Applicability of Isolates and Fractions of Plant Extracts in Murine Models in Type II Diabetes: A Systematic Review

Table 1

Table of qualitative descriptors of the studies of the effects of fractions and isolates from the plants on the treatment of the type II diabetes.

(a)

	Title	Author/publication year	Country
Isolates	[25] A Polysaccharide Extract of Mulberry Leaf Ameliorates Hepatic Glucose Metabolism and Insulin Signaling In Rats with Type 2 Diabetes Induced by High Fat-Diet and Streptozotocin	Ren et al. (2015)	China
	[26] Antidiabetic Activity of a Xanthone Compound, Mangiferin	Miura et al. (2001)	Japan
	[27] Anti-Diabetic Effect of a Novel N-Trisaccharide Isolated from Cucumis prophetarum on Streptozotocin-Nicotinamide Induced Type 2 Diabetic Rats	Kavishankar and Lakshmidevi (2014)	India
	[28] Antidiabetic Effects of the Cimicifuga racemosa Extract Ze 450 In Vitro and In Vivo in ob/ob Mice	Moser et al. (2014)	Switzerland
	[29] Borapetoside C from Tinospora crispa Improves Insulin Sensitivity in Diabetic Mice	Ruan et al. (2012)	Taiwan
	[30] Dehydrotrametenolic Acid Induces Preadipocyte Differentiation and Sensitizes Animal Models of Noninsulin-Dependent Diabetes Mellitus to Insulin	Sato et al. (2002)	Japan
	[31] Effects of Ingested Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on Glycemic Responses in Normal and Diabetic Rats	Lo et al. (2006)	Taiwan
	[32] Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)	Yoshida et al. (2013)	Japan
	[33] Isolation and Antihyperglycemic Activity of Bakuchiol from Otholobium pubescens (Fabaceae), a Peruvian Medicinal Pant Used for the Treatment of Diabetes	Krenisky et al. (1999)	USA
	[34] LBP-4a Improves Insulin Resistance via Translocation and Activation of GLUT4 in OLETF Rats	Zhao et al. (2014)	China
	[35] Meliacinolin: A Potent Α-Glucosidase and Α-Amylase Inhibitor Isolated from Azadirachta indica Leaves and In Vivo Antidiabetic Property in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Mice	Perez-Gutierrez and Damian-Guzman (2012)	Mexico
	[36] Novel Terpenoid-Type Quinones Isolated from Pycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes	Luo et al. (1999)	USA
	[37] Platyconic Acid, A Saponin from Platycodi radix, Improves Glucose Homeostasis by Enhancing Insulin Sensitivity In Vitro and In Vivo	Kwon et al. (2012)	South Korea
	[38] Rhaponticin from rhubarb Rhizomes Alleviates Liver Steatosis and Improves Blood Glucose and Lipid Profiles in KK/Ay Diabetic Mice	Chen et al. (2009)	China
	[39] Rutin Potentiates Insulin Receptor Kinase to Enhance Insulin-Dependent Glucose Transporter 4 Translocation	Hsu et al. (2014)	Taiwan
	[40] Type 2 Antidiabetic Activity of Bergenin from the Roots of Caesalpinia digyna Rottler	Kumar et al. (2012)	India
Fractions	[41] A Study on Hypoglycaemic Health Care Function of Stigma maydis Polysaccharides	Zhang et al. (2013)	China
	[1] Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase	Jeong and Song (2011)	Korea
	[42] Antidiabetic Activity of Alkaloids of Aerva lanata Roots on Streptozotocin-Nicotinamide Induced Type-II Diabetes in Rats	Agrawal et al. (2013)	India
	[43] Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint	Paramaguru et al. (2014)	India
	[44] Antidiabetic Activity of Caesalpinia bonducella F. in Chronic Type 2 Diabetic Model in Long-Evans Rats and Evaluation of Insulin Secretagogue Property of Its Fractions on Isolated Islets	Chakrabarti et al. (2005)	India
	[45] Antidiabetic Effect of an Acidic Polysaccharide (TAP) from Tremella aurantia and Its Degradation Product (TAP-H)	Kiho et al. (2001)	Japan
	[46] Antidiabetic Effect of Orally Administered Conophylline-Containing Plant Extract on Streptozotocin-Treated and Goto-Kakizaki Rats	Fujii et al. (2009)	Japan
	[47] Antidiabetic Effect of Total Flavonoids from Sanguis d raxonis  in Type 2 Diabetic Rats	Chen et al. (2013)	China
