Review Articles

2019  |  Vol: 5(3)  |  Issue: 3 (May- June)  |  https://doi.org/10.31024/ajpp.2019.5.3.1
Role of herbs in the amelioration of memory loss due to diabetes mellitus: A brief review

Poonam1Manjusha Choudhary1*, Dinesh Kumar1, Vikas Budhwar2

1Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136118, Haryana, India

2Department of Pharmaceutical Sciences, Maharishi Dayanand University Rohtak-124001, India

*Address for Corresponding Author:

Manjusha Choudhary

Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136118, Haryana, India


Abstract

Present review gives emphasis on the role of herbal plant and polyherbal formulation in diabetes and associated CNS complication. Diabetes mellitus is categorized as a gathering of metabolic syndromes described via high blood sugar level (hyperglycaemia) and disturbances of carbohydrates and protein metabolism caused by deficiency of insulin release or insulin resistance or both. It is the most well-known endocrine issue and for the most part connected with high danger of delivering changes in different organs of the body, for example, kidney, liver, mind and heart. The negative impacts of diabetes on the focal sensory system have been accounted as a progression of neurochemical, neurophysiological and basic irregularities. Cognitive disturbances have likewise been perceived in diabetic patients. Diabetes additionally appears twofold the likelihood of building up Alzheimer's diseases and memory shortfalls. A few factors, for example, hyperglycaemia, expanded oxidative stress, brokenness of cholinergic framework and an irregularity in nitric oxide (NO) generation have been involved in CNS complication of diabetes. There has been expanded logical enthusiasm for therapeutic plants that have been accounted for to be utilized customarily to treat diabetes and complication in people. This is because of expanded adequacy of new plant-determined medications, developing interests in herbal medication and the presence of adverse reactions of synthetic drug. Herbal plants are useful in treatment of diabetes and associated CNS complication due to their antioxidant, antihyperglycemic and anti-inflammatory activity. Contrasted with the single herb, the polyherbal formulation has better and broadened restorative potential since it contain blend of different plant and indicated viability because of combined impact of these ingredients. In this way, present review provide information about the traditional medicinal antidiabetic plants, antidiabetic plants with CNS ameliorating effect, isolated constituents and polyherbal formulation in treatment of diabetes. And give peruses and specialists the essential ideas of understanding the neuroprotective and hypoglycemic impacts of herbal medicinal plants.

Keywords: Antidiabetic, hyperglycaemia, neuroprotective, insulin, antioxidant, anti-inflammatory


Introduction

Diabetes mellitus (DM) is ordered as a gathering of metabolic disorders described by high  blood glucose level (hyperglycaemia) and aggravations of starches and protein digestion caused by insufficiency of insulin discharge or insulin resistance or both (Sharifzadeh M et al., 2017; Afolayan et al., 2010). It is the most well-known endocrine issue and connected with high danger of delivering changes in different organs of the body, for example, kidney, liver, brain and heart (Nishikawa et al., 2000). Chronic hyperglycemia influences the focal sensory system and upgrades the likelihood of creating unsettling influences, for example, neurobehavioral changes, adjusted neuroendocrine capacities and neurotransmitter changes and hence, every one of these progressions were lead to end organ destruction (Brands et al., 2004). Occurrence of each kind of diabetes shifts all through the world day by day. It was evaluated that in 2017 there are 451 million (age 18-99 years) individuals with diabetes around the world. These figures were relied upon to increment to 693 million by 2045 (Cho et al., 2018). In India, around 20 million people groups are influenced by diabetes mellitus and this figure is expected to reach to 57 million by 2025 (Arvind et al., 2002; Seema et al., 2014).

Unending hyperglycemia in diabetes prompts an assortment of CNS entanglements. Neurological shortages in diabetes have been seen in both the peripheral and focal sensory system. Negative impacts of diabetes on the focal sensory system have been accounted for as a progression of neurochemical, neurophysiological and basic variations from the norm. Intellectual brokenness has likewise been perceived in diabetic patients (Tirgar et al., 2010; Sutalangka C et al., 2017). This in turn, leads to diabetic complications which may further enhance the diabetic conditions such as neurological, cardiovascular, renal and visual complications etc (Brownlee et al., 2001). In the event of diabetic patient, subjective brokenness has likewise been accounted for because of unending hyperglycaemia showed as shortfalls in learning and memory, diminished mental adaptability (Brands et al., 2007; Harten et al., 2006). Diabetic encephalopathy is also known as malfunction of brain. The complications associated with high blood glucose level include impaired spatial cognitive functions, memory loss, dementia, coma, seizures and death. Persistent high blood glucose level causes destruction of neurons (Chen et al., 2011). Chances of having Alzheimer’s diseases and memory deficits are more in diabetes (Biessels et al., 2006). For example, in case of STZ induced diabetic rats cognitive impairments, memory deficits and passive avoidance learning have also been reported (Kuhad et al., 2008; Kucukatay et al., 2007). Hyperglycaemia initiated by diabetes is ordinarily connected with improved generation of free radicals and receptive oxygen species or hindered antioxidant defences in various areas of the mind (Mastrocola et al., 2005). Synthetic drugs (Table 1) such as insulin preparations, sulfonylureas, bigaunides etc. are currently available for the better management of DM. In spite of expected advancement made in the management of DM utilizing synthetic drugs, look for the natural prescription still proceeds because of antagonistic impacts of these customary medications (Mohammad  et al., 2013).

Types of Diabetes Mellitus (DM)

Diabetes is classified into two major categories i.e., insulin dependent diabetes mellitus or juvenile onset IDDM (Type-1 diabetes) and non-insulin dependent diabetes mellitus or adult onset NIDDM (Type-2 diabetes). Type-1 diabetes occurs due to an autoimmune destruction of beta cells (Islets of Langerhans present in pancreas) or any other unknown reason leading to absolute decrease in insulin secretion or insulin deficiency. In this kind of diabetes, flowing insulin level is low because of immune system pulverization of beta cells by body’s own imuune system. Based on etiological factor, it has been additionally arranged into immune mediated and idiopathic types. In case of immune intervened DM, cell-mediated immune system decimation of beta cells happens by antigen counter acting agent response. Though in the event of idiopathic type-1, no counter acting agent aginst beta cell has been demonstrated (Wais et al., 2012). This type of diabetes is not connected with Histocampatibility antigen and absolutely inherited. While type 2 diabetes (T2DM) occours because of insulin obstruction and by dynamic hindrance of insulin discharge by pancreatic β cells. Insulin is secreted by β-cells of pancreas to maintain normal range of glucose in the blood. Generally, both types of diabetes have similar symptoms but they vary in degree and developement. There are some basic manifestations generally connected with diabetic patients, for example, blurry visions, polydipsia (a considerable measure drinking), fatigue, polyuria (a lot urine), polyphagia (a lot eating), weight reduction etc (Bharti et al., 2018). Diabetic Ketoacidosis (body produces abundance measure of blood acids normally ketone bodies found in the blood) is the real side effect of type 1 diabetes mellitus and caused by tireless hyperglycemic state and portrayed by nausea, vomiting and abnormal state of ketone bodies in blood (Ali et al., 2011).

