Protective Effects of Medicinal Plant-Based Foods against Diabetes: A Review on Pharmacology, Phytochemistry, and Molecular Mechanisms
Abstract
:1. Introduction
2. Methods
3. The Pathophysiology of Diabetes
4. Medicinal Plant-Based Foods Recommended for the Treatment of DM
4.1. Althaea officinalis L.
4.2. Anethum graveolens L.
4.3. Allium sativum
4.4. Brassica oleracea L.
4.5. Cicer arietinum L.
4.6. Cinnamomum verum J. Presl.
4.7. Crocus sativus L.
4.8. Cuminum cyminum L.
4.9. Eugenia caryophyllata Thunb.
4.10. Foeniculum vulgare Mill.
4.11. Hordeum vulgare L.
4.12. Juglans regia L.
4.13. Lens culinaris L.
4.14. Nigella sativa L.
4.15. Olea europaea L.
4.16. Pinus gerardiana Wall. ex D. Don
4.17. Piper nigrum L.
4.18. Pistacia vera L.
4.19. Vitis vinifera L.
4.20. Zingiber officinale Roscoe
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AchE | Acetylcholinesterase |
Akt | Serine/threonine kinase |
AGEs | Advanced glycated end products |
BW | Body weight |
cAMP | Cyclic adenosine monophosphate |
CVDs | Cardiovascular disorders |
CREB | cAMP-response element protein |
DHA | Docosahexaenoic acid |
EPA | Eicosapentaenoic acid |
FBG | Fasting blood glucose |
GSH | Glutathione |
GLUT2 | Glucose transporter 2 |
HbA1c | Glycated hemoglobin |
HDL | High-density lipoprotein |
LDL | Low-density lipoprotein |
PEPCK | Phosphoenolpyruvate carboxykinase |
PUFA | Polyunsaturated fatty acid |
PKA | Protein kinase A |
ROS | Reactive oxygen species |
STZ | Streptozotocin |
TC | Total cholesterol |
TG | Triglyceride |
VLDL | Very low-density lipoprotein |
WWI | World war I |
WWII | World war II |
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Medicinal Plants | Plants Parts | Traditional Uses | Recipients | Pharmacological Effects | Dose Administered | Duration of Treatment | References |
---|---|---|---|---|---|---|---|
Althaea officinalis L. | Leaves, flowers, roots | Diabetes, inflammation, skin infection, digestive and respiratory disorders | Alloxan-induced diabetic rats | ↓ Glutamate pyruvate transaminase (GPT), ↓ cholesterol, ↓ serum glucose levels, ↓ alkaline phosphate level (APL) | Powdered leaves (5% of the diet) | 28 days | [33] |
Anethum graveolens L. | Leaves, stems, and seeds | Diabetes, digestive disorders, cancer, microbial infections, inflammation, hyperlipidemia, | STZ-induced diabetic rats | ↓ Inflammatory cytokines, ↓ triglycerides, ↓ total cholesterol, ↓ LDL-C, ↓ VLDL-C, ↓ blood glucose, ↓ AGEs, ↓ protein glycation, ↓ fructosamine level, ↓ fasting blood glucose | 300 mg/mL | 56 days | [38,39] |
Allium sativum L. | Pulp | Diabetes, respiratory tract disorders, bacterial and fungal infections, wounds, cancers, CVDs, abdominal discomfort, diarrhea, cold, asthma, hay fever, inflammation, obesity | STZ-induced diabetic rats | ↓ LDL, ↓ total cholesterol, ↓ oxidative stress, ↑ HDL, ↓ blood glucose, ↓ intestinal glucose absorption, ↓ ROS generation, ↑ intracellular GSH content, ↓ endothelial dysfunction | 200 mg/kg | 21 days | [43,44,45] |
Brassica oleracea L. | Leaves | Inflammation, digestive disorders, cancer, peptic ulcer, gout, detoxification | STZ-induced diabetic rats | ↑ Glucose homeostatic regulation, ↓ organ damage from T2DM, ↓ oxidative stress, ↓ obesity, ↓ LDL cholesterol, ↓ total cholesterol, ↓ lipid peroxidation, ↑ pancreatic β-cells functions | 250 mg/kg | 40 days | [52,53,55] |
