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Table 4 Anti-diabetic, anti-lipidemic, and antioxidative properties of medicinal plants used for treating DM in Uganda based on global scientific investigations

From: Ethnomedicine and ethnopharmacology of medicinal plants used in the treatment of diabetes mellitus in Uganda

Plant

Part used

Extracts/formulation

Dose and route of administration

Test modal

Activity

Result

Active phytochemicals and toxicity information

References

Tithonia diversifolia (Hemsl.) A.Gray

Leaf

Ethanol

25, 50, and 100 mg/kg body weight (p.o)

STZ rat

Anti-hyperglycemic

↓ Blood glucose and ↓polyphagia

 

[156]

 

Leaf

Aqueous fraction

200 and 300 mg/kg body weight (p.o)

Alloxan rat

Anti-hyperglycemic and antioxidant

↓ Blood glucose, ↑ serum insulin, ↓ oxidative damage of β-cells, and ↑ Immunoexpression of GLUT2

 

[157]

 

Aerial part

Isolates

10 µg/mL

In vitro

Anti-hyperglycemic

↑ glucose uptake in 3T3-L1 adipocytes

Monoterpene (1S,2R,3R,5S)-2-hydroxymethyl-6,6-dimethylbicyclo [3.1.1] heptane-2,3- diol and sobrerol

[125]

 

Leaf

Aqueous and n-butanol extracts

100, 200, and 300 mg/kg body weight

Alloxan mice and In vitro

Anti-hyperglycemic and antioxidant

↓ Blood glucose, ↑ serum insulin, ↓ the liver and pancreatic injuries, showed antioxidant and free radicals scavenging activities

 

[158]

  

Isolates

 

In vitro

Anti-hyperglycemic

↓ Insulin resistance and ↑ PPARγ activity

Sesquiterpene lactone, thyrotundin, and tagitinin A;

aerial parts exhibited cytotoxicity against cells from the human fetal lung fibroblast cell line; aerial part ethanol extract showed dose and time dependent toxic effect on the kidney and liver morphology in rats with LD50 > 1600 mg/kg/ day

[140, 159, 160]

Erythrina abyssinica DC

Stem bark

Aqueous

500 mg/kg body weight

Guinea pigs administered glucose solution

Anti-hyperglycemic

↓ Postprandial plasma glucose levels

 

[161]

 

Stem bark

Aqueous

50, 100, and 150 mg/kg body weight (i.p)

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose levels

 

[162]

 

Stem bark

Isolates

 

In vitro

Anti-hyperglycemic

Inhibited PTP1B activity

Flavanones

[163]

 

Stem bark

Isolates

10 μM

In vitro

Anti-hyperglycemic and anti-hyperlipidemic

↑ AMPK activation by stimulating the phosphorylation

Erythribyssin N and three other unnamed compounds; seed is reported to be poisonous; root extract produced oral LD50 of 776.2 mg/kg in mice and showed dose dependent acute toxicity

[141, 164, 165]

Moringa oleifera Lam

Seed

Powder

50 and 100 mg/kg body weight (p.o)

STZ Albino rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ lipid peroxide lipid, ↓ HbA1c, ↓ antioxidant enzymes, alleviated the pathological changes in the kidney and pancreas tissues to physiological levels

 

[166]

 

Leaf

Aqueous

200 mg/kg body weight (p.o)

STZ Sprague–Dawley rats

Antioxidant

↓ FBG, ↓ glutathione, ↓ ROS, ↓ malondialdehyde, and alleviated the pathological changes in the kidney

Intake is safe at levels ≤ 1000 mg/kg body weight

[167, 168]

 

Seed

Oil

2.0 mL/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperlipidemic

↓ Cholesterol, ↓ LDL, ↓ TG, ↓ serum total bilirubin, ↓ TP, ↓urea, and ↓ creatinine

 

[169]

 

Leaf

Methanol

250 and 500 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ FBG, ↓ bodyweight gain, ↓ plasma albumin, and ↑ glucose tolerance

 

[170]

 

Leaf

Aqueous

50 µl and 100 µl

In vitro

anti-hyperglycemic and antioxidant

Inhibited α-amylase and α-glucosidase activities, and radical scavenging activities,

