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

Table 2

Brief summary of medicinal plant extracts targeting β-cells via undiscovered mechanisms.

Plant	Family	Part of the plant used	Type of extract	Secondary metabolite of interest	Experimental model	Effects on β-cells	Reference
Abrus precatorius L.	Fabaceae	Leaves	Ethanol	NM	Sprague–Dawley rats induced with NA (110 mg/kg, i.p.) and STZ (60 mg/kg, i.p.)	Recovery of damaged pancreatic β-cells increase in median cross-sectional area of pancreatic islets	[63]
Aegle marmelos (L.) Corr. Serr.	Rutaceae	Leaves	95% ethanol	NM	Albino rats induced with STZ (55 mg/kg, i.p.)	Protection of pancreatic β-cells from oxidative stress	[64]
Aegle marmelos (L.) Corr. Serr.	Rutaceae	Bark	Methanol	Aegelin (alkaloid) and lupeol (triterpenoid)	Wistar rats induced with STZ (60 mg/kg, i.p.)	Regeneration of β-cells; Increase in insulin producing β-cells	[65]
Aloe vera (L.) Burm. f.	Asphodelaceae	Leaves	Aqueous	NM	Wistar rats induced with STZ (30 mg/kg, i.p.)	Restoration of pancreatic islet mass	[66]
Althaea officinalis L.	Malvaceae	Seeds	Methanol	NM	Wistar rats induced with STZ (90 mg/kg, i.p.)	Increase in islet number and diameter	[67]
Antidesma bunius L.	Phyllanthaceae	Leaves	Methanol	NM	Albino mice induced with alloxan (150 mg/kg, i.p.)	Improvement in pancreatic structure; Regeneration of the β-cells	[68]
Aronia melanocarpa (Michx.) Elliott	Rosaceae	Fruits	Aqueous	NM	RINm5F insulinoma cells	Protection of pancreatic β-cell from oxidative damage	[69]
Artocarpus altilis (Parkinson) Fosberg	Moraceae	Leaves	Ethanol	NM	Albino rats induced with STZ (50 mg/kg, i.p.)	Increase in insulin expression in β-cells	[70]
Aster spathulifolius Maxim.	Asteraceae	Whole plant	Ethanol	3, 5−/4, 5-Dicaffeoylquinic acid and chlorogenic acid	C57BL/KsJ-db/db diabetic mice	Upregulation of insulin production by increasing pancreatic β-cell mass	[71]
Atriplex polycarpa (Torr.) S. Watson	Amaranthaceae	Stem bark	Aqueous	Alkaloids and phenolics (flavonoids)	ICR mice induced with alloxan (150 mg/kg, i.p.)	Regeneration of β-cells	[72]
Azadirachta indica A. Juss. Bougainvillea spectabilis Willd.	Meliaceae; Nyctaginaceae	Leaves	Chloroform; Aqueous, Methanol	NM	Swiss mice induced with STZ (120 mg/kg, i.p.)	Regeneration of β-cells	[73]
Calotropis gigantean (L.) W.T. Aiton	Apocynaceae	Flowers	Chloroform	NM	Wistar rats induced with STZ (40 mg/kg, i.p.)	Protection of β-cells from oxidative stress by decreasing pancreatic thiobarbituric acid-reactive substances (TBARS) levels increasing the SOD, CAT, and GSH levels	[74]
Canscora decussata (Roxb.) Schult.	Gentianaceae	Whole plant	Methanol	NM	Rabbits induced with alloxan (150 mg/kg, iv)	Regeneration of β-cells	[75]
Carica papaya L. Pandanus amaryllifolius Roxb.	Caricaceae; Pandanaceae	Leaves	Ethanol	NM	Mice induced with STZ (60 mg/kg, i.p.)	Regeneration of β-cells	[76]
Cassia occidentalis Linn.	Fabaceae	Whole plant	Ethanol	NM	Wistar rats induced with alloxan (120 mg/kg, i.p.)	Regeneration of β-cells	[77]
Chiliadenus iphionoides (Boiss. and Blanche) Brullo	Asteraceae	Aerial parts	95% ethanol	NM	Pancreatic RIN-5F cells	Increase in insulin secretion	[78]
