EFFICACY AND MECHANISM OF ACTION OF MORINGA OLEIFERA IN DIABETESHTML Full Text
EFFICACY AND MECHANISM OF ACTION OF MORINGA OLEIFERA IN DIABETES
Sneha 1, Monika Kaurav 2 and Satyender Kumar * 3
HIMT College of Pharmacy 1, 8-Institutional Area, Knowledge Park I, Greater Noida - 201301, Uttar Pradesh, India.
KIET School of Pharmacy 2, Delhi-NCR, Meerut Road, Ghaziabad - 201206, Uttar Pradesh, India.
Department of Pharmaceutical Sciences 3, Indira Gandhi University, Rewari - Lokri Rd, Meerpur - 123401, Haryana, India.
ABSTRACT: Diabetes mellitus (DM) is a globally spreading metabolic disorder with a high incidence rate. About 425 million cases took place in 2017 and expected to rise up to 693 million by 2045. In diabetes, the patient elevation of blood glucose level occurs due to the deformation of insulin receptor action/secretion or both. Long term increases in blood glucose level causes chronic effects such as dysfunction and damage of various organs such as eyes, nerves, kidney heart and blood vessels. There are many treatment regimens available in market, but do not able to provide complete relief and cause severe side effects. To overcome these types of problems it becomes important to find different therapeutic targets and use it in combination with conventional medicine for the treatment of diabetes. To surmount the side effect of presently available treatments, now researchers relay on herbal plants. In this review, we discussed the diabetes occurrence, epidemiology, types, different target receptors, and available treatments and describe briefly role of different plant constituents in diabetes management and focused on a main plant, Moringa oleifera.
Diabetes mellitus, Moringa oleifera, Therapeutic, Efficacy, Mechanism, Receptor
INTRODUCTION: Diabetes mellitus (DM) is a metabolic disorder, and its incidence is spreading globally 1. As per the previous reports, approximately 425 million people were found with diabetes in 2017 and expected to rise up to 693 million by 2045 2. DM is characterized by high blood glucose (HBG) level due to deformation in insulin receptor action/or secretion or both. HBG for a long time causes chronic effects like dysfunction and damage of various organs such as eyes, nerves, kidney heart and blood vessels 3. Such complications are due to disarrangement in body system for storing and mobilizing of metabolic components of carbohydrate, protein, and lipid 1.
Type 1 Diabetes mellitus (Type-1 DM) is related to childhood and well known as insulin-dependent and juvenile-onset diabetes. In this type of diabetes, due to dysfunctioning/impairment in pancreatic cells, these cells are unable to produce insulin sufficiently. Its reason can be a genetic predisposition or faulty beta cell that produces insulin 4. Type 2 Diabetes mellitus (Type-2 DM), also known as non-insulin dependent and adult-onset diabetes, but nowadays, over weighted people are more likely to develop this type of diabetes. It happens when the pancreas unable to produce enough insulin as it should be or because of insulin resistance 5.
Gestational diabetes developed during pregnancy and diagnosed between the middle or late period of pregnancy due to this growth, and the development of baby can be effected. It resolves after pregnancy. It happens as hormonal change is more likely to develop during pregnancy, which leads to insulin resistance 6.
Different Target in Diabetes: In all diabetic patients, 90-95% is from type 2 diabetes the most prevailing type of diabetes. The cause of type 2 diabetes is complex and multifactorial, and it can be affected by both genetically as well as environmentally. Many therapeutic targets are there for the treatment of type 2 diabetes, but there is a chance to develop resistance by using conventional medicine as a monotherapy. In addition, monotherapy treatment regimens do not provide relief from the complications permanently and also cause many side effects itself, so it becomes important to find different therapeutic targets and use it in combination with conventional medicine for the treatment of diabetes 7-9.
Different targets such as GLP-1, GIP, DPP4 inhibitor, GPR119, GPR40 and GPR120, SGLT2, Diacylglycerolacyltransferase, 11β-hydroxysteroid dehydrogenase-1, Peroxisome proleiferator-activated receptor.
GLP-1: GLP 1 is mainly secreted by the small intestine in response to a meal and stimulates insulin secretion, also inhibits glucagon secretion, gastric emptying, and food intake. A small percentage of GLP1 is secreted from the pancreas and follows the ingestion of food. GLP1 amino acid sequence is different according to the origin of a peptide. GLP1, which is derived from the intestine, is of 7-36 amino acids that are present in high amount in plasma as compared to pancreatic origin derived GLP1, which is of 1-36 amino acids. The metabolism and degradation of GLP1 are done rapidly by DPP4. GLP1 receptor is widely present in the pancreas, lungs, kidney, stomach, intestine, heart, pituitary, and in skin 10. GLP1 analogs are classified as following and displayed below in Fig. 1.
Exendin-Based Therapies: Exendin contains 39 amino acid, a naturally occurring peptide from the venom of Heloderma lizard. The homology of exendin is 53% similar to human GLP1. Glycine replaces the second amino acid residue of the N-terminal region. e.g., Exenatide and Exenatide LAR. It is resistant to DPP4 inhibition.
DPP-IV-Resistant GLP-1 Analogs: Potential sites are modified on the bases of the half-life of GLP1. Lixisenatide a 44 amino acid containing drug based on the structure of exendin, is modified in c-terminus with six lysine residue that prevents it from metabolism by DPP-4.
Analogs of Human GLP-1: GLP-1 can be conjugated to substances, for example, unsaturated fats, egg whites, in order to hinder its renal discharge. Unsaturated fat conjugation of GLP-1 encourages its authoritative to serum egg whites and has been utilized to create enduring peptide analogs E. gliraglutide 11.
Advantage: No risk of hypoglycemia, weight loss is also seen.
Disadvantage: Injection form, Limited by Gastrointestinal tract tolerance/nausea. In rare cases, May increases pancreatitis and thyroid cancers 12.
FIG. 1: SITE AND ACTION OF GLP1
DPP4 Inhibitor: DPP4 inhibitors are the class of oral hypoglycemic agents. They act by inhibiting the DPP4 enzyme. DPP4 is present all over the surface of most types of cells that deactivates an assortment of other bioactive peptides includes GLP1 and GIP 13.
FIG. 2: MECHANISM OF ACTION OF DPP4 INHIBITOR
DPP4 inhibitor which are available in markets are sitagliptin, linagliptin, saxagliptin, alogliptin and they comes in combination with metformin also 14. Advantage includes almost no risk of hypoglycemia, well-tolerated and Weight neutral and disadvantage includes modest efficacy, rarely it can increases pancreatitis and some chances of interference with the immune system 12.