Phenolics

[171]

 

Leaf

 

1 g and 2 g (p.o)

Pilot clinical study

Anti-hyperglycemic

↓ Postprandial glycemia

 

[172]

 

Leaf

Powder

p.o

Clinical

Anti-hyperglycemic

↓ Serum glucose and ↓ LDL

 

[173]

Persea americana Mill

fruit

Juice

1,264 and 1,896 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ bodyweight, ↓ FBG, and ↓ LDL, and ↑ HDL

 

[174]

 

Fruit

Oil

5–20% (p.o)

Glucose tolerance and insulin resistance Wistar rats

Anti-hyperglycemic

↓ blood glucose levels and ↓ insulin resistance

 

[175]

 

Seed

Methanol

300 and 600 mg/kg body weight

Alloxan Wistar rats

Anti-hyperglycemic

↓ FBG, ↑ insulin, ↑ c-peptide, and ↑ β-cell function, and ↓ insulin resistance

Seed ethanol extract showed no genotoxic activity in micronucleus test. Acute toxicity study revealed a relatively low LD50 for seed extract of 751.6 mg/kg body weight

[176,177,178]

 

Seed

Aqueous

20, 30, 40 g/L (p.o)

Alloxan Wister rats

Anti-hyperglycemic and organ protective effect

↓ Blood glucose and exerted protective effects on kidneys, pancreas, and liver

 

[179]

 

Seed

Powder

500 mg (p.o)

Fructose- fed insulin resistance Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ LDL, ↑ HDL, ↓ ALT, ↓ bilirubin, ↓ FBG, ↓ HbA1c, improved coronary risk index and fasting insulin resistance index

 

[131]

 

Leaf

Hydroalcohol

0.15 and 0.3 g/kg bodyweight/day (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ Blood glucose levels and mitigated the dysregulated metabolism, and activated serine-threonine kinase Akt

Leaf chloroform–methanol extract of 1900 and 2600 mg/Kg body weight showed no obvious sign of toxicity in mice

[180, 181]

 

Leaf

Hydroalcohol

100 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↑ total cholesterol, and ↑ HDL

 

[182]

 

Leaf

Methanol

10 μL

In vitro

anti-hyperglycemic

Inhibited α-glucosidase, aldose reductase, maltase-glucoamylase, and aldehyde reductase activities

 

[120]

 

Leaf

Aqueous

125–500 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ hyperlipidaemia, ↓ AST, ↓ urea, ↓ TP, ↓ ALB, ↓ ALT, and ↓ ALP

 

[183]

Vernonia amygdalina Del

Leaf

Methanol

200 and 400 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ LDL, and ↑ body weight

 

[184]

 

Leaf

Aqueous

15, 30, 60, 120, and 240 µg/ml

In vitro

anti-hyperglycemic and anti-hyperlipidemic

Inhibited α-glucosidase and pancreatic lipase activities, and ↑ muscle glucose uptake

Aqueous leaf extract showed no acute hepatotoxicity in rats with LD50 of 500 mg/kg; No toxicity signs and mortality observed at up to 5000 mg/kg body weight in rats

[185,186,187]

 

Leaf

Ethanol

400 mg/kg body weight (p.o)

Alloxan rats

anti-hyperglycemic

Inhibited α-amylase activity and regeneration of pancreatic beta cells

 

[188]

 

Root

Ethanol

500 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ the cholesterol, ↓ serum protein, and ↓ total lipid

 

[130]

 

Leaf

Ethanol

400 mg/kg body weight (p.o)

STZ rats

Anti-hyperglycemic and anti-hyperlipidemic

↑ Glucose tolerance, ↓ FBG, ↓ TG, ↓total cholesterol, protective effect on pancreatic β-cells, ↑ GLUT 4 translocation, and inhibited hepatic G6Pase activity

 

[122]

 

Leaf

Chloroform

1 g/kg (p.o)

STZ Sprague Dawley rats

Anti-hyperglycemic

↓ Serum glucose, suppression of gluconeogenesis, and ↑ glucose oxidation through the pentose phosphate pathway in the liver

