INTRODUCTION:

Hyperglycaemia, or elevated blood sugar, is a comorbid condition known as diabetes mellitus. This condition is brought on by insufficient insulin secretion, action, or both Diabetes is a severe health issue that has gotten out of control. In the world today, type 2 diabetes affects around 500 million people. The number of diabetics worldwide is anticipated to increase from 171 million in 2000 to 366 million by 2030, a doubling that will mostly benefit India. By 2030, 79.4 million Indians may suffer from diabetes. The WHO predicts that the majority of the costs would be borne by the poorest countries. These metabolic imbalances can lead to long-term pathogenic issues such as macro- and microvascular effects retinopathy, nephropathy, neuropathy¹. A complex metabolic condition called diabetes mellitus is linked to human β-cell, insulin signalling, and insulin resistance failure, abnormal lipid and glucose metabolism, elevated oxidative stress, and subclinical inflammation. It was calculated to impact 2.8% of people on the planet in 2000, and it is likely to have an impact of 4.4% in 2030 as a result of population aging and a continuous rise in obesity². These metabolic problems cause long-term pathogenic conditions such as nephropathy, neuropathy, retinopathy, and micro-and macrovascular results. Resulting in a decline in life quality and a rise in the frequency of death .1–3 Among the several risk factors that contribute to the occurrence .With the development of type 2 diabetes mellitus, the primary adjustable factor is nutrition³.

Diabetes is becoming more and more common, particularly in developing nations. It is powered by rising rates of obesity throughout life, primarily as a result of a lack of exercise and unhealthy eating habits. In not too distant a future, diabetes is estimated to affect 9.3% of the world's population. Over 500 million people worldwide suffer from type 2 diabetes (T2D), and an additional 500 million have impaired glucose tolerance, partly as a result of poor dietary consumption. About 60% of people in Portugal are overweight due to a diet based on the Mediterranean diet that is gradually shifting toward unhealthy Westernized eating habits and a decline in physical activity. Europe has one of the highest rates of T2D prevalence⁴. Around the world, diabetes mellitus is a very common condition that is linked to higher rates of illness and death.

Diabetes-related metabolic diseases are crucial to the therapeutic management of diabetes because they cause disruptions in insulin secretion or action efficiency, which results in hyperglycaemia and elevated advanced glycated haemoglobin (HbA1c). as well as pathophysiology. Furthermore, individuals with diabetes frequently have dyslipidaemia, which is defined by elevated triglycerides (TG), cholesterol, low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL). Diabetes type 2 is the most common type of the disease. It is well recognized that obesity plays a significant role in the incidence of type 2 diabetes and it's linked to an excess of free fatty acid (FFA) synthesis. Among the flowering plants in the Mallow family is Abelmoschus esculentus (AE), popularly referred to as okra. In many nations, the fruit of AE is eaten as a favourite vegetable⁵.

Apart from its elevated levels of fibre, vitamins, and trace elements, AE is recognized for its therapeutic properties, particularly in relation to its anti-hyperglycaemic impact. A few numbers of scientific studies have determined the therapeutic targets that AE acts on, notwithstanding its benefits for diabetic patients. In a prior study, Sabitha et al. found that AE decreased blood glucose and lipids, as well as elevated body weight in diabetic rats produced by streptozotocin (STZ)⁶. Due to its strong anti-oxidation properties, AE has been demonstrated to reduce lipid peroxidation. raise the concentrations of catalase, superoxide dismutase. Our earlier study clearly showed the extraction processes and produced a number of subfractions from AE, which were then examined for their molecular targets and individual impacts to stop diabetic renal epithelial to stromal change. Furthermore, it has been shown recently that AE subfractions can stop FFA-induced β cell death by blocking dipeptidyl peptidase-4, a crucial target for type 2 diabetes treatments. In light of this, we employed modified extraction procedures in the current study and examined AE subfractions in insulin-resistant type 2 diabetic rats. Our goal was to investigate if AE subfractions can alleviate the insulin-induced metabolic disruptions⁷.

