Pancreatic beta cell protection/regeneration with
               phytotherapy

Hosseini, Azar; Shafiee-Nick, Reza; Ghorbani, Ahmad

doi:10.1590/S1984-82502015000100001

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Brazilian Journal of Pharmaceutical Sciences

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Review • Braz. J. Pharm. Sci. 51 (1) • Jan-Mar 2015 • https://doi.org/10.1590/S1984-82502015000100001 copy

Pancreatic beta cell protection/regeneration with phytotherapy

Authorship SCIMAGO INSTITUTIONS RANKINGS

Although currently available drugs are useful in controlling early onset complications of diabetes, serious late onset complications appear in a large number of patients. Considering the physiopathology of diabetes, preventing beta cell degeneration and stimulating the endogenous regeneration of islets will be essential approaches for the treatment of insulin-dependent diabetes mellitus. The current review focused on phytochemicals, the antidiabetic effect of which has been proved by pancreatic beta cell protection/regeneration. Among the hundreds of plants that have been investigated for diabetes, a small fraction has shown the regenerative property and was described in this paper. Processes of pancreatic beta cell degeneration and regeneration were described. Also, the proposed mechanisms for the protective/regenerative effects of such phytochemicals and their potential side effects were discussed.

Diabetes mellitus/treatment; Diabetes mellitus/phytotherapy; Phytotherapy/Diabetes mellitus; Islets/endogenous regeneration; Beta cells/protection; Beta cells/regeneration; Pancreas; Medicinal plants/regenerative properties

