Antidiabetic Herbs and Polyherbal Antidiabetic Formulations –An Overview

                             M.Y. Mohammad Ismail*¹; Dr. A. B. Roge²

1. Research Scholar, SRTM University, Nanded, MS India

2. Centre for Research in Pharmaceutical Science, Nanded Pharmacy College, Nanded, MS India

*Correspondence: yahyashaikh1980@gmail.com;

DOI: https://doi.org/10.71431/IJRPAS.2025.41204  

INTRODUCTION

Diabetes Mellitus (DM), particularly Type 2 Diabetes Mellitus (T2DM), is a global metabolic pandemic characterized by high blood glucose levels resulting from insulin resistance and/or insufficient insulin secretion. [1-2]

Diabetes mellitus, particularly type 2 diabetes (T2DM), is a major and growing public health challenge in India. Conventional pharmacotherapy (e.g., insulin, biguanides, and sulfonylureas) effectively manages hyperglycemia but can have side effects, cost burdens, and may not fully prevent complications. In this context, herbal medicines (derived from plants) have drawn substantial interest as complementary or alternative interventions, especially in India, owing to:

• Rich traditional medicinal heritage (Ayurveda, Siddha, Unani, folk medicine)
• High biodiversity of medicinal plants
• Cultural acceptability and lower cost for many patients
• Perceived lower adverse effects

Herbal therapies in diabetes are used to (a) reduce hyperglycemia, (b) mitigate oxidative stress, (c) improve insulin sensitivity or secretion, and (d) prevent or delay complications (like neuropathy, nephropathy).

India carries one of the world’s highest burdens of diabetes, with lifestyle shifts, genetic predisposition, and urbanization contributing to rising prevalence. The limitations of conventional drugs—such as adverse effects, cost, and limited efficacy against complications—have renewed interest in herbal medicines. Ayurveda describes Madhumeha, a condition analogous to diabetes, and prescribes various botanical remedies for its management. Many of these herbs exhibit antihyperglycemic, antioxidant, and insulin-sensitizing actions, making them candidates for modern herbal formulations. While conventional pharmaceuticals offer effective management, the associated side effects and long-term costs have driven significant interest in phyto-therapy —the use of medicinal plants. Traditional medicine systems worldwide, such as Ayurveda and Unani Medicine, have historically utilized hundreds of plants for their antidiabetic potential. This review summarizes key antidiabetic herbs, their active compounds, mechanisms of action, and supporting clinical evidence. [3-4]

TRADITIONAL AND HISTORICAL BASIS

India’s traditional medicine systems (especially Ayurveda) have used numerous plants for managing “Madhumeha” (a term roughly corresponding to diabetes). Key historical texts and practices endorse many of these herbs in various preparations (decoctions, powders, polyherbal mixtures). Modern scientific research has begun to validate many such uses.

In Ayurvedic literature, the concept of polyherbal formulations is well established: combining several herbs may yield synergistic effects, enhance efficacy, and lower individual herb dosages to minimize toxicity.

ANTIDIABETIC HERBS IN INDIAN TRADITIONAL MEDICINE

A number of Indian medicinal plants have been studied for antidiabetic potential. Below are some of the well-researched ones, along with their mechanisms, efficacy, and evidence:

1. Gymnema sylvestre (“gurmar”)
• Often called “sugar destroyer” in Ayurveda.
• Mechanisms: enhances insulin secretion, regenerates pancreatic β-cells, and reduces intestinal glucose absorption.
• Evidence: Included in many preclinical and clinical studies; has been one of the most studied herbs.

Gymnema contains gymnemic acids that reduce intestinal glucose uptake and stimulate insulin secretion. It is one of the most researched Indian antidiabetic plants, with studies demonstrating β-cell regeneration and glycemic improvement. [5]

2. Momordica charantia (Bitter Gourd / Karela)
• Contains polypeptide-p (an insulin-like peptide), charantin, and other bioactive compounds.
• Mechanisms: mimics insulin, improves glucose uptake, and may modulate lipid metabolism.
• Evidence: Widely studied in animal models; traditional use is also well documented.