	[48] Antidiabetic Effects of Bitter Gourd Extracts in Insulin-Resistant db/db Mice	Klomann et al. (2010)	Germany
	[49] Anti-Diabetic Effects of Centratherum anthelminticum Seeds Methanolic Fraction on Pancreatic Cells, Β-TC6 and Its Alleviating Role in Type 2 Diabetic Rats	Arya et al. (2012)	Malaysia
	[17] Anti-Diabetic Effects of Polysaccharides from Talinum triangulare in Streptozotocin (STZ)-Induced Type 2 Diabetic Male Mice	Xu et al. (2015)	China
	[50] Anti-Diabetic Effects of the Acetone Fraction of Senna singueana Stem Bark in a Type 2 Diabetes Rat Model	Ibrahim and Islam (2014)	South Africa
	[51] Antidiabetic Potential of Polysaccharides from the White Oyster Culinary-Medicinal Mushroom Pleurotus florida (Higher Basidiomycetes)	Ganeshpurkar et al. (2014)	India
	[52] Antihyperglycemic Effects of Total Flavonoids from Polygonatum odoratum in STZ and Alloxan-Induced Diabetic Rats	Shu et al. (2009)	China
	[53] Antioxidant and Anti-Inflammatory Effects of a Hypoglycemic Fraction from Cucurbita ficifolia  Bouché in Streptozotocin-Induced Diabetic Mice	Roman-Ramos et al. (2012)	Mexico
	[54] Effect of Lycium barbarum Polysaccharide on the Improvement of Insulin Resistance in NIDDM Rats	Zhao et al. (2005)	China
	[55] Effects of Grape Seed Extract and Its Ethylacetate/Ethanol Fraction on Blood Glucose Levels in a Model of Type 2 Diabetes	Hwang et al. (2009)	South Korea
	[56] Hypoglycemic Effect of Astragaluspolysaccharide and Its Effect on PTP1B1	Wu et al. (2005)	China
	[57] Hypoglycemic Effects of MDG-1, a Polysaccharide Derived from Ophiopogon japonicus, in the ob/ob Mouse Model of Type 2 Diabetes Mellitus	Xu et al. (2011)	China
	[58] Isolation and Pharmacological Activities of the Tecoma stans Alkaloids	Costantino et al. (2003)	Italy
	[58] Potent Effects of the Total Saponins From Dioscorea nipponica Makino against Streptozotocin-Induced Type 2 Diabetes Mellitus in Rats	Yu et al. (2015)	China
	[59] Tocopherol from Seeds of Cucurbita pepo against Diabetes: Validation by In Vivo Experiments Supported by Computational Docking	Bharti et al. (2013)	India
	[60] Trapa natans L. Root Extract Suppresses Hyperglycemic and Hepatotoxic Effects in STZ-Induced Diabetic Rat Model	Kharbanda et al. (2014)	India

(b)

	Title	Animal model/strain	Number of animals	Sex	Age	Weight	Housing of animals	Animals per cage	Groups and number of animals in each group	Randomization
Isolates	[25] A Polysaccharide Extract of Mulberry Leaf Ameliorates Hepatic Glucose Metabolism and Insulin Signaling in Rats with Type 2 Diabetes Induced by High Fat-Diet and Streptozotocin	Wistar rats	18	M	7 w	200 g	Cages	5	3 groups (6 in each group)	Yes
	[26] Antidiabetic Activity of a Xanthone Compound, Mangiferin	Mice	?	M	12 w	?	?	?	?	?
	[27] Anti-Diabetic Effect of a Novel N-Trisaccharide Isolated from Cucumis prophetarum on Streptozotocin-Nicotinamide Induced Type 2 Diabetic Rats	Wistar rats	36	M&F	?	150–180 g	Cages	?	6 groups (6 animals in each)	?
	[28] Antidiabetic Effects of the Cimicifuga racemosa Extract Ze 450 In Vitro and In Vivo in ob/ob Mice	ob/ob mice	68	M	7-8 w	?	Cages	1	8 groups (8 animals in each)	?
	[29] Borapetoside C from Tinospora crispa Improves Insulin Sensitivity in Diabetic Mice	Mice	?	M	8–10 w	?	?	?	?	?
	[30] Dehydrotrametenolic Acid Induces Preadipocyte Differentiation and Sensitizes Animal Models of Noninsulin-Dependent Diabetes Mellitus to Insulin	C57BLK mice	?	M	7 w	?	?	?	?	?
	[31] Effects of Ingested Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on Glycemic Responses in Normal and Diabetic Rats	Wistar rats	102	M	?	200 g	Cages	1	6 groups (12 animals in each group) and 3 groups (10 animals in each group)	Yes
	[32] Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)	GK rats	12	M	?	?	Cages	1	2 groups (6 animals in each group)	?
