Indian medicinal plants with antidiabetic potential: An overview

 

Monika Sahu1, Vinod Kumar2, Veenu Joshi1*

1Center for Basic Sciences, Pt. Ravishankar Shukla University, Raipur-492010.

2Govt. NPG Science College, Raipur.

*Corresponding Author E-mail: vinu.jsh@gmail.com

 

ABSTRACT:

Diabetes Mellitus is the most prevalent metabolic disorder which has made it a major health threat worldwide. The available synthetic drugs for the cure of Diabetes mellitus are associated with high cost, various side effects and several limitations. Medicinal plants are the rich depots of the phytochemicals which can be useful for the treatment of chronic disorders. These plants are the better alternative to chemical drugs causing less or no harm to the body. Several plants are traditionally known for their antidiabetic properties but the detail investigation of their active molecules is required in order to be developed as therapeutic drug. Therefore, the present review aims to provide comprehensive information on various Indian medicinal plants, their constituents and mechanism of action for the cure of diabetes mellitus.

 

KEYWORDS: Antidiabetic, Drug, Medicinal Plants, Phytochemicals, Treatment.

 

 


INTRODUCTION:

Diabetes mellitus is the world‘s fastest growing metabolic disorder, characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and proteins1. It is a global public health threat and is listed as the third major ―killer of mankind, along with cancer and cardiovascular diseases2. Data shows that every one person in six persons with diabetes in the world is from India. It is one of the leading diseases found among the Indian population. The numbers place the country among the top 10 countries for people with diabetes, India coming in at number two with an estimated 77 million diabetics. China leads the list with over 116 million diabetics.  It has been predicted that India will have around 134 million people with diabetes by the year 20453.

 

Diabetes mellitus is a disease in which glucose is not sufficiently metabolized which results in high glucose levels in blood and urine. Cells can starve because glucose is not being metabolized. There are two major forms of this disease – Type 1 and Type 2 diabetes mellitus.

 

Type 1 - insulin-dependent diabetes mellitus, is an autoimmune condition in which body’s own antibodies destroy the beta cells of pancreas which could no longer produce any insulin. It most often occurs in children and young adults. Type 1 diabetes accounts for 5–10% of diabetes. Type 2 is noninsulin-dependent diabetes mellitus also called as adult-onset diabetes. It results due to improper production of insulin or resistance of cells to insulin. Type 2 diabetes accounts for 90–95% of diabetes and thus is the most common form of diabetes4. Type 2 diabetes is nearing epidemic proportions, due to an increased number of elderly people, and a greater prevalence of obesity and sedentary lifestyles.

 

Most diabetic patients rely on expensive chemical drugs that may have various side effects. The present therapies available like oral hypoglycemics (sulfonylurea, metformin and alpha-glucosidase) and insulin have their own limitations. Most hypoglycemic drugs have side effects like severe  hypoglycemia,  lactic  acidosis,  idiosyncratic liver  cell  injury,  permanent  neurological  deficit,  digestive discomfort, headache and dizziness5. Moreover, Diabetes is not a single disease but a group of disorders which affects different organs of the body and thus no particular line of treatment can be followed. The treatment protocol needs a strategy which should be such that it varies from person to person to fulfill individual body requirement6. Since diabetes is a multifaceted disease with an effect on almost all the organs7, there is a need of better therapeutic molecules which are safe and effective alternative to the available synthetic therapeutics of herbal origin with fewer side effects. The present review focuses on the various medicinal plants, their bioactive constituents with antidiabetic potential with mechanism of their action in combating this deadly disorder.

 

Medicinal plants with antidiabetic potential:

India is one of the 12 mega diversity countries in the world with rich deposits of medicinal plant resources. The medicinal value of these plants lies in chemical substances that produce a positive physiological action on the human body8. Since plants synthesize an extremely diverse range of chemical compounds, they represent a great potential for the discovery and development of new pharmaceuticals9. Also, people are again returning back towards herbal medicines that are easily available, involve no or less side effects, and cost effective. About 80% of the world’s population depends on medicinal plants for their health care need10. Over a period of years, various plant based active compounds and its active principles have been analyzed for phytochemicals active against one of the deadly disorder Diabetes. More than 800 plant species with hypoglycemic activity have been examined and identified yet11,12. Still, the search for more plant species with hypoglycemic activity is needed to know more about their particular bioactive molecules and the mechanism of action for the future development of drug. List of plants with antidiabetic activity, their active constituents is presented in table1.