Fatty acids (linoleic acid and α-linolenic acid) and phytols

[189]

Artocarpus heterophyllus Lam

stem bark

Acetone and ethyl acetate

400 mg/kg body weight (p.o)

In vitro and

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

Inhibited the α-amylase and α-glucosidase activities, ↑ insulin, ↑ glycogen, ↑ hexokinase activities, ↑ pancreatic β-cell scores, ↑ antioxidant enzymes, and ↑ glucose transporter concentration,

↓ FBG, ↓ lipid peroxidation, and ↓ glucose-6-phosphatase

Free and bound phenols

[126]

 

Stem bark

Ethanol

50, 100 and 150 mg/kg body weight (p.o)

Alloxan rats

anti-hyperglycemic

↓ Weight reduction, ↓ LD, ↓ creatinine, ↓ bilirubin, ↓ urea, and ↑ albumin

 

[118]

 

Leaf

Aqueous

250 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Serum glucose, ↓ total cholesterol, and ↑ HDL

Aqueous leaf extract showed no adverse effects on liver function, haematological parameters, reproductive ability, and histology of the heart, lung, kidney, intestines and pancreas in rats

[190, 191]

 

Leaf

ethanol and n-butanol

200 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ TC, ↓ lipid peroxides, ↓ HbA1c, ↓ LDL, ↑ insulin, ↑ total protein, and ↑ HDL

 

[192]

 

Leaf

Decoction

96 mL (p.o)

Clinical study

Anti-hyperglycemic and anti-hyperlipidemic

↓ Post-prandial blood glucose, ↓ FBS, and ↓ TC, mitigated symptoms including polyphagia, polydipsia, joint pain, polyuria, lassitude, excessive sweating, and dryness of the mouth

 

[193]

Azadirachta indica A. Juss

Leaf

Ethanol

200 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ TC, ↓ LDL, ↓ TG, and ↑ HDL

Neem extracts/subproducts are nontoxic or less toxic when orally administered in rats; animals only show acute toxicity when treated by intramuscular injection or the i.p route. Extracts show dose dependent subacute and subchronic toxicity at high doses thus safe at lower doses

[194, 195]

 

Leaf and seed oil

Aqueous

500 (Leaf extract) and 5 mL/kg (seed oil) (p.o)

Normal rabbits and alloxan diabetic rabbits

Antidiabetic and anti-hyperglycemic

Protected against the development of DM in pre-treated rabbits and ↓ blood glucose

Neem oil produced different pharmaco-toxic effects (LD50 of 14 and 24 ml/kg) in rats and rabbits respectively; suggesting a narrow margin of safety when used therapeutically

[196, 197]

 

Root

Ethanol

800 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose

 

[198]

 

Leaf, seed, root, and stem back

Isolates

 

In vitro

Anti-hyperglycemic

Inhibited α-glucosidase and α-amylase activities

Limonoids, meliacinolin 1, and nimbidiol

[119, 142, 199]

 

Seed

Powder

6 g daily (p.o)

Clinical study

Anti-hyperglycemic

↓ FBG and ↓ postprandial blood glucose

 

[200]

 

leaf and twig

Aqueous

125, 250, and 500 mg twice a day (p.o)

Clinical study

Anti-hyperglycemic

↓ FBG, ↓ postprandial blood glucose, ↓ HbA1c, and ↓ insulin resistance

 

[201]

 

Leaf

Powder

2 g/ day (p.o)

Clinical study

Antidiabetic

alleviated the symptoms of polydipsia, polyphagia, and headache by 33%, 35%, and 38%, respectively

 

[202]

 

Leaf

Aqueous

400 mg/kg body weight (p.o)

High-fat and fructose Wister rats

Anti-hyperglycemic

↓ blood glucose, ↑ serum insulin, ↑ insulin signaling molecules, and ↑ GLUT4

 

[203]

Psidium guajava L

Leaf

Ethyl acetate fraction

25 and 50 mg/kg body weight (intragastric)

STZ Sprague–Dawley rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ fructosamine, ↓ HbA1c, and did not affect the levels of toxicity markers, including serum glutamate oxaloacetate transaminase and serum glutamate pyruvic transaminase

