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Role of Herbal Medicines in the Treatment of Diabetes Mellitus: An Updated Review

Jyoti Rathi

1

, Sunil Kumar

1

, Beena Kumari

1,2*

, Aparna Khansili

2

, Sangeeta Narwal

1,3

, Deepika Purohit

1

,Deeksha Manchanda

1

, Manish Makhija

1

,Sangita Saini

3

, Parijat Pandey

4

1,Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Rewari, Haryana, India - 123401

2*Department of Pharmacy, G.D. Goenka University, Gurugram, Haryana, India – 122103

3Shri Baba Mastnath Institute of Pharmaceutical Sciences, Baba Mastnath University, Rohtak, Haryana-124021

4Department of Pharmaceutical Sciences, Gurugram University, Gurugram, Haryana-122413

*[email protected]

ABSTRACT

Diabetes is a serious public health problem because 70% of the patients have uncontrolled diabetes which leads to complications early. Poor monitoring is the main reason because many of the patients are not monitoring at all. So this is the main challenge to know about controlling parameters for this disease. But the best news is that major strides are operative in diabetes prohibition, diagnosis, and care. For the treatment of type 1 diabetes patients require administration of insulin 3-4 times in a day during their lives and the blood sugar level of patients should be observed routinely to prevent obstacles such as retinopathy and cardiovascular disease risks.

Well-monitored glycemic control is required for the management of type 2 diabetes. As it may results in the loss of glycemic regulation, the need to regulation the continuing degradation of β-cell function is necessary.

Insulin and conventional drugs are effective, but the associated glucoregulatory and metabolic dysfunctions can not be repaired. Over the years, herbal medicine has been used to cure various illnesses, such as diabetes. In addition to their mainstream therapies, herbal medicines with antidiabetic properties are used by many diabetic patients, which can present both an advantage and a possible risk for successful control of their disease. The review provides detailed report of diabetes, its diagnosis and role of herbal medicines in its treatment.

Keywords

Diabetes Mellitus, Diagnosis, Drugs, Herbs, Applications

Introduction

Diabetes mellitus (DM) is a chronic condition characterized by insulin synthesis lack and its intervention, or together. This results to chronic hyperglycemia with disruptions in most of the human body's metabolic processes [1]. Untreated cases display vascular damage and severe tissue which leads to severe complications such as neuropathy, retinopathy, cardiovascular complications and ulcerations [2-4]. Polyuria, polydipsia, weight loss, polyphagia, cardiac arrhythmia, tachycardia and hypotension are signs and symptoms of hyperglycemia [5-7].

Diabetes mellitus is categorized into 3 types: Type 1, Type 2 and third one is gestational diabetes mellitus.

Type 1 Diabetes mellitus is referred to as insulin-dependent DM due to non-functioning of the β-cell of the pancreatic islets of langerhans.

Type 2 Diabetes mellitus is referred to insulin independent DM in which transient loss of β cell mass arises that is attributed to hereditary predisposition which often occurs in obese people and is related to high cholesterol level and high blood pressure. Type 2 DM therapy aims at decreasing the insulin conflict and increasing secretion of insulin.

Gestational diabetes is a form of diabetes that found in pregnant women with hyperglycemia. It typically occurs in the 2nd or 3rd trimester in 2-4 percent pregnancies [8].

Diagnosis of Diabetes Mellitus

Random plasma test: This is the easiest test, and before taking the rest, it does not require fasting. If blood sugar is 200 or more than 200 mg / dl, it is most likely to suggest diabetes but must be reconfirmed.

Fasting plasma glucose test: Before taking the test, there should be eight hours of fasting. A diagnosis of diabetes is confirmed by glucose greater than 130 mg/dl on performed two or more than two tests on entirely separate days [9].

Oral glucose tolerance test: If the value is 160-200 mg / dl for random plasma glucose test and 110-125 mg/dl for the fasting plasma test then this test is carried out. This blood test assesses the reaction to glucose in the body. This

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test requires at least eight hours of fasting, but not more than 16 hours. If the amount of glucose is determined for fasting, then 75gm of glucose and 100gm for pregnant women are given. Then the blood is checked for two to three hours every thirty minutes to one hour. If level of glucose is below 140 mg/dl for two hours, this test is normal. The diagnosis of diabetes is indicated by a fasting level of 130 mg/dl or above and a level of glucose 200 mg/dl or above for two hours [9].