 

Table 1- List of plants with antidiabetic activity

Name of Plant

Common name

Parts of plant used

Constituents

Activity

Acacia arabica

Babool

Seed

Arabin

Initiation of insulin release13

Aegle marmelos

Bael tree

Fruit

alkaloids, Glycosides, Coumarins

Hypoglycemic activity14,15

Allium cepa

Pyaz

Bulb

Vit. A,B,C, allyl propyl-disulfide

Inducing effect for the utilization of glucose16

Allium sativum

Lehsun

Root

Allin, allicin

Antihyperglycemic activity17

Aloe vera

Gwarpatha

Entire  plant

Pseudoprototinosaponin AIII and prototinosaponins

Lowers  Blood sugar and triglyceride levels18

Annona squamosa

Sharifa

Leaves

Squamosamide,  isoquamosin

Hypoglycemic activity19

Areca catechu

supari

Leaves, Seed

Flavonols and tannins, alkaloids

Antihyperglycemic effect20

Azadirachta indica

Neem

Leaves

Nimbidin, nimbosterol, nimbin

Inhibition of glycogenolytic21

Bauhinia variegata

Kachnar

Leaves

Roseoside

Increase insulin secretion22

Beta vulgaris

Chukandar

Leaves

 Saponins, flavonoids

Regenerated beta cells and decrease blood glucose levels23

Brassica juncea

Rai

Leaves and seeds

Glycoside singrin, protein, fixed oil

Act as food adjuvants for patients of diabetes24

Caesalpinia bonducella

Karanja

Seed kernel

Fatty oil

Acts as scavenger of free radicals25

Camellia sinensis

Green tea

Leaves

Polyphenolic constituents, Epigallocatechin gallate

Enhance insulin release26,27

Capsicum frutescens

Mirch

Entire plant

Capsaicin, pritein

Enhance insulin release and decrease in binding of insulin on the insulin receptor28,29

Carica    papaya

Papita

Fruit, leaves

Alkaloids,  flavonoids, tannins

Enhance insulin release30,31

Catharanthus roses

Sadabahar

Leaves, flower

Indole alkaloid, vincristine, vinblastin

Enhance glucose metabolism32

Cinnamon zeylanicum

Dalchini

Bark, leaves

Alkaloids, proteins, tannins, cardiac glycosides and saponins.

Shows the insulin potentiating activity. Thus it plays a role in in-vivo glucose control and insulin sensitivity in humans33

Citrus sinensis

Mosambi

Fruit

Flavonoids, saponins, terpenes

Decrease blood glucose level34

Coccinia grandis

Kundru

Fruit, leaves

β- Amyrin Acetate, Cucurbitacin B, Alkaloids Cephalandrins A and B

Decrease Blood sugar level35

Coriandrum sativum

 Dhania

Seed

Tannins, essential oils, alkaloids, phenolics, flavonoids

Decrease blood sugar level36,37

Cuminum

cyminum

Zeera

 

Seed

Anthraquinone, coumarin, flavonoid, glycoside, protein, resin, saponin, tannin and steroid

Oral and administrtion                                       of these seeds shows hypoglycemic activity38

Curcuma longa

Haldi

Rhizome

Curcumin (diferu curcuminoids atlantone, loylmethane),

Induced insulin secretion. In bloodstream, inhibit glucose synthesis39

 Emblica   officinalis

Amla

Fruit

Quercitin, Nicotinic acid, vitamin C,  vitamin B

Improve glucose utilization and maintain glucose homeostasis, stimulate pancreatic insulin secretion40

Ephedra distachya

Somlatha

Whole plant

Ephedran and glycan

Regenerate atrophied pancreatic islets, restore the secretion of insulin41,42

Eucalyptus globulus

Eucalyptus

Leaves

Cineol

Enhance insulin release43

Ficus bengalensis

Bargad

Bark

Tannin, Leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside

Increase serum insulin18,27

Ficus religiosa

Peepal

Entire plant

Tannin

Initiate insulin secretion44

Glycyrrhizae uralensis

Mulahatti

Root

Glycyrrhetinic acid, dihydroxy gymnemic triacetate, Pioglitazone

glycyrrhizin

Enhace the insulin-stimulated glucose uptake through peroxisome proliferation-activated receptor activation 45

Hibiscus rosa sinesis

Gudhal (china rose)

Entire plant

Vit.B, C, fat

Induce insulin secretion46

Ipomoea batata

Shakarkand

Tubers

 Glycoproteins

Reduces insulin resistance47

Lupinus albus

Turmas

Seed

Alkaloid, asparagines, fatty oil.