Citrullus colocynthis (L.) Schrad.	Cucurbitaceae	Seeds	Petroleum ether	NM	Wistar rats induced with alloxan (65 mg/kg, i.p.)	Partial preservation/restoration of pancreatic β-cell mass	[79]
Clitoria ternatea L.	Fabaceae	Aerial parts	Ethanol	Polyphenols	Wistar rats induced with alloxan (45 mg/kg, sc)	Regeneration of β-cells	[80]
Crassocephalum crepidioides (Benth.) S. Moore	Asteraceae	Aerial parts	80% methanol	NM	Wistar rats induced with alloxan (150 mg/kg, i.p.); INS-1 cells	Increase in the percentage of β-cells; Protection of pancreatic β-cell from alloxan-induced apoptosis and from intracellular reactive oxygen species (ROS) accumulation	[81]
Coccinia grandis (L.) Voigt	Cucurbitaceae	Leaves	Aqueous	NM	Wistar rats induced with alloxan (150 mg/kg)	Regeneration of β-cells	[82]
Costus igneus N.E.Br.	Costaceae	Rhizome	Ethanol	Quercetin and kaempferol (flavonoids)	Albino rats induced with STZ (40 mg/kg, i.p.)	Regeneration of β-cells	[83]
Curcuma longa L.	Zingiberaceae	Roots	Hydroalcoholic extract	NM	RINm5F cell line induced with STZ (2 mM)	Inhibition of MDA release; Inhibition of β-cell apoptosis	[84]
Dacryodes edulis (G. Don) H.J. Lam	Burseraceae	Fruit	Hexane	NM	Albino rats induced with alloxan (150 mg/kg, i.p.)	Restoration of the damaged pancreatic β-cell architecture	[85]
Dacryodes edulis (G. Don) H.J. Lam	Burseraceae	Leaves	Ethanol	Phenolics-gallic acid, vanillic acid, vanillin, and (−)-epicatechin	Albino rats induced with 10% fructose and STZ (40 mg/kg, i.p.)	Increase in HOMA-β; Improvement in pancreatic morphology	[86]
Eriobotrya japonica (Thunb.) Lindl.	Rosaceae	Leaves	Aqueous	Cinchonain Ib	INS-1 cell	Increase in insulin secretion	[87]
Eurycoma longifolia Jack	Simaroubaceae	Root	NA	NM	db/db diabetic mice	Proliferation of β-cell and increase in β-cell number and PDX1 expression	[88]
Ficus carica L.	Moraceae	Leaves	Ethyl acetate	NM	Wistar rats induced with HFD and STZ (40 mg/kg, i.p.)	Protection of β-cells from oxidative stress; Improvement of OGTT and ITT	[89]
Gastrodia elata Blume	Orchidaceae	Whole plant	Aqueous	NM	Sprague–Dawley rats induced by 90% pancreatectomy	Induction of hypothalamic insulin signaling; Increase in mass of β-cells by potentiating proliferation and decreasing apoptosis	[90]
Gossypium herbaceum L.	Malvaceae	Seeds	Ethanol	NM	Rabbits induced with alloxan-induced (100 mg/kg, iv) diabetic rabbits	Protection of β-cells from oxidative stress	[91]
Gmelina arborea Roxb.	Verbenaceae	Stem bark	Aqueous	NM	Wistar rats induced with alloxan (150 mg/kg, i.p.); Wistar rats induced with STZ (65 mg/kg, i.p.)	Regeneration of β-cells; Regeneration of β-cells	[82, 92]
Gymnema montanum (Roxb.) Hook.f. var. montanum	Apocynaceae	Leaves	Ethanol	NM	HIT-T15 β-cell line	Protection of pancreatic β-cells from alloxan-induced oxidative stress	[93]
Gymnema sylvestre (Retz.) Schult.	Apocynaceae	Leaf and callus	Methanol	Gymnemic acid	Wistar rats induced with alloxan (100 mg/kg, i.p.)	Regeneration of β-cells	[94]
Hibiscus sabdariffa L.	Malvaceae	Calyx	Methanol	NM	Wistar rats induced with STZ (80 mg/kg, i.p.)	Improvement of the volume of the pancreatic islets and the numerical density of β-cell (number of β-cells per unit area of islet)	[95]