Etiology & Pathogenesis of Diabetes Mellitus

Type-1 diabetes mellitus (IDDM) involves autoimmune destruction of beta cells by its own body system. Pathogenesis of type 1 involves environmental factors that may activate autoimmune destruction of beta cell (antigen-antibody reaction) in genetically susceptible individuals, resulting in deficiency in insulin secretion and hence leads to a state of hyperglycemia (Harrison et al., 1999). Pathogenesis of type 2 diabetes mellitus (NIDDM) includes both insulin obstruction and impeded insulin discharge for the most part connected with obesity because of the arrival of free unsaturated fats (FFA) and incendiary cytokines by fat tissue. Beta cell dysfunction results in impaired secretion of insulin in the body. Insullin resistance is defined as a condition in which body produces enough insulin but body tissues show resistance to the insulin action, resulting in high blood glucose level (down regulation of insulin receptor). Instabilities of lipids metabolism in the body lead to expansion of insulin resistance (Ragheb et al., 2011) as mentioned in figure 1.

Figure 1. Chemical structure of isolated constituents having antidiabetic activity

 

Despite appreciable progress made in the management of DM using synthetic drugs, search for the herbal medicine still continues due to adverse effects of these conventional drugs. Synthetic drugs (Table 1) such as insulin preparations, sulfonylureas, bigaunides etc. are currently available for the better management of DM (Mohammad et al., 2013). Treatment of diabetes and related intricacies is more troublesome because of the absence of medications with security and viability. Despite the fact that a few medications are not capable for managed clinical, biochemical and histological fix. Unexpectedly, the herbal drugs and plant based pharmaceutical have developed broad significance around the world, for the most part because of higher security, less number of antagonistic impacts, effective cost and consistent blood glucose lowering capacity and also shown effectiveness in treatment of diabetes related complications (Modak et al., 2007). Hence, in the developed countries, use of herbal drugs and plant based formulations has been increased due to the beneficial effect of these preparations in comparision with synthetic drugs (Seyed et al., 2015).  Bioactive consistuents of herbal drugs such as alkaloids, peptidoglycan, glycosides, steroids, glycopeptides, terpenoides, amino acid, guinindine and inorganic ions etc. have also gained effectiveness in the treatment of DM and associated complications. According to ethno-botanical survey, there are about 800 plants which have shown antidiabetic potential. Bioactive consistuents of natural medications, for example, alkaloids, peptidoglycan, glycosides, steroids, glycopeptides, terpenoides, amino acid, guinindine and inorganic particles and so on have additionally picked up adequacy in the treatment of DM and related complications. As per ethno-plant study, there are around 800 plants which have demonstrated antidiabetic potential. Thus, many plants and plants based medicines alone and in combination have been used for diabetes and its management (Alarcon et al., 1998). Medicinal plants used in treatment of diabetes and antidiabetic plants ameliorating CNS functions have been listed in Table 2 and 3 (Kiritikar et al., 1991; Nandkarni et al., 1976).

Table 1. Currently available synthetic antidiabetic drugs along with side effects

Class of drug

Name of drug

Adverse effects

Insulin preparations

rapid or short acting (insulin lispro, insulin aspart, semilente) Intermediate acting (lente) slow or long acting include protamine, zinc insulin, insulin glargine

Hypoglycaemia is the most common side effect of insulin glargine

Meglitinides

Repaglinide

Nateglinide

Weight gain, Arthralgia

  Dyspepsia

Sulfonylureas

Tolbutamide, chlorpropamide

Glibenclamide, glimepride

Hypoglycaemia, weight gain

Bigaunides

Metformin

Phenformin

Git disturbances, kidney complications

Thiazolidinedione’s

Rosiglitazone

Pioglitazone

Weight gain, fluid retention

α-glucosidase inhibitors

Acarbose, miglitol

Abdominal discomfort, loose stool

Table 2. List of medicinal plants traditionally used to treat diabetes

S. No.

Name of plants

Family

Common name

Parts used

1.

Acacia arabica  Willd.

Mimosaceae

Babul, Kikar

B

2.

Acacia senegal  Willd.

Mimosaceae

Gum acacia, Kher

G

3.

Aconitum ferox Wall.

Ranunculaceae

Indian aconite

TR

4.

Alpinia galangal  Willd.

Zingiberaceae 

Blue ginger

Rh, F

5.

Anacylus  pyrethrum Linn.

Asteraceae

Mount atlas daisy

R

6.

Andropogen  muricatus Linn.

Poaceae

Beard grass

R

7.

Arachis hypogaea Linn.              

Papilionaceae

Peanut

S

8.

Benincasa cerifera Savi.

Cucurbitaceae

Wax gourd

S, FJ

9.

Casearia esculent Roxb.

Samydaceae

Chinese salacia

R, B

10.

Cassia fistula Linn.

Caesalpiniaceae

Golden rain tree

Pu

11.

Cephalandra indica Linn.

Cucurbitaceae

Kundru ki bail

L, RB, F

12.

Citrus aurantium Linn.

Rutaceae

Bitter orange

F

13.

Cocculus cordifolius DC.

Menispermaceae

Moonseed

S, L, R

14.

Eleusine coracana Gaertn.

Poaceae

Finger millet

S

15.

Emblica officinalis Linn.

Euphorbiaceae

Anwla

F, L , R , S

16.

Eriodendron afractuosum Linn.

Bombacace

White silk cotton tree

G

17.

Erythrina indica Lam.

Papilionaceae

Indian coral tree

B, L, J

18.

Eugenia  jambolana Lam.

Myrtaceae

Java plum, Black plum

F, L, S, B

19.

Ficus bengalensis Linn.

Moraceae

Banyan

B

20.

Geranium wallichianum Oliv.

Geraniaceae

Lal jari

RH

21.

Gymnema sylvestre Retz.

Asclepiadaceae

Gurmar

R, L

22.

Hemidesmus indicus Linn.