Decrease level of glucose in the serum48

Mangifera indica

Mango

Seed, leaves

Flavonoid, Phenolic constituents

Hypoglycemic activity49

Momordica charantia

Karela

Fruit

Ascorbic acid, momordicine, charantin, and galactose-binding lectin alkaloid

Lower blood glucose level50,51

Morus alba

Shehtut

Leaves, Fruit

Moracin, Steppogenin

Decrease Blood sugar level52

Murraya koeingii

Curry leaf

Leaves

Alkaloid

Glycogenesis, reduce glycogenolysis and gluconeogenesis53

Musa sapientum

Banana

Flower

 NA

Lower blood glucose level54,55

Ocimum sanctum

Tulsi

Leaves

Phenol, aldehyde, alkaloid

Decrease blood sugar level56

Phyllanthus amarus

Bhui amla

Entire plant

Phyllanthin

Lower serum glucose57,58

Piper nigrum

Kali mirch

Root, Leaves, Seed

Piperine,  alkamide piptigrines,

It is useful for the decrease in blood cholesterol and blood glucose concentration59

Psidium guajava

Guava

Leaves

Strictinin, isostrictinin and pedunculagin

Decrease blood glucose levels60,61

Punica granatum

Anar

Seed

Protein, tannin, gallic acid, vit. C, punicalagin

Lower blood sugar level62

Rauwolfia serpentina

Sarpgandha

Root

Alkaloids , reserpine

Antihyperglycemic activity63

Stevia rebaudiana

Madhupatra

leaves

Stevioside, steviol

Insulinotropic and glucaganostatic effect64,65

Swertia chirayita

Chirata

Whole plant

Swerchirin

Lower blood glucose by stimulating insulin18

Syzygium cumini

Jamun

Seed

Flavonoids, anthocyanins

Reduce blood glucose level66

Tinospora cordifolia

Giloe

Stem

 Berberine

Antihyperglycemic properties67

Trigonella foenum-graecum

Methi

Seed

Fixed oil, protein 4-hydroxyleucine and hydroxyisoleucine

Lower the concentration of glucose in the blood68,69,70,71

Withania somnifera

Ashwagandha

Root

Somnine, withanolides

Lower blood sugar level72

Zingiber officinale

Adrak

Rhizome

Sesquiterpene

Reduce fasting-glucose level and enhance insulin level73

 

Table 2: Various secondary metabolites, their mechanism of action and bioactives responsible for antidiabetic properties

Constituents

Actions

Example bioactives

Alkaloids

Reduces transportation of glucose through the intestinal epithelium and inhibits an enzyme alpha- glucosidase.

Berberine67, Aegiline15, Mycaminose75, Catharanthine76

Imidazoline compounds

Insulin secretagogues activity in glucose-dependent manner, decrease the level of glucose in the blood and enhance glucose tolerance77

 

Saponin

Induces insulin secretion. Inhibits glucose synthesis, enhances the endogenous insulin release, inhibits a-glycosidase activity

Gymnemasaponins, Gymnemasides78, Ginsenoside79

Dietary fibers

Adsorbs glucose, reduces glucose diffusion and blocks alpha-amylase activity80

 

Flavonoids

Represses the glucose level, decreases plasma cholesterol and triglycerides considerably. By increasing the secretion of insulin from pancreatic islets, enhances the activity of an enzyme hepatic glucokinase

Quercetin81,  Strictinin60

Phenols

Decreases blood glucose levels, Reduces plasma glucose levels 

Trigonelline82, Gallic acid83, Gymnemic acid84

Glycosides

Decreases Hb1Ac level, triglyceride level and fatty acid synthase activity, inhibits a-glucosidase activity