Hyperglycaemia is a feature of diabetes mellitus (DM), one of the most common metabolic diseases in the world. In recent decades, DM has become more commonplace worldwide. By 2045, 693 million persons worldwide will be impacted by diabetes, according to figures from the International Diabetes Federation (IDF). Type 2 diabetes (T2DM), which accounts for 90–95% of cases, is the most prevalent type of the disease. Untreated type 2 diabetes (T2DM) causes severe macrovascular and microvascular effects that put great pressure on health care systems and increase mortality, renal failure, blindness, and overall reduced quality of life. Treatment options for type 2 diabetes include anti-diabetic medications, dietary and lifestyle modifications, and physical activity to lower blood sugar levels⁸ .

Type of Diabetes mellitus⁹:

1. Type 1 Diabetes Mellitus

2. Type 2 Diabetes Mellitus

3. Gestational Diabetes Mellitus

Symptoms for both diabetes conditions may include¹ :

· High levels of sugar in the blood

· Unusual thirst

· Frequent urination

· Extreme hunger and Loss of weight

· Blurred vision

· Nausea and Vomiting

· Extreme Exhaustion and Weakness

· Irritability and Mood Swings

Fig. 1: Symptoms for both diabetes conditions.

If a woman does not already have diabetes, she may acquire gestational diabetes during pregnancy. Women who have gestational diabetes subsequently acquire type 2 diabetes in around 50% of cases, without symptoms and this affects somewhere between two and ten percent of pregnancies each year in USA.

1. Diabetes brought on by conditions affecting the pancreas, including pancreatitis, trauma, infection, pancreatic cancer, and pancreatectomy.

2. Drug and chemical-induced diabetes from drugs that disrupt insulin secretion or insulin action.

3. Due to endocrine disorders that cause excess secretion of hormones that antagonize insulin like Cushing’s syndrome.

4. Other genetic syndromes sometime associated with this such as Prader-Willi syndrome, Down’s syndrome, Friedreich’s ataxia.

5. Uncommon specific forms of immune-mediated diabetes for example immunological disorders other than those that cause type 1 diabetes.

6. Infection-related diabetes caused by viral infection associated with beta cell destruction¹.

The normal range for blood glucose levels, which helps diagnose diabetes mellitus, is defined based on the following tests¹⁰ :

1. Fasting Blood Glucose (Fasting Plasma Glucose - FPG):

Normal: Less than 100mg/dL (5.6mmol/L)

Prediabetes: 100 to 125mg/dL (5.6 to 6.9mmol/L)

Diabetes: 126mg/dL (7.0mmol/L) or higher on two separate tests

2. Oral Glucose Tolerance Test (OGTT):

Normal: Less than 140mg/dL (7.8 mmol/L) two hours after drinking a glucose-rich drink

Prediabetes: 140 to 199mg/dL (7.8 to 11.0mmol/L)

Diabetes: 200mg/dL (11.1mmol/L) or higher

3. Random Blood Glucose Test:

Normal: Less than 140mg/dL (7.8mmol/L)

Diabetes: 200mg/dL (11.1mmol/L) or higher with symptoms of diabetes

4. Hemoglobin A1c (HbA1c) Test:

Normal: Below 5.7%

Prediabetes: 5.7% to 6.4%

Diabetes: 6.5% or higher on two separate tests

Table 1: Blood Glucose Chart.

Blood Glucose Chart
Mg/DL	Fasting	After Eating	2-3 hours After eating
Normal	80-100	170-200	120-140
Impaired Glucose	101-125	190-230	140-160
Diabetic	126+	220-300	200+

Nutraceuticals:

Stephen De Felice, founder and chairman of the Foundation for Innovation in Medicine, Cranford, NJ, invented the phrase "nutraceutical" in 1989 by combining the words "nutrition" and "pharmaceutical." A food or component of food that offers medical or health advantages, such as the prevention and/or treatment of an illness, is referred to as a nutraceutical, in De Felice's definition. The Greek physician and inventor HIPPOCRATES once remarked, "Let food be your medicine." "Focus on prevention" is the guiding principle¹¹.