Asclepiadaceae

Indian Sarsaparilla, Anantamul

R, RB

23.

Hydrocotyle asiatica Linn.

Umbelliferae

Indian Pennywort

WP, L, F

24.

Juneperus communi  Linn.

Coniferae

Juniper

F

25.

Linaria cirrhosa Linn.

Scrophulariaceae

Toadflax

WP

26.

Linaria ramosissima Wall.

Scrophulariaceae

Linaria

WP

27.

Melia azadirachta Linn.

Meliaceae

China berry tree

WP, RB, L

28.

Musa sapientum var.syalvesteris.

Musaceae

Banana

F, L, S

29.

Nymphaea lotus Linn.

Nymphaeceae

Blue lotus

S, F

30.

Orchis mascula Linn.

Orchidaceae

Orchis

RP

31.

Oryza sativa Linn.

Gramineae

Rice

WP

32.

Pandanus adoratissimus Willd.

Pandanaceae

Kewda

R

33.

Papaver somniferum Linn.

Papaveraceae

Opium poppy

C, P, S

34.

Phaseolus roxburgii Linn.

Papilionaceae

Vigna mango

WP

35.

Phyllanthus niruri Linn.

Phyllanthaceae

Gale of the wind

WP

36.

Physalis alkekenji Linn.

Solanaceae

Strawberry groundcherry

WP

37.

Prunus amygdalus Baill.

Rosaceae

Sweet  almond

S

38.

Psidium guyava Linn.

Myrtaceae

   Guava

B, F, L

39.

Rourea santaloides Gaertn.

Connaraceae

Vardhara Mool

R

40.

Striga orboanchoides Benth.

Scrophulariaceae

Witchweed

R

41.

Terminalia chebula Retz.

Comberetaceae

Myrobalan

F

42.

Tribulus terrestris Linn.

Zygophyllaceae

Bindii

F, R, WP

43.

Trigonella foenum graecum Linn

Papilionaceae

Fenugreek

S, L

44.

Vitis vinifera Linn

Vitaceae

Grape vine

F, L

45.

Tinospora cordifolia Willd.

Menispermaceae

guduchi, giloy

SJ

46.

Ceiba pentandra Linn.

Bombaceae

kapok, white silk cotton tree

R

47.

Boswellia serrata Roxb.

Burseraceae

Indian Olibanum

G

48.

Sesbania aegyptiaca Pers.

Leguminosae

Sesbania

R

49.

Pongamia glabra Vent.

Leguminosae

Karanj

F

50.

Cassia sophera Linn.

Fabaceae

Kasaundi

B

51.

Cassia auriculata Linn.

Fabaceae

Matura tea tree

F

52.

Cassia glauca Linn.

Fabaceae

Cassia glauca

B, L

53.

Acacia arabica Willd.

Fabaceae

Babool

L, G

54.

Acacia Senegal Willd.

Fabaceae

Gum acacia Kher

G

55.

Pithecellobium  bigeminum Linn

Fabaceae

Kalitiya

S

56.

Rhizophora mucronata Lam.

Rhizophoraceae

Red mangrove

B

57.

Kandelia rheedii Linn.

Rhizophoraceae

Pisang pisang

B

58.

Eugenia jambolana Linn.

Myrtaceae

Java plum

S

59.

Casearia esculenta Roxb.

Salicaceae

Saptrangi

R

60.

Coccina indica

Cucurbtaceae

Baby watermelon

WP

61.

Jasminum officanale Linn.

Oleaceae

Jasmine

F

62.

Strychnos potaorum Linn.

Loganiaceae

Clearning nut tree

F, S

63.

Premna integrifolia Linn.

Verbenaceae

Agia, Arni

R

64.

Actinodaphne hookeri Meissn.

Lauraceae

Pisa

L

65.

Ficus bengalensis Linn.

Moraceae

Bar

B

66.

Ficus glomerata Roxb. 

Moraceae 

Cluster fig  tree

R

67.

Alpinia galangal Roxb.

Zingiberaceae

Thai ginger

Rh

68.

Musa sapientum Linn.

Musaceae

Banana

R, F

69.

Borassus flabellifer Linn.

Arecaceae

Palm tree

WP

Abbreviation used: Type of part used: Rh-Rhizome; SB-Stem bark; B-Bark; L-Leaves; S-Seeds; R-Root; WP-Whole plant; F-fruit; ST-Stem; Po-Pods; P-Petals; C-Capsules; TR-Tuberous Root; RJ-Root juice; FJ-Fruit Juice; RB-Root bark; Pu- Pulp; G-Gum

Plants with Antidiabetic and CNS activity

Zingiber officinale Rosace [ZO]

ZO is commonly known as Ginger; belonging to family Zingiberaceae. Ginger and its active constituent such as gingerol also exhibit hypoglycaemic effect and play a significant role in controlling of diabetes related complications (Wattanathorn et al., 2011). A study on antidiabetic activity showed that administration of ethanolic extract of ginger by oral route at a dose of 200 mg/kg significantly decreased fasting blood glucose, cholesterol, triglycerides level in STZ induced diabetic rats (Bhandari et al., 2005). In another study it has been investigated that ginger (500 mg/kg/day) showed neuroprotective effect in the brain of streptozotocin induced diabetic rats via reducing oxidative stress and reducing AChE expression (EL- Akabawy et al., 2014). Recent evidence shows that ginger has neuroprotective effect by increasing brain antioxidant level and reducing the malondialdehyde (MDA) level. In case of diabetic rats, a marked decrease in activities of antioxidant enzymes such as catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase were observed. These results provide signal for the neuroprotective effect of ginger on CNS and in treatment of diabetes related central nervous system complications (Kondeti et al., 2011).

Embelica officinalis Linn. [EO]               

Embelica officinalis Linn. (Euphorbiaceae) is commonly known as Indian Gooseberry or Amla. The plant parts such as fruits, roots and leaves are commonly used as important herbal medicines in Unani and Ayurvedic system of medicines. Various studies showed that fruit of EO have potent antioxidant, anti-inflammatory, hepatoprotective and antiulcer property. It is also used as stimulant for the brain in Unani system of medicine. It is the main ingredient of chyawanprash that affords protection to brain and increases coordination and memory (Vasudevan et al., 2007). Earlier study demonstrated that upon oral administration of hydro-methanolic leaves extract in STZ induced diabetic rats, hypoglycaemic effect was observed on various doses (100-400 mg/kg b.w.). The extract also helps in inhibition of diabetic complications by its antioxidant potential (Nain et al., 2012). It has also been studied that EO and its active constituents such as gallic acid, ellagic acid possess antidiabetic effect and avoid diabetic complications through their antioxidant, free radical scavenging potential (Tirgar et al., 2010).