Kaempferol 3-O-ß-D-glucopyranosy85, Casuarine 6-O-glucoside86

Triterpenes

Decreases blood glucose level, stimulates insulin secretion

Bacosine87, Stevioside4 , Alpha amyrin88

Polysaccharides

Decrease the glucose level in the blood and enhances glucose tolerance

Turmerin39, Momordicosides89, Ginseng polypeptides90

 


 

Phytoconstituents and mechanism of action:

Huge medicinal plant resource is a natural factory which generates variety of phytomolecules with magical qualities to cure any kind of ailment. These phytomolecules are the secondary metabolites which serve as defense molecules of the plants. More than 13,000 secondary metabolites have been isolated from the medicinal plants74. Still there is a need to understand the chemical properties and mechanism of action of these molecules for their better application in the cure of human ailments. The lead molecules of the plants which are responsible for profound antidiabetic potential can be classified into following groups of phytomolecules- alkaloids, polysaccharides, saponins, flavonoids, glycosides, phenolics, triterpenes etc. The mechanism of their action and some example bioactives are presented in table 2.

 

Common plants useful in diabetes mellitus

Several plants which are commonly used ingredients of daily food like onion, cinnamon, garlic, fenugreek, turmeric etc. are also documented to possess potential hypoglycemic property.

 

Allium cepa- It is also known as Onion. It exhibits hypoglycemic activity by stimulating insulin production. The major phytoconstituent in onion allyl propyl disulfide91 have antidiabetic properties. It is also expected that onions extracts like glibenclamide may induce hypoglycaemia by stimulating insulin release and action, thereby enhancing cellular uptake and utilization of glucose in rats. It remains unclear whether the cellular glucose uptake may be due to increased insulin secretion or decreased insulin degradation rate92.

 

Allium sativum- It is also called as Garlic and “Lahsun” in hindi. It is essential dietary spice component cultivated throughout India and is known for various uses. It has the capacity to stimulate insulin production by pancreatic beta cells to control diabetes. The studies showed that garlic can reduce blood glucose levels and increase plasma insulin in diabetic rats, mice, rats and rabbits93,94. Garlic contains allicin compound which has antioxidant effects and increases the amount of catalase and glutathione peroxidase and a precursor of allicin-S-allyl cystein sulphoxide stimulate the insulin secretion in isolated beta-cells in normal rats95,70.

 

Brassica nigra- It is also known as Mustard or rhai. Oral administration of mustard exerts considerable hypoglycemic activity. The hypoglycemic effect is due to the stimulation of glycogen synthetase and the repression of various glycogenic enzymes. Further, in one study the hypoglycemic effect of the seed extract of B. juncea was attributed to stimulation of glycogen synthesis leading to increase in hepatic glycogen content and suppression of glycogen phosphorylase and other gluconeogenic enzymes96.

 

Cinnamomum zeylanicum and C. verum- Cinnamon is usually called as “Dalchini” in Hindi. Phenolic extract of cinnamon shows the insulin potentiating activity and in-vivo glucose control effects in humans. Also, oral administration of its ethanolic extract produced a dose dependent decrease in blood glucose levels in alloxan induced rats97. While another species (C. verum) exhibits hypoglycemic activity by increasing the activity of insulin. It also shows an increase in lipid metabolism. According to another study, Cinnamon hypoglycaemic activity may be recognized to numerous mechanisms of action, comprising the stimulation of insulin release and insulin receptor signaling, the activation and regulation of enzymes involved in carbohydrate metabolism, glycolysis, gluconeogenesis, stimulation of cellular glucose uptake and increased glucose transporter-4 receptor synthesis98. Another study shown that cinnamtannin B1, a proanthocyanidin isolated from the stem bark of ceylon cinnamon, stimulates the phosphorylation of the insulin receptor β-subunit on adipocytes as well as other insulin receptors99,34.

 

Coccinia grandis- It is also known as kundru. Oral administration of C. grandis leaves extract exerted both acute and long term antihyperglycemic effects in healthy, alloxan induced and streptozotocin induced diabetic rats100.

 

Cuminum cyminum- It is usually called as “Jeera”. Oral administration of cumin seeds has been reported to possess hypoglycemic activity. Also the ethanolic extract of cumin reduces the glycemic levels. Plasma levels and elevates insulin levels in diabetic rats. Moreover, in another study analysis of its essential oils showed major presence of α-pinene which exhibited mild antidiabetic activity101.