European medicine law has defined nutraceuticals as a medicine because of these reasons:

1. It can be used for the prevention, treatment, or cure of a disease condition.

2. It can be administered with a view to restoring, correcting, or modifying physiological functions in human beings.

Nutraceuticals may range from isolated nutrients, herbal products, dietary supplements, and diets to genetically engineered designer foods and processed products like cereals, soups, oats and beverages. Nutraceuticals used as anti-arthritic, in cold and cough, sleeping disorders, digestion and prevention of certain cancers, osteoporosis, blood pressure, cholesterol control, pain killers, depression, diabetes, cardiovascular disease, and other chronic and degenerative diseases like Parkinson’s and Alzheimer’s diseases.

Health benefits of nutraceuticals:

1. Less/No the side effect.

2. May increase the health beneficial effect.

3. May have naturally dietary supplement, without any unpleasant side effect.

4. May increase the health value, our diet and improve medical condition of human.

5. Easily available and economically affordable¹² .

Table 2: Nutraceuticals Available in market¹³ .

S. No.	Product Brand Name	Plant constituents/Extract	Functions
1)	Fenulife	Fenugreek galactomannan	Controls Blood sugar
2)	Teamax	Green tea extract	Potent Antioxidant
3)	Cholestaid	Saponin	Reduce Cholesterol
4)	Soylife	Soybean phytoestrogen	Maintains Bone health
5)	Betatene	Carotenoids	Immune Function
6)	Clarinol	CLA	Weight loss ingredient
7)	Glucocare	Bitter melon	Control Blood sugar

Fig. 2: Nutraceutical medicine.

Classification of Nutraceuticals¹⁴:

1. Functional foods: It provides nutrition’s; it also contains antioxidants compounds that prevent diabetes.

2. Carotenoids: They are pigmented compounds like alpha-carotene, beta carotene and beta cryptoxanthin. These compounds have antioxidant and anti-inflammatory properties, used to improve vision, prevent certain cancer and improve the immune system.

3. Collagen hydrolysate: It is essential human protein secreted from skin. It has several medicinal properties.

4. Dietary fibres: They are non-starchy poorly digestible vegetable carbohydrates found in vegetables fruits, wheat bran and oats. It improves digestion and reduces Crohn’s disease and ulcerative colitis.

5. Fatty acids: These cover all vegetable oil like olive oil.

6. Phytochemicals: They are active compounds that work on balance inside the body and nervous activity, so they decrease the cancer. One of the most important of these compounds is lutein and lycopene.

7. Herbs: They are plants that do not have side effects and having antioxidant properties, for example garlic extract, ginger used for treatment of cholesterol, wound healing and antiulcer.

8. Probiotics: Microbes are considered to have many used in the medicinal field and human health. They are found in milk products and they have antioxidant properties. They work to regulate the growth of gut microbiota.

9. Dietary supplements: Tablets are dietary supplements that are taken from different sources.

Fig.3: Classification of nutraceutical.

Herbs with Anti-diabetic properties¹⁵ :

1) Momordica charantia (Bitter gourd)

Common Name: Karela

Family: Cucurbitaceae

Parts used: Fruit, seed, bark, root, leaves, oil

Oxidative stress is a contributing element to the development of problems in diabetes, and the antioxidants in bitter melon help lower it. Blocking the absorption of glucose from the intestines is another way that bitter melon lowers blood sugar levels postprandial, or after meals. By influencing the enzymes involved in the metabolism of carbs, bitter melon improves the breakdown of carbohydrates and lowers blood sugar levels. Charantin, a substance found in bitter melon, is known to reduce blood sugar levels. It functions by enhancing the liver, muscles, and adipose tissue's absorption of glucose and production of glycogen. This is a bitter melon chemical that affects insulin. It helps reduce blood sugar levels by acting in the body similarly to how insulin does¹⁶ .

Fig. 4: Momordica charantia.