Cicer arietinum L. | Leaves, fruits, seeds | Diabetes, constipation, diarrhea, dyspepsia, flatulence, weight loss, inflammation, microbial infections | STZ-induced diabetic rats | ↑ Glycemic control, ↓ total cholesterol, ↓ α-amylase and α-glucosidase activity, ↑ insulin secretion and receptor activity, ↓ insulin deficiency, ↓ LDL | 200 mg/kg | 30 days | [58,61,62] |
Cinnamomum verum J. Presl. | Dried bark (inner part) | Diabetes, arthritis, diarrhea, hemorrhoids, toothache, cough, cold, menstrual irregularities, inflammation, bacterial infections | T2DM patients | ↓ GI enzymes, ↑ insulin response and sensitivity, ↑ glucose uptake, ↑ glycogen synthesis, ↓ gluconeogenesis, ↓ AGE formation, ↑ phosphorylation, ↑ GLUT4 | 1000 mg/day | 84 days | [67,68,69] |
Crocus sativus L. | Flower stigma | Diabetes, hepatic and cognitive disorders, lumbago, asthma, cough, bronchitis, CVDs, cancer, hyperlipidemia | Alloxan-induced diabetic rats | ↓ ROS, ↓ TG, ↓ TC, ↓ blood glucose, ↓ insulin resistance, ↑ insulin secretion and sensitivity, ↓ LDL, ↑ HDL, ↑ serum insulin, ↓body weight, ↓ lipid level | 25, 50, 100, 200 mg/kg | 60 days | [75,76] |
Cuminum cyminum L. | Seeds | Diabetes, chronic diarrhea, dyspepsia, asthma, hypertension, inflammation, bronchitis, dizziness, eczema, gastrointestinal disturbances | T2DM patients | ↓ Blood glucose, ↓ glycosylated hemoglobin, ↓ body weight, ↓ phospholipid, ↓ cholesterol, ↓ free fatty acid, ↓ TG, ↑ insulin secretion, ↓ aldose reductase, ↓ α-amylase and ɑ-glucosidase activity, ↓ AGEs | 50,100 mg/kg | 56 days | [83,84,85,86] |
Eugenia caryophyllata Thunb. | Unopened dried flower buds, stems, leaves, and fruits | Nausea, hepatic, bowel and stomach disorders, vomiting, microbial and protozoal infections, cholera, malaria, tuberculosis | STZ-induced diabetic rats | ↓ PEPCK, ↓ G6Pase gene expression, ↓ AChE, ↓ α-glycosidase, ↓ α-amylase, ↓ elevated blood sugar, ↓ lipid peroxidation | 100 mg/kg | 105 days | [88,90,91,92] |
Foeniculum vulgare Mill. | Seeds and fruits | Diabetes, lactation, menstruation irregularities, libido, tumor, inflammatory disease, cancer, hepatic disorders | STZ-induced diabetic male rats | ↑ GSH, ↓ α- amylase and α- glucosidase activity, ↓ breakdown of carbohydrates, ↑ glycemic control, ↓ cholesterol, ↓ TG, ↓ LDL, ↑ HDL | 150 mg/kg | 28 days | [95,96,98] |
Hordeum vulgare L. | Grains, leaves, sprouts | Diabetes, skin infections, arthritis, digestive diseases, weight loss, cancer, detoxification, lipid metabolism | STZ-induced diabetic rats | ↓ Blood glucose, ↓ cholesterol, ↓ hepatic cholesterol synthesis, ↓ α-glucosidase, ↓ α-amylase, ↑ insulin secretion | 100, 250, 500 mg/kg | 11 days | [101,102,103,104] |
Juglans regia L. | Husks, kernels, shells, seeds, flowers, barks, and leaves | Diabetes, asthma, arthritis, eczema, stomachache, sinusitis, diarrhea, astringent, antiseptic | T2DM patients | ↓ Blood glucose, ↑ insulin, ↓ HbA1c, ↑ GLUT2, ↓ glucose intestinal absorption, ↓ FBG, ↓ TG | 100 mg/kg | 90 days | [105,106,107] |
Lens culinaris L. | Seeds and sprouts | Diabetes, meat substitutes, obesity, inflammation, hyperlipidemia | STZ-induced diabetic mice | ↓ ROS, ↑ lipoprotein metabolism improvement, ↑ glycemic control, ↓ fasting blood glucose, ↓ serum blood glucose, ↑ gut motility, ↓ body weight | 100, 200, 400 mg/kg | 21 days | [113,114,115,117] |