Antidiabetic drugs

It is possible to avoid diabetes mellitus disease by controlling blood sugar levels with different medications, acquiring various exercise or yoga therapies or diet plans [10]. Actually available diabetes mellitus therapies include insulin therapy for the type 1 DM and some other oral hypoglycemic medicines i.e. peptide analogues, thiazolidinediones and sulphonylureas for type 2 diabetes treatment [11,12]. Different side effects like sickness, malignant anaemia, vomiting, swelling, dysentery, migraine and faintness are associated with synthetic drugs used for diabetes care, so the need of herbal medicines created [13]. In ancient times, traditional plants with therapeutic value were used by physicians and lay public for the treating various diseases i.e. Cardiac disease, cancer, skin diseases and diabetes etc. Traditional plants used to regulate diabetes have a long history in India and China. Several books are available like CharakaSamhita and SusrutaSamhita that describe the phytopharmacology characteristics of diabetes and its adverse effect [14]. The details of some drugs with their class, action and disadvantages are summarized in table 1.

Table 1: Representative antidiabetic agents used in the treatment of T2DM patients

Drug (s) Class Action Disadvantages References

Acarbose/

Miglitol/

Voglibose

AGIs Decrease absorption of carbohydrate

GI side effects and high dose frequency

[15]

Metformin Biguanides Enhance sensitivity of insulin, decreases risk of cardiovascular and hypoglycemia.

Side effects of Gastrointestinaland too much lactic acid produces in the body

[16]

Repaglinide (Prandin) Nateglinide (Starlix)

Meglitinides Stimulate the release of insulin

Decreases blood glucose level and increases body weight

[17]

Pioglitazone/Roziglitazone/

Troglitazone

TZDs High sensitivity of insulin and low risk of hypoglycemia

Increases risk of cancer and

weight of body

[18,19]

Saxagliptin (Onglyza) Sitagliptin (Januvia) Linagliptin (Tradjenta) Alogliptin

Dipeptidyl- peptidase 4 (DPP-4)

inhibitors

Enhances insulin release and inhibits glucose release

Infection of upper respiratory tract, headache and pharyngitis

[20,21]

Liraglutide/ Exenatide Glucagon like peptide -1 receptor

agonists

Increases secretion of insulin and decreases secretion of glucagon

Side effects of gastrointestinal tract, renal dysfunction and acute pancreatitis

[15,22]

Empagliflozin/

Dapagliflozin/ Canagliflozin

Sodium-glucose transporter 2 inhibitors

Inhibits reabsorption of glucose

Nausea or vomiting [23]

Glyburide/

Glipizide/

Gliclazide/

Glimepiride

Sulfonylureas Incresease secretion of insulin

Hypoglycemia weight gain

[15,23]

Colesevelam (Welchol) Bile acid sequestrants

Reduces level of cholesterol and blood glucose

Flatulence Constipation Indigestion

[22]

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Pramlintide (Symlin) Amylin mimetics

help in controlling level of blood sugar

Hypoglycemia Nausea or vomiting

[24]

Role of herbs in the treatment of Diabetes Mellitus

Due to fewer bad effects and adverse effects, natural medications have proven to be a safer option over prescription drugs.

Herbal formulations can be purchased without prescription. These are safe natural drugs i.e. no adverse effects are present. Herbal preparations include natural herbs and extracts of fruits and vegetables that are effective without harmful effects in the treatment of multiple diseases. In the other hand, chemicals are synthetically prepared, which also have side effects. Herbal formulations compared with allopathic drugs are inexpensive. Herbal formulations are Enviroment friendly because these are made from normal products whereas allopathic drugs are made from substances which are chemically modified. Herbal preparations are available without prescription while most allopathic medicines required prescription [25-26].