Rich in charantin and polypeptide-P, bitter gourd exerts insulin-like and glucose-lowering effects. Animal and human studies show reduced fasting glucose and improved lipid profile. [6]

3. Trigonella foenum-graecum (Fenugreek / Methi)
• Rich in soluble fiber, 4-hydroxyisoleucine, and other bioactives.
• Mechanisms: delays glucose absorption, increases insulin sensitivity, and possibly stimulates insulin secretion.
• Evidence: Several in-vivo studies and human trials have shown improved glycemic control.

Fenugreek seeds contain soluble fiber and 4-hydroxyisoleucine, which enhances insulin release and delays carbohydrate absorption. Clinical studies demonstrate improvements in postprandial glucose.

      4. Tinospora cordifolia (Giloy / Guduchi)

• A climbing shrub widely used in Ayurveda.
• Mechanisms: antioxidant effects, enhancement of insulin secretion, and protective effects on tissues.
• Evidence: Experimental animal studies show significant reduction in blood glucose.

Giloy shows antioxidant, immunomodulatory, and insulin-enhancing effects. It reduces oxidative stress and improves β-cell function in diabetic models. [7]

5. Pterocarpus marsupium (Vijaysar)

• The heartwood is traditionally used for diabetes.
• Mechanisms: regeneration of pancreatic islets, insulin secretagogue properties, antioxidant.
• Evidence: Both in vitro and in vivo studies support its hypoglycemic effect.

Vijaysar heartwood contains epicatechin, which aids β-cell regeneration and improves insulin sensitivity. Traditional use involves drinking water kept overnight in wooden tumblers.

6. Azadirachta indica (Neem)

• Leaf extracts have shown hypoglycemic activity.
• Mechanisms: increasing glucose uptake, improving glycogenesis, antioxidant properties.
• Toxicity / safety: Some studies on higher doses in animals have shown good tolerability.

7. Ficus religiosa (Peepal)

• Uses: Decoctions from bark, etc., traditionally used.
• Mechanisms: Contains polyphenols, flavonoids, tannins, sterols; sitosterol-d-glucoside may play a role in hypoglycemia.

8. Syzygium cumini (Jamun)

Seeds have been used traditionally; contain jamboline, which may inhibit carbohydrate metabolism Jamun seed powder contains jamboline and ellagic acid, which inhibit starch-to-sugar conversion and exhibit antioxidant effects. [8]

       9. Curcuma longa (turmeric) – anti-inflammatory and insulin-sensitizing

10. Other notable herbs

• Allium sativum (Garlic): Allicin and related sulfur compounds enhance insulin secretion and may have insulin-sparing effects.
• Aegle marmelos (Bael): Aqueous extracts reduce blood sugar in animal models.

Indian medicinal plants exhibit antidiabetic effect by multiple pharmacological pathways such as:

1. Stimulation of pancreatic β-cells (e.g., Gymnema, Fenugreek)

2. Insulin-mimetic activity (e.g., Momordica)

3. Inhibition of α-amylase and α-glucosidase, reducing carbohydrate absorption

4. Antioxidant activity, limiting oxidative stress-induced damage

5. Modulation of glucose transporters (e.g., GLUT-4 upregulation)

6. Improved lipid metabolism

7. These multitarget actions make polyherbal formulations particularly attractive

POLYHERBAL ANTIDIABETIC MARKETED FORMULATIONS

Ayurveda traditionally uses polyherbal blends to enhance therapeutic synergy and minimize toxicity. Scientific studies support such combinations; for example, a formulation combining Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica significantly lowered glucose in STZ-induced diabetic rats.[9]

Systematic reviews report that herbs like Gymnema sylvestre, Trigonella foenum-graecum, Momordica charantia, and Eugenia jambolana are frequently evaluated in clinical studies. [10]

In traditional Indian medicine, combining herbs is common. Scientific efforts have also focused on standardizing such formulations and testing them.

• BGR-34 (AIMIL/CSIR-NBRI & CIMAP)
• Ingredients: This is a well-known commercial Ayurvedic antidiabetic drug in India.
• Ingredients: Berberis aristata (Daruharidra), Tinospora cordifolia (Guduchi), Pterocarpus marsupium (Vijaysar), Gymnema sylvestre (Gurmar), Rubia cordifolia (Manjeestha), and Trigonella foenum-graecum (Fenugreek).
• Recognition: Claimed to be first Indian ayurvedic anti-diabetic drug; awarded by CSIR.  It Acts on carbohydrate metabolism, pancreatic function, and antioxidant pathways. It is promoted as India’s first scientifically validated Ayurvedic antidiabetic formulation developed by CSIR. [11]

·         D-400 / Diabecon (Himalaya)

Ingredients:
Includes Gymnema sylvestre, Pterocarpus marsupium, Shilajit, Commiphora mukul, Azadirachta indica.