GPR119: GPR119 is a G protein-coupled receptor. It is mainly present in the pancreases and GI tract. Its activation causes a reduction in meal intake. GPR119 has shown the function of regulating incretin as well as secretion of insulin hormone. Hence new drug acting on this receptor can be suggested for the treatment of diabetes 15. GPR119 agonists act on the GPR119 receptor to increase cAMP level in beta cells of the pancreas thus increases glucose-stimulated insulin secretion in the same manner as GLP1 and GIP do 16. GPR119 agonists regulate the release of insulin from beta cells and metabolic function in skeletal and cardiac muscle 12.
FIG. 3: SITE AND ACTION OF GPR119
GPR40 and GPR120: GPR40 a class of G-protein coupled receptor mostly present in beta cells of pancreas 17. GPR40 is a receptor for medium-chain and long-chain free fatty acids. Free fatty acids are not just only a nutrient but also shows function as cell signaling mediator and implicated in much metabolic disorder which includes diabetes also 18. Long term exposure of the beta cell to fatty acid can increase the release of basal insulin, but it inhibits glucose-induced insulin secretion 19. It acts by increasing intracellular calcium concentration that leads to glucose-induced insulin secretion and also the secretion of GLP-1, GIP, and CCK 20, 21.
FIG. 4: MECHANISM OF ACTION OF GPR 40
GPR120 is a G-protein coupled receptor that responds to long-chain fatty acids mainly by omega-3 fatty acid 22, 23 present in small intestine, pancreas, adipocytes, and macrophages also. It induces various cellular functions by several secondary pathways thus increase hormone release like cholecystokinin and GLP1 in the response of intestinal fatty acid 24, 25. GPR120 has a role in improving bone density and metabolism. Disadvantage – GPR40 can cause lipotoxicity 12.
SGLT2: Sodium-glucose co-transporter 2 (SGLT2) is a transport protein present in proximal tubules of the kidney that facilitate reabsorption of glucose back into the kidney. SGLT2 inhibitors are also known as gliflozin drugs. It is recommended that people who have poor blood glucose control and a high HbA1c level. SGLT2 inhibitors act by blocking the reabsorption of glucose in the kidney that results in glucose excretion, which lowers the blood glucose level. SGLT2 is responsible for the 90% reabsorption of glucose in the kidney. SGLT2 also allows uptake of glucose in the muscle cells, increases insulin sensitivity, decreases gluconeo-genesis also it improves the first phase of insulin release from beta-cell 26, 27.
SGLT2 drugs that are available in the market are canagliflozin, dapagliflozin, and empagliflozin 28. SGLT-2 drugs cause weight loss, low risk of hypoglycemia, and reduction in blood pressure. The disadvantage includes vulvovaginal candidiasis, mycotic infections, reduce intravascular volume, orthostatic hypotension, hyperkalemia, renal insufficiency and increase LDL cholesterol 29. The mechanism of action of SGLT2 is given in Fig. 5.
FIG. 5: MECHANISM OF ACTION OF SGLT-2
Diacylglycerol Acyltransferase (DGAT-1): DGAT-1 is a key enzyme that plays a significant role in the last step of triglyceride biosynthesis. DGAT-1 is used as a therapeutic target for diseases, such as obesity and diabetes, as excessive deposition of triglyceride is the cause of these diseases. The human liver is a significant organ for triglyceride synthesis, and DGAT1 is richly present in that 30. Other parts where DGAT1 is expressed are the small intestine, adipose tissue and mammary gland 31. The mechanism of action of DGAT-1 is given in Fig. 6.
FIG. 6: MECHANISM OF ACTION OF DGAT-1
Abbreviations- GPAT: Glycerol-3-phosphate; acyltransferase; AGPAT: 1-acylglycerol-3-phosphate acyltransferase; PAP: lipin: phosphatidate phosphatase; DGAT: Diacylglycerol acyltransferase)
11β-hydroxysteroid dehydrogenase-1 (11β-HSD1): Glucocorticoids such as cortisol is important mediators in the regulation of cardiovascular and metabolic functions. Through activation of glucocorticoid or mineralocorticoid receptors, glucocorticoids impact vascular, adipose, liver, and kidney functions 32, 33. Diabetes is related to abnormal regulation of glucocorticoid metabolism; glucocorticoids antagonize the function of insulin and also inhibit secretion of insulin from beta-cell of pancreas 34. 11β‐HSD1 catalyses the intracellular conversion of cortisone to cortisol. Inhibition of 11β‐HSD1 has therapeutic benefits in type 2 diabetes 35. Disadvantage - mineralocorticoid induced side effects 12.
Peroxisome proliferator-activated receptor (PPAR): PPARs are the group of nuclear receptor protein that plays a role in transcription factor which regulates the expression of gene. PPARs comprises of three types PPARα, PPARγ, and PPARβ/δ. PPARα regulates energy homeostasis by reducing triglyceride level. PPAR-γ regulates glucose metabolism by insulin sensitization, whereas PPAR-β/δ regulates fatty acid metabolism 36, 37. Fatty acid and eicosanoid derivatives are the natural PPAR ligands. On the other hand, fibrates and thiazolidinediones are synthetic ligands used for glucose and lipid metabolism control 38. Disadvantage - congestive heart failure, fluid retention, and edema 12.
Treatment Available for the Diabetes: The major goal in the treatment of diabetes mellitus is to control blood glucose level to prevent compli-cations which are associated with this 39.
Diabetes is a diagnosis by various following test:
Random Blood Sugar Test: A blood sample is taken after food if blood sugar level showing the value of 200mg/dl or high it will be considered as diabetic.
Fasting Blood Glucose Test: A blood sample is taken before morning food intake, and the sugar level should be below 126 mg/dl otherwise, it will consider as diabetic. Between 100 mg/dl to 125 mg/dl is called prediabetic.
Oral Glucose Tolerance Test: Test is done after overnight fasting and then taking sugary liquid containing 75 gm of glucose. The blood sugar level is tested after two hrs. The blood sugar level should be below 141 mg/dl.
Glycated Hemoglobin Test (HbA1C): It shows the history of blood sugar levels for the past three months. The blood sugar level should be below 5.7; the value between 5.7 to 6.4 is considered prediabetic.
Zinc Transporter 8 Auto Antibody: This test is used to determine type1 diabetic patients 40, 41.
To maintain good metabolic control in diabetes mellitus, change in lifestyle, and pharmacological treatment, both are required 42.
Lifestyle Changes: Dietary modification and physical exercise are considered as two basic factors of energy balance as well as in the treatment of diabetes. Appropriate rest is required for maintaining energy levels so to be fit. It is advised to sleep for 7 h daily at night, which reduces many cardiovascular and metabolic risks 43-46.