Herbal antidiabetic drugs

The medicinal plants and herbs are currently used for their anti-diabetic activity in extract forms and restore the action of pancreatic β- cells [27]. Flavonoids, tannins, phenolics, and alkaloids are the basic most usual herbal active ingredients used in the diabetes treatment [28]. The continuation of these substances implies the significance of the anti-diabetic properties of these plants [29]. Tannin, for instance, increases the function of beta cells of pancrease and enhance insulin discharge. Quercetin is an antioxidant that interacts with many oxygen radicals removal pathways, preventing peroxidation of lipid and chelation of metal ion [29]. In fact, the mechanisms of actions for hypoglycemic plants include: increase in the secretion of insulin, increase in the absorption by muscle and adipose tissues, from the intestine preventing the incorporation of glucose, and preventing the output of glucose by the cells of liver [30]. The reduction or removal of diabetes complications is mainly responsible for these factors and the medicinal plants list used for antidiabetic activity is given in table 2, while marketed herbal formulations for antidiabetic activity are enlisted in table 3.

Table 2: List of herbal plants used in diabetes mellitus S.

No .

Plant species

Family Common

Name

Plant Part

Main Chemical constituents

Mechanism of action Ref

1. Aeglemarme los

Rutaceae Golden apple

Leaves extracts

Aeglemarmelos ine

Enhance the functional c ondition of pancreatic β- cells

[31]

2. Allium cepa Lilliaceae Pyaaz Bulbs Allyl propyl disulphide and diallyldisulphid e

Improve antioxidant activity

[32]

3. Allium sativum

Lilliaceae Garlic Petroleum ether exract of bulbs

Allylpropyldisu lphide oxide, allicin

Improve plasma lipid metabolism and plasma antioxidant activity

[33]

4. Aloe barbadensis

Asphodelacea e

Ghikanwa r

Leaf pulp extract

β- sitosterol, campesterol

Improvement in

impaired glucose tolerance

[34]

5. Andro- graphispani culata

Acanthaceae Kalmegh Ethanolic extract of plant

Kalmeghin Increases the glucose utilization and lower plasma glucose

[35]

6. Annonasqua mosa

Annonaceae Sharifa Leaves Borneol, camphor, eugenol

Improve tolerance of glucose

[36]

7. Azadirachtai ndica

Meliaceae Margosa Leaf extract

Nimbin, quercetin

Glycogenolytic effect was blocked because of epinephrine action

[37]

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8. Brassica juncea

Brassicaceae Mustard Aqueous extract

Sulforaphane Enhances Glycogen synthetase activity

[38]

9. Cajanuscaja n

Leguminosae Pigeon pea

Seeds 2’-2’ methyl cajanone, isoflavones, cajanin, cahanones

Substantialdecrease in serum glucose level

[39]

10. Carica papaya

Caricaceae Papaya Aqueous seed extract

Papain, chymopapain

Lowered fasting blood sugar, triglyceride, total cholesterol

[40]

11. Carumcarvi Apiaceae Caraway Aqueous extract of seed

Furfurol, carvone

Substantial decrease in blood glucose level

[41]

12. Cassia auriculata

Leguminosae Tanner’s cassia

Aqueous extract of seed

Limonene, terpinol

Enhances the activity of hepatic hexokinase, phosphor-fructokinase

[42]

13. Catharanthu sroseus

Apocynaceae Vinca Hot water decoction of leaves

Catharanthine, vincristine, vinblastine

Lowering of glycemia [43]

14. Cocciniaindi ca

Cucurbitacea e

Baby water- melon

Ethanolic extract of whole plant

Glutamic acid, Asparagine

Lesser blood glucose level because of suppressed glucose synthesis

[44]

15. Coriandrum sativum

Apiaceae Coriander Seed extract

p-cymene, linalool

Enhancing the activity of β-cells and decrease serum glucose

[45]

16. Cinnamomu m cassia

Lauraceae Cinnamon Bark Cinnam-

aldehyde, eugenol

Increases the sensitivity of insulin receptor

[46]

17. Cinnamomu m

tamala

Lauraceae Tejpatta Leaf extract

Linalool, β- caryophyllene

Insulin release from pancreatic β-cells

[47]

18. Curcuma longa

Zingiberaceae Turmeric Rhizomes Curcuminoids, bisdemethoxy -curcumin, dimethoxy- curcumin

Reduces blood sugar level, Improves metabolism of glucose

[48]

19. Eugenia jambolana

Myrtaceae Jambolan Fruit pulp Oleanolic acid, gallic acid

Decreases blood glucose level

[49]