	[33] Isolation and Antihyperglycemic Activity of Bakuchiol from Otholobium pubescens (Fabaceae), a Peruvian Medicinal Plant Used for the Treatment of Diabetes	C57BL/K mice & Sprague- Dawley rats	?	M	8 w	?	?	4	? Groups (8 animals in each group)	?
	[34] LBP-4a Improves Insulin Resistance via Translocation and Activation of GLUT4 in OLETF Rats	Otsuka Long-Evans Tokushima Fatty (OLETF) rats	18	M	26 w	?	?	?	3 groups (6 animals in each group)	Yes
	[35] Meliacinolin: A Potent Α-Glucosidase and Α-Amylase Inhibitor Isolated from Azadirachta indica Leaves and In Vivo Antidiabetic Property in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Mice	?/mice	42	M	?	20–25 g	Cages	2	7 groups (6 animals in each group)	?
	[36] Novel Terpenoid-Type Quinones Isolated from Pycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes	C57BLK mice	?	M	7-8 w	?	Cages	4	? groups (5–8 animals in each group)	?
	[37] Platyconic Acid, a Saponin from Platycodi radix, Improves Glucose Homeostasis by Enhancing Insulin Sensitivity In Vitro and In Vivo	C57BLK mice	90	M	8–10 w	?	?	1	6 groups (15 animals in each group)	Yes
	[38] Rhaponticin from rhubarb Rhizomes Alleviates Liver Steatosis and Improves Blood Glucose and Lipid Profiles in KK/Ay Diabetic Mice	Mice	30	M&F	8–12 w	?	Cages	1	3 groups (10 animals in each group)	Yes
	[39] Rutin Potentiates Insulin Receptor Kinase to Enhance Insulin-Dependent Glucose Transporter 4 Translocation	Mice	?	M	8 w	?	?	?	?	?
	[40] Type 2 Antidiabetic Activity of Bergenin from the Roots of  Caesalpinia digyna Rottler	Charles Foster Albino rats	30	M	?	?	?	?	5 groups (6 animals in each group)	?
Fractions	[41] A Study on Hypoglycaemic Health Care Function of Stigma maydis Polysaccharides	SPF km mice	?	M	?	20 ± 2 g	?	?	7 groups (animals in each group?)	Yes
	[1] Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase.	C57BLK mice	?	?	5 w	?	Cages	5	5 groups (animals in each group?)	?
	[42] Antidiabetic Activity of Alkaloids of Aerva lanata Roots on Streptozotocin-Nicotinamide Induced Type-II Diabetes in Rats	Wistar rats	?	M	?	200–250 g	?	?	?	?
	[43] Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint	Albino Wistar rats	66	M	?	180–200 g	Cages	?	11 groups (6 animals in each group)	?
	[44] Antidiabetic Activity of Caesalpinia bonducella F. in Chronic Type 2 Diabetic Model in Long-Evans Rats and Evaluation of Insulin Secretagogue Property of Its Fractions on Isolated Islets	Long-Evans rats	?	M&F	12–14 w	150 g	?	?	5 groups (6–9 animals in each group)	?
	[45] Antidiabetic Effect of an Acidic Polysaccharide (TAP) from Tremella aurantia and Its Degradation Product (TAP-H)	KK- Ay-TA mice	?	M	5 w	25–30 g	?	1	3 groups (animals in each group?)	?
	[46] Antidiabetic Effect of Orally Administered Conophylline-Containing Plant Extract on Streptozotocin-Treated and Goto-Kakizaki Rats	Goto-Kakizaki rats	14	M	5 w	?	?	?	3 groups (animals in each group?)	Yes
	[47] Antidiabetic Effect of Total Flavonoids from Sanguis draxonis  in Type 2 Diabetic Rats	Sprague-Dawley rats	72	M	?	180–220 g	?	?	6 groups (6 animals in each group) for SD; 6 groups (6 animals in each group) for SDF	?
	[48] Antidiabetic Effects of Bitter Gourd Extracts in Insulin-Resistant db/db Mice	db/db mice	45	M	5 w	?	Cages	1	5 groups (9 animals in each group)	?
	[49] Anti-Diabetic Effects of Centratherum anthelminticum Seeds Methanolic Fraction on Pancreatic Cells, Β-TC6 and Its Alleviating Role in Type 2 Diabetic Rats	Sprague-Dawley rats	72	M&F	?	180–200 g	?	?	12 groups (6 animals in each group)	?