 

Curcuma longa- It is also called as turmeric. It is responsible for the decrease in blood glucose levels by reducing the effect of enzymes responsible for converting dietary carbohydrates into glucose. Ferulic acid or 4-hydroxy-3-methoxy-cinnamic acid found in turmeric have hypoglycemic properties. Some ferulic acid-derived amide compound has evidence for insulin secretion from pancreatic beta cells. Curcumin and its analogues have a mechanism of action similar to that of thiazolidinedione, an anti-diabetic drug, through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation102. Thus, curcumin may be effective in the regulation of glycaemia and lipidaemia103.

 

Murraya koenigii- This plant is commonly called as Curry plant. It is used as a spice in food for taste and odor. Its aqueous extract has been reported to possess effective hypoglycemic property. It has also been reported to reduce blood cholesterol levels. In another study its ethanolic extract showed a significant reduction in blood glucose level in Nicotinamide-Streptozotocin induced diabetic rats53.

 

Phyllanthus niruri- The methanolic extract of aerial parts lowered blood glucose, suppressed postprandial rise in blood glucose following a glucose meal, reduced hemoglobin glycation and increased absolute and relative weights as well as glycogen content of liver in diabetic rats. The extract also inhibited α-amylase and α-glucosidase activities104 in in vitro studies.

 

Phyllanthus amarus- It is also known as bhui amla. It has been reported that ethanolic extract of its leaves results in drastic reduction of the blood glucose levels and significant recovery in body weight of diabetic mice105.

 

Piper nigrum and P. longum- It is also known as black pepper. It is used in various antidiabetic polyherbal formulations. Piperine, the active alkaloid of Pepper has been tested for its glucose regulatory efficacy and daily oral administration for 2 weeks lowered blood glucose concentrations and hepatic glucose-6-phosphatase enzyme activity. It has also reported to possess alpha-glucosidase, alpha-amylase and aldose reductase inhibitory activity59. In another study it is also reported to reduce hyperlipidemia, increase serum insulin levels and improve liver functions in diabetic rats106.

 

Punica granatum- It is commonly known as pomegranate. It has been reported that when alloxan-diabetic male wistar rats were administered with pomegranate fruits aqueous extract in different doses showed significant reduction in fasting blood107. In another study ethanolic extract of leaves of P. granatum were reported to show antidiabetic and antihyperlipidemic effects in alloxan-induced type 2 diabetes mellitus albino rats108.

 

Syzigium cumini- It is also known as jamun. It has been reported that ethyl acetate and methanol extract produced significant reduction in blood glucose level. In another study, jamun fruit and seed's ethanolic extracts resulted in the reduction of the blood glucose level, improvement in insulin levels in hyperglycemic rats. While the improvement was much more significant in seed extract in comparison to the fruit extract66.

 

Trigonella foneum graecum- It is also called as Fenugreek or Methi. It is used in food and medicine. It is a good source of iron, phosphorus, sulfur etc. It is a hypoglycemic agent used in traditional Indian medicinal practice. Methi extract prepared with different parts of the plant shows hypoglycemic activity. An amino acid ‘4-hydroxyleucine’ is a component of fenugreek which increases glucose-induced-insulin resistance and reduces the blood glucose level. Also the administration of methi seed powder solution had pronounced effects in improving lipid metabolism in type II diabetic patients with no adverse effects68.

 

Zingiber officinale- It is also known as Ginger and is a spice which possesses hypoglycemic activity. Studies reported its significant antidiabetic activity on type I diabetes. It also increases insulin level and decreases fasting glucose levels in diabetic rats through improving pancreatic beta-cells activity, increasing insulin sensitivity and enhancing peripheral utilization of glucose. Other mechanisms include improving the glycogen regulatory enzyme expression in liver and inhibiting carbohydrate metabolizing enzymes109.

 

CONCLUSION:

Medicinal plants have been used for the treatment of various ailments since ancient times. These plants are rich source of bioactive molecules which can be used to develop new drugs. There are several phytochemicals which play important role in lowering blood glucose levels with different mechanisms of action. But still there is a need to explore these phytomolecules for their safety and toxicity to be used as drug.

 

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Received on 04.08.2020            Modified on 11.09.2020

Accepted on 05.10.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(4):2328-2335.

DOI: 10.52711/0974-360X.2021.00411