20. Ficusbengal ensis

Moraceae Bargad Alcoholic extract of stem bark

Leucodelphinidi n

Enhanced insulin secretion from β-cells

[50]

21. Ficushispida Moraceae Daduri Alcoholic extract of leaves

Ficustriol, O- methyltylophori nidine

Reduces level of blood glucose and improved level of serum insulin

[51]

22. Gymnemasyl vestre

Asclepidacea e

Gudmar Dried leaves

Gymnemic acid, dammarene

Decreases blood glucose level

[52]

23. Mangiferain dica

Anacardiacea e

Mango Extract of leaves

Mangiferin Reduces intestinal absorption of glucose

[53]

24. Momordicac harantia

Curcubitacea e

Bitter gourd

Fresh green leaves

Charantin, sterol

Activates PPARs alpha a nd lowers plasma apo β100 in high- fat diet mice

[54]

25. Musa Musaceae Banana Flower Tryptophan, Reduces blood [55]

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Paradisia tannin, serotonin

glucose and glycosylated haemoglobin levels 26. Ocimum

sanctum

Labiateae Tulsi Whole

plant

Eugenol Increases release of insulin

[56]

27. Panax ginseng

Araliaceae Ginseng Root extract

Ginsenosideprot opanaxdiol

Inhibit activity of α- glycosidase and reduces absorption of glucose

[57]

28. Phyllanthus emblica

Euphorbiacea e

Amla Entire plant

Alkaloids Reduces level of blood glucose

[58]

29. Punicagrant um

Puniaceae Pomegran ate

Seeds Gallic acid, protein, tannin, vitamin C

Decreases the blood glucose level

[59]

30. Swertiachira ta

Gentinaceae Chirata Whole plant

Gentianine, Xanthonemangi ferin,

Methyl swertianin

Reduces level of blood glucose

[60]

31. Terminaliaa rjuna

Combretacea e

Arjuna Bark and stem

Arjunolic acid, arjunic acid

Decreases blood glucose level and Glucose-6- Phosphate activity

[61]

32. Terminaliac atappa

Combretacea e

Almond Petroleum ether fruit extract

Omega-9-ftty acid

Reduction in blood glucose level

[62]

33. Tinosporaca rdifolia

Menispermac eae

Giloy Aqueous extract of root

Tinosporone, tinosporic acid

Declineinglycemia as well aslipids of brain

[63]

34. Trigonellafo enum

Fabaceae Methi Seeds Fat, volatile oil, carbohydrate, protein

Stimulating insulin relea se, reducing insulin resistance, and reducing blood sugar levels

[64]

35. Zingiberoffi cinalis

Zingiberaceae Sunth Rhizome Gingerol Insulin level improved [65]

Table 3: Antidiabetic herbal formulation marketed in India [66]

Sr.

No.

Brand Name Manufecturer Ingredients

1. Diabecon Himalaya Asparagus racemosus, Balsamodendronmukul, Trikatu, Aloe vera, Caseariaesculenta, Gymnemasylvestre, Ocimum sanctum, Swertiachirata, Abutilon indicum, Tribulusterrestris, Shilajit, Gmelinaarborea, Berberisaristata, Boerhaaviadiffusa, Sphaeranthusindicus,powders of Momordicacharantia, Eugenia jambolana, Piper nigrum, Tinosporacordifolia, Curcuma longa, Rumexmaritimus, Phyllanthusamarus, Gossypiumherbaceum, Pterocarpusmarsupium.

2. Pancreatic tonic 180 cp Ayurvedic herbal supplement

Aeglemarmelos, Cinnamomumtamala, Ficusracemosa, Momordicacharantia, Azadirachtaindica, Gymnemasylvestre,

Trigonellafoenumgraceum,Syzygiumcumini, Pterocarpusmarsupium

3. Bitter gourd powder Garry and Sun natural Remedies

Momordicacharantia

4. Diasulin Curcuma longa, Cassia auriculata, Momordicacharantia,

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Tinosporacordifolia, Syzygiumcumini, Gymnemasylvestre, Scopariadulcis, Cocciniaindica, Emblicaofficinalis, Trigonellafoenumgraecum