 

[204]

 

Fruit

 

125 and 250 mg/kg body weight (p.o)

STZ Sprague–Dawley rats

Anti-hyperglycemic

↓ Bodyweight loss, ↓blood glucose, and ↑ insulin concentration

 

[205]

 

Fruit peel

Aqueous

400 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ FBG, ↓ postprandial glucose, and ↓ urinary glucose

 

[206]

 

Stem bark

Ethanol

250 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose

 

[207]

 

Leaf

Methanol, aqueous, and ethanol

50 g plant extract/l

In vitro

Anti-hyperglycemic

Inhibited α-glucosidase and α-amylase activities

 

[208, 209]

 

Leaf

 

200 mg/kg/d (p.o)

STZ Kunming mice

Anti-hyperglycemic

↓ FBG, ↑ glucose tolerance, ↓ insulin resistance index, ↓ serum total cholesterol, and ↓ LDL

Flavonoids

[210]

 

Leaf

 

60, 120, and 240 mg/kg body weight

 

Anti-hyperglycemic and anti-oxidant

↓ FBG, ↑ serum insulin and insulin sensitivity index, protected the pancreatic cells such as islet β-cells, against lipid peroxidation

Total triterpenoids

[211]

 

Leaf

Aqueous

200 and 400 μg/mL

In vitro

Anti-hyperglycemic

↑ glucose uptake

 

[212]

Cucurbita maxima Duchesne

Pulp

Powder

5 g (p.o)

Clinical study

Anti-hyperglycemic

↓ average glucose

 

[213]

 

Seed

petroleum ether, ethyl acetate, alcohol, and aqueous

200 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ blood glucose, ↓ serum total cholesterol, ↓ LDL, ↓ VLDL, ↓ TG, ↑ insulin, and ↑ HDL

Hydroalcoholic extract of seeds exhibited no acute and subacute toxicity at 5000 mg/kg and 1000 mg/kg, respectively in mice

[214, 215]

 

Seed

Oil

100 mg/kg body weight (p.o)

High-fat diet-induced obesity rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Body weight gain, ↓ glucose, and ↑ insulin, and ↓ LDL

 

[216, 217]

 

Leaf

Methanol

 

In vitro

Anti-hyperglycemic

Inhibited α-amylase activity

 

[218]

 

Pulp

Methanol

200 and 400 mg/kg body weight (p.o)

STZ rats

Anti-hyperglycemic and antioxidant

↓ Serum levels of hepatic enzyme activities and oxidative stress markers, ↓ blood glucose, restored serum proteins and lipid profile

 

[129]

Citrus sinensis (L.) Osbeck

Fruit

Juice

2, 5, and 8 mL/kg (p.o)

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose and ↑ plasma insulin

 

[219]

 

Fruit peel

Methanol

50 and 100 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ FBG, ↑ PPARγ in adipose tissues, ↑ GLUT 4, and ↑ insulin receptors

 

[124]

 

Fruit peel

Ethanol and acetone

125, 250, and 500 mg/kg body weight

Alloxan rats

Anti-hyperglycemic and anti-hypercholesterolemic

↓ Blood glucose and ↓ blood cholesterol

 

[220]

 

Leaf

Essential oil

110 mg/kg body weight (i.p)

Alloxan rats

Anti-hyperglycemic

↓ FBG and ↓ hepatic glucose, and ↑ hepatic glycogen

 

[221]

 

Stem bark

Aqueous

400 mg/kg body weight (p.o)

Wistar rats

Anti-hyperglycemic

↓ Postprandial glucose

 

[222]

 

Seed

Oil

1000 mg/kg body weight

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose

 

[223]

Bidens pilosa L

Leaf

Methanol and

Polyacetylenes

10, 50, or 250

0.5 for Polyacetylenes mg/kg body weight (p.o)

db/db mice

Anti-hyperglycemic

↓ Postprandial glucose, ↑ serum insulin, and ↓ glycosylated HbA1c

Polyacetylenes

[224]

 

Whole plant

Aqueous

50 mg/kg body weight (p.o)

Alloxan db/db mice

Anti-hyperglycemic

↓ Postprandial glucose and ↑ serum insulin

Showed no adverse effects in mice and chickens at dose 5% or less of food

[225, 226]

 

Whole plant

butanol fraction

10 mg/kg body weight (i.p.)