Cyperus rotundus Linn. [CR]

A study showed that Cyperus rotundus Linn. (Cyperaceae) exhibits neuroprotective and cognitive enhancing effects. Its chemical constituent such as quercetin, tannins, starch, gallic acid and p-coumaric acid are reported to produce antioxidant, neuroprotective, anticholinesterase activity (AchEI) and memory enhancing effect (Kilani et al., 2014). It has also been explored that administration of ethanolic extract of CR rhizomes at doses of 250 and 500 mg/kg b.w. possess antidiabetic activity (Sutalangka et al., 2017).

Alpinia galangal Willd. [AG]

Alpinia galangal [AG] belonging to family Zingiberaceae, is commonly known as Blue ginger. Prior examination reveales that AG indicates neuroprotective impact by diminishing free radicals generation and expanding action of antioxidant enzymes on odministration of extract at 200 and 400 mg/kg for 14 (Hanish  et al., 2011). Methanol and aqueous extracts of AG rhizome significantly reduce the blood glucose levels (Akhtar et al., 2002). Further, oral administration of methanol concentrate of AG (200 and 400 mg/kg) in Streptozotocin induced diabetic rats was compelling in controlling blood glucose levels and advancement lipid profile in diabetic rats (Verma et al., 2015).

Terminalia Chebula Retz. [TC]

Terminalia Chebula Retz. (Comberetaceae) is commonly known as myrobalan. Active constituent (chebulic acid) from the fruit of TC exhibits antihyperglycemic effect on oral administration at a dose of 100 mg/kg b.w. (Huang et al., 2012). It has also been explored that hydro-alcoholic fruit extract of TC at a dose of (250, 500 and 1000 mg/kg) in wistar rats, exhibits antioxidant, anticonvulsant and protective effect against cognitive impairment (Kumar et al., 2018).

Mangifera indica Linn. (MI)

Mangifera indica (Anacardiaceae) is commonly known as mango. Its fruit extract upon oral administration in male wistar rats (180-200 g) at various doses 15, 50 and 200 mg/kg b.w. exhibited protective effect against mild cognitive impairments. Oxidative stress also play important role in pathology of cognitive impairement. Thus, result gives suggestion for the potential protective effect against oxidative stress which in turn improves memory (Areekul et al., 2014). It has also been inspected that MI exhibits antidiabetic effect in STZ induced diabetic rats due to presence of flavonoids and phenolic acid (Irondi et al., 2016).

Centella asiatica Linn. [CA]

CA (Umbelliferae) is most commonly known as Indian pennywort. Recent, study reveales that its active constituent (asiatic acid) possesses neuroprotective effect in aluminium chloride induced rat model of Alzheimer’s diseases (Ahmad et al., 2018). It has also been used for the enhancement of memory and intellectual function from ancient times. A study recommends that water extract from the plant exhibits neuroprotective effect in cognitive impairment in rat model of Alzheimer’s diseases (Defillipo et al., 2012). It has also been reported that CA extract possesses defence to the hippocampus against diabetic induced dysfunction which may further support in enhancement of memory (Giribabu et al., 2014).

Punica granatum Linn.  [PG]

Punica grantum Linn. (Lythraceae) is commonly known as Anar. It has been investigated that pomegrante flower recovers learning and memory in STZ induced diabetic rats by reducing oxidative stress due to its antioxidant activity. PG flower supplementation expressively decreases oxidative stress, glutathione (GSH) content, glial-fibrilan acidic protein. When administered at doses of (300, 400 and 500 mg/kg/day) in STZ induced diabetic rats, it showed improvement in learning and memory. Thus, results show that PG administration may be significantly useful in treating learning and memory deficit in diabetic patients (Combay et al., 2011).

Calendula officinalis Linn. [CO]

Calendula officinalis Linn. (Asteraceae)  is regularly known as normal marigold. It has been accounted for that oral administration of hydro alcoholic concentrate of CO at a measurement of 300 mg/kg essentially enhances learning and memory in STZ induced diabetic rats.  CO extract has significant antioxidant, anticholinergic and antidiabetic activities (Mordkhani et al., 2015).

Glycyrrhiza glabral Linn. [GG]

GG belonging to family Leguminosae is known as Liquorice. Early study, reveals that glabridin, a major active flavonoids in GG at different dose levels (5, 25 and 50 mg/kg, p.o) improves learning and memory dysfunction in STZ induced diabetic rats. GG possesses antioxidant, neuroprotective and anticholinesterase effects that may be responsible for amending effect in learning and memory impairments (Hasanein et al., 2011).

There are wide ranges of herbal plants that have been utilised for the diabetic treatment. Various herbal plants have been explored with reported antidiabetic activity (as mentioned in table 4).

Marketed herbal formulation

Many herbal formulations (as mentioned in Table 5) available in the market are used for the effective treatment of diabetes such as diabecon, diabeta, epiinsuluin, gurmar powder and Chandraprabha vati etc (Modak et al., 2007; Suresh et al., 1995).

(i) Diabecon is an herbal formulation manufactured by Himalaya, it contains combination of many Indian herbs and plants such as Gymnema sylvestre, Glycyrrhiza glabra, Asparagus racemosus, Tinospora Cardifolia, Aloe Vera, Curcuma longa, Momordica charantia, Piper nigrum, Triphala, and Phyllanthus amarus etc. Diabecon demonstrated its antidiabetic action by means of expanding peripheral usage of glucose, hepatic and muscle glucagon substance, additionally advance beta cells recovery and increment C-peptide level. It has been reported that diabecon protects beta cell from oxidative stress reaction via its antioxidant potential. It produces insulin like action by decreasing the glycated haemoglobin levels, and modifies the fatty acid profile. Hence, it reduces the long term effect of diabeties and its complications. Some of these plants have also been traditionally used in memory improvement (Modak et al., 2007).

(ii) Diabeta is also well known marketed herbal formulation available in the capsule form manufactured by Sanofi-Aventis. It contains many ingredients such as Curcuma longa, Momordica chirantia, Acacia Arabica, Tinospora cardifolia, Zingiber officinale etc. It is used as an antidiabetic drug, as well as also also correct the deteriorating complications associated with diabetes mellitus. It is safe and effective in controlling of DM and associated complications and had shown fewer side effects in comparision of synthetic antidiabetic drugs. It is effective in controlling of blood glucose level via acting different sites and pathways that act as activator of diabetic condition. Zingiber officinale belonging to family Zingiberaceae has been explored for its neuroprotective effect in STZ induced diabetic rats (Modak et al., 2007).