5. Dia-care Admark Herbals

Limited

Himej, Neemchal, Kadu, Namejav, Jambubeej, SanjeevanMool

6. Diabetes-daily care Nature’s Health Supply

Momordicacharantia extract, Gymnemasylvestreextract, Chromax, Alpha Lipoic acid, Vanadium, Fenugreek extract, Cinnamon exract, Liquorice Root extract

7. Gurmar powder Garry and Sun

Natural Remedies

Gymnemasylvestre 8. Ayurveda alternative

herbal formula to Diabetes

Chakrapani Ayurveda

Azadirachtaindica, Tinosporacordifolia, Trigonellafoenumgraecum, Inularacemosa, Syzigiumcumini, Gymnemasylvestre, Momordicacharantia

9. Epinsulin Swastik

Formulations

Pterocarpusmarsupium

10. Diabeta Ayurvedic cure

Ayurvedic Herbal Health Products

AzadirachtaIndica, Momordicacharantia, Acacia arabica, Curcuma longa, Vincarosea, Gymnemasylvestre, Pterocarpusmarsipium, Tinosporacordifolia, Syzigiumcumini, Zingiberofficinale

11. Syndrex Plethico

Laboratories

Germinated Fenugreek seed extract

12. Diabecure Nature beautesanté Taraxacum, Erythereacentaurium, Berberis vulgaris, Juglansregia, Millefolium,

13.

MahumehaKusumakara Rasa

Shree

Dhoothapapeshwar Limited

Aeglemarmelos, Curucma longa, Pterocarpusmarsupium, Vasantkusumakar Rasa, Emblicaofficinalis,ShudhShilajit, Yashadabhasma, Enicostemmalittorale, Tinosporacordifolia, Vasantkusumakar Rasa

14. Zypter Om

Pharmaceuticals Limited

Vijayasar, Haridra, Bibhitaki, Amalaki, Guduchi and Gurmar, Haritaki, JasadBhasma, Chtak, Dalchini

15. HypoNIDD CharakPharma Shilajit, Curcuma longa,Meliaazadirachta,

Emblicaofficinalis, Momordicacharantia, Eugenia jambolana, Gymnemasylvestre, Pterocarpusmarsupium, EnicostemmalittoraleTinosporacordifolia, Cassia auriculata, Swertiachirata, YashadBhasma

16. DaburMadhuRakshak Dabur Eugenia jambolana, Piper nigrum, Terminaliachebula, Pterocarpusmarsupium, Gymnemasylvestre, Azadirachtaindica, Phyllanthusemblica, Trigonellafoenum- graecum, BhavanaDravyas, ShudhShilajit, MomordicaCharantia, Cinnamomumtamala, Terminaliabelerica

17. Ojamin Tates remedies Aeglemarmelos, Meliaazadirachta, Gymnemasylvestre, Carumcarvi, Terminaliachebula, Curcuma longa, Eugenia jambolana, Picrorrhizakurroa, Trigonellafoenum-graecum, Emblicaofficinalis, Terminaliabelarica, Swertiachirata, Salaciachinensis, Tinosporacordifolia

18. Madhumehari Granules Baidyanath Aeglemarmelos, Azadirachtaindica, Emblicaofficinalis, Curcuma longa, PicrorrhizaKurroa, Gymnemasylvestre, Tinosporacordifolia, Syzygiumcumini, Momordicacharantia, Acacia catechu, Cinnamomumtamala, ShilajitAsphaltum,

Ficusglomerata, Plumbagozeylanica,

Pterocarpusmarsupium, Trigonellafoenum-graecum

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Conclusion

Diabetes mellitus, which affects millions of individuals worldwide, is the most common endocrine condition. There are so many compounds that assist in the treatment of diabetes, but as such no fixed therpy is there that can cure a patient completely from this disease. After doing a large number of trials, several modern medicines have been reported for diabetes. Isolated constituents and extracts from various ordinary resources, mainly plants have various constituests that results in control and treatment of diabetes problems and complications. Plants, partially because of their antidiabetic compounds, such as flavonoids,tannins, phenolics, and alkaloids are natural antioxidants and powerful herbal medicines. This review paper plays a very important role in the design of drugs and the treatment of diabetes mellitus hyperglycemic issues and it can be useful to establish result based different medicines using herbal preparation to cure different types of diabetes problem for health practitioners, scientists and scholars.

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