Plants	Animal model	Treatment	Effects on pancreas	Other effects	Reference
Abroma augusta	ALO-induced diabetic rabbits	Aqueous extract of leaves (2 mL/kg, twice daily, PO) for 21 days	↑beta cell number	↓FBG, ↓blood urea, ↓serum creatinin	Mir, Darzi, Mir, 2013
Alchornea cordifolia	ALO-induced diabetic rabbits	Ethanolic extract of leaves (250 & 500 mg/kg, PO) for 28 days	Regeneration of beta cells (at 500 mg/kg)	-	Eliakim-Ikechukwu, Obri, 2009
Allium sativum	STZ-induced diabetic rats	Aqueous extract (100 mg/kg/day) for 30 days	↑islets diameter	↓FBG, ↑serum insulin	Albajali et al., 2011
		Allicin (8 & 16 mg/kg, IP) for 30 days	↓anti-islet cell antibodies; ↓beta cell degeneration	↑serum insulin, ↓FBG, ↓weight lost,	Osman et al., 2012
		A. sativum oil (10 & 20 mg/kg, IP)for 30 days	Regeneration of pancreatic islets (at 20 mg/kg)	↓FBG, ↑serum insulin, ↓weight lost	Alashkham et al., 2013
Amaranthus caudatus	STZ-induced diabetic rats	Methanolic extract of leaves (200 & 400 mg/kg, PO) for 21 days	Slight regeneration of beta cells (at 400 mg/kg)	↓FBG, ↓weight lost, ↓serum lipids	Girija et al., 2011
Amaranthus spinosus	STZ-induced diabetic rats	Methanolic extract of leaves (200 & 400 mg/kg, PO) for 21 days	Slight regeneration of beta cells (at 400 mg/kg)	↓FBG, ↓weight lost, ↓serum lipids	Girija et al., 2011
Amaranthus viridis	STZ-induced diabetic rats	Methanolic extract of leaves (200 & 400 mg/kg, PO) for 21 days	Slight regeneration of beta cells (at 400 mg/kg)	↓FBG, ↓weight lost, ↓serum lipids	Girija et al., 2011
Anacardium occidentale	STZ-induced diabetic rats	A. occidentale extract (300 & 500 mg/kg, twice daily) for 28 days	Regeneration of pancreatic beta cells	↓FBG	Bassey, Eliakim-Ikechukw, Ihentuge, 2012
Anastatica hierochuntica	STZ-induced diabetic rats	Aqueous extract (12.5 mg/rat, PO) for 2 weeks	↑beta cell number	↓FBG	Rahmy, El-Ridi, 2002
Anastatica hierochuntica	ALO-induced diabetic rats	Methanolic extract (100 mg/kg, PO) for 4 weeks	↑volume density of islets, ↑percentage of beta cells	↓FBG, ↓serum lipids, ↓weight lost, ↓liver enzymes activity, ↑antioxidant enzymes activity	Shaban, Al-Azzawie, Mohamme, 2011
Annona muricata	STZ-induced diabetic rats	Aqueous extract of leaves (100 mg/kg, PO) for 25 days	↑beta cell number	↓FBG, ↑serum insulin, ↓oxidative stress indexes in blood	Adewole, Caxton-martins, 2006
Annona muricata	STZ-induced diabetic rats	Methanolic extract of leaves (100 mg/kg, IP) for 2 weeks	↑islets number, ↑beta cell number, ↓inflammatory infiltration	↓FBG	Adeyemi et al., 2008
Artanema sesamoides	STZ-induced diabetic rats	Methanolic extract of aerial parts (200 & 400 mg/kg, PO) for 14 days	↓necrosis of islet cells, ↓degeneration of the islets	↓FBG, ↓serum lipids, ↓liver enzymes activity, ↓liver and kidney damage, ↑antioxidant defense in liver and kidney	Selvan et al., 2008
Azadirachta indica	ALO-induced diabetic rats	Alcoholic extract of leaves (400 mg/kg, twice daily, PO) for 14 days	Regeneration of new islets	↓FBG	Ebong et al., 2006
Azadirachta indica	STZ-induced diabetic rats	Ethanolic extract of leaves (500 mg/kg, twice daily, PO) for 50 days	↑beta cell density; ↓pancreatic lipid hydroperoxide levels	↓FBG	Akinola, Caxton-Martins, Dini, 2010
Bauhinia variegata	ALO-induced diabetic rats	Ethanol extract of bark (500 mg/kg, PO) for 15 days	Restored the cellular size and number of islets towards normal	↓FBG, ↓serum lipids	Koti et al., 2009
Berberine	ALO-induced diabetic rats	berberine (100 & 200 mg/kg, PO) for 21 days	Moderate expansion of islets, ↓damage scores	↓FBG, ↓serum lipids, ↓oxidative stress in the heart	Tang et al., 2006
Berberine	STZ- and high carbohydrate/fat diet-induced diabetic rats	berberine (75-300 mg/kg, PO) for 16 weeks	↑beta cells number, ↑insulin expression, ↓oxidative stress indexes	↑serum insulin	Zhou et al., 2009
Cassia alata	STZ-induced diabetic rats	Ethanolic extract of leaves (500 mg/kg, twice daily, PO) for 28 days	Regeneration of beta cells	↓FBG	Eliakim-Ikechukwu et al., 2013
Cassia occidentalis	ALO-induced diabetic rats	Aqueous extract of whole plant (200 mg/kg, PO) for 21 days	Partial restoration of cellular population and size of islet cells	↓FBG, ↓serum lipids	Verma et al., 2010