Diet: At the point when healthful mediation is mulled over, the co-morbidities that can coincide in a diabetic patient additionally must be considered. The suggestions on dietary viewpoints can add to accomplish the ideal blood glucose, pulse, lipid profile, and weight total caloric intake depend upon various factors like overweight or obesity 42. Most diabetic patients are overweighed, which is directly related to insulin resistance and insulin secretion, which worsens the condition of diabetes. In this case, the main objective is to reduce weight by reducing caloric intake. Reduction in weight will improve insulin sensitivity hence parameters of glycemic control, and if the patient is not overweighed diet for them should be isocaloric, so caloric intake management should be according to individual patient requirements 44-46.
Exercise: Exercise and physical activity can play a significant role in the treatment of diabetes. Exercise increases insulin sensitivity, which improves sugar control that gives benefits in blood pressure, lipid profile, maintenance or weight loss, other cardiovascular benefits, improvement of depression, psychological well-being, and better quality of life 43, 47.
Exercise also decreases HbA1C level and improvement in other metabolic parameters. Both resistance and aerobic exercise have shown benefits in the treatment of diabetes. Unstructured physical activity such as walking more climbing stairs are advised to patients of diabetes 42.
Pharmacological Treatment: Type 1 diabetes is treated with insulin as the pancreas is unable to produce insulin; insulin is taken in the form of injection.
Type of injectable insulin
- Rapid-acting: It shows its effect within few minutes, which last upto 4 h.
- Regular or short-acting: It shows its effect within 1 to 2 h, which last upto 6 h.
- Intermediate-acting: It shows its effect within 1 to 2 h and last upto 8 h.
- Long-acting: It shows its effect within 1 to 2 h and last beyond 24 h.
- Ultra long-acting: It shows its effect within 1 to 2 h and last upto 24 h.
Depending upon the individual patient requires different types of insulin is recommended for the patient. One patient can be advised for different types of insulin to meet the requirement of insulin 48.
Many oral hypoglycemic drugs are recommended for the treatment of type 2 diabetes. They are of seven different classes, such as biguanides, sulfonylureas, an alpha-glucosidase inhibitor, thiazolidinediones, a DPP4 inhibitor, GLP1 agonist, SGLT2 inhibitors. All of them have advantages and disadvantages. The oral combination increases patient compliances. The selection of appropriate drugs is based on the patient clinical condition and economic condition. Metformin is a first-line treatment for diabetes type 2. It is useful in decreasing weight and insulin resistance. Sulfonylureas are given when a patient is less than 40 years. Thiazolidinediones have a significant role in maintaining blood sugar levels and also improve the function of the beta cell. DPP4 inhibitor and GLP1 agonist are important for lowering HbA1C level. Most of them are used in combination with metformin. Clinical advantage of pharmacological treatment increases when went with non-pharmacological medications 42, 49.
Role of Different Plants and their Chemical Constituents with their Structures: In the present available treatment of diabetes is done with insulin and other oral hypoglycemic drugs such as sulfonylurea, biguanides, DDP4 inhibitors, and others. Oral hypoglycemic drugs have so many adverse effects, so it is a challenge to manage diabetes without side effects. Thus people relay on herbal substituent 50; many traditional drugs are used for the prophylaxis and therapeutic effect of many diseases including diabetes also. Most of them are used as a dietary supplement 51.
TABLE 1: SOME COMMON HERBAL DRUGS FOR THE TREATMENT IN DM DESCRIBED BELOW
|Part of plant used||Extract/Suspension/Powder/juice||Dose||Pharmacological model|
|1||Acacia arabica||Leguminosae||Babul||Bark||Chloroformic extract||200
|Streptozotocin (STZ) induced diabetic rat 52|
|2||Adhatoda zeylanica||Acanthaceae||Malabar nut or adusa||Leaves||Aqueous and methanolic extract||100
|Alloxan induced diabetic rats 53, 54|
|3||Aegle marmelos||Rutacae||Bengal quince, bel or bilva||Fruit||Aqueous extract||250
|STZ induced diabetic rat 55|
|4||Acosmium panamense||Fabaceae||Benth||Bark||Aqueous and butanolic extract||220
|STZ induced diabetic rat 54|
|5||Allium cepa||Liliaceae||Onion||Bulb||Aqueous extract||300
|Alloxan induced diabetic rat 56|
|6||Allium sativum||Liliaceae||Garlic||Bulb||Ethanolic extract||0.5
|STZ induced diabetic rat 57|
|7||Aloe barbadensis||Liliaceae||Aloe||Leaves||Ethanolic extract
|STZ induced diabetic rat 58|
|8||Artemicia species||Compositae||Artemisia||Whole plant||Methanolic extract||250
|STZ induced diabetic rat 59|
|Alloxan induced diabetic rat 60|
|10||Caesalpiniabonducella||Leguminosae||Fever nut||Seed||Aqueous extract||65
|STZ induced diabetic rat 61|
|11||Coccina indica||Curcurbitaceae||Little gourd||Leaves||Aqueous extract||200
|Alloxan induced diabetic 62|
|12||Cyamopsis tetragonoloba||Fabaceae||Guar||Beans||Methanolic extract||400
|STZ induced diabetic rat 63|
|Indian gooseberry||Seed||Ethanolic extract||250
|STZ induced diabetic rat 64|
|14||Gymnema sylvestre||Apocynaceae||Gurmar||Leaves||Methanolic extract||30
|STZ induced diabetic rat 65|
|15||Mangifera indica||Anacardiaceae||Mango||Leaves||Aqueous extract||200
|Alloxan induced diabetic rat 66|
|16||Momordica charantia||Cucurbitaceae||Bitter gourd||Fruit||Fruit juice||10
|STZ induced diabetic rat 67|
|17||Ocimum sanctum||Lamiaceae||Holy basil||Leaves||Methanolic extract||2.5
|Alloxan induced diabetic rat 68|
|18||Tinospora cordifolia||Menispermaceae||Giloy||Root||Aqueous extract||50
|Alloxan induced diabetic rat 69|
|19||Withania somnifera||Solanaceae||Ashwagandha||Root||Methanolic extract||300
|STZ induced diabetic rat 70|
|20||Zingiber officinale||Zingiberaceae||Ginger||Root||Aqueous extract||500
|STZ induced diabetic rat 71|
Moringa oleifera: Moringa oleifera is also known as horseradish tree, drumstick, benzolive tree, moonga, kelor tree, never die tree, mothers best friend, mlonge, mulangay and so many others, belonging to the family Moringaceae 72. Due to its numerous application also known as the miracle tree as most of its parts can be used for pharmacological activities. It is widely found around the world as it can withstand in both condition mild frost as well as in severe dry condition 73, 74. It can also tolerate a wide range of rainfall with a minimum 200 mm to a maximum 3000 mm. Moringa mostly found in the western part and in Himalayan tracts of India, Pakistan, other parts of Asia, Arabia, Africa, now found in Cambodia, Phillippines, Caribbean islands all parts of America, including central, north and south part of it 75. Moringa is well used in malnutrition especially in nursing mothers and infants, prescribed for mothers as galactagogues so-called mother’s best friend.