Hypoxis argentea Harv. ex Baker	Hypoxidaceae	Corms	Aqueous	NM	INS-1 cells	A significant () increase in total INS-1 cell numbers	[96]
Ichnocarpus frutescens (L.) W.T.Aiton	Apocynaceae	Leaves, stem, and flowers	Methanol	NM	Wistar rats induced with NA (230 mg/kg, i.p.) and STZ (65 mg/kg, i.p.)	Regeneration of β-cells	[97]
Khaya senegalensis (Desr.) A. Juss.	Meliaceae	Root	Butanol fraction of ethanol extract	NM	Sprague–Dawley rats induced with fructose (10%) and STZ (40 mg/kg, i.p.)	Improvement in of HOMA-β	[98]
Laurus nobilis L.	Lauraceae	Leaves	Ethanol	NM	Wistar rats induced with STZ (70 mg/kg, i.p.)	Regeneration of pancreatic islets	[99]
Leea macrophylla (Roxb.) ex Hornem	Vitaceae	Root	Ethanol	NM	Wistar rats induced with STZ (60 mg/kg, i.p.)	Reduction of oxidative stress; Repair of β-cell damage	[100]
Mangifera indica L.	Anacardiaceae	Leaves	Alcohol	NM	Swiss albino mice induced with alloxan (150 mg/kg, i.p.)	Regeneration of β-cells	[101]
Momordica charantia L.	Cucurbitaceae	Fruit pulp	Ethanol	NM	Wistar rats induced with STZ (100 mg/kg, i.p.)	Improvement of HOMA-β; Increase in islet size, total β-cell area and number of insulin-positive β-cells	[102]
Momordica charantia L.	Cucurbitaceae	Fruit	NA	NM	Wistar rats induced with HFD and STZ (40 mg/kg, i.p.)	Regeneration of β-cells	[103]
Momordica charantia L.	Cucurbitaceae	Fruit	Aqueous	NM	Albino rats induced with STZ (55 mg/kg, i.p.)	Regeneration of β-cells	[104]
Moringa oleifera Lam.	Moringaceae	Leaves	Aqueous	NM	Wistar rats induced with alloxan (120 mg/kg, i.p.)	Regeneration of damaged hepatocytes and pancreatic β-cells	[105]
Nypa fruticans Wurmb.	Arecaceae	Vinegar	Aqueous	NM	Sprague–Dawley rats induced with STZ (55 mg/kg, i.p.); RIN-5F cell culture	Increase in insulin production; Stimulatory effect on insulin release at a basal glucose concentration (1.1 mM)	[106]
Otostegia persica Boiss	Lamiaceae	Aerial parts	Methanol	NM	C187 pancreatic β-cells	Increase in GSIS	[107]
Parkia biglobosa (Jacq.) G. Don	Fabaceae	Leaves	Butanol fraction	NM	Sprague–Dawley rats induced with STZ (40 mg/kg, i.p.)	Improvement of HOMA-β	[108]
Phyllanthus emblica L.	Phyllanthaceae	Fruits	Hydroalcoholic extract	NM	RINm5F cell line induced with STZ (2 mM)	Inhibition of MDA release; Inhibition of β-cell apoptosis	[84]
Prosopis cineraria (L.) Druce	Fabaceae	Pods	Ethanol	NM	Albino rats induced with high sucrose diet and dexamethasone (1.5 mg/kg, i.p.)	Increase in HOMA-β-increase in pancreatic cell proliferation	[109]
Pseuduvaria macrophylla (Oliv.) Merr.	Annonaceae	Stem bark	Methanol and chloroform	Polyphenols	Sprague–Dawley rats induced with NA (210 mg/kg, i.p.) and STZ (55 mg/kg, i.p.)	Reduction of oxidative stress; Downregulation of the levels of proinflammatory cytokines	[110]
Spondias pinnata (Linn. f.) Kurz	Anacardiaceae	Stem bark	Aqueous	NM	Wistar rats induced with alloxan (150 mg/kg)	Regeneration of β-cells	[82]
Spondias pinnata (Linn. f.) Kurz.	Anacardiaceae	Stem bark	Aqueous	NM	Wistar rats induced with STZ (65 mg/kg, i.p.)	Islet cell regeneration as noted by the increase in insulin-secreting β-cells and increase in islet profile diameter in the pancreas	[111]