Actions:
Enhances insulin secretion, delays glucose absorption, and supports β-cell health. [12]

·         Ayush-82 (CCRAS, Ministry of AYUSH)

Ingredients: Gymnema sylvestre, Pterocarpus marsupium, Momordica charantia, Syzygium   cumini

Actions:
Traditional polyherbal blend for managing Madhumeha; shown to reduce fasting glucose and improve lipid profile in observational studies.[13]

·         IME-9 (CCRUM/Multani Pharmaceuticals)

Ingredients:
Formulated from herbs such as Pterocarpus marsupium, Gymnema sylvestre, Syzygium cumini, Momordica charantia, and others.

Action: It Supports glycemic control and pancreatic regeneration and also marketed widely in India. [14]

·         Madhumeha Kusumakar Ras (Classical Ayurveda)

Ingredients:
A classical mineral-herbal formulation containing gold bhasma, silver bhasma, and herbs like Asparagus racemosus.

    It is a Potent formulation; should be used only under trained Ayurvedic physician supervision.

·         Other marketed products

·         Jambavasava – Jamun-based traditional liquid formulation

·         Diasulin (AYUSH) – multi-herb blend including amalaki, neem, and giloy

·         Diabeta (Baidyanath) – contains karela, jamun, methi, kutki

·         Glymin Plus – herbal-nutraceutical blend with bitter melon extract

• Herbal formulation developed in research:
  A research study formulated a decoction/tablet using Eugenia jambolana (Jamun), Gymnema sylvestre, Tinospora cordifolia, Pterocarpus marsupium, Terminalia bellerica, etc., and evaluated its anti-diabetic effect.
• Other marketed / researched formulations:
  Some reviews and pharmaceutics studies list multiple marketed herbal formulations; for example, A Review on Antidiabetic Medicinal Plants and Marketed Herbal Formulations compiled many such products.

MECHANISMS OF ACTION

Herbal antidiabetic formulations work via multiple mechanisms, such as:

1. Insulin secretion enhancement: Some herbs (e.g., Gymnema sylvestre, Pterocarpus marsupium) can stimulate β-cells to release insulin. [15]
2. Insulin sensitization: Bioactives may improve insulin receptor sensitivity or downstream signaling.
3. Inhibition of carbohydrate absorption: Some compounds reduce intestinal glucose absorption, slow digestion, or inhibit α-glucosidase/α-amylase.
4. Regeneration / protection of β-cells: Antioxidants in herbs protect pancreatic cells from oxidative damage; some may induce regeneration.
5. Antioxidant and anti-inflammatory effects: Many herbs reduce oxidative stress, a key player in diabetic complications.[16]
6. Glucose uptake enhancement: Some herbs improve peripheral uptake of glucose (e.g., in muscle) by modulating GLUT transporters.
7. Lipid-lowering effects / metabolic regulation: By reducing dyslipidemia, herbs can mitigate comorbid risks associated with diabetes.[17]

EVIDENCE: PRECLINICAL AND CLINICAL STUDIES

Preclinical Evidence

• Numerous in vitro (cell line) and in vivo (animal) studies have demonstrated that extracts of many Indian herbs (mentioned above) significantly lower blood glucose, improve glucose tolerance, and reduce biomarkers of oxidative stress.
• The polyherbal formulation study (Glycosmis + Tridax + Mango) in diabetic rats showed synergy and efficacy.
• Toxicology / safety: Some studies (e.g., with Azadirachta indica) have assessed tolerability at high doses in animals without serious adverse effects. [18-19]

Clinical Evidence

• A systematic review of Ayurvedic therapies found in different studies (both randomized controlled trials and controlled clinical trials) on botanical/herbal treatments for diabetes.
• Most-studied herbs in these trials included Gymnema sylvestre, Momordica charantia, Trigonella foenum-graecum, Eugenia jambolana.
• Some widely studied polyherbal formulas included Ayush-82 and D-400.
• Reviews summarizing traditional plants and their clinical relevance: Indian Traditional Medicinal Plants as a Source of Potent Anti-diabetic Agents presents multiple herbs with both preclinical and limited clinical data.
• A pharmaceutics study formulated a multi-herb anti-diabetic tablet (Amla, Gymnema, Giloy, Vijaysar, Baheda, Jamun) and evaluated it (though mostly in preclinical).[20]

ADVANTAGES OF HERBAL FORMULATIONS SYNERGISTIC EFFECTS:

Combining herbs may enhance efficacy and reduce required doses.