NOD mice

Anti-hyperglycemic

Regeration of pancreatic β islets, inhibited β-cell death and leukocyte infiltration

 

[117]

 

Formulation (probetacell)

 

400 mg (p.o)

Pilot clinical study

Anti-hyperglycemic

↓ FBG, ↓ glycosylated HbA1c, ↑ β-cell function

 

[25]

Aloe vera (L.) Burm.f

Leaf pulp

phosphate buffered saline

500 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ Blood glucose

Observed acute and subacute toxicity, cytotoxicity, and mutagenicity associated with constituent anthraquinones of whole leaf extract; produced LC50 of 3.59 µg/ml in brine shrimp and LD50 of 120.65 mg/kg in mice; LD50 of 250 mg/kg in rats; HeLa and HepG2 cells with CC50 of 413.9 and 439.0 mg/ml, respectively, after 4-h

[227,228,229,230,231]

 

Leaf pulp

Aqueous

150 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic and anti-hypercholesterolemic

↓ Bodyweight loss, ↓ ALP, ↓ AST, ↓ ALT, ↓ cholesterol, and ↓ LDL

 

[232]

 

Leaf pulp

Juice

One tables spoonful, twice a day for 2 weeks (p.o)

Clinical study

Anti-hyperglycemic

↓ Blood glucose and ↓ TG

 

[233]

 

Leaf pulp

Phosphate buffered saline

500 for leaf pulp and

63 for leaf gel

mg/kg body weight (p.o)

STZ Wister rats

Protective effect

Mitigated hepatic damages

 

[234]

 

Leaf pulp

Chloroform and methanol, and isolation

1 μg/mouse/d of compounds

25 μg /mouse/d of extract (p.o)

T2D db/db mice

Anti-hyperglycemic

↓ FBG and ↓ HbA1c

Phytosterols (lophenol, 24-ethyl-lophenol, 24-methyl-lophenol, cycloartanol, and 24-methylene-cycloartanol)

[235]

Annona muricata L

Leaf

Aqueous

100 and 200 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ serum creatinine, ↓ AST, ↓ MDA, ↓ ALT, ↓ LDL, restored the levels of total cholesterol, TG, and SOD activity

Aqueous (LD50 > 5 g/kg), ethanol, and methanol (LD50 of > 2 g/kg) of leaves, flowers and pulp showed no acute toxicity in rats

[236,237,238]

 

Leaf

Aqueous

100 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic, anti-hyperlipidemic, and anti-oxidant

↓ Blood glucose, ↓ TGs, ↓ ROS, ↓ TC, and ↓ LDL, ↑ antioxidant enzymes activities, ↑ serum insulin, ↓ lipid peroxidation

 

[239]

 

Leaf

Aqueous

100 mg/kg body weight (i.p)

STZ Wister rats

anti-hyperlipidemic

↓ Serum TC, ↓ TG, ↓LDL, ↑ serum HDL levels and ↑ antiatherogenic index

 

[240]

  

Purchased Annona liquid extract

100 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↑ insulin, ↓ insulin resistance, ↓ HbA1c, ↑ total proteins, and improved activities of liver function enzymes

 

[241]

 

Fruit-pulp, leaf, stem-bark and root-bark

Methanol

100, 200, 400, 600, and 800 mg/kg body weight (p.o)

In vitro and

Wister rats

Anti-hyperglycemic

Inhibited α-glucosidase and α-amylase activities

Fruits (dichloromethylenic extracts), leaves (aqueous extracts), exhibited acute neurotoxicity in rats associated with constituent annonacin and reticuline which are Acetogenins and alkaloid, respectively

[237, 242, 243]

Schkuhria pinnata (Lam.) Kuntze ex Thell

Leaf

Ethanol and acetone

50 g/mL

In vitro

Anti-hyperglycemic

↓ Blood glucose

 

[244]

 

Leaf

Methanol, acetone, and hexane

100 μg/mL

In vitro

Anti-hyperglycemic

↑ Glucose utilization

 