Syzygium densiflorum Wall. ex Wight and Arn	Myrtaceae	Fruits	Methanol	NM	Wistar rats induced with NA (110 mg/kg, i.p.) and STZ (65 mg/kg, i.p.)	Regeneration of β-cells	[112]
Swertia macrosperma C.B.Clarke	Gentianaceae	Whole plant	90% ethanol	Polyphenols	Wistar rats induced with high-fat-high fructose diet and STZ (35 mg/kg, i.p.)	Protection of pancreatic β-cells from oxidative stress; Stimulation of insulin secretion from the remaining pancreatic β-cells	[113]
Tamarindus indica L.	Fabaceae	Seed coat	95% ethanol	Polyphenols	Wistar rats induced with alloxan (120 mg/kg, i.p.)	Protection of pancreatic β-cells from oxidative stress	[114]
Tamarix stricta Boiss.	Tamaricaceae	Aerial parts	70% ethanol	NM	Pancreatic RIN-5F cells; Albino BALB/c mice induced with HFD and STZ (40 mg/kg, i.p.)	Preservation of β-cells	[115]
Teucrium polium L.	Lamiaceae	Methanol	Methanol	Rutin and apigenin (flavonoids)	Isolated rat pancreatic islets	Increase in insulin release	[116]
Tinospora cordifolia (Thunb.) Miers	Menispermaceae	Stem	Hexane, ethyl acetate, and methanol	NM	Albino rats induced with STZ (55 mg/kg, i.p.)	Regeneration of β-cell	[117]
Tinospora cord folia (Thunb.) Miers	Menispermaceae	Stems	Hydroalcoholic extract	NM	RINm5F cell line induced with STZ (2 mM)	Inhibition of MDA release; Inhibition of β-cell apoptosis	[84]
Urena lobata L.	Malvaceae	Leaves	Aqueous	NM	Sprague–Dawley rats induced with high fructose diet and STZ (25 mg/kg, i.p.)	Improvement in the structure and function of β-cells; Prevention of degradation of GLP-1 by inhibition of DPP-4 activity	[118]
Urtica dioica L.	Urticaceae	Leaves	90% ethanol	NM	Wistar rats induced with STZ (50 mg/kg, i.p.) RIN-5F cells	Regeneration of β-cells and reduction of β-cell damage; Increase in insulin secretion	[119]
Vitex doniana Sweet.	Verbenaceae	Leaves	Aqueous and ethanol	NM	Albino rats induced with STZ (60 mg/kg, i.p.)	Regeneration of β-cells along with repair of β-cells	[120]
Vitellaria paradoxa C.F. Gaertn.	Sapotaceae	Barks	Aqueous	NM	Wistar rats induced with HFD and STZ (35 mg/kg, i.p.)	Increase in the size and number of islets in the pancreas	[121]
Zingiber officinale Roscoe	Zingiberaceae	Rhizome	96% ethanol and supercritical CO2 extracts	NM	INS-1 cells	Modulation of insulin release by interacting with serotonin (5-HT) receptor channel system	[122]

DM, diabetes mellitus; STZ, streptozotocin; NA, nicotinamide; i.p., intraperitoneal; iv, intravenous; sc, subcutaneous; HFD, high-fat diet; homeostatic model assessment-β-cell function HOMA-β; malondialdehyde, MDA; superoxide dismutase, SOD; neurogenin 3, Ngn3; natural killer cell transcription factor-related, gene family 6, locus 1, Nkx6.1; TBARS, thiobarbituric acid-reactive substances; CAT, catalase; GSH, reduced glutathione; ROS, reactive oxygen species; PDX1, pancreatic duodenal homeobox-1; OGTT, oral glucose tolerance test; ITT, GSIS, glucose-stimulated insulin secretion; GLP-1, glucagon-like peptide-1; DPP-4, dipeptidyl peptidase inhibitor-4; 5-HT, serotonin; NA, not applicable; NM, not mentioned.