Moringa is known to contain almost 7 times more vitamin c as compared to oranges, 9 times more protein than yogurt, 10 times more vitamin A than carrot, 15 times more potassium than bananas, 17 times more calcium than milk, 25 times more iron than spinach. It is easily available with affordable price that also makes it suitable for malnutrition remedy. Moringa nutritive properties are present in the whole plant so most of the part of moringa can be eaten like leaves, bark, seeds, pods, flower, pods, and roots 73, 76, 77. Apart from medicinal and nutraceuticals use, Moringa is also used for its water purification and biodiesel production. Moringa purifies water by its water-soluble proteins, which act as coagulants. Moringa seed oil is commonly known as Ben oil that is used for biodiesel production, as it contains a high value of monounsaturated fatty acids in the form of oleic acid 78.
Taxonomy: The taxonomical classification of Moringa oleifera is given below in Fig. 7.
FIG. 7: TOXONOMICAL CLASSIFICATION OF MORINGA OLEIFERA
Chemical Constituents: Every part of Moringa is full of nutrients and phytochemical chemicals. Leaves of Moringa contain a high amount of minerals like potassium, calcium, magnesium, zinc, copper, and iron. Vitamins like vitamin A, B, C, D, and E are also present 79, 80. In phytochemicals, moringa contains tannins, terpenoids, sterols, flavonoids, anthraquinones, saponins, alkaloids, phenolic compounds and reducing sugar 79, 81. Different parts contain different types of phytochemicals and nutrients, which are shown below in Table 2.
TABLE 2: PARTS OF MORINGA OLEIFERA CONTAINING DIFFERENT AMOUNT OF PHYTOCHEMICAL CONSTITUENTS AND NUTRIENTS
|Leaves||Glycoside niazirin, niazirinin and three mustard oil glycosides, 4-[4’-O-acetyl- α -L-rhamnosyloxy) benzyl] isothiocyanate, niaziminin A and Balpha and gamma-tocopherol 14-15flavanoid such as apigenin-8-C-glucoside, quercetin 3-O-β-d-glucopy-ranoside, kaempferol-7-O-α-l-rhamnoside, and 5, 7, 2′, 5′-tetrahydroxyflavone, phenolic like chlorogenic acid 80, 82|
|Mature flowers||Carotenoids, low saturated fatty acid (SFAs) content and high MUFA and PUFA, glucosinolates, 4-O-(a-L-rhamnopyranosyloxy)-benzylglucosinolate (glucomoringin) 83, 84|
|Whole gum exudates||D-galactose, L-arabinose, L-rhamnose, D-glucuronic acid, D-xylose, D-xylose and leucoanthocyanin 12-13 83|
|Stem||4-hydroxylmellein, octacosonoic acid, vanillin, β - sitosterone and β – sitosterol 85|
|Bark||4-(α-L-rhamnopyranosyloxy)-benzylglucosinolate 10 83|
|Whole pods||Isothiocyanate, thiocarbamates,O-(1heptenyloxy) propyl undecanoate, nitrites, O-ethyl-4-(alpha-L-rhamnosyloxy) benzyl carbamate, β-sitosterol, methyl- p-hydroxybenzoate 85|
|Mature seed||Methyl esterhexadecanoic acid, L-(+)-ascorbic acid 2, 6dihexa-decanoate, Methyl ester-9- octadecenoic acid, Oleic acid, 9-octadecenamide 86|
|Seed oil||MUFA, Saturated Fats, high oleic acid ( omega-9 ), behenic acid 87|
Pharmacological Activities of Moringa oleifera:
FIG. 8: PHARMACOLOGICAL ACTIVITIES OF MORINGA OLEIFERA
Moringa oleifera due to its high nutritive and phytochemical value has many pharmacological activities such as:
- Antihypertensive: Aekthammarat et al., reported that antihypertensive activity of Moringa oleifera (aqueous extract) has effectively treat hypertension in Nω-nitro-L-arginine methyl ester (L-NAME) induced hypertension on dosing with 30 mg/kg and 60 mg/kg in dose depending manner by antioxidant effect and promote endothelium dependent vasorelaxation 88.
- Antitumor: Khalil et al., study has reported that ethanolic extract of Moringa oleifera has shown antitumor activity on Ehrlich’s solid tumor implanted in Swiss male albino mice on different dosing such as 125 mg/kg, 250 mg/kg, and 500 mg/kg. 125 mg/kg and 250 mg/kg shows the degradation of genomic DNA in Ehrlich’s solid tumor-mice. Along with 500mg/kg shows delay in growth of the tumor by internucleosomal DNA fragmentation 89.
- Antiulcer: Ijioma et al., study reported that ethanolic extract in aspirin-induced ulcer in rat at dosing with 800 mg/kg exhibit antiulcer activity by increasing mucus globules on surface epithelium 90.
- Hepatoprotective: Toppo et al., study has evaluated that ethanolic leaves extract significantly decrease raised biochemical liver markers such as AST, ALT, ALP, LPO level and increase SOD level on dosing with 500 mg/kg in cadmium-induced toxicity in wistar albino rat by free radical scavenging and antioxidant property 91.
- Anti-inflammatory: Alimuddin et al., a study has shown that ethanolic leaves extract with 400 mg/kg in carrageenan-induced inflammatory in male Wistar albino rats reported for anti-inflammatory action by inhibition of histamine and serotonin mediated effect and also by inhibiting prostaglandin synthesis 92.
- Antibacterial Activity: Priya et al., a study has reported for aqueous extract of fresh stem bark (3.0-4.2 mg/ml), seed (0.5-1.25 mg/ml), and dry pods husk (4.0-5.6 mg/ml) has shown inhibitory activity against many microorganisms in different agar plates of suitable media 93.
- Antifungal: Patel et al., a study has reported that ethanolic and aqueous leaves extract (300 µl) was effective against fungus like Candida tropicalis and Saccharomyces cerevisiae activity was determined by agar well diffusion method 94.
- Antifertility: Aggarwal et al., a study has reported that ethanolic leaves extract at a dose of 500 mg/kg has shown antifertility activity in female Wistar rats by antiprogestogenic and antiestrogenic effect 95.