(iii) Epinsulin is an Ayurvedic marketed herbal formulation manufactured by Swastik formulations, contains epicatechin, an active constituent. Epicatechin act as an insulin enhancer via increasing the cAMP content of the Islets of Langerhans present in pancreas. It acts via increasing cathepsin activity which in turn enhances insulin secretion by converting proinsulin to insulin. Additionally it has been reported that it also possesses neuroprotective effect and correct diabetic complications such as retinopathy and disturbed metabolism of glucose and lipids. Hence, it is useful in treatment of diabetes and associated complications (Modak et al., 2007).

(iv) Gurmar powder is also a well known Herabl antidiabetic drug, manufactured by Garry and Sun Pharmaceuticals. It helps in reducing blood glucose level via decreasing the intestinal absorption of sacharides, also maintain metabolic activities of liver, kidney.It act as an insulin secretion enhancer and prevent hyperglycemic state (Modak et al., 2007).

(v) Chandraprabha vati (CPV) is an Ayurvedic formulation available in classical Vati form. It contains 37 herbomineral ingredients. The ingredients like Acorus calamus, Cyperus rotundus, Tinospora cordiofoli, Curcuma longa, Berberis aristata, Piper longum, Coriandrum sativum, Terminalia chebula, Terminalia belerica, Embelica officinalis, Zingiber officinale, Piper nigrum and so on have been assessed for their antidiabetic and memory upgrading impacts in a few animals considers by means of alloxon model. It acts by means of lessening blood glucose and lipid profile (Wanjari et al., 2016).

Isolated constituents having antidiabetic potential

There are wide varities of phytoconstituents valuable in treatment of diabetes. These incorporate alkaloids, glycosides, peptidoglycan, hypo-glycan, steroids, guanidine, glycopeptides, terpenoides, amino acids and inorganic particles. Chemical structure of isolated constituents having antidiabetic activity has been shown in figure 1.

Mangiferin is an active constituent isolated from Anemarrhena asphodeloides (Asparagacea). It showed significant antidiabetic activity after oral administration at a dose level of 30 mg/kg b.w for 3 weeks in KK-Ay mice. It showed significant reduction in blood glucose level and prevent hyperglycemic state in case of diabetic rats. It also showed significant improvement in hyperinsulinemia when subjected to insulin tolerance test (Miuri et al., 2001).

Stevioside is an active constituent isolated from the leaves of Stevia rebaudiana Bertoni (Asteraceae). Stevioside showed significant decrease in blood glucose level and act as insulin secretogoges by enhancing insulin secretion in the body and also inhibit the secretion of glucagon hormone. Stevioside at a dose of 0.2 g/kg b.w. indicated antihyperglycaemic, insulinotropic, and glucagonostatic activities in diabetic Goto-Kakizaki (GK) rats. Hence, stevioside possesses significant antihyperglycaemic, insulinotropic activity (Jeppesen et al., 2002).

Mycaminose is also an active moiety of Syzygium cumini which is commonly known as jamun (Myrtaceae). It has been investigated that mycaminose showed significant antidaibetic activity after oral administration at a dose of 50 mg/kg b.w for 15 days in STZ induced diabetic rats. It posseses significant antidiabetic activity by enhancing insulin secretion from the beta cell of pancreas (Kumar et al., 2008).

Ficanone is an active principal isolated from the bark of Ficus arnottiana which is commonly known as Indian Rock Pig (Moraceae). It has been investigated that significant reduction in fasting blood glucose level was found upon oral administration of metanolic, ethanolic extract of ficanone at a dose level of 50 mg/kg for 21 days. Ficanone posseses antidiabetic and antioxidant activity by reducing fasting blood glucose and significantly reduced glutathione, catalase and superoxide dismutase level. Histopathological study also showed significant increase in beta cell mass (Mazumder et al., 2008).

Subcoriacin (3-aryl-6-prenylcoumarin) is also an active constituent isolated from the plant Eysenhardita subcoriacea (Leguminosae). It has been investigated that Subcoriacin shows significant antidiabetic and antioxidant activity after 5 days treatment at a dose level of 100 mg/kg by intraperitonial route in STZ treated diabetic rats. It showed significant decrease in blood glucose level and increase activities of antioxidant enzyme suc as superoxide dismutase (SOD) and catalase (CAT) etc (Mastache et al., 2010).

Thymoquinone is an isolated constituent of plant Nigella sativa (Ranculaceae). It showed significant antidiabetic and antioxidant activity at doses (2.5 and 5 mg/kg)   by intraperitonial route in STZ induced diabetic rats. It showed significant improvement in spatial learning and memory by reducing oxidative stress and blood glucose level (Saheli et al., 2012;  Vafee et al., 2015). Quinone constituent of plant seed Nigella sativa (NS) has been reported to possess beneficial effect in the treatment of diseases such as immunopotentiation, and antidiabetic and gastroprotective. Thymoquinone has been reported for its neuroprotective effect in STZ induced diabetic rats. It prevent cognitive decline associated with diabetes mellitus by reducing oxidative stress. In another study it has also been reported that thymoquinone have potential to restore the normal oxidative balance, inhibition of cholinesterase activity and mitochondrial dearrangement (Sahak et al., 2016).

Glabridin (major flavonoid) is an active constituent of Glycyrrhiza glabra L. (Fabaceae). Glabridin has been investigated for its antidiabetic effect in STZ induced diabetic rats. Administration of glabridin at doses 25 & 50 mg/kg in STZ induced diabetic rats showed significant reduction in blood glucose, lipid profile, LDL, triglycerides, cholesterol level and improvement in body weight, HDL Level and antioxidant enzyme level (EI Ghffar et al., 2016).

Gingerol isolated constituent of Zingiber officinale (Zingiberaceae), was already reported to decrease blood glucose level in type 2 diabetic mice. Endocrine signaling is usually associated with insulin discharge and is irritated in db/db Type-2 diabetic mice. [6]-Gingerol increased glucose-stimulated insulin secretion and improved glucose tolerance after 4 week treatment of diabetic mice. Plasma GLP-1 was observed to be essentially elevated in the treated mice (Samad et al., 2017).