Clitoria ternatea	STZ-induced diabetic rats	Ethanolic extract of aerial parts (200 mg/kg, PO) for 21 days	↓necrosis of islets, ↓fibrosis of islets, improvement in beta cell granulation	↓FBG, ↓weight lost, ↓serum lipids	Verma, Itankar, Arora, 2013
Curcumin	STZ-induced diabetic mice	Curcumin (200 mg/kg, IP) for 12 weeks	↓lymphocytes infiltration in the islets, ↑islets number	↓FBG, ↓weight loss	Chanpoo, Petchpiboonthai, 2010
Curcumin	STZ-induced diabetic rats	Curcumin derivative (150 mg/kg, PO) for 40 days	↑islet cells number, ↑insulin positive cells	↓FBG, ↑serum insulin, ↑C-peptide	Abdel Aziz et al., 2013
Crocus sativus	ALO-induced diabetic rats	Ethanolic extract of stigmas (40 mg/kg, IP) for 14 days	↑beta cell number, ↑immunoreactivity of insulin in beta cells	↓FBG, ↑serum insulin	Mohajeri, Mousavi, Doustar, 2009
Crocus sativus	ALO-induced diabetic rats	Ethanolic extract (200 - 600 mg/kg, PO) for 4 weeks	The animals had normal histological structure (at 600 mg/kg)	↓FBG, ↓serum lipids, ↓weight lost, ↑serum insulin, improved kidney and liver function	Elgazar et al., 2013
Elephantopus scaber	ALO-induced diabetic rats	Aqueous extract of root and leaves (0.3 g/kg, PO) for 12 weeks	↑beta cell number per islet	↓FBG, ↓serum lipids, ↓serum urea, ↓creatinine	Daisy, Rayan, Rajathi, 2007
Epicatechin	ALO-induced diabetic rats	Epicatechin (30 mg/kg, twice daily, IP) for 4-5 days	↑beta cell number per islet	↓FBG, ↑serum insulin	Chakravarthy, Gupta, Gode, 1982
Gymnema sylvestre	STZ-induced diabetic rats	Water soluble extract of leaves	↑islets number, ↑beta cell number	↓FBG, ↑serum insulin	Shanmugasundaram et al., 1990
	STZ-induced diabetic rats	Standardized extract of leaves (200 & 400 mg/kg, PO) for 40 days	↓congestion, ↑normal beta cells	↓FBG, ↓HbA1c, ↓serum lipids, ↓weight lost, ↑serum insulin, ↑glycogen content in liver	Aralelimath, Bhise, 2012
	ALO-induced diabetic rats	Methanol extract of leaves and callus for 45 days	↑beta cell regeneration	↑body weight, ↑glycogen content in liver	Ahmed, Rao, Rao, 2010
Juglans regia	ALO-induced diabetic rats	Diet supplemented with 60 g/kg of leaves for 15 days	↑islets density, ↑percent of beta cells, ↑islets size	↓FBG	Jelodar, Mohsen, Shahram, 2007
	ALO-induced diabetic rats	Ethanolic extract of leaf (200 mg/kg)	Enlargement of islets size	↑serum insulin, ↓HbA1c	Asgary et al., 2008
	STZ-induced diabetic rats	Methanolic extract of leaves or peel (200 mg/kg, PO) for 4 weeks	↑beta cell number	↓FBG, ↑serum insulin, ↓HbA1c	Javidanpour et al., 2012
	STZ-induced diabetic rats	Aqueous extract of shell septum (200 - 800 mg/kg, PO) f or 4 weeks	No effect	↓FBG	Dehghani, Mashhoody, Panjehshahin, 2012
Leucaena leucocephala	STZ-induced diabetic rats	Extract of seed (0.25 - 1 g/kg, PO) for 14 days	↑beta cell number per islets, ↑islets diameter	↓FBG, ↓serum lipids	Darmono Syamsudin, Simanjuntak, 2006
Mangiferin	Partial pancreatectomy-induced diabetic mice	Mangiferin (30 & 90 mg/kg, IP) for 14 days	↑beta cell hyperplasia, ↑beta cell proliferation, ↓beta cell apoptosis	↓FBG, ↑serum insulin, ↑glucose tolerance	Wang et al., 2014
Momordica charantia	STZ-induced diabetic rats	Fruit juice (10 mL/kg, PO) for 10 weeks	↑beta cell number	↑serum insulin	Ahmed et al., 1998
	ALO-induced diabetic rats	Acetone extract of fruit (250-750 mg/kg, PO) for 30 days	Recovery of beta cells of the islets of Langerhans	Hepatoprotection	Singh, Gupta, 2007b
	ALO-induced diabetic rats	Alcoholic extract of fruit (250-750 mg/kg, PO) for 30 days	Recovery of beta cells of the islets of Langerhans	↓FBG	Singh et al., 2008
	Neonatal STZ-induced type-2 diabetic rats	Aqueous extract of fruit (20 mg/kg, PO) for 4 weeks	↑beta cell number per islet	↓FBG, ↑ serum insulin	Abdollahi et al., 2011
Momordica charantia	Neonatal STZ-induced type-2 diabetic rats	Ethanolic extract of fruit (400 mg/kg, PO) for 4 weeks	↑islet size, ↑total beta cell area, ↑beta cell number	↓FBG, ↑serum insulin	Hafizur, Kabir, Chishti, 2011