- CNS Depressant: Yunusa et al., a study has reported that ethanolic leaves extract at a dose of 400 mg/kg has antidepressant activity by increasing neurotransmitters level in the brain. The activity was determined by the Tail suspension method and Forced swim test 96.
Specific Role in the Treatment of Moringa oleifera in DM: Several studies have reported the hypoglycemic activity of Moringa oleifera. Khan et al., the study reported that Aqueous leaf extract of Moringa oleifera with dosing with 100 mg/kg to STZ induced diabetic rat has shown antidiabetic activity by inhibiting the action of α-glucosidase and α-amylase, which improve antioxidant activity, rate of glucose uptake and glucose tolerance 97. In another study of Une et al., a study has shown that ethanolic pod extract in alloxan-induced diabetic rat with 200mg/kg results in hypoglycemic effect by increasing insulin action through potentiating insulin secretion from the pancreas or by its secretion from bound form 98.
Onyagbodorn et al., the study reported that ethanolic leaves extract at 100 mg/kg along with seed powder at 100 mg/kg in alloxan-induced diabetic Wistar rat has hypoglycemic action as it increases glucose uptake in muscles, decreases serum HbA1C level and fasting blood sugar thus improves insulin resistance 99. Patel et al., the study reported that methanolic extract of Moringa oleifera flower and fruit at 200 mg/kg dose in STZ induced diabetic Wistar female rat shows hypoglycemic action by oxidative properties 100.
Chemical Constituent of Moringa oleifera Responsible for Anti-diabetic Action: Moringa oleifera contains a great amount of flavonoids, triterpenoids, sterols, phenolic, alkaloidal constituents responsible for antidiabetic property 101. Quercetin and kaempferol are present in predominant in flavanols. Chlorogenic acid and quinic acid is major phenolic acid 102.
Quercetin: Quercetin is found in large concentrations and potent antioxidants with multiple therapeutic activities. It is reported that quercetin can protect β cells of the pancreas from STZ induced diabetes and apoptosis in rat 103. The structure of quercetin is given Fig. 9.
FIG. 9: STRUCTURE OF QUERCETIN
Chlorogenic Acid: It significantly effect glucose metabolism. In oral glucose tolerance test experiment performed on both rats and humans has shown reduced glycemic response in the rat as well as in humans. It inhibits glucose-6-phosphate translocase in diabetes-induced rats thus reduces hepatic glycogenolysis and gluconeogenesis 104. Structure of chlorogenic acid is given in Fig. 10.
FIG. 10: STRUCTURE OF CHLOROGENIC ACID
Moringinine: Alkaloidal moringinine was initially obtained from the root bark of Moringa oleifera, later it was also found in leaves. Several studies reported this substance lower hyperglycemic effect.
On dosing with 386 mg/kg in drinking water for 17 weeks to diabetes-induced rat has shown a reduction in weight gain, decreases fasting glucose level, plasma triglycerideimprove glucose tolerance 105.
Niaziminin: 2 Nitrile glycosides, aniazirinin and niazirin, 3 mustard oil glycosides, niaziminin A, niaziminin B and isothiocyanate are identified in leaves of Moringa oleifera. This compound is also responsible for hypotension action at dosing with 1mg and 3 mg/kg 106.
Different Clinical Trials Related to Moringa oleifera: Various clinical trials are going on with Moringa oleifera which are given below in Table 3.
TABLE 3: CLINICAL TRIALS OF MORINGA OLEIFERA
|Phase||Drug candidate||Protocol id||Current status|
|Not applicable||Moringa oleifera||NCT03189407||Completed|
|Phase 1||Moringa oleifera||NCT02308683||Completed|
The given data is collected from clinicaltrails.gov.in
CONCLUSION: Moringa oleifera isan important herbal medicinal plant which is reported for various pharmacological treatments. In this review, the various different targets in Diabetes and mechanism of action of various phytoconstituents present in Moringa oleifera in the treatment of diabetes have discussed. This review will promote the growth in research related to medicinal plant Moringa oleifera.
ACKNOWLEDGEMENT: The authors wish to thank to Dr. Vikram Sharma, Principal, HIMT college of Pharmacy, Greater Noida for providing support for this study.
CONFLICTS OF INTEREST: The authors declare that there are no conflicts of interest.
- Piero MN, Nzaro GM and Njagi JM: Diabetes mellitus-a devastating metabolic disorder. Asian J Biomed Pharm Sci 2015; 4(40): 1-7.
- Viswanathan V, Krishnan D, Kalra S, Chawla R, Tiwaskar M and Saboo B: Insights on Medical Nutrition Therapy for Type 2 Diabetes Mellitus: An Indian Perspective. Adv Ther 2019; 36: 520-47.
- Chamberlain JJ, Doyle-Delgado K, Peterson L and Skolnik N: Diabetes technology: Review of the 2019 American Diabetes Association standards of medical care in diabetes. Ann Intern Med 2019; 171(6): 415-20.
- Kahanovitz L, Sluss PM and Russell SJ: Type 1 diabetes-a clinical perspective. Point Care 2017; 16(1): 37-40.
- Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G and Mathieu C: 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43(2): 487-93.
- Mishra S, Bhadoria AS, Kishore S and Kumar R: Gestational diabetes mellitus 2018 guidelines: An update. J Fam Med Prim Care 2018; 7(6): 1169.
- Panunti B, Jawa AA and Fonseca VA: Mechanisms and therapeutic targets in type 2 diabetes mellitus. Drug Discov Today Dis Mech 2004; 1(2): 151-7.
- Chaurasia A, Mallya R and Khan T: Novel Therapeutic Targets for Management of Type-2 Diabetes Mellitus. Immunol Endocr Metab Agents Med Chem 2016; 16(1): 18-30.
- Banu S and Bhowmick A: Therapeutic Targets of Type 2 Diabetes: an Overview. MOJ Drug Des Dev Ther 2017; 1(3). Available from: http://medcraveonline.com/ MOJDDT/ MOJDDT-01-00011.php
- Consoli A, Formoso G, Baldassarre MPA and Febo F: A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment. Expert Opin Drug Saf 2018; 17(3): 293-302.
- Fremaux J, Venin C, Mauran L, Zimmer RH, Guichard G and Goudreau SR: Peptide-oligourea hybrids analogue of GLP-1 with improved action in-vivo. Nat Commun 2019; 10(1): 924.
- Tiwari N, Thakur AK, Kumar V, Dey A and Kumar V: Therapeutic Targets for Diabetes Mellitus: An Update. Clin Pharmacol Biopharm 2014; 3(1): 1-10.