2) Syzygium cumini (Blackberry)

Common name: Jamun

Family: Myrtaceae

Parts used: Seeds, leaves, fruit, bark

These substances found in Syzygium cumini seeds have been shown to have hypoglycaemic effects by increasing the body's use of glucose and insulin secretion. Diabetes development is thought to be influenced by chronic inflammation. The anti-inflammatory qualities of Syzygium cumini aid in the management of insulin resistance brought on by inflammation. It has been shown that syzygium cumini lowers the post-meal spike in blood sugar, which is particularly significant for the control of diabetes. It has been shown that syzygium cumini lowers the post-meal spike in blood sugar, which is particularly significant for the control of diabetes¹⁷.

Fig. 5: Syzygium cumi.

3) Trigonella foenum-graecum (fenugreek)

Common name: Methi

Family: Fabaceae

Parts used: Leaves, seeds

Flavonoids, one type of antioxidant found in fenugreek seeds, aid in the fight against oxidative stress, a growing in diabetes that can result in consequences like neuropathy, nephropathy, and cardiovascular disease. Studies have shown that fenugreek reduces LDL cholesterol and triglycerides, which is especially advantageous for diabetics who are more susceptible to cardiovascular illnesses. Fenugreek seeds' soluble fibre slows down the pace at which carbs are absorbed and digested, assisting in the maintenance of lower blood sugar levels¹⁸ .

Fig. 6: Trigonella foenum-graecum.

4) Cinnamomum zeylanicum (cinnamon)

Common name: Dalchini

Family name: Lauraceae

Parts used: Leaves, bark

Type 2 diabetes and insulin resistance are linked to chronic inflammation. Because of its anti-inflammatory qualities, cinnamon may be able to lessen inflammation and maybe enhance insulin action. Strong antioxidants called polyphenols are found in Ceylon cinnamon. These substances aid in the reduction of oxidative stress, which is linked to the development of insulin resistance and the difficulties associated with diabetes. Cinnamon helps lessen the postprandial (after-meal) surge in blood glucose levels by slowing down the process of food leaving the stomach¹⁹.

Fig. 7: Cinnamomum zeylanicum.

5) Nigella sativa (Black cumin)

Common name: Kalonji

Family: Ranunculaceae

Part used: seeds

Nigella sativa has a high antioxidant content that lowers oxidative stress. A major factor in the onset and evolution of diabetes and its after effects, including neuropathy, nephropathy, and cardiovascular disorders, is oxidative stress. Diabetes development and insulin resistance are linked to chronic inflammation. Because of its anti-inflammatory qualities, Nigella sativa may help lower inflammation and enhance insulin action. Studies have indicated that the consumption of Nigella sativa supplements can lead to a significant decrease in both fasting blood glucose levels and HbA1c, an indicator of sustained blood sugar regulation²⁰.

Fig.8: Nigella sativa.

6) Allium sativum (Garlic)

Common name: Garlic

Family: Amaryllidaceae

Parts used: leaves, flower, cloves

Research indicates that a consistent intake of garlic may result in a noteworthy decrease in both fasting blood glucose levels and HbA1c, an indicator of sustained blood sugar regulation. Antioxidants found in garlic include flavonoids, selenium, and vitamins C and E. These antioxidants aid in lowering oxidative stress, a significant factor in the onset and progression of diabetes. Diabetes development and insulin resistance are intimately linked to chronic inflammation. Because of its anti-inflammatory qualities, garlic may help lower inflammation, which will enhance insulin activity and blood sugar regulation. Patients with diabetes have an increased risk of cardiovascular illnesses. Garlic has been demonstrated to lower blood pressure, raise HDL cholesterol, decrease LDL cholesterol, and enhance heart health overall—all of which are critical for diabetics ²¹.

Fig. 9: Allium sativum.

7) Gymnema sylvestre

Common name: Gurmar

Family name: Asclepiadaceae

Parts used: Rhizomes, leaves, volatile oils

It has been shown that gymnemic acids decrease the intestinal absorption of sugar, resulting in a decrease in postprandial (after-meal) blood glucose levels. This impact facilitates more efficient blood sugar management. It has been discovered that gymnema sylvestre stimulates the pancreas to produce more insulin, especially in people with type 2 diabetes. This may aid in lowering blood sugar levels and enhancing glucose metabolism. Many antioxidants included in gymnema sylvestre aid in lowering oxidative stress, which is linked to the advancement of diabetes and its side effects, including neuropathy, nephropathy, and cardiovascular disorders. Gymnema sylvestre regular use has been linked to a reduction in HbA1c levels, which are a measure of long-term blood sugar regulation. Better overall blood glucose control is indicated by lower HbA1c value²².