Nigella sativa L. | Seeds | Diabetes, digestive disorders, diarrhea, warts, toothaches, swellings, dyspnea, microbial infections, fever, inflammation, hypertension, allergy, infertility, tumors | STZ-induced diabetic rats | ↑ Serum insulin, ↓ serum glucose, ↓ LDL, ↓ TG, ↓ total cholesterol, ↑ proliferation of β-cells, ↓ oxidative stress | 300, 400 mg/kg | 84 days | [118,119,120,121] |
Olea europaea L. | Fruit, pulp, leaves | Diabetes, hypertension, inflammation, diarrhea, respiratory and urinary tract infections, hemorrhoids, rheumatism, laxative, intestinal diseases, asthma, hyper uremia, hyperlipidemia | STZ-induced diabetic rats | ↓ α-glucosidase and digestive enzymes activity, ↓ postprandial hyperglycemia, ↑ insulin action, ↑ functionality and survival of β-cells | 1mL/100 bw/day (oil) | 42 days | [127,128,129,131,163] |
Pinus gerardiana Wall. ex D. Don | Seeds, leaves, barks | Diabetes, hypertension, sepsis, fungal and microbial infections | STZ-induced diabetic rats | ↓ Body weight, ↓ oxidative stress, ↓ hyperglycemia, ↑ expression of PPARγ gene, ↑ Akt, ↑ insulin secretion, ↓ malondialdehyde, ↓ fasting blood glucose levels | 3% and 6% w/w, (Powder) | 42 days | [133,135] |
Piper nigrum L. | Seeds, leaves, flowers, and fruits | Diabetes, menstrual problems, atrophic arthritis, digestive problems, influenza, bacterial infection, inflammation, fever, hypertension, cancer, depressants, diarrhea | Alloxan-induced diabetic rats | ↓ ROS generation, ↓ lipid peroxidation, ↓ lipogenesis, ↑ insulin secretion, ↓ blood glucose, ↓ triglyceride, ↓ total cholesterol, ↑ HDL, ↓ LDL, ↑ total antioxidant capacity | 50 mg/kg | 56 days | [137,141,143] |
Pistacia vera L. | Seeds, leaves, fruits | Diabetes, coughs, stomach diseases, asthma, sores, chest ailments, rheumatism, trauma, gynecological ailments, hemorrhoids | Pre-diabetic patients | ↓ Fasting blood glucose, ↓ insulinemia, ↓ Serum IL-6, ↓ fructosamine, ↓ insulin resistance, ↓ LDL, ↓ malondialdehyde, ↓ proinflammatory cytokines, ↓ glucose absorption | 57 g/day | 28 days | [145,146,149,164] |
Vitis vinifera L. | Dried fruits | Diabetes, cancer, obesity, inflammation, hyperlipidemia | T2DM patients | ↓ LDL oxidation and LDL-cholesterol, ↓ blood glucose control, ↓ postprandial glucose levels, ↓ HbA1c, ↓ blood pressure | 36 g/day | 168 days | [152,154,155] |
Zingiber officinale Roscoe | Roots and rhizomes | Diabetes, digestive disorders, nausea, rheumatism, respiratory tract infection, cough, hypercholesterolemia, neurological diseases, asthma, stroke, constipation, cancer | STZ-induced diabetic rats | ↓ Superoxide anion, ↓ hydroxyl radicals, ↓ α-glucosidase and α-amylase activity, ↓cholesterol, ↓ serum glucose, ↓ triglyceride, ↑ HDL, ↑ insulin sensitivity | 400 mg/kg | 56 days | [158,159,160] |
Medicinal Plants | Parts Used | Phytoconstituent Studied | Diabetic Model | Dose Administered | Duration of Treatment | Pharmacological Effects of the Phytoconstituents Used | References |
---|---|---|---|---|---|---|---|
Althaea officinalis L. | Leaves, roots, seeds | Lauric acid | Insulin resistance induced in macrophage THP-1 cells | 5 μM–50 μM | 1 day | Increases glucose uptake in skeletal muscles and improves mitochondrial dysfunction, insulin sensitivity, and GLUT-1 and GLUT-3 expression | [165] |