Quercetin isolated constituent of Phyllanthus emblica L. fruit (Phyllanthaceae). Administration of quercetin at a dose of 75 mg/kg b.w in STZ induced diabetic rats showed significant decrease 14.78% in blood glucose levels in the diabetic rats after 7 days of treatment. It showed significant improvement in profiles of triglycerides, LDL, HDL, VLDL and total cholesterol at doses of 50 and 75 mg/kg in STZ induced diabetic rats (Srinivasan et al., 2018).

Gallic acid isolated constituent present in various plants such as Zingiber officinale, Punica grantum showed significant antidiabetic and antioxidant activity in alloxon induced diabetic rats. It has been investigated that administration of gallic acid at doses of 5, 10, and 20 mg/kg b.w. for 45 days showed significant reduction in blood glucose level and increase antioxidant enzyme level in alloxon induced diabetic rats (Ramkumar et al., 2014).

Chebulic acid isolated constituent of Terminalia chebula Retz. (Comberetaceae). Active constituent (chebulic acid) from the fruit of Terminalica chebula exhibits antihyperglycemic effect on oral administration at a dose of 100 mg/kg b.w. The outcome demonstrated that the maltose-hydrolysis action was down-directed by chebulagic acid, which turned out to be a reversible inhibitor of maltase in Caco-2 cells (Huang et al., 2012).

Ellagic acid isolated constituent of Embelica officinalis Linn. (Euphorbiaceae) is commonly known as Indian Gooseberry or Amla. Administration of methanolic exract of Ellagic acid at doses 250 and 500 mg/kg b.w. showed significant decrease in fasting blood glucose level after 28 days of treatment in diabetic rats. It produces significant increase in plasma antioxidants level, Liver GSH and decrease in Liver TBARS level (Fatima et al., 2017).

Chlorogenic acid showed significant antidiabetic activity in STZ induced type 2 diabetic rats. Administration of extract of Mulberry leaves at doses 250 and 750 mg/kg b.w. showed significant dose dependent decrease in blood glucose level after 11 days. Chlorogenic acid showed significant antidiabetic activity in type 2 diabetic rats.

Valoneic acid dilactone isolated constituent of Punica grantum Linn. (Lythraceae) showed significant antidiabetic activity in alloxon induced diabetic model of rats. Oral administartion of valoneic acid dilactone at doses of 10, 25 and 50 mg/kg showed significant dose dependent decrease in blood glucose level in alloxon induced diabetic rats (Jain et al., 2012).

Coagulanolide, a withanolide isolated from Withania coagulans fruits and showed significant antidiabetic activity by inhibiting postprandial increase in blood glucose level and significant inhibitin of post-sucrose load in normal rats as well as STZ induced diabetic rats (Mayur et al., 2008).

Conflicts of interest: Not declared.

References

Afolayan AJ, Sunmonu TO. 2010. In Vivo Studies on Antidiabetic Plants used in South African Herbal Medicine. Journal of Clinical Biochemistry Nutrition, 47(2):98-106.

Ali KM, Naryan KM, Tandon N. 2010. Diabetes and coronary artery disease: Current perspectives. Indian Journal of Medical Research, 132 (5):584-597.

Ali ZH. 2011.  Health and knowledge progress among diabetic patients after Implementation of a nursing care program based on their Profile. Journal of Diabetes and Metabolism, 2:121.

Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, Aguilar-Contreras A, Contreras-Weber CC, Flores-Saenz J.L. 1998. Study of the anti-hyperglycemic effect of plants used as antidiabetics. Journal of Ethno pharmacology, 61(2):101-10.

Adisa RA, Choudhary MI, Olorunsogo OO. 2011. Hypoglycemic activity of Buchholzia coriacea (Capparaceae) seeds in streptozotocin-induced diabetic rats and mice. Experimental and Toxicological Pathology, 63(7-8):619-25.

Akhtar MS, Khan MA,  Malik MT. 2002. Hypoglycemic activity of Alpinia galangal rhizome and its extracts in rabbits. Fitoterpia, 73(7-8):623-8.

Areekul SW. 2014. Mangifera indica fruit extract improves memory impairement, cholinergic dysfunction and oxidative stress damage in Animal model of mild cognitive imapirement. Oxidative Medicine and cellular longevity, 7 doi:http://dx.doi.org/10.1155/2014/132097

Ahmad RM, Justin TA, Manivasagam T, Dhivya BM, Essa MM, Guillwmin GJ. 2018. Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Front Bioscience, 1(10):262-275.

Brands AM, Kessels RP, de Haan EH, Kappelle LJ, Biessels GJ. 2004. Cerebral dysfunction in type I diabetes: effects of insulin, vascular risk factors and blood glucose levels. European Journal of Pharmacology, 490 (1-3):159-68.

Bharti SK, Krishnan S. 2018.  Antidiabetic phystoconstituents and their mode of action on metabolic pathways. Therapeutic Advances in Endocrinology and metabolism, 9(3):81 –100.

Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P.  2006. Risk of dementia in Diabetes mellitus: a systematic review. Lancet Neurology, 5(1):64-74.

Bhandari U, Kanojia R, Pillai KK. 2005.  Effect of ethanolic extract of Zingiber officinale on dyslipidemia in diabetic rats. Journal of Enthno-Pharmacolgy, 97(2):227-30.

Chen D, Huang H, Xing Y, Liu Y, Xu Y. 2011.  A New Vanadium Complex Improves the Spatial Learning and Memory by Activation of Caveolin-MAPK-CREB Pathway in Diabetic Mice. Journal of Diabetes and Metabolism, 2:114.

Combay Z, Baydas G, Tuzca M, Bal R. 2011. Pomegrante (Punica granatum L) flower improves learning and memory performances impaired by diabetes mellitus in rats. Acta Physiologica Hungarica, 98(4):409-20.

Cho NH, Shaw JE, Karuanga S, Huang Y, da Rocha Fernades JD, Ohirogge AW. 2018.  IDF Diabetes Atlas: global estimates of diabetes Prevalence for 2017 and Projections for 2045. Diabetes Research Clinical Practice, 138:271-281.

Cetto AA, Wiedenfeld H. 2001. Hypoglycaemic effect of Cecropia obtusifolia on streptozotocin diabetic rats. Journal of Ethnopharmacolog, 78:145-194.

Dinesh K, Sunil K, Sonia K, Renu A, Jyoti G. 2011. Antidiabetic activity of methanolic bark extract of Albizia odoratissima Benth in alloxan induced diabetic albino mice. Asian Pacific Journal of Tropical Medicine, 4:900-903.