[245]

 

Leaf

Aqueous and butanone

 

In vitro

Anti-hyperglycemic

Upregulated the expression levels of insulin receptor, GLUT-4, glycogen synthase, pyruvate carboxylase, and pyruvate kinase in C2C12 muscle cells, ↑ AMPK

2-(2–4,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl) prop-2- enoic acid; Schkuhrin I and schkuhrin II; methanol extract showed low cytotoxicity against human

cells; aqueous extracts showed no toxicity in mice

[123, 246]

Solanum melongena L

Skin and pulp

Aqueous

500 μl

In vitro

Anti-hyperglycemic and antioxidant

Inhibited α-glucosidase activities and showed radical scavenging activity

Aqueous fruit extract showed no acute toxicity in rats (LD50 > 3000 mg/kg/oral). However, the extract exhibited relative acute toxicity in guinea pigs [LD50: 1098] and relative toxicity in rabbits under repeat dose evaluations

[247, 248]

 

Skin

Ethanol

25, 50, and 100 mg/kg body weight

 

Anti-hyperglycemic

↓ Blood glucose levels and promoted pancreatic β cell regeneration

 

[249]

 

Cap

Ethanol

100 and 200 mg/kg body weight (i.p)

STZ Wister rats

Anti-hyperglycemic and anti-oxidant

↓ FBG, ↓ NO, ↓ ALT, ↓ ALP, ↓ AST, ↑ TP, and ↑ total antioxidant capacity

 

[250]

 

Peels

Phenolic compounds

100 mg/kg body weight

Alloxan rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ TG, ↓ TC, ↓ LDL, ↑ HDL, ↓ SGOT, and ↓ SGPT

Phenol

[139]

Toddalia asiatica (L.) Lam

Leaf

Ethyl acetate

250 and 500 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ Blood glucose and ↑ insulin

Leaves ethyl acetate extract showed no acute toxicity

[251]

 

Leaf

Methanol and petroleum ether

400 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic

↓ Blood glucose

 

[252]

 

Stem

Isolate

 

In vitro

Anti-hyperlipidemic

Promoted the differentiation and lipolysis of adipocytes

Aculeatin

[143]

Cajanus cajan (L.) Huth

Leaf

Methanol

400 and 600 mg/kg body weight (p.o)

Alloxan Swiss albino rats

Anti-hyperglycemic

↓ FBG

Aqueous and ethanol leaf extract showed no acute and sub-chronic toxicity

[253, 254]

 

Leaf

Ethanol

200, 400 and 800 mg/kg body weight (p.o)

Alloxan rats

Anti-hyperglycemic

↓ Blood glucose

 

[255]

 

Germinated pigeon pea

Acetone

p.o

STZ Wister rats

Anti-hyperglycemic and antioxidant

↓ FBG and ↓ lipid peroxidation

 

[256]

 

Pigeon pea beverage diet

 

2.7 g/kg body weight (p.o)

Alloxan Sprague Dawley rats

Anti-hyperglycemic and hypocholesterolemic

↓ Blood glucose and ↓cholesterol

 

[257]

Kigelia africana (Lam.) Benth

Fruit

Aqueous

500 and 1000 mg/kg body weight (p.o)

Alloxan mice

Anti-hyperglycemic

↓ Blood glucose

Exhibited genotoxicity in the micronucleus of human WBCs, in the form of structural and numerical chromosome aberrations

[258, 259]

 

Fruit

Hexane fraction

100, 200 and 400 mg/kg body weight (p.o)

STZ Wister rats and in vitro

Anti-hyperglycemic and anti-hyperlipidemic

Alleviated oxidative stress, ↓ FBG, ↓ hyperlipidemic biomarkers, promoted pancreatic β-cell regeneration and ↑ glucose uptake in 3T3 L1 adipocytes

Aqueous fruit extract at low doses showed no acute and chronic toxicity in rats but high doses may cause hepatorenal toxicity in rats; methanol fruit leaf, and stembark extract showed no sub-acute toxicity at 1000 mg/ kg body weight in rats

[260, 261]

 