Anethum graveolens L. | Leaves, seeds | Carvone | STZ-induced diabetic rats | 25, 50, 100 mg/kg | 30 days | Alleviates insulin resistance, improves insulin secretion, and reverses glycoprotein abnormalities | [166] |
Allium sativum L. | Fruits | Allicin | STZ-induced diabetic rats | 15, 30, 45 mg/kg | 84 days | Improves insulin sensitivity and glucose tolerance, ameliorates diabetes-induced morphological alterations in the kidney, and decreases FBG and triglyceride | [167] |
Brassica oleracea L. | Leaves | Anthocyanin | T2DM patients | 160 mg/kg | 168 days | Improves lipid metabolism and insulin resistance, decreases LDL, total cholesterol, and postprandial glucose, and ameliorates diabetic complications | [168] |
Cicer arietinum L. | Seeds | Quercetin | Alloxan-induced diabetic rats | 50 mg/kg | 30 days | Decreases blood glucose, total cholesterol, total bilirubin, creatinine, and oxidative stress, regulates glucose homeostasis and improves insulin resistance | [169] |
Cinnamomum verum J. Presl. | Bark | Cinnamaldehyde | STZ-induced diabetic rats | 5, 10, 20 mg/kg | 45 days | Elevates HDL level, plasma insulin, and hepatic glycogen and decreases serum glucose, total cholesterol, triglyceride, and LDL level | [170] |
Crocus sativus L. | Flower stigma | Crocin | T2DM patients | 15 mg/kg | 84 days | Enhances GLUT-4 expression, inhibits TNF-α, IL-6, alleviates blood glucose, and improves glucose homeostasis and insulin resistance | [171] |
Cuminum cyminum L. | Seeds | Cuminaldehyde and cuminol | STZ-induced diabetic rats | 5, 10 mg/kg | 45 days | Increases insulin secretion and insulin sensitivity, lowers blood glucose, provides β-cell protection, and improves lipid profile | [172] |
Eugenia caryophyllata Thunb. | Flower buds, leaves, stem, fruits | Eugenol | STZ-induced diabetic mice | 100 mg/kg bw (I.P. route) | 45 days | Lowers blood glucose, blood lipids, and AGEs formation and inhibits α-amylase and α-glucosidase enzymes | [173] |
Foeniculum vulgare Mill. | Seeds | Kaempferol | STZ-induced diabetic mice | 50 mg/kg | 84 days | Suppresses gluconeogenesis, enhances glucose uptake in skeletal muscles, and restores hexokinase activity | [174] |
Hordeum vulgare L. | Grains, leaves, sprouts | β-glucan | STZ-induced diabetic rats | 80 mg/kg | 28 days | Alleviates diabetic complications, reduces oxidative stress, and lowers blood glucose, total cholesterol, total triglyceride, and LDL level | [175] |
Juglans regia L. | Husks, kernels, seeds, flowers, bark, leaves | β-carotene | STZ-induced diabetic rats | 10, 20 mg/kg | 14 days | Improves glucose metabolism and lipid accumulation, lowers inflammatory cytokines, nitric oxide production, and oxidative stress, and enhances glucose uptake in skeletal muscle | [176] |
Lens culinaris L. | Seeds, sprouts | Saponins | STZ-induced diabetic rats | 100, 200 mg/kg | 14 days | Ameliorates postprandial hyperglycemia and diabetic complications and inhibits α-glucosidase and aldose reductase enzymes | [177] |
Nigella sativa L. | seeds | Thymoquinone | STZ-induced diabetic rats | 50 mg/kg | 28 days | Attenuates blood glucose, lipid peroxidase, nitric oxide production, and oxidative stress and alleviates diabetic nephropathy | [178] |