- Spanopoulos D, Barrett B, Busse M, Roman T and Poole C: Prescription of DPP-4 Inhibitors to Type 2 Diabetes Mellitus Patients With Renal Impairment: A UK Primary Care Experience. Clin Ther 2018; 40(1): 152-4.
- DPP-4 Inhibitors – Diabetes Daily [Internet]. [cited 2019 Jul 2]. Available from: https://www.diabetesdaily.com/l earn-about-diabetes/overview-of-diabetes-drugs/dpp-4-inhibitors/
- Yang JW, Kim HS, Choi Y, Kim Y and Kang KW: Therapeutic application of GPR119 ligands in metabolic disorders. Diabetes, Obes Metab 2018; 20(2): 257-69.
- Overton HA, Fyfe MCT and Reynet C: GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharmacol 2008; 153(S1): S76-81.
- Sundaresan S and Abumrad NA: Dietary Lipids Inform the Gut and Brain about Meal Arrival via CD36-Mediated Signal Transduction. J Nutr 2015; 145(10): 2195-200.
- Chen C, Li H and Long YQ: GPR40 agonists for the treatment of type 2 diabetes mellitus: The biological characteristics and the chemical space. Bioorganic Med Chem Lett 2016; 26(23): 5603-12.
- Ueno H, Ito R, Abe SI, Ookawara M, Miyashita H and Ogino H: SCO-267, a GPR40 full agonist, improves glycemic and body weight control in rat models of diabetes and obesity. J Pharmacol Exp Ther 2019 1; 370(2): 172-81.
- Shapiro H, Shachar S, Sekler I, Hershfinkel M and Walker MD: Role of GPR40 in fatty acid action on the β cell line INS-1E. Biochem Biophys Res Commun 2005; 335(1): 97-104.
- Chen C, Li H and Long YQ: GPR40 agonists for the treatment of type 2 diabetes mellitus: The biological characteristics and the chemical space. Bioorg Med Chem Lett 2016; 26(23): 5603-12.
- Carpino PA and Hepworth D: Beyond PPARs and Metformin: New Insulin Sensitizers for the Treatment of Type 2 Diabetes. Annu Rep Med Chem 2012; 47: 177-92.
- Burns RN and Moniri NH: Agonism with the omega-3 fatty acids α-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem Biophys Res Commun 2010; 396(4): 1030-5.
- Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H and Fan W: GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010; 142(5): 687-98.
- Stone VM, Dhayal S, Brocklehurst KJ, Lenaghan C, Sörhede Winzell M and Hammar M: GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia 2014; 57(6): 1182-91.
- Joffe DL: SGLT2 Inhibitors: A New Class of Diabetes Medications [Internet]. 2018 [cited 2019 Jul 3]. Available from: http://www.diabetesincontrol.com/sglt2-inhibitors-a-new-class-of-diabetes-medications/
- Seel M: SGLT2 Inhibitors - The Johns Hopkins Patient Guide to Diabetes 2019. Available from: http://hopkinsdiabetesinfo.org/sglt2-inhibitors/
- List of SGLT-2 inhibitors (sodium-glucose cotransporter-2 inhibitors) [Internet]. [cited 2019 Jul 3]. Available from: https://www.drugs.com/drug-class/sglt-2-inhibitors.html
- Fattah H and Vallon V: The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus. Drugs 2018; 78(7): 717-26.
- Chang S, Sung PS, Lee J, Park J, Shin EC and Choi C: Prolonged silencing of diacylglycerol acyltransferase-1 induces a dedifferentiated phenotype in human liver cells. J Cell Mol Med 2016; 20(1): 38-47.
- Jo S Il, Bae JH, Kim SJ, Lee JM, Jeong JH and Moon JS: PF-04620110, a potent antidiabetic agent, suppresses fatty acid-induced NLRP3 inflammasome activation in macrophages. Diabetes Metab J 2019; 43(5): 683-99.
- Goodwin JE and Geller DS: Glucocorticoid-induced hypertension. Pediatr Nephrol 2012; 27(7): 1059-66.
- Walker BR: Glucocorticoids and Cardiovascular Disease. Eur J Endocrinol 2007; 157(5): 545-59.
- Yao F, Chen L, Fan Z, Teng F, Zhao Y and Guan F: Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes mellitus. Bioorganic Med Chem Lett 2017; 27(17): 4107-13.
- Zhao L, Pan Y, Peng K, Wang Z, Li J and Li D: Inhibition of 11β-HsD1 by LG13 improves glucose metabolism in type 2 diabetic mice. J Mol Endocrin 2015; 55(2): 119-31.
- Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK and Gonzalez FJ: International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006; 58(4): 726-41.
- Tyagi S, Gupta P, Saini AS, Kaushal C and Sharma S: The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011; 2(4): 236-40.
- Polvani S, Tarocchi M, Tempesti S, Bencini L and Galli A: Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer. World J Gastroenterol 2016; 22(8): 2441-59.
- Chamberlain JJ, Herman WH, Leal S, Rhinehart AS, Shubrook JH and Skolnik N: Pharmacologic therapy for type 2 diabetes: Synopsis of the 2017 American diabetes association standards of medical care in diabetes. Ann Intern Med 2017; 166(8): 572-8.
- Understanding Diabetes -- Diagnosis and Treatment 2019. Available from: https://www.webmd.com/diabetes/guide/ understanding-diabetes-detection-treatment#1
- Health NI of. Diabetes Tests & Diagnosis [Internet]. National Institutes of Health 2018. Available from: https://www.niddk.nih.gov/health-information/diabetes/ overview/tests-diagnosis
- Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C and Del Cañizo Gómez FJ: Update on the treatment of type 2 diabetes mellitus. Wor J Diab 2016; 7(17): 354-95.
- Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C and Cañizo-Gómez FJ del: Update on the treatment of type 2 diabetes mellitus. World J Diabetes 2016; 7(17): 354.
- Shoelson SE, Lee J and Goldfine AB: Inflammation and insulin resistance. J Clin Invest 2006; 116(7): 1793-801.
- Pulido ME, Herrera AE, Najar MEM and Salazar MA: Effects of weight loss on insulin secretion and in-vivo insulin sensitivity in obese diabetic and non-diabetic subjects. Diabetes Nutr Metab 2013; 16(5-6): 277-83.
- Manuel MGF, Lesmes IB, Marset JB, Izquierdo JQ, Sala XF and Salas-Salvadó J: Evidence-based nutritional recommendations for the prevention and treatment of overweight and obesity in adults (FESNAD-SEEDO consensus document). The role of diet in obesity treatment (III/III). Nutr Hosp 2012; 27(3): 833-64.