Fruit

Powder

0.5 mL fruit powder filtered solution and 1 mL fruit powder solution

Dexamethasone rats

Anti-hyperglycemic

↓ Blood glucose

 

[262]

 

Stem

Aqueous

1 mL

In vitro

Anti-hyperglycemic

Inhibited α-amylase activity

Flavonoids;

[263]

 

Stem bark and leaf

Ethanol and methanol

300 mg/kg body weight (p.o)

Alloxan rats

Anti-hyperglycemic

↓ FBS, ↓ creatinine, and ↓ ALT

Stembark aqueous extract showed acute toxicity in Oreochromis niloticus (L.) (fish)

[264, 265]

 

Leaf and fruit

Methanol

200 and 500 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose and ↓ lipid levels

 

[264]

Cymbopogon citratus Stapf

Leaf

Tea

0.25% or 0.5% (p.o)

STZ rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Serum glucose, ↓ lipids, ↓ insulin resistance index, ↑ serum insulin, ↑ β-cell function, and ↑ liver glycogen

 

[266]

 

leaf sheath

Essential oil

400 and 800 mg/kg body weight

Poloxamer-407 Wistar rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Glycemia, ↓ lipid dysmetabolism, ↓ insulinemia, ↑ GLP-1, ↑ β-cell number, and ↑ islet number

Essential oils at doses less than 1,500 mg/kg body weight showed no acute and subacute toxicity in rats and also dose 2000 mg/kg body weight showed no acute and subacute toxicity in rats

[267,268,269]

 

Leaf

Ethanol and aqueous

200 mg/kg body weight (p.o)

Wistar rats

Anti-hyperglycemic

↓ Blood glucose

 

[270]

Gynandropsis gynandra (L.) Briq

Root

Aqueous

100, 200, and 400 mg/kg body weight (p.o)

 

Anti-hyperglycemic

↓ Blood glucose

 

[271]

 

Root

Methanol

100, 250, and 500 mg/kg body weight (p.o)

Alloxan Wistar rats

Anti-hyperglycemic

↓ Blood glucose

 

[272]

 

Whole plant

Ethanol

5 mg/ml

In vitro

Anti-hyperglycemic

Suppressed the inhibition of glucose diffusion

 

[273]

Syzygium cumini (L.) Skeels

Seed

Chloroform, aqueous, and methanol

 

In vitro

Anti-hyperglycemic

Inhibited α-amylase and α-glucosidase activities

 

[274]

 

Leaf

Ethanol

200 and 400 mg/kg body weight (p.o)

Alloxan mice

Anti-hyperglycemic

↓ Blood glucose, ↑ insulin secretion, ↑ glucose tolerance, ↓ creatinine kinase, ↓ lactate dehydrogenase, and ↓ HbA1c

Hydroalcoholic leaves extract exerted no acute and chronic toxicity in rats (p.o); additionally, methanol, aqueous, ethanol extracts of leaf, seed, stem bark, and root exhibited no acute toxicity in rats

[275,276,277]

 

Seed

Powder & ethanol

1.25 mg/kg body weight (p.o)

STZ Long‐Evans rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ LDL-cholesterol, and ↓ atherogenic lipids

 

[278]

 

Stem

Beverage

4 mg/mL (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose and ↓ lipid

 

[279]

Sesbania sesban (L.) Merr

Leaf

Aqueous

250 and 500 mg/kg body weight (p.o)

STZ Wister rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ blood glucose, ↓ HbA1c, ↓ total cholesterol, ↓ serum TG, ↑ hepatic glycogen and ↑serum insulin

 

[280]

 

Root

Petroleum ether

250, 500, and 1000 mg/kg body weight (p.o)

STZ Swiss mice

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ cholesterol, ↓ urea, ↓ TG, and ↓ creatinine

 

[281]

Ageratum conyzoides L

Leaf

Aqueous

500 mg/kg body weight (p.o)

Alloxan Wister rats

Anti-hyperglycemic

↓ FBG

 

[282]

 

Leaf, stem, and root

Ethanol

100 mg/kg body weight (p.o)

STZ rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ FBG, ↓ total cholesterol and ↓TG