Morus alba	STZ-induced diabetic rats	Ethanolic extract of leaves (400 & 600 mg/kg, PO) for 35 days	↑islets diameter, ↑beta cell number	↓FBG	Mohammadi, Prakash, 2008
Nigella sativa & Thymoquinone	STZ-induced diabetic rats	Volatile oil (0.2 mL/kg, IP) for 30 days	Regeneration/proliferation of pancreatic β-cells	↓FBG, ↑serum insulin	Kanter et al., 2003
		Volatile oil (0.2 mL/kg, IP) for 30 days	Preserving beta cell numbers, ↓oxidative stress	↓oxidative stress parameters in blood	Kanter et al., 2004
		Thymoquinone (50 mg/kg, PO) for 4 weeks	↓islet degeneration and necrosis	↓FBG, ↑serum insulin	Kanter, 2009
		N. sativa oil (0.2 mL/kg) for 30 days	↑islets diameter	↓FBG, ↑serum insulin	Albajali et al., 2011
		Aqueous extract (2 mL/kg, IP), oil (0.2 mL/kg, IP) or thymoquinone (3 mg/kg, IP) for 30 days	↓oxidative stress indexes, partial regeneration of the islets and beta cells	↓FBG, ↑serum insulin	Abdelmeguid et al., 2010
	STZ + nicotinamide-induced diabetic rats	Thymoquinone (80 mg/kg) for 45 days	Preservation of islet cells against beta cell damage	↓oxidative stress in liver and kidney	Sankaranarayanan, Pari, 2011
Prangos ferulacea	STZ-induced diabetic rats	Hydroalcoholic extract of leaves, stem and root (100 mg/kg, PO) for one month	↓lymphocytes infiltration, ↓necrotic cells, regeneration of islets	↓FBG, ↓weight loss, ↓HbA1c	Soltani Band et al., 2011
Pterocarpus marsupium	ALO-induced diabetic rats	A flavonoid fraction extracted from the bark	Regeneration of beta cells	↓FBG	Chakravarthy et al., 1980
Sansevieria trifasciata	ALO-induced diabetic rats	Decoction of leaves (100 - 200 mg/kg, PO) for 30 days	↑granule density in beta cells of islets	↓FBG	Qomariyah, Sarto, Pratiwi, 2012
Solanum nigrum	ALO-induced diabetic rats	Aqueous extract of leaves (400 mg/kg) for 21 days	Partial restoration of islets population and hyperplasia of islet cells	↓FBG	Maniyar, Umamageswari, Karthikeyan, 2012
Syzygium cumini	ALO-induced diabetic rats	Alcoholic extract of seeds (250-750 mg/kg, PO) for 30 days	Hypertrophy of certain islets, ↑granule density in beta cells	↓FBG, ↑body weight,	Singh, Gupta, 2007a
Teucrium polium	STZ-induced diabetic rats	Hydroalcoholic extract (equivalent to 0.5 g plant/kg, PO) for 6 weeks	↑islets number, ↑beta cell number, ↓lymphocytes and macrophages number	↓FBG, ↓bilirubin, ↓glutamate oxaloacetate transferase, ↓glutamate pyruvate transferase, ↑serum insulin	Yazdanparast, Esmaeili, Ashrafi, 2005
Tinospora cordifolia	STZ-induced diabetic rats	Methanolic extract of stem (250 mg/kg, PO) for 100 days	Regeneration of beta cells	↓FBG, ↓HbA1c, ↑serum insulin, ↑C-peptide	Rajalakshmi et al., 2009
Trigonella foenum- graceum	Neonatal STZ-induced type-2 diabetic rats	Hydroalcoholic extract of seeds (100 mg/kg, PO) for 28 days	↑beta cell number, ↑islet size	↓FBG, ↓weight lost, ↓HbA1c, ↑serum insulin	Kulkarni et al., 2012
Thunbergia laurifolia	ALO-induced diabetic rats	Extract of leaves (60 mg/rat, PO) for 15 days	Recovery of some beta cells	↓FBG	Aritajat, Wuteerapol, Saenphet, 2004
Vernonia amygdalina	ALO-induced diabetic rats	Pre-treated with aqueous extract (250 mg/kg, PO) for 21 days	Moderate regeneration of islets	↓FBG	Sunday et al., 2012
Vernonia amygdalina	ALO-induced diabetic rats	Ethanolic extract of leaves (400 mg/kg, PO) for 14 days	Regeneration of new islet cells	↓FBG, ↓serum alpha-amylase activity	Atangwho et al., 2007
Vinca rosea		Methanolic extract of leaves (300 & 500 mg/kg, PO) for 14 days	Partial restoration of normal cellular population and enlarged size of beta cells	↓FBG, ↑glucose tolerance, ↓serum lipids, ↓weight lost, ↓creatinine, ↓urea, ↓alkalin phosphatase	Ahmed et al., 2010
Urtica dioica	STZ-induced diabetic rats	Hydroalcoholic extract (100 mg/kg, IP) for 5 days before induction of diabetes	↑beta cells number	↓FBG	Golalipour et al., 2010
Urtica pilulifera	STZ-induced diabetic rats	Lectin isolated from seeds (100 mg/kg, IP) for 4 weeks	↓cellular damage in pancreas	↓FBG, ↓weight lost	Kavalali et al., 2003

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: Ahmad Ghorbani. Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. E-mail: ghorbania@mums.ac.ir