Fig.10: Gymnema sylvestre.

8) Ocimum sanctum:

Common name: Tulsi

Family: Lamiaceae

Parts used: Whole plant and leaf oil

Studies on holy basil have demonstrated a reduction in blood glucose levels during fasting and postprandial (after eating) periods. It enhances the metabolism of carbs, assisting in better blood sugar regulation. Antioxidants such as flavonoids and phenolic substances abound in holy basil. These antioxidants aid in the reduction of oxidative stress, which is a significant contributor to the development of diabetes and its side effects, including neuropathy and cardiovascular disease. Type 2 diabetes and insulin resistance are closely associated with chronic inflammation. The anti-inflammatory qualities of holy basil aid in reducing inflammation, which may enhance insulin action and improve metabolic health in general²³.

Fig.11: Ocimum sanctum.

Table 5:Marketed Antidiabetic Nutraceuticals⁸ .

S. No.	Plant name	Chemical constituents		Marketed formulation
1	Bitter Melon	Charantin, Polypeptide-p, Vicine		Capsules, Extracts, Juices
2	Fenugreek	4-Hydroxyisoleucine, Trigonelline, Saponins		Powders, Capsules, Tablets, Seeds
3	Cinnamon	Cinnamaldehyde, Polyphenols, Proanthocyanidins		Capsules, Powders, Bark, Essential Oil
4	Turmeric	Curcumin, Demethoxycurcumin		Capsules, Tablets, Powders, Extracts
5	Aloe Vera	Polysaccharides (acemannan), Aloin, Glucomannan		Juices, Gels, Capsules, Tablets
6	Green Tea	Epigallocatechin gallate (EGCG), Catechins	Capsules, Teas, Powders, Extracts
7	Garlic	Allicin, S-allyl cysteine, Sulfur compounds	Tablets, Capsules, Aged Garlic Extract, Oil

Categories in nutraceuticals and their role in diabetes²⁶:

Nutraceutical are non-specific biological therapies used to promote wellness, prevent malignant processes and control symptoms. These can be grouped into the following three broad categories:

a. Nutrients: Substance with established nutritional functions, such as vitamins, minerals, amino acid, and fatty acids.

b. Herbals: Herbs or botanical products as concentrates and extracts.

c. Dietary supplements: Reagents derived from other sources (e.g., pyruvate, chondroitin sulphate, steroid hormone precursors) serving specific functions, such as sports nutrition, weight-loss supplements and meal replacements.

Fig.13: Need for diabetes-preventive nutraceutical.

Antioxidant of vitamins:

Research on animals has shown that by protecting against oxidative stress, a sufficient intake of dietary antioxidants can either avoid or delay the effects of diabetes, such as renal and neurological damage. There isn't enough conclusive data on humans, though³.

Vitamins C:

A chain-breaking antioxidant, vitamin C (ascorbic acid) directly removes reactive oxygen species (ROS) and stops chain reactions from starting that would otherwise reduce protein glycation. Lipid peroxides in erythrocytes and sorbitol formation brought on by diabetes are also lessened in animals by vitamin C. Insulin resistance and endothelial dysfunction are not improved by vitamin C (800 mg/day), although it did partially restore vitamin C levels in patients with type 2 diabetes and low vitamin C levels²⁷ .

Calcium/Vitamin D:

High calcium intake was found to be protective against diabetes in one of the first large prospective studies to look at the impact of habitual diet on the risk of the disease. After adjusting for a number of potential confounders, women in the top quintile of calcium intake were 30% less likely to develop diabetes over a 6-year follow-up. Unexpectedly, it doesn't seem like any more research have taken this line. There are no prospective studies that look at how sun exposure or regular vitamin D intake affects the risk of diabetes. However, there is theoretical reason to believe that maintaining a healthy calcium and vitamin D status may help to sustain insulin sensitivity and hence help prevent diabetes mellitus by decreasing the secretion of parathyroid hormone (PTH)²⁸.