Olea europaea L. | Fruits, leaves | Lutein | ARPE-19 cells | 0.5–1 μM | 24 h | Ameliorates diabetic retinopathy and hyperglycemia, Improves SOD2, HO-1, Nrf2, GSH and catalase regulation | [179] |
Pinus gerardiana Wall. ex D. Don | Nuts | Linoleic acid | PTPN1, PTPN9, PTPN11 cell lines | 0.5–300 μM | 7 days | Inhibits the catalytic activity of PTPN1, PTPN9, and PTPN11 and improves glucose uptake by activating AMPK and Akt pathway | [180] |
Piper nigrum L. | Seeds, flowers fruits, leaves | β-caryophyllene | STZ-induced diabetic rats | 200 mg/kg | 42 days | Decreases glucose absorption and increases glucose uptake in skeletal muscles, ameliorates glucose tolerance, pancreatic cell damage, oxidative stress, and lipid and blood glucose levels | [181] |
Pistacia vera L. | Fruits, nuts, leaves | Procyanidins | STZ-induced db/db type 2 diabetic mice | 250 mg/kg | 45 days | Enhances GLUT-4 translocation and glucose uptake on skeletal muscles, possesses insulinotropic ad anti-hyperglycaemic effects | [182] |
Vitis vinifera L. | Fruits | Ferulic acid | STZ-induced diabetic rats | 10 mg/kg | 14 days | Alleviates body weight, and blood glucose, attenuates diabetes-associated symptoms, and lowers total triglyceride, total cholesterol, LDL and VLDL levels | [183] |
Zingiber Officinale Roscoe | Roots | Gingerol | Type 2 diabetic mice (Leprdb/db) | 200 mg/kg | 28 days | Induces insulin secretion, elevates plasma GLP-1, activates cAMP, PKA, and CREB in the pancreatic islets, and enhances GLUT-4 translocation | [184] |
Medicinal Plant | Antidiabetic Phytoconstituent | Chemical Structure |
---|---|---|
Althaea officinalis L. | Lauric acid | |
Anethum graveolens L. | Carvone | |
Allium sativum L. | Allicin | |
Brassica oleracea L. | Anthocyanins | |
Cicer arietinum L. | Quercetin | |
Cinnamomum verum J. Presl. | Cinnamaldehyde | |
Crocus sativus L. | Crocin | |
Cuminum cyminum L. | Cuminaldehyde | |
Eugenia caryophyllata Thunb. | Eugenol | |
Foeniculum vulgare Mill. | Kaempferol | |
Hordeum vulgare L. | β-glucan | |
Juglans regia L. | β-carotene | |
Lens culinaris L. | Saponins | |
Nigella sativa L. | Thymoquinone | |
Olea europaea L. | Lutein | |
Pinus gerardiana Wall. ex D. Don | Linoleic acid | |
Piper nigrum L. | β-caryophyllene | |
Pistacia vera L. | Procyanidins | |
Vitis vinifera L. | Ferulic acid | |
Zingiber Officinale Roscoe | Gingerol |
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Ansari, P.; Samia, J.F.; Khan, J.T.; Rafi, M.R.; Rahman, M.S.; Rahman, A.B.; Abdel-Wahab, Y.H.A.; Seidel, V. Protective Effects of Medicinal Plant-Based Foods against Diabetes: A Review on Pharmacology, Phytochemistry, and Molecular Mechanisms. Nutrients 2023, 15, 3266. https://doi.org/10.3390/nu15143266
Ansari P, Samia JF, Khan JT, Rafi MR, Rahman MS, Rahman AB, Abdel-Wahab YHA, Seidel V. Protective Effects of Medicinal Plant-Based Foods against Diabetes: A Review on Pharmacology, Phytochemistry, and Molecular Mechanisms. Nutrients. 2023; 15(14):3266. https://doi.org/10.3390/nu15143266
Chicago/Turabian StyleAnsari, Prawej, Jannatul F. Samia, Joyeeta T. Khan, Musfiqur R. Rafi, Md. Sifat Rahman, Akib B. Rahman, Yasser H. A. Abdel-Wahab, and Veronique Seidel. 2023. "Protective Effects of Medicinal Plant-Based Foods against Diabetes: A Review on Pharmacology, Phytochemistry, and Molecular Mechanisms" Nutrients 15, no. 14: 3266. https://doi.org/10.3390/nu15143266