Das SN, Patro VJ,  Dinda SC. 2012. Evaluation of Anti-Inflammatory, Antidiabetic activity of Indian Bauhinia vahlii (stem bark). Asian Pacific Journal of Tropical Biomedicine, 2:1382-1387.

Defillipo PP, Raposo AH, Fedoce AG, Ferreirra AS, Polonini HC,Gattaz WF. 2012. Inhibition of cpla2 and spla2 activities in primary cultures of rat cortical neurons by Centella asiatica water extract. Nutritional Product Community, 7(7):841-843.

EI-Akabawy G, EI-Kholy W. 2014. Neuroprotective effect of ginger in the brain of streptozotocin induced diabetic rats. Annals of  Anatomy, 196(2-3):119-28.

EI Ghffar, Eman A Abd. 2016. Ameliorative effect of glabridin, a main component of Glycyrrhiza glabra L. roots in streptozotocin induced Type 1 diabetes in male albino rats. Indian journal of Traditional Knowledge, 15(4):570-579.

Fatima N, Hafizur RM, Hameed A, Ahmed S, Nisar M, Kabir N. 2017. Embelica officinalis excerts anti-diabetic activity through the action on beta-cells of pancreas. European Jorunal of Nutrition, 56(2):591-601.

Gandhi GR, Sasikumar P. 2012. Antidiabetic effect of Merremia emarginata Burm in streptozotocin induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine, 2:281-286.

Giribabu N, Srinivasarao N, Swapna RS, Muniandy S, Salleh N. 2014. Centella asiatica attenuates diabetes induced hippocampal changes in experimental diabetic rats. Evidence Based Complementory  Alternatative Medicine. 2014:10  doi:10.1155/2014/592062.

Harrison LC, Honeyman MC. 1999. Cow’s milk and type 1 diabetes: the real debate is about mucosal immune function.  American Diabetes Association, 48(8):1501-7.

Harten BV, De Leeuw FE, Weinstein HC, Scheltens P, Biessels GJ. 2006. Brain imaging in patients with diabetes-a systematic review. Diabetes Care, 29:2539-2548.

Huang YM, Zhao DD, Gao B, Zhong K, Zhu RX, Zhang Ye. 2012. Antihyprglycemic effect of chebulagic acid from the fruits of Terminalia Chebula Retz. International Journal of Molecular Science, 13(5):6320-33.

Hasanein P. 2011. Glabridin as a major active isoflavon from Glycyrrhiza glabra (liquorice) reverses learning and memory deficits in diabetic rats. Acta Physiologica Hungarica, 98(2):221-30.

Irondi EA, Oboh G, Akindahani AA. 2016. Antidiabetic effects of Mangifera indica kernel flour supplemented diet in Streptozotocin induced type 2 diabetes in rats. Food Science and Nutrition, 4(6):823-839.

Jeppesen PB, Gregersen S, Alstrup SS, Hermansen K. 2002. Stevioside induces antihyperglycemic, insulinotropic & glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats. Phytomedicine, 9:9-14.

Jain V, Viswanatha GL, Manohar D, Shivprasad HN. 2012. Isolation of antidiabetic principle from fruit rinds of Punica granatum. Evidence-Based Complementary and Alternative Medicine, 1-11.

Kuhad A, Chopra K. 2008. Effect of sesamol on diabetes associated cognitive decline in rats. Experimental Brain Research, 85(3):411-20.

Kucukatay V, Agar A, Gumuslu S, Yargiçogl P. 2007. Effect of sulphur dioxide on active and passive avoidance in experimental diabetes mellitus: relation to oxidant stress and antioxidant enzymes. International Journal of Neuroscience, 117(8):1091-107.

Kritikar KR, Basu BD. 1991. Indian Medicinal Plants.2nd ed., Periodical Export, New Delhi. 108-3547.

Kumar R, Patel DK, Prasad SK, Sairam K, Hemalatha S. 2012. Antidiabetic activity of alcoholic root extract of Caesalpinia digyna in streptozotocin nicotinamide induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine, 2:934-940.

Kondeti SR, Mallikarjuna K, Kesireddy N, Reddy SK. 2011. Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin induced diabetic rats. Food and chemical toxicology. 249:893-897.

Kilani JS,Ghedira Z, Masr N, Krifa M, Ghedira K, France DM. 2014. Evaluation of invitro antioxidant and apoptotic activities of Cyperus rotundus. Asian Pacific Journal Tropical Disorder, 7(2):105-112.

Kumar A, Lavarasan R, Jayachandran T, Deecarman M, Aravindan P, Padmanabhan N. 2008. Antidiabetic activity of Syzygium cumini and its isolated compound against streptozotocin induced diabetic rats. Journal of medicinal plants Research, 2(9):246-249.

 Brownlee M. 2001. Biochemistry and molecular cell biology of diabetic complications. Nature, 414:813-820.

Mastrocola R, Restivo F, Vercellinatto I, Danni O, Brignardello E, Aragno M. 2005. Oxidative and nitrosative stress in brain mitochondria of diabetic rats. Journal of Endocrinology, 187(1):37-44.

Mohammad SA, Yaquab AG, Sanda KA, Nicholas AO, Arastus W, Muhammad M.  2013. Review on diabetes, synthetic drugs and glycemic effects of medicinal plants. Journal of Medicinal Plants Research, 7(36):2628-2637.

Moradkhani S, Salhi I, Abdolmaleki S, Komaki A. 2015. Effect of Calendulla officinalis hydroalcoholic extract on passive avoidance learning and memory. Ancient Science Life, 34(3):56-61.

Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayum TP. 2007. Indian herbs and Herbal drugs used for the treatment of diabetes. Journal of Clinical Biochem Nutrition, 40(3):163-173.

Mazumder PM, Farswan M, Parcha V, Singh V. 2008. Hypoglycemic and antioxidant activity of an isolated compound from Ficus arnottiana bark. Pharmacologyonline, 3:509-19.

Mastache JM, Soto C, Delgado G. 2010. Hypoglycemic and antioxidant effects of Subcoriacin in normal and streptozotocin induced diabetic rats. Journal of Mexican Chemical Society, 54(4):240-44.

Maurya R, Singh AB, Srivastava AK. 2008. Coagulanolide, a withanolide from Withania coagulans fruits and antihyperglycemic activity. Bioorganic and Medicinal Chemistry Letters, 18:6534-37.

Nandkarni KM. 1976. Indian Materia Medica. Karnataka Printing Press and Popular Press LTD, Bombay, 10-1300.