- Phielix E, Meex R, Moonen-Kornips E, Hesselink MKC and Schrauwen P: Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals. Diabetologia 2010; 53(8): 1714-21.
- Freeland B and Farber MS: A Review of Insulin for the Treatment of Diabetes Mellitus. Home Healthc now 2016; 34(8): 416-23.
- Ibrahim R: Diabetes mellitus type ii: review of oral treatment options. Int J Pharm Pharm Sci; 2(1): 21-30.
- Farzaei F, Morovati MR, Farjadmand F and Farzaei MH: A mechanistic review on medicinal plants used for diabetes mellitus in traditional persian medicine. J Evid Based Complementary Altern Med 2017; 22(4): 944-55.
- Karthikeyan J, Kavitha V, Abirami T and Bavani G: Medicinal plants and diabetes mellitus: A review. J Pharmacogn Phytochem 2017; 6(4): 1270-9.
- Rajvaidhya S, Nagori BP, Dubey BK, Desai P, Alok S and Jain S: A review on Acacia Arabica-an Indian medicinal plant. IntJ Pharm Sci Res 2012; 3(7): 1995-2005.
- Adhatoda Zeylanica Medicus 2019. Available from: https://www.ayurvista.net/herbalplants/adhatoda-zeylanica- medicus/
- Khera N and Bhatia A: Medicinal plants as natural anti-diabetic agents. Int J Pharm Sci 2014; Available from: http://ijpsr.com/bft-article/medicinal-plants-as-natural-anti-diabetic-agents/?view=fulltext
- Arawwawala M and Jayaratne M: Aegle marmelos (L.) Correa as a potential candidate for treatment of diabetes mellitus: A review. J herbmed Pharmacol 2017; 6(4): 141-7.
- Ozougwu JC: Anti-diabetic effects of Allium cepa (onions) aqueous extracts on alloxan-induced diabetic Rattus novergicus. J Med Plants Res 2011; 5(7): 1134-9.
- Eidi A, Eidi M and Esmaeili E: Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine 2006; 13: 624-9.
- Noor A, Gunasekaran S, Amirtham SM and Vijayalakshmi MA: Antidiabetic activity of Aloe vera and histology of organs in streptozotocin-induced diabetic rats. Curr Sci 2008; 94(8): 1070-6.
- Bordoloi R and Dutta KN: A review on herbs used in the treatment of diabetes mellitus [Internet]. Vol. 2, Journal of Pharmaceutical, Chemical and Biological Sciences. 2014 [cited 2019 Jul 8]. Available from: http://www.jpcbs.info
- Patil P, Patil S, Mane A and Verma S: Antidiabetic activity of alcoholic extract of neem (Azadirachta Indica) root bark prabhakar. Natl J Physiol Pharm Pharmacol 2013; 2(2): 142-6.
- Modak, D: A review: anti-diabetic activity of herbal drugs. PharmaTutor 2015; 3(9): 36-42.
- Manjula S and Ragavan B: Hypoglycemic and hypolipidemic effect of Coccinia indica Wight &Arn in alloxan induced diabetic rats. Anc Sci Life 2007; 27(2): 34-7.
- Gandhi GR, Vanlalhruaia P, Stalin A, Irudayaraj SS, Ignacimuthu S and Paulraj MG: Polyphenols-rich Cyamopsis tetragonoloba (L.) Taub. beans show hypoglycemic and β-cells protective effects in type 2 diabetic rats. Food Chem Toxicol 2014; 66: 358-65.
- Mahajan S, Chauhan P, Mishra M, Yadav D, Debnath M and Prasad G: Antidiabetic potential of Eugenia jambolana ethanolic seed extract: effect on antihyperlipidemic and antioxidant in experimental streptozotocin-induced diabetic rats. Adv Complement & Alternative Med 2018; 2(3): 2637-58.
- Kumar P, Rani S, Arunjyothi B, Chakrapani P and Rojarani A: Evaluation of antidiabetic activity of Gymnema sylvestre and Andrographis paniculata in streptozotocin induced diabetic rats. Int J Pharmacogn Phytochem Res 2017; 9(1): 22-5.
- Madhuri AS and Mohanvelu R: Evaluation of antidiabetic activity of aqueous extract of Mangifera indica leaves in alloxan induced diabetic rats. Biomed Pharmacol J 2017; 10(2): 1029-35.
- Mahmoud MF, El Zahraa El Ashry FZ, El Maraghy NN and Fahmy A: Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats. Pharm Biol 2017; 55(1): 758-65.
- Jayant SK and Srivastava N: Photochemical screening of Ocimum santum leaves and inorganic components and its effects on diabetic rats. . J Diab Clin Stud 2017; 1(1): 001-005.
- Tamboli SB, Sontakke SP and Parsode RB: Study of hypoglycemic activity of Tinospora cordifolia in alloxan induced diabetic rabbits. Int J Basic Clin Pharmacol 2013; 2(5): 559-61.
- Jena S, Jena RC, Bhol R, Agarwal K, Sarangi A and Sahu PK: A comparative study of the anti-oxidative and anti-diabetic potential of in-vitro and in-vivo root and leaf extracts of withania somnifera on streptozotocin induced diabetic rats. Int J Pharm Pharm Sci 2016; 8(10): 85-91.
- Al-Amin ZM, Thomson M, Al-Qattan KK, Peltonen-Shalaby R and Ali M: Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr 2006; 96: 660-66.
- Saini RK, Sivanesan I and Keum YS: Phytochemicals of Moringa oleifera: a review of their nutritional, therapeutic and industrial significance. 3 Biotech 2016; 6(203): 1-14.
- Gopalakrishnan L, Doriya K and Kumar DS: Moringa oleifera: a review on nutritive importance and its medicinal application. Food Sci Hum Wellness 2016; 5(2): 49-56.
- Moringa oleifera: Benifits & Uses 2019. Available from: http://www.liebertpub.com/doi/10.1089/jop.2012.0089
- Gopalakrishnan L, Doriya K and Kumar DS: Moringa oleifera: a review on nutritive importance and its medicinal application. Food Sci Hum Wellness 2016; 5(2): 49-56.
- Rockwood JL, Anderson BG and Casamatta DA: Potential uses of Moringa oleifera and an examination of antibiotic efficacy conferred by oleifera seed and leaf extracts using crude extraction techniques available to underserved indigenous populations. Int J Phytothearpy Res 2013; 3(2): 61-71.
- Fahey JW: Moringa oleifera: A review of the medical evidence for its nutritional, therapeutic, and prophylactic properties. Part 1. Tree life J 2005; 1(5). Available from: https://www.tfljournal.org/article.php/20051201124931586/
- Ragasa YC, Antonio SV and Shen CC: Chemical constituents of Moringa oleifera Seeds. Int J Pharmacogn Phytochem Res 2016; 8(3): 495-8.