	[17] Anti-Diabetic Effects of Polysaccharides from Talinum triangulare in Streptozotocin (STZ)-Induced Type 2 Diabetic Male Mice	SPF km mice	50	M	?	20 ± 2 g	?	?	5 groups (10 animals in each group)	Yes
	[50] Anti-Diabetic Effects of the Acetone Fraction of Senna singueana Stem Bark in a Type 2 Diabetes Rat Model	Sprague-Dawley rats	48	M	6 w	207.60 ± 4.27 g	Cage	2	6 groups (8 animals in each group)	Yes
	[51] Antidiabetic Potential of Polysaccharides from the White Oyster Culinary-Medicinal Mushroom Pleurotus florida (Higher Basidiomycetes)	Wistar rats	20	M	?	150–200 g	?	?	4 groups (5 animals in each group)	?
	[52] Antihyperglycemic Effects of Total Flavonoids from Polygonatum odoratum in STZ and Alloxan-Induced Diabetic Rats	Sprague-Dawley rats	?	?	?	220 ± 4.5 g	Special animal house	?	?	?
	[53] Antioxidant and Anti-Inflammatory Effects of a Hypoglycemic Fraction from Cucurbita ficifolia  Bouché in Streptozotocin-Induced Diabetic Mice	CD-1 mice	?	M	?	30–35 g	?	?	?	?
	[54] Effect of Lycium barbarum Polysaccharide on the Improvement of Insulin Resistance in NIDDM Rats	Wistar rats	40	M	?	230–250 g	Cages	?	?	Yes
	[55] Effects of Grape Seed Extract and Its Ethylacetate/Ethanol Fraction on Blood Glucose Levels in a Model of Type 2 Diabetes	C57BL/KsJ-leprdb/leprdb mice	98	M	3 w	9.7–14.2 g	Conventional state	?	7 groups (14 in each group)	?
	[56] Hypoglycemic Effect of Astragaluspolysaccharide and Its Effect on PTP1B1	Sprague-Dawley rat	34	M	8 w	200 g	?	5	4 groups (2 groups with 10 animals and 2 groups with 12 animals in each)	?
	[57] Hypoglycemic Effects of MDG-1, a Polysaccharide Derived from Ophiopogon j aponicus, in the ob/ob Mouse Model of Type 2 Diabetes Mellitus	ob/ob mice	?		6-7 w	?	?	?	4 groups (8 animals in each group)	?
	[58] Isolation and Pharmacological Activities of the Tecoma stans Alkaloids	C57BL/KsJ db/db mice	?	M	8 w	?	?	?	?	?
	[61] Potent Effects of the Total Saponins from Dioscorea nipponica Makino against Streptozotocin-Induced Type 2 Diabetes Mellitus in Rats	Wistar rats	70	M	?	190–200 g	Cages	1	7 groups (8 animals in each group)	Yes
	[59] Tocopherol from Seeds of Cucurbita pepo against Diabetes: Validation by In Vivo Experiments Supported by Computational Docking	Albino Wistar rats	24	M	?	150–160 g	?	?	4 groups (6 animals in each group)	?
	[60] Trapa natans L. Root Extract Suppresses Hyperglycemic and Hepatotoxic Effects in STZ-Induced Diabetic Rat Model	Albino Wistar rats	90	?	?	150–200 g	Cages	?	15 groups (6 animals in each group)	?

(c)

	Title	Plant species	Isolate/fraction	Administration	Doses used	Duration of treatment
Isolates	[25] A Polysaccharide Extract of Mulberry Leaf Ameliorates Hepatic Glucose Metabolism and Insulin Signaling in Rats with Type 2 Diabetes Induced by High Fat-Diet and Streptozotocin	Mulberry	Mulberry leaf polysaccharide	Gavage	200 mg/kg	6 days of treatment
	[26] Antidiabetic Activity of a Xanthone Compound, Mangiferin	Anemarrhena asphodeloides Bunge	Mangiferin	Orally	30 mg/kg	?
	[27] Anti-Diabetic Effect of a Novel N-Trisaccharide Isolated from Cucumis prophetarum on Streptozotocin-Nicotinamide Induced Type 2 Diabetic Rats	Cucumis prophetarum	N-Trisaccharide	Gavage	50, 5 mg/kg	28 days of treatment
	[28] Antidiabetic Effects of the Cimicifuga racemosa Extract Ze 450 In Vitro and In Vivo in ob/ob Mice	Cimicifuga racemosa	Ze 450	Gavage	10, 30, 90 mg/kg	7 days of treatment
	[29] Borapetoside C from Tinospora crispa Improves Insulin Sensitivity in Diabetic Mice	Tinospora crispa	Borapetoside C	Orally	5 mg/kg	4 weeks of treatment
	[30] Dehydrotrametenolic Acid Induces Preadipocyte Differentiation and Sensitizes Animal Models of Noninsulin-Dependent Diabetes Mellitus to Insulin	Poria cocos Wolf	Dehydrotrametenolic acid	Gavage	110 mg/kg	14 days of treatment
	[31] Effects of Ingested Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on Glycemic Responses in Normal and Diabetic Rats	Tremella mesenterica	Acidic polysaccharide glucuronoxylomannan (GXM)	Gavage	1 g/kg	15 days of treatment
	[32] Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)	Oenanthe javanica	falcarindiol	Orally	15 mg/kg	?
