching electronic databases "PubMed," "ScienceDirect," and "Google Scholar" and studied for this review. Single herbal extracts, polyherbal mixtures, and isolated compounds derived from approximately 110 medicinal plants belonging to 51 different plant families had been investigated in recent years and found to be targeting β-cells. Many herbal medicines showed improvement of β-cell function as observed through homeostatic model assessment-β-cell function (HOMA-β). Pancreatic β-cell regeneration as observed in histopathological and immunohistochemical studies in terms of increase of size and number of functional β-cells was also prominent. Increasing β-cell mass via expression of genes/proteins related to antiapoptotic actions and β-cell neogenesis/proliferation, increasing glucose-stimulated insulin secretion via activating glucose transporter-2 (GLUT-2) receptors, and/or increasing intracellular Ca2+ levels were observed upon treatment of some herbal medicines. Some herbal medicines acted on various insulin signaling pathways. Furthermore, many herbal medicines showed protective effects on β-cells via reduction of oxidative stress and inflammation. However, there are many unexplored avenues. Thus, further investigations are warranted in elucidating mechanisms of improving β-cell function and mass by herbal medicines, their structure-activity relationship (SAR), and toxicities of these herbal medicines.

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Conflict of interest statement

The authors declare that there are no conflicts.

Figures

Figure 1
Figure 1
An overview of mechanisms involved in β-cell damage and dysfunction in (a) type 1 diabetes mellitus and (b) type 2 diabetes mellitus.
Figure 2
Figure 2
Study selection process.
Figure 3
Figure 3
Structures of metabolites: (a) myricetin (1), (b) syringic acid (2), (c) ferulic acid (3) present in Hibiscus rosa sinensis Linn., and (d) cyanidin-3-glucoside (4) present in Myrica rubra Sieb. and Zucc. targeting β-cells.
Figure 4
Figure 4
Structures of metabolites (a) speciophylline (5), (b) mitraphylline (6), (c) uncarine F (7), (d) pteropodine (8), (e) isomitraphylline (9), and (f) isopteropodine (10) present in Uncaria tomentosa (Willd.) DC targeting β-cells.
Figure 5
Figure 5
Structures of metabolites (a) salidroside (11), (b) puerarin (12), (c) vitexin (13), (d) andrographolide (14), (e) geniposide (15), (f) asiatic acid (16), and (g) rosmarinic acid (17) isolated from medicinal plants targeting β-cells.
Figure 6
Figure 6
Structures of metabolites (a) umbelliferone beta-D-galactopyranoside (18), (b) saffron (19), (c) diosgenin (20), (d) swertiamarin (21), (e) quercetin (22), and (f) genistein (23) isolated from medicinal plants targeting β-cells.
Figure 7
Figure 7
Structures of metabolites (a) morin (24), (b) berberine (25), (c) thymoquinone (26), (d) nymphayol (27), (e) methyl caffeate (28), (f) gallic acid (29), and (g) 20-hydroxyl ecdysone (30) isolated from medicinal plants targeting β-cells.
Figure 8
Figure 8
Summary of mechanisms by which natural products improve β-cell function and regeneration. TNF-α, tumor necrosis factor-α; NF-κB, nuclear factor κB; IkB, inhibitor of NF-κB; IKK, IκB kinase; ATP, adenosine triphosphate; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; FOXO-1, forkhead box O1; GLUT-2, glucose transporter-2; IGF-1, insulin-like growth factor-1; IR, insulin receptor; IRS-2, insulin receptor substrate-2; PI3K, phosphoinositide 3-kinase; PDK, phosphoinositide-dependent protein kinase; Akt, protein kinase B; ACC, acetyl-CoA carboxylate; CXCL-12, C-X-C motif chemokine 12; ERK 1/2, Extracellular signal-regulated protein kinase 1/2; PKA, protein kinase A; cAMP, cyclic AMP; GLP-1R, Glucagon-like peptide-1 receptor; SOD, superoxide dismutase; CAT, catalase; ROS, reactive oxygen species; PDX-1, pancreatic duodenal homeobox-1; MafA, v-maf musculoaponeurotic fibrosarcoma oncogene family protein A; INS-1, insulin-1; INS-2, insulin-2; GK, glucokinase; IGF-2, insulin-like growth fator-2; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2-associated X, caspase-3, cysteinyl aspartate specific proteinase-3.
Figure 9
Figure 9
Compounds targeting β-cells as evidenced by SAR studies: (a) p-tyrosol (31), (b) oleuropein (32), (c) (E)-3-(3-phenylbenzo[c]isoxazol-5-yl) acrylic acid (33), (d) 2,4-diaminoquinazoline (34), (e) herbacetin (35), (f) sorbifolin (36), and (g) (4Z, 12Z)-cyclopentadeca-4,12-dienone (37).
Figure 10
Figure 10
Structures of metabolites isolated from Morus alba Linne targeting β-cells as evident by SAR studies. (a) Iristectorigenin A (38), (b) 4-prenylresveratrol (39), (c) moracin H (40), (d) moracin C (41), (e) isoramanone (42), (f) moracin E (43), and (g) moracin D (44).
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