Vitamin E:

The main role of vitamin E, an important fat-soluble vitamin, is that of an antioxidant. Diabetes incidence has been linked to low vitamin E levels, and some study indicates that antioxidant levels may be lower in diabetics. Further data suggests that individuals with diabetes may also require higher levels of antioxidants since their hyperglycaemia increases the formation of free radicals. It is generally accepted that vitamin E dosages up to 400 IU are safe. Supplement trials that have tracked subjects' Prothrombin times have not shown any increases in prothrombin times, but doses more than 800 IU may affect blood coagulation²⁹ .

Carbohydrates:

The energy substrate that has the biggest effect on glycaemic levels is carbohydrate. The post-prandial reaction is mainly caused by the overall amount of carbs used, but other factors may also be involved, including the kind of carbohydrates, fibre content, cooking method, maturity level, etc. Additionally, pre-prandial glycaemia, the distribution of macronutrients throughout the meal (fats and proteins), and the type of hypoglycaemic medication used—insulin or oral tablets—can all have an impact on post-radial glycaemia. The majority of scientific societies support the idea that each person's daily intake of carbs should be customized and concur that fruits, cereals, pasta, legumes, vegetables, and tubers are good sources of carbohydrates. Eating legume starches appears to have a beneficial effect on glycaemia, despite the lack of long-term research; this is because the effect is stable and does not increase suddenly after a meal; this suggests that it may avoid both post-prandial hyperglycaemia and late hypoglycaemia³⁰.

Fats:

High fat intake has been linked to impaired glucose tolerance, obesity, dyslipidaemia, and atherosclerotic heart disease, according to a number of studies. Research additionally indicates that lowering consumption of saturated fat might alleviate or correct these same metabolic problems. The current guidelines for fat consumption for the general public also apply to individuals with diabetes: cut back on cholesterol to 300 mg/d or fewer and saturated fats to 10% or less of total caloric intake. The best substitute for saturated fat, polyunsaturated fat, monounsaturated fat, or carbohydrate calories is still up for scientific dispute. Studies indicate that monounsaturated fats, including those found in canola, olive, and peanut oils, may help lower triglycerides and improve glucose regulation in certain diabetics; however, caution must be exercised to prevent weight gain. Omega-3 fatty acids, which are present in fish like mackerel and salmon, have the potential to lower serum triglycerides without compromising glycaemic management³¹.

Fibre:

Whole grains are particularly noted. Fruits and vegetables that are high in dietary fibre are still advised. While fibres have a well-established protective impact against many chronic diseases, their efficacy in managing lipid and glycaemic metabolism is yet unknown. For the general population, it is advised that men and women consume 38g and 26g daily, respectively. There's no justification for giving diabetic patients more fibre³².

Magnesium:

Diets high in magnesium are associated with a lower risk of diabetes, according to prospective epidemiology. Intake of magnesium is inversely correlated with fasting insulin levels, indicating increased insulin sensitivity. Limited clinical evidence and animal research showing magnesium helps maintain dipocyte insulin sensitivity support this perspective. Due to its high concentration of easily oxidized polyunsaturated fatty acids, which are primarily located in photoreceptor outer membranes, the retina is especially susceptible to oxidative damage.37 Age-related macular degeneration (AMD) has been the subject of nutritional supplementation research. The Age-Related Eye Disease Study found that individuals with later stages of AMD who took a high-dose zinc plus antioxidants supplement had a 25% lower risk of developing advanced AMD³³.

Protein:

Current evidence indicates people with diabetes have similar protein requirements to those of the general population-about 0.86 g/kg per day. Although protein plays a role in stimulating insulin secretion excessive intakes should be avoided as it may contribute to the pathogenesis of diabetic nephropathy. Some evidence suggests eating vegetable protein rather than animal protein is better for reducing serum cholesterol and managing nephropathy. There are a number of different types of protein supplements include liquid protein supplements, protein powders and liquid protein shots. There are a number of sources for protein supplements. Some of these sources include: Whey, Casein, Soy, Rice, and Egg³⁴ .