	[33] Isolation and Antihyperglycemic Activity of Bakuchiol from Otholobium pubescens (Fabaceae), a Peruvian Medicinal Plant Used for the Treatment of Diabetes	Otholobium pubescens	Bakuchiol	Gavage	1, 150, 250 mg/kg	2 weeks of treatment
	[34] LBP-4a Improves Insulin Resistance via Translocation and Activation of GLUT4 in OLETF Rats	Lycium barbarum	Lycium barbarum polysaccharide (LBP-4a)	Orally	10 mg/kg	4 weeks of treatment
	[35] Meliacinolin: A Potent Α-Glucosidase and Α-Amylase Inhibitor Isolated from Azadirachta indica Leaves and In Vivo Antidiabetic Property in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Mice	Azadirachta indica	Meliacinolin	Orally by gastric intubations	20 mg/kg	28 days of treatment
	[36] Novel Terpenoid-Type Quinones Isolated from Pycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes	Pycnanthus angolensis	Novel terpenoid-type quinones (SP-18904 and SP-18905)	Gavage	100 mg/kg	4 days of treatment
	[37] Platyconic Acid, a Saponin from Platycodi radix, Improves Glucose Homeostasis by Enhancing Insulin Sensitivity In Vitro and In Vivo	Platycodi radix	Platyconic acid (PA), platycodin D (PD), platycoside E (PE), and saponin with low activity (DPE)	Gavage	20 mg/kg	8 weeks of treatment
	[38] Rhaponticin from rhubarb Rhizomes Alleviates Liver Steatosis and Improves Blood Glucose and Lipid Profiles in KK/Ay Diabetic Mice	Rheum franzenbachii Munt	Rhaponticin	Orally	125 mg/kg	4 weeks of treatment
	[39] Rutin Potentiates Insulin Receptor Kinase to Enhance Insulin-Dependent Glucose Transporter 4 Translocation	Toona sinensis	Flavonoid rutin	Gavage	25 mg/kg	?
	[40] Type 2 Antidiabetic Activity of Bergenin from the Roots of Caesalpinia digyna Rottler	Caesalpinia digyna Rottler	Bergenin	Orally	2.5, 5, and 10 mg/kg	14 days of treatment
Fractions	[41] A Study on Hypoglycaemic Health Care Function of Stigma maydis Polysaccharides	Stigma maydis	Stigma maydis polysaccharides	?	20 mg/kg	4 weeks of treatment
	[1] Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase	Malva verticillata	Ethanol extract of M. verticillata and N-hexane (MVE-H)	Orally	3 different concentrations of MVE-H (10, 20, or 40 mg/kg)	4 weeks of treatment
	[42] Antidiabetic Activity of Alkaloids of Aerva lanata Roots on Streptozotocin-Nicotinamide Induced Type-II Diabetes in Rats	Aerva lanata Linn.	The partially purified alkaloid basified toluene fraction (PPABTF)	Orally	10, 20 mg/kg	2 weeks of treatment
	[43] Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint	Pterospermum acerifolium	Ethyl acetate fraction (PAFEF) and subfractions PAFE1, PAFE2, and e PAFE3	Intragastric tube	200, 400 mg/kg, and 15, 30 mg/kg	30 days of treatment
	[44] Antidiabetic Activity of Caesalpinia bonducella F. in Chronic Type 2 Diabetic Model in Long-Evans Rats and Evaluation of Insulin Secretagogue Property of Its Fractions on Isolated Islets	Caesalpinia bonducella F.	Caesalpinia bonducella aqueous and alcoholic extracts (BM-170 and BM-171)	Orally	250 mg/kg	28 days of treatment
	[45] Antidiabetic Effect of an Acidic Polysaccharide (TAP) from Tremella aurantia and Its Degradation Product (TAP-H)	Tremella aurantia	Acidic polysaccharide (TAP) and the degradation product (TAP-H)	Orally	0.5 g/L, 1.5 g/L	10 weeks of treatment
	[46] Antidiabetic Effect of Orally Administered Conophylline-Containing Plant Extract on Streptozotocin-Treated and Goto-Kakizaki Rats	Tabernaemontana divaricata	The Crude Conophylline Preparation I (CCP-I)	Orally	200, 50 g/kg	15 days of treatment
	[47] Antidiabetic Effect of Total Flavonoids from Sanguis draxonis  in Type 2 Diabetic Rats	Dracaena cochinchinensis	Sanguis draxonis (SD) and total flavonoids from SD (SDF)	Gavage	?	21 days of treatment
	[48] Antidiabetic Effects of Bitter Gourd Extracts in Insulin-Resistant db/db Mice	Momordica charantia	The lipid fraction, the saponin fraction, or the hydrophilic residue of bitter gourd	Orally	150 mg/kg	5 weeks of treatment