Hydroalcoholic leaf extract showed no chronic hepatotoxicity in rats. The extract also showed relative safety in acute and sub-chronic toxicity tests (p.o)

[283,284,285]

 

Leaf

Aqueous

150, 300, 450 and 600 mg/kg body weight (p.o)

Rats

Anti-hyperglycemic

↓ Blood glucose and ↓ creatinine

 

[286, 287]

 

Leaf

Aqueous

200 and 300 mg/kg body weight (p.o)

STZ rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ BLOOD glucose, ↑ serum insulin and ↑ protein, ↑ HDL, ↓ LDL, and ↓ TG

 

[286, 287]

 

shoot

Ethanol

100, 200, and 400 mg/kg body weight (p.o)

Alloxan rats

Anti-hyperglycemic

↓ FBG

 

[137]

Vigna unguiculata (L.) Walp

Leaf

Ethanol

50 and 25 mg/mL

In vitro

Anti-hyperglycemic

Inhibited α-glucosidase and α-amylase activities, and ↑ GLUT4

 

[288]

 

Seed

Peptides

0.1, 1, 10, and 100 ng

In vitro

Anti-hyperglycemic

Promoted Akt phosphorylation in rat skeletal muscles

Peptides

[289]

 

Seed

Oil

200 mg/kg body weight (p.o)

Alloxan rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood glucose, ↓ AST, ↓ LDL, ↓ TG, ↓ total cholesterol, ↓ ALT, and ↑ HDL

 

[290]

 

sprouted

Isolates

50, 100, 200, and 400 mg/kg body weight (p.o)

Alloxan Sprague Dawley rats

Anti-hyperglycemic and anti-hyperlipidemic

↓ Blood total cholesterol, ↓ TG, and ↓ LDL

Proteins

[291]

 

Seeds

Methanol

50, 100, 200 and 400 mg/kg body weight (p.o)

Swiss mice

Anti-hyperglycemic

↓ Blood glucose

 

[292]

Indigofera arrecta Hochst. ex A. Rich

Leaf

Aqueous

3.75–120 mg/kg body weight (p.o & i.p)

STZ Fischer rats

Anti-hyperglycemic

↓ Blood glucose and ↑ insulin

No acute and subchronic toxic effects recorded in mice

[293]

 

Leaf

Aqueous

7 mL/day (p.o)

db/db mice

Anti-hyperglycemic

Mitigated the development of obesity-associated hyperglycemia

 

[294]

 

Leaf

Aqueous

p.o

Clinical study

Anti-hyperglycemic

↓ Blood glucose, ↓ TG and ↓ aspartate aminotransferase, ↓ blood creatinine

No effects of nephrotoxicity recorded in humans

[295]

Oxalis corniculata L

   

Sprague Dawley rats

Antioxidant

Exhibited a protective effect and ↓ oxidative stress

Aqueous, methanol and ethanol whole plant extracts showed relatively mild cytotoxic activity on brine shrimp larvae (LC50 of 156 µg/ml)

[86, 144]

Solanum indicum Roxb

Fruit

Ethanol

100 mg/kg body weight (p.o)

Alloxan rats

Protective effect

Exhibited renoprotective properties

 

[145]

  1. i.p Intraperitoneal route, p.o oral route,↑ increase,↓decrease, STZ streptozotocin, FBG fasting blood glucose, HbA1c glycosylated haemoglobin, HDL high density lipoprotein, LDL low density lipoprotein, VLDL very low density lipoprotein, SOD superoxide dismutase, PPARγ peroxisome proliferator-activated receptor-gamma, GLUT2 glucosetransporter2, GLUT4 glucosetransporter4, PTP1B protein tyrosine phosphatase 1 B, AMPK AMP protein kinase, ROS reactive oxygen species, AST aspartate transaminase, TP total protein, ALB albumin, ALT alanine transaminase, ALP alkaline phosphatase, TG triglyceride, GLP1 glucagonlikepeptide1, MDA malondialdehyde, SGOT serum glutamate oxaloacetate transaminase, SGPT serum glutamate pyruvic transaminase, LD50 the median lethal dose, LC50 the median lethal concentration, CC50 half-maximal cytotoxic concentration