Anti-diabetic claims of herbs³⁵:

Diabetes mellitus, a metabolic disease that affects lipid and carbohydrate metabolism and has a negative impact on a person's physical and mental well-being, is a global threat that is rapidly spreading throughout India. As our understanding of the variability of this order advances, so does the need for more tailored therapy. Because synthetic drugs have a limited role in treating non-insulin dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) and have a high risk of drug tolerance, which can lead to dosage increases or medication changes, traditional herbal medicines are used as a safe alternative to conventional hypoglycaemic agents. Ayurvedic herbs may act as "Potentiators" for these medications and perform a supportive role in maintaining the quality of life for diabetics due to their richness in vital phytonutrients. Selected therapeutic herbs from Indian traditional medicine and Ayurveda have enormous potential. The significance of herbal nutraceuticals, nutritional’s, and naturals in metabolic illnesses like diabetes has been the subject of numerous attempts by CSIR, ICMR, DBT, and academics (Table 6).

Future aspects of nutraceutical in diabetes mellitus³⁶:

Nutraceuticals are dietary supplements or food products that provide health and medical benefits, including the prevention and treatment of disease. The future of nutraceuticals in managing diabetes mellitus appears promising, with several potential aspects shaping their role:

1. Personalized Nutrition and Precision Medicine:

Genomics and Nutrigenomics: Advances in genomics will enable personalized nutraceutical interventions based on an individual's genetic makeup. This could improve the effectiveness of nutraceuticals for diabetes management by targeting specific metabolic pathways.

Gut Microbiome Modulation: Research is increasingly showing the importance of gut health in diabetes. Nutraceuticals aimed at modulating the gut microbiome, such as prebiotics, probiotics, and postbiotics, may improve glucose metabolism and insulin sensitivity.

2. Plant-Derived Compounds:

Phytochemicals: Compounds like polyphenols, flavonoids, and carotenoids found in plants may help manage diabetes by reducing oxidative stress and inflammation, improving insulin sensitivity, and regulating blood sugar.

Examples: Curcumin, resveratrol, quercetin, and berberine are already being studied for their anti-diabetic properties.

Herbal Extracts: Traditional herbs like Gymnema sylvestre, Bitter melon (Momordica charantia), and Fenugreek could become more refined in formulation and delivery to maximize their efficacy in blood sugar control.

3. Omega-3 Fatty Acids and Anti-inflammatory Compounds:

Chronic low-grade inflammation is closely linked to insulin resistance and type 2 diabetes. Nutraceuticals rich in omega-3 fatty acids (like fish oil or algae oil), and other anti-inflammatory agents like ginger or turmeric, could help manage diabetes by reducing systemic inflammation.

4. Bioactive Peptides and Proteins:

Certain peptides, such as those derived from soy, milk, or fish, have been shown to improve insulin sensitivity, enhance glucose uptake, and reduce blood sugar levels. Research on bioactive peptides is expected to grow, leading to more targeted diabetic therapies.

5. Vitamin D and Other Micronutrients:

Vitamin D: Deficiency in vitamin D is associated with a higher risk of type 2 diabetes. Supplementation with vitamin D may improve insulin sensitivity and glucose metabolism. More studies are focusing on the role of this and other micronutrients like magnesium, chromium, and zinc in diabetic control.

6. Role of Antioxidants:

Oxidative Stress: As oxidative stress contributes to the development and progression of diabetes, nutraceuticals with antioxidant properties (e.g., vitamins C and E, alpha-lipoic acid, and coenzyme) may be crucial in reducing complications related to diabetes, such as neuropathy, nephropathy, and retinopathy.

7. Nutraceutical Delivery Systems:

Advances in delivery systems, such as nanoencapsulation and liposomal formulations, could enhance the bioavailability of nutraceuticals, ensuring that compounds like polyphenols and curcumin are more efficiently absorbed and utilized by the body.