	[49] Anti-Diabetic Effects of Centratherum anthelminticum Seeds Methanolic Fraction on Pancreatic Cells, Β-TC6 and Its Alleviating Role in Type 2 Diabetic Rats	Centratherum anthelminticum	Crude methanolic fraction (CAMF)	Injected intraperitoneally (IP) or orally	50 and 100 mg/kg	4 weeks of treatment
	[17] Anti-Diabetic Effects of Polysaccharides from Talinum triangulare in Streptozotocin (STZ)-Induced Type 2 Diabetic Male Mice	Talinum triangulare	Polysaccharides obtained from Talinum triangulare (TTP)	Orally	150 and 300 mg/kg	2 weeks of treatment
	[50] Anti-Diabetic Effects of the Acetone Fraction of Senna singueana Stem Bark in a Type 2 Diabetes Rat Model	Senna singueana	Senna singueana acetone fraction (SSAF)	Orally	150 mg/kg and 300 mg/kg	4 weeks of treatment
	[51] Antidiabetic Potential of Polysaccharides from the White Oyster Culinary-Medicinal Mushroom Pleurotus florida (Higher Basidiomycetes)	Pleurotus florida	P. florida polysaccharides (PFPs)	Orally	200 and 400 mg/kg	21 days of treatment
	[52] Antihyperglycemic Effects of Total Flavonoids from Polygonatum odoratum in STZ and Alloxan-Induced Diabetic Rats	Polygonatum odoratum	Total flavonoids of Polygonatum (P) odoratum (TFP)	Orally	50, 100, and 200 mg/kg	30 days of treatment
	[53] Antioxidant and Anti-Inflammatory Effects of a Hypoglycemic Fraction from Cucurbita ficifolia  Bouché in Streptozotocin-Induced Diabetic Mice	Cucurbita ficifolia	Aqueous-precipitate fraction (AP-fraction)	Gavage	200 mg/kg	15 days of treatment
	[54] Effect of Lycium barbarum Polysaccharide on the Improvement of Insulin Resistance in NIDDM Rats	Lycium barbarum	Lycium barbarum polysaccharide (LBP)	Orally	10 mg/kg	3 weeks of treatment
	[55] Effects of Grape Seed Extract and Its Ethylacetate/Ethanol Fraction on Blood Glucose Levels in a Model of Type 2 Diabetes	Vitis vinifera grape	Grape seed extract (GSE), ethylacetate (e), and ethylacetate/ethanol (ee)	Orally	50 and 30 mg/kg	8 weeks of treatment
	[56] Hypoglycemic Effect of Astragaluspolysaccharide and Its Effect on PTP1B1	Astragalus membranaceus	Astragalus polysaccharide (APS)	Orally	400 mg/kg	5 weeks of treatment
	[57] Hypoglycemic Effects of MDG-1, a Polysaccharide Derived from Ophiopogon japonicus, in the ob/ob Mouse Model of Type 2 Diabetes Mellitus	Ophiopogon japonicus	Water-soluble β-d-fructan (MDG-1)	Intragastrically	150 and 300 mg/kg	23 days of treatment
	[58] Isolation and Pharmacological Activities of the Tecoma stans Alkaloids	Tecoma stans	Tecoma stans alkaloids	Gavage	50 mg/kg and 63.4 mg/kg	7 days of treatment
	[61] Potent Effects of the Total Saponins from Dioscorea nipponica Makino against Streptozotocin-Induced Type 2 Diabetes Mellitus in Rats	Dioscorea nipponica	Saponins from D. nipponica Makino (TSDN)	Orally	200, 100, and 50 mg/kg	12 weeks of treatment
	[59] Tocopherol from Seeds of Cucurbita pepo against Diabetes: Validation by In Vivo Experiments Supported by Computational Docking	Cucurbita pepo	Tocopherol	?	2, 5 g/kg	6 weeks of treatment
	[60] Trapa natans L. Root Extract Suppresses Hyperglycemic and Hepatotoxic Effects in STZ-Induced Diabetic Rat Model	Trapa natans L.	Methanol fraction, chloroform fraction, and petroleum ether fraction	Orally	50, 100, and 200 mg/kg	15 days of treatment

(d)

	Title	Drug for diabetes induction	Route of induction	Hyperglycemia	Control of glycemia	Insulin tolerance test
Isolates	[25] A Polysaccharide Extract of Mulberry Leaf Ameliorates Hepatic Glucose Metabolism and Insulin Signaling in Rats with Type 2 Diabetes Induced by High Fat-Diet and Streptozotocin	Diet with 41.2% fat and a low-dose STZ (35 mg/kg body weight)	Intraperitoneal	Glucose ≥ 7.8 mmol/L	?	Yes
	[26] Antidiabetic Activity of a Xanthone Compound, Mangiferin	Genetically modified	—	—	?	Yes
	[27] Anti-Diabetic Effect of a Novel N-Trisaccharide Isolated from Cucumis prophetarum on Streptozotocin-Nicotinamide Induced Type 2 Diabetic Rats	Nicotinamide (NA) at 230 mg/kg and STZ at 65 mg/kg	Intraperitoneal	Glucose ≥ 250 mg/dL	Yes	Yes
	[28] Antidiabetic Effects of the Cimicifuga racemosa Extract Ze 450 In Vitro and In Vivo in ob/ob Mice	Genetically modified	—	—	?	?