- Amabye TG: Chemical compositions and nutritional value of Moringa oleifera available in the market of Mekelle. J Food Nutr Sci 2015; 3(5): 187.
- Saini RK, Sivanesan I and Keum YS: Phytochemicals of Moringa oleifera: a review of their nutritional, therapeutic and industrial significance. 3 Biotech 2016; 6(2): 203.
- Lin H, Zhu H, Tan J, Wang H, Wang Z and Li P: Comparative analysis of chemical constituents of Moringa oleifera leaves from China and India by Ultra-Performance Liquid Chromatography coupled with Quadrupole-Time-of-flight mass spectrometry. Molecules 2019; 24(5). Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 30866537
- Lin H, Zhu H, Tan J, Wang H, Wang Z and Li P: Comparative analysis of chemical constituents of Moringa oleifera Lleaves from China and India by Ultra-Performance Liquid Chromatography Coupled with Quadrupole-Time-Of-Flight Mass Spectrometry. Molecules 2019; 24(5): 942.
- Kamal M: Moringa oleifera The miracle tree [Internet]. [cited 2019 Jul 11]. Available from: http://www.ttiitn.com/M/pci.html
- Saini RK, Shetty NP and Giridhar P: GC-FID/MS Analysis of Fatty Acids in Indian Cultivars of Moringa oleifera: Potential Sources of PUFA. J Am Oil Chem Soc 2014; 91(6): 1029-34.
- Paikra BK, Kumar H, Dhongade J and Gidwani B: Phytochemistry and pharmacology of Moringa oleifera J Pharmacopuncture 2017; 20(3): 190-200.
- Aja PM, Nwachukwu N, Ibiam UA, Igwenyi IO, Offor CE and Orji UO: Chemical constituents of Moringa oleifera leaves and seeds from Abakaliki, Nigeria. Am J Phytomedicine Clin Ther 2014; 2(3): 310-21.
- Basuny AM and Al-Marzouq MA: Biochemical studies on Moringa oleifera seed oil. MOJ Food Process Techno 2016; 2(2): 40-6.
- Aekthammarat D, Pannangpetch P and Tangsucharit P: Moringa oleifera leaf extract lowers high blood pressure by alleviating vascular dysfunction and decreasing oxidative stress in L-NAME hypertensive rats. Phytomedicine 2019; 54: 9-16.
- Khalil WKB, Ghaly IS, Diab KAE and ELmakawy AI: Antitumor activity of Moringa oleifera leaf extract against Ehrlich solid tumor. Int J Pharm 2014; 4(3): 68-82.
- Ijioma SN, Nwaogazi EN, Nwankwo AA, Oshilonya H, Ekeleme CM and Oshilonya LU: Histological exhibition of the gastroprotective effect of Moringa oleifera leaf extract. Comp Clin Path 2018; 27(2): 327-32.
- Toppo R, Roy BK, Gora H, Baxla SL and Kumar P: Hepatoprotective activity of Moringa oleifera against cadmium toxicity in rats. Vet World 2015; 8(4): 537-40
- Alimuddin S and Bonde VN: To evaluate the anti-inflammatory activity of ethanolic leaf extract of Moringa oleifera plant in albino wistar rats Shaikh. Eur J Pharm Med Res 2016; 3(12): 295-7.
- Priya V, Abiramasundari P, Devi GS and Jeyanthi GP: Antibacterial activity of the leaves, bark, seed and flesh of Moringa oleifera. Int J Pharm Sci Res 2011; 2(8): 2045-9.
- Patel P, Patel N, Patel D, Desai S and Meshram D: Phytochemical analysis and antifungal activity of Moringa oleifera. Int J Pharm Pharm Sci 2014; 6(5): 144-7.
- Agrawal SS, Vishal D, Sumeet G, Shekhar C, Ashish N and Parul D: Antifertility activity of ethanol leaf extract of Moringa oleifera Lam in female wistar rats. Indian J Pharm Sci 2018; 80(3): 565-70.
- Yunusa S and Musa A: Evaluation of antidepressant effect of ethanol extract and chloroform fraction of Moringa oleifera (Moringaceae) leaf in mice. J Drug Res Dev 2018; 4(1): 1-6.
- Khan W, Parveen R, Chester K, Parveen S and Ahmad S: Hypoglycemic potential of aqueous extract of Moringa oleifera leaf and in-vivo GC-MS metabolomics. Front Pharmacol 2017; 8(577): 1-16.
- Une HD, Shingane P and Patave TR: A study on the effects of Moringa oleifera pod extract on alloxan induced diabetic rats. Asian J Plant Sci Res 2014; 4(1): 36-41.
- Onyagbodor OA and Aprioku JS: Moringa oleifera leaf extract inhibits diabetogenic effect of alloxan in rats. IOSR Journal of Pharmacy 2017; 7.
- Patel C, Mohammed Ayaz R and Parikh P: Studies on the osteoprotective and antidiabetic activities of Moringa oleifera plant extract. IOSR Journal of Pharmacy 2015; 5.
- Ali FT, Hassan NS and Abdrabou RR: Potential activity of Moringa oleifera leaf extract and some active ingredients against diabetes in rats. Int J Sci Eng Res 2015; 6(5): 1490-1500.
- Mbikay M: Therapeutic potential of Moringa oleifera leaves in chronic hyperglycemia and dyslipidemia: a review. Front Pharmacol 2012; 3: 24.
- Panya T, Chansri N, Sripanidkulchai and Daodee S: Additional antioxidants on the determination of quercetin from Moringa oleifera leaves and variation content from different sources. International Food Research Journal. 2018; 25.
- Jimenez MV, Almatrafi MM and Fernandez ML: Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease. Antioxidants 2017; 6(91): 1-13.
- Ali FT, Hassan NS and Abdrabou RR: Potential activity of Moringa oleifera leaf extract and some active ingredients against diabetes in rats. Int J Sci Eng Res 2015; 6(5): 1490-500.
- Singh A and Navneet: Ethnomedicinal, pharmacological and antimicrobial aspects of Moringa oleifera: a review. The Journal of Phytopharmacology 2018; 7.
How to cite this article:
Sneha, Kaurav M and Kumar S: Efficacy and mechanism of action of Moringa oleifera in diabetes. Int J Pharm Sci & Res 2020; 11(9): 4201-13. doi: 10.13040/IJPSR.0975-8232.11(9).4201-13.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Sneha, M. Kaurav and S. Kumar *
Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Haryana, India.
09 December 2019
24 March 2020
26 March 2020
01 September 2020