8. Probiotic and Symbiotic Formulations:

Probiotics (beneficial bacteria) and symbiotic (a combination of probiotics and prebiotics) may offer another avenue for diabetes management by improving gut health and enhancing insulin sensitivity. They could help regulate blood glucose levels by reducing gut permeability and inflammation.

9. Innovations in Fiber Supplements:

Dietary fibre plays a significant role in glycaemic control by slowing the absorption of sugar. Future nutraceuticals may focus on enhancing the impact of soluble fibres like psyllium husk, β-glucans, and resistant starches on blood sugar levels.

10. Functional Foods and Fortified Foods:

Functional foods designed with added nutraceuticals such as fortified cereals, energy bars, or beverages with blood glucose-regulating properties could provide convenient options for diabetes management.

11. Research in Epigenetics:

Nutraceuticals that can modify epigenetic markers influencing the development of diabetes are an emerging area of research. This could lead to the development of compounds that target gene expression to improve metabolic health.

12. Prevention of Diabetes Complications:

The role of nutraceuticals in preventing diabetes-related complications, such as cardiovascular disease, neuropathy, nephropathy, and retinopathy, is another area of focus. For instance, nutraceuticals like alpha-lipoic acid and coenzyme Q10 have shown potential in preventing nerve damage in diabetic neuropathy.

13. Combining Nutraceuticals with Pharmaceuticals:

The future may see more integrative approaches where nutraceuticals are used in conjunction with pharmaceutical treatments for diabetes, allowing for lower doses of medication and fewer side effects.

CONCLUSION:

There is growing recognition for the potential role those bioactive substances called nutraceuticals—found in foods and dietary supplements—may have in the management of diabetes mellitus. They might lessen insulin resistance, aid in glycaemic control, and shield against diabetes-related problems. Numerous nutraceuticals have been effective in both clinical and preclinical investigations, including omega-3 fatty acids, fibre, vitamins, minerals (including magnesium and chromium), polyphenols, and botanical extracts (such berberine, fenugreek, and cinnamon). Nutraceuticals show potential as adjunctive treatments, but they cannot take the place of traditional diabetes care techniques such as medication, diet, and exercise. Individual differences in genetics, lifestyle, and disease severity can all affect how effective they are. Therefore, in order to prevent negative effects or interactions with other medicines, it is imperative that healthcare specialists be consulted prior to introducing nutraceuticals into a diabetes care plan. To determine standardized dosage, safety profiles, and mechanisms of action for particular nutraceuticals in the setting of diabetes, more research is required.

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Received on 10.10.2024 Revised on 04.11.2024

Accepted on 19.11.2024 Published on 05.03.2025

Available online from March 11, 2025

Res. J. Pharmacognosy and Phytochem. 2025; 17(1):27-37.

DOI: 10.52711/0975-4385.2025.00006

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

S. No.	Plant Common Name	Biological source	Phytoconstituent	Health Benefits
1	Karela	Momordica charantia	Charanti, Vicine, Polypeptide-p, antioxidant	Anti-diabetic Properties
2	Jamun	Syzygium cumini	Flavonids, saponins, glycoside	Anti-diabetic properties, Reduce BP
3	Methi	Trigonella foenum graecum	Saponin,4-Hydroxy isoleucine and Trigonelline, Alkaloid	Hypoglycemic agent
4	Dal Chini	Cinnamonium zeylanicum	Cinnamaldehyde	Anti-diabetic
5	Kalonji	Nigella sativa	Thymoquinone	Hypoglycemic Agent
6	Garlic	Allium sativum	Allicin	Anti-diabetic
7	Gurmar	Gymnema sylvestre	Triterpene saponins	Hypoglycemic Agent

S. No.	Vitamins	Source	Health benefits
1)	Vitamin A	Green leafy vegetables, Guava, Ripe yellow fruits, Milk, Broccoli	Reduce blood sugar and Potent Anti-oxidant, Improve skin health
2)	Vitamin B1 (Thymine)	Fresh fruits, Potatoes, Sweet potatoes, Peas, Corn, Cashew, Nuts, Milk	Control Diabetes and essential neurologic
3)