	[29] Borapetoside C from Tinospora crispa Improves Insulin Sensitivity in Diabetic Mice	STZ 150 mg/kg	Intraperitoneal	Glucose ≥ 150 mg/dL	Yes	Yes
	[30] Dehydrotrametenolic Acid Induces Preadipocyte Differentiation and Sensitizes Animal Models of Noninsulin-Dependent Diabetes Mellitus to Insulin	Genetically modified	—	—	?	?
	[31] Effects of Ingested Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on Glycemic Responses in Normal and Diabetic Rats	STZ (65 mg/kg) and nicotinamide (200 mg/kg)	Intraperitoneal	Glucose > 250 mg/100 mL	Yes	Yes
	[32] Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)	Genetically modified	—	—	?	Yes
	[33] Isolation and Antihyperglycemic Activity of Bakuchiol from Otholobium pubescens (Fabaceae), a Peruvian Medicinal Plant Used for the Treatment of Diabetes	STZ 50 mg/kg	Intravenous	Glucose 300–600 mg/dL	Yes	?
	[34] LBP-4a Improves Insulin Resistance via Translocation and Activation of GLUT4 in OLETF Rats	Genetically modified	—	—	?	Yes
	[35] Meliacinolin: A Potent Α-Glucosidase and Α-Amylase Inhibitor Isolated from Azadirachta indica Leaves and In Vivo Antidiabetic Property in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Mice	Nicotinamide (120 mg/kg) and STZ (60 mg/kg)	Intraperitoneal	Glucose > 250 mg/dL	Yes	?
	[36] Novel Terpenoid-Type Quinones Isolated from Pycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes	STZ 150 mg/kg	Intravenous	Glucose 300–600 mg/dL	Yes	Yes
	[37] Platyconic Acid, a Saponin from Platycodi radix, Improves Glucose Homeostasis by Enhancing Insulin Sensitivity In Vitro and In Vivo	STZ 20 mg/kg	?	?	Yes	Yes
	[38] Rhaponticin from rhubarb Rhizomes Alleviates Liver Steatosis and Improves Blood Glucose and Lipid Profiles in KK/Ay Diabetic Mice	STZ/?	?	?	Yes	?
	[39] Rutin Potentiates Insulin Receptor Kinase to Enhance Insulin-Dependent Glucose Transporter 4 Translocation	Insulin receptor antagonist S960 (50 nmol/kg)	Intravenous injection	?	Yes	?
	[40] Type 2 Antidiabetic Activity of Bergenin from the Roots of Caesalpinia digyna Rottler	STZ (65 mg/kg) and nicotinamide (110 mg/kg)	Intraperitoneal injection	Glucose 200 mg/dL	Yes	Yes
Fractions	[41] A Study on Hypoglycaemic Health Care Function of Stigma maydis Polysaccharides	High fat-diet and low-dose alloxan (90 mg/kg)	Intraperitoneal	Glucose ≥ 10 mmol/L	Yes	?
	[1] Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase	Genetically modified	—	—	Yes	?
	[42] Antidiabetic Activity of Alkaloids of Aerva lanata Roots on Streptozotocin-Nicotinamide Induced Type-II Diabetes in Rats	STZ and nicotinamide	Intraperitoneal	?	Yes	?
	[43] Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint	STZ (60 mg/kg) and nicotinamide (120 mg/kg)	Intraperitoneal	Glucose > 250 mg/dL	Yes	?