• Lower side-effect profile: Compared to synthetic drugs, many herbs have fewer adverse effects when used appropriately.
• Cost-effectiveness & accessibility: Many herbs are readily available or can be produced locally, which can be economically favorable.
• Multitargeted approach: Since diabetes involves complex pathology (insulin resistance, β-cell dysfunction, oxidative stress), herbs targeting multiple pathways may be beneficial.[21]

CHALLENGES, RISKS, AND LIMITATIONS

While promising, herbal formulations also face several challenges:

1. Standardization: Variability in plant source, extraction method, and batch-to-batch consistency can affect efficacy.
2. Dose determination: Unlike synthetic drugs, establishing effective and safe doses is more complex.
3. Quality control: Risk of adulteration, contamination (heavy metals, pesticides), or misidentification of plants.
4. Limited high-quality clinical trials: Though many preclinical studies exist, robust large-scale randomized controlled trials (RCTs) are fewer.
5. Regulatory issues: In India and globally, herbal medicines face regulatory hurdles for classification, safety, and marketing.
6. Interactions: Herbal formulations may interact with conventional antidiabetic drugs, risk of hypoglycemia, or other pharmacodynamic/pharmacokinetic interactions.
7. Long-term safety: Less data on long-term use, especially in comorbid conditions or in the presence of complications.

SCIENTIFIC AND CLINICAL EVIDENCE IN INDIA

While a substantial body of laboratory research supports the glucose-lowering effects of Indian herbs, clinical validation remains modest. A systematic assessment of studies conducted in India found that many herbal formulations demonstrate improvements in fasting glucose, postprandial glucose, and lipid parameters, but sample sizes are generally small, and study quality varies. Polyherbal blends such as Ayush-82 and Diabecon show potential but require larger trials to substantiate claims. [22-23].

FUTURE DIRECTIONS AND RESEARCH NEEDS

To better leverage herbal formulations for diabetes in India, the following steps are crucial:

• Rigorous clinical trials: Well-designed, large-scale RCTs to evaluate efficacy, safety, and dose-response of herbal formulations.
• Standardization of extracts: Development of pharmacognostic standards, chemical fingerprinting, and quality control protocols.
• Integration with conventional care: Studies to assess additive or synergistic effects of herbs when used alongside standard antidiabetic drugs, and monitor for interactions.
• Pharmacokinetic and mechanistic studies: To understand how bioactive compounds are absorbed, metabolized, and exert action in the body.
• Regulatory framework strengthening: Clear guidelines for herbal drug approvals, safety monitoring, and good manufacturing practices (GMP) for herbal formulations.
• Public awareness and education: Informing patients and healthcare providers about evidence-based herbal options and potential risks.

CONCLUSION

Herbal formulations have a long and well-established history in India’s medical systems. A substantial number of medicinal plants—Gymnema sylvestre, Momordica charantia, Tinospora cordifolia, Pterocarpus marsupium, among others—have shown promising antidiabetic effects in preclinical and some clinical settings. Polyherbal products like BGR-34 illustrate how traditional knowledge can be translated into modern therapeutic options.

However, to fully realize their potential, challenges around standardization, clinical evidence, regulatory oversight, and quality control must be addressed. With systematic research and integration into mainstream care, herbal therapies could serve as complementary strategies in diabetes management in India, providing cost-effective, culturally consonant, and relatively safe options.

India’s traditional medicinal heritage provides a rich resource for managing diabetes through herbal formulations. Numerous plants—such as Gymnema sylvestre, Pterocarpus marsupium, Momordica charantia, and Tinospora cordifolia—show strong antidiabetic potential. Marketed products like BGR-34, Diabecon, and Ayush-82 illustrate the application of polyherbal science in contemporary settings. However, robust clinical trials, standardization, and pharmacovigilance remain essential to ensure safety and efficacy.

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