Nain P, Saini V, Sharma S, Nain J. 2012. Antidiabetic and antioxidant potential of Embelica officinalis Gaertn leaves extract in streptozotocin induced type 2 diabetes mellitus (T2DM) rats. Journal of Ethnopharmacology, 142(1):65-71.

Oyedemi SO, Adewusi EA, Aiyegoro OA, Akinpelu DA. 2011. Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats. Asian Pacific Journal of Tropical Biomedicine, 1: 353-358.

Olubomehin OO, Abo KA, Ajaiyeoba EO. 2013. Alpha-amylase inhibitory activity of two Anthocleista species and in vivo rat model anti-diabetic activities of Anthocleista djalonensis extracts and fractions. Journal of Ethnopharmacolgy, 146:811-814.

Prisilla DH, Balamurugan R, Shah HR. 2012. Antidiabetic activity of methanol extract of Acorus calamus in STZ induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine, 2: 941-946.

Purushoth P, Suresh R, Selvakumari. 2012. Phytochemical Analysis of Ethanolic Extract of Merremia emaraginata Burm, F by GC-MS. Research Journal of Pharmaceutical Biological and Chemical Sciences, 10:3.62.

Prashant C, Bharat G, Ashoke KG. 2012. Antidiabetic activity of Adina cordifolia (Roxb) leaves in alloxan induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine, 2:630-632.

Srinivasan P, Vijayakumar S, Kothandaraman S, Palani H. 2018. Antidiabetic activity of quercetin extracted from Phyllanthus embelica L. fruit: In silico and in vivo approaches. Journal of Pharmaceutical Analysis, 8(2):109-118.

Ramkumar KM, Vijayakumar RS, Vanitha P, Suganya N, Manjula C, Rajaguru P. 2014. Protective effect of gallic acid on alloxon- induced oxidative stress and osmotic fragility in rats. Human Experimental Toxicology, 33(6):638-649.

Saheli P, Nasri S, Roghani M. 2012. Poordahandeh on short-term spatial memory, passive avaidence learning and memory of diabetic rats and the involvement of hippocampal oxidative stress. Pajoodahandeh journal, 17(5):219-227.

Samad MB, Mohsin MNAB, Razu BA, Hossain MT, Mahzabeen S, Unnoor N. 2017. Gingerol from Zingiber officinanale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathaway in Pancreatic beta cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporter in skeletal muscle to improve hyperglycemia in Lepr db/db type 2 diabetic mice. BMC Complementary Alternative Medicines, 17(1):395.

Sharifzadeh M, Ranjhar A, Hoseeini A, Khanavi M. 2017. The effect of green tea extracts on oxidative stress and spatial learning in STZ siabetic rats. Iranian Journal of Pharmaceutical Researchs, 16(1):201-209.

Sahak MKA, Kabir   N, Abbas G, Draman S,  Hashim NH, Adli DSH. 2016.  The role of Nigella sativa and its active constituents in lerning and memory. Evidence-Based Complementary and Alternative Medicine, 2016:6.

Subramaniam R, Koikaramparambil RN, Baskaran R, Mohammad A. 2012. Antidiabetic, antihyperlipidemic and in vivo antioxidant potential of aqueous extract of Anogeissus latifolia bark in type 2 diabetic rats. Asian Pacific Journal of Tropical Disease, 2:596-602.

Seema AK, Jon C. 2014. The Current State of diabetes mellitus in India. Australasian Medical Journal, 7(1):45-48.

Saenghong N, Wattanathorn J, Muchimapura S, Tongun T, Piyavhatkul N, Banchonglikitkul C. 2012. Zingiber officinale improves cognitive function of the middle-aged healthy women. Evidence Based Complementory Alternative Medicine, 9 doi:10.1155/2012/383062.

Suresh P, Dixit SK, Gode KD, Joshi D.1995.  Anti-Diabetic effect of   Chandraprabha vati-a reappraisal (experimental study). Sachitra Ayurveda, 48:395-9.

Semalty A, Semalty M, Kumar P, Mir SR, Ali.M, Amir S. 2012. Isolation and hypoglycemic activity of a novel Pongamiaflavonyl from Pongamia pinnata pods. International Journal of Pharmacology, 8:265-70.

Teshome HM, Ayalew GD, Shiferaw FW, Leshargie CT, Boneya DJ. 2018. The prevalence of depression among diabetic patients in Ethiopia: A systematic Review and Meta-analysis. Depression Research and Treatment, 1-8 doi:org/10.1155/2018/6135460.

Tirgar PR, Shah KV, Patel VP, Desai TR, Goyal RK. 2010. Investigation into mechanism of action of anti-diabetic activity of Emblica officinalis on streptozotocin induced type 1 diabetic rats. Research Journal of Pharm Biology Chemistry Science, 1:672-82.

Verma RK, Mishra G, Singh P, Jha KK, Khosa RL. 2015.  Antidiabetic activity of methanolic extract of Alpinia galangal linn. Aerial parts in streptozotocin induced diabetic rats.  An International Quarterly Journal of Research in Ayurveda, 36(1):91-5.

Vasudevan M, Parle M. 2007. Effect of Anwala Churna: an Ayurvedic Preparation on memory deficit Rats. Yakugaku Zasshi, 127(10):1701-1707.

 Vafaee F, Hosseini M, Hassanzadeh Z et al. 2015. “The effects of Nigella sativa hydro-alcoholic extract on memory and brain tissues oxidative damage after repeated seizures in rats. Iranian Journal of Pharmaceutical Research, 14(2):547–557.

Wattanathorn J, Jittiwat J, Tongun T, Muchimapura S, Ingkaninan K. 2011. Zingiber officinale mitigates brain damage and improves memory impairment in focal cerebral ischemic rat. Evidence Based Complement Alternative Medicine.

Wais M, Nazish I, Samad A, Beg S, Abusufyan S, Ajaj SA, Aqil M. 2012. Herbal drugs for Diabetic treatment. An updated Review of patents. Recent Patents on Anti-Infective Drug Discovery, 7:1-7.

 Wanjari MM, Mishra S, Dey NY, Sharma D, Gaidhani NS, Jadhav DA. 2016.  Antidiabetic activity of Chandraprabha vati-A classical Ayurvedic formulation. Journal of Ayurveda and Integrative Medicine, 7:144-150.

Wild S, Roglic G, Green A, Sicree R. 2004. King Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27:1047- 1053.

Manuscript Management System
Submit Article Subscribe Most Popular Articles Join as Reviewer Email Alerts Open Access
Our Another Journal
Another Journal
Call for Paper in Special Issue on

Call for Paper in Special Issue on