	[44] Antidiabetic Activity of Caesalpinia bonducella F. in Chronic Type 2 Diabetic Model in Long-Evans Rats and Evaluation of Insulin Secretagogue Property of Its Fractions on Isolated Islets	STZ 90 mg/kg	Intraperitoneal injection	Glucose 7–12 mmol/L	Yes	Yes
	[45] Antidiabetic Effect of an Acidic Polysaccharide (TAP) from Tremella aurantia and Its Degradation Product (TAP-H)	Genetically modified	—	—	?	Yes
	[46] Antidiabetic Effect of Orally Administered Conophylline-Containing Plant Extract on Streptozotocin-Treated and Goto-Kakizaki Rats	Streptozotocin 60 mg/kg	Intraperitoneal	Glucose > 250 mg/dL	Yes	?
	[47] Antidiabetic Effect of Total Flavonoids from Sanguis draxonis  in Type 2 Diabetic Rats	High fat-diet and a singular injection of streptozotocin (STZ) (35 mg/kg)	Intraperitoneal	Glucose ≥ 11.1 mmol/L	Yes	Yes
	[48] Antidiabetic Effects of Bitter Gourd Extracts in Insulin-Resistant db/db Mice	Genetically modified	—	—	?	?
	[49] Anti-Diabetic Effects of Centratherum anthelminticum Seeds Methanolic Fraction on Pancreatic Cells, Β-TC6 and Its Alleviating Role in Type 2 Diabetic Rats	Streptozotocin (STZ) (65 mg/kg)	Intraperitoneal	Glucose 22–26 mmol/L	Yes	?
	[17] Anti-Diabetic Effects of Polysaccharides from Talinum triangulare in Streptozotocin (STZ)-Induced Type 2 Diabetic Male Mice	Streptozotocin (STZ) (70 mg/kg)	Intraperitoneal	?	Yes	?
	[50] Anti-Diabetic Effects of the Acetone Fraction of Senna singueana Stem Bark in a Type 2 Diabetes Rat Model	STZ 40 mg/kg	Intraperitoneal injection	Glucose > 18 mmol/L	Yes	?
	[51] Antidiabetic Potential of Polysaccharides from the White Oyster Culinary-Medicinal Mushroom Pleurotus florida (Higher Basidiomycetes)	STZ 50 mg/kg	Intraperitoneal	Glucose > 200 mg/100 mL	Yes	?
	[52] Antihyperglycemic Effects of Total Flavonoids from Polygonatum odoratum in STZ and Alloxan-Induced Diabetic Rats	Alloxan (100 and 120 mg/kg)	Intraperitoneal	Glucose > 11.0 mmol/L	Yes	?
	[53] Antioxidant and Anti-Inflammatory Effects of a Hypoglycemic Fraction from Cucurbita ficifoliaBouché in Streptozotocin-Induced Diabetic Mice	STZ 137 mg/kg	Intraperitoneal	?	?	?
	[54] Effect of Lycium barbarum Polysaccharide on the Improvement of Insulin Resistance in NIDDM Rats	STZ 50 mg/kg	Intraperitoneal	Glucose > 16 mmol/L	Yes	Yes
	[55] Effects of Grape Seed Extract and Its Ethylacetate/Ethanol Fraction on Blood Glucose Levels in a Model of Type 2 Diabetes	Genetically modified	—	—	Yes	?
	[56] Hypoglycemic Effect of Astragalus Polysaccharide and Its Effect on PTP1B1	STZ 30 mg/kg	Intravenous injection	Glucose > 6.7 mmol/L	Yes	Yes
	[57] Hypoglycemic Effects of MDG-1, a Polysaccharide Derived from Ophiopogon japonicus, in the ob/ob Mouse Model of Type 2 Diabetes Mellitus	Genetically diabetic model	—	—	Yes	Yes
	[58] Isolation and Pharmacological Activities of the Tecoma stans Alkaloids	Genetically diabetic model	—	—	?	Yes
	[61] Potent Effects of the Total Saponins from Dioscorea nipponica Makino against Streptozotocin-Induced Type 2 Diabetes Mellitus in Rats	STZ 30 mg/kg	Intraperitoneal	Glucose > 16.7 mmol/L	Yes	Yes
	[59] Tocopherol from Seeds of Cucurbita pepo against Diabetes: Validation by In Vivo Experiments Supported by Computational Docking	PX-407 solution (10 mg/kg)	?	Blood glucose level of 200 mg/dL or higher	Yes	Yes
	[60] Trapa natans L. Root Extract Suppresses Hyperglycemic and Hepatotoxic Effects in STZ-Induced Diabetic Rat Model	STZ (45 mg/kg)	Intraperitoneal	Glucose > 200 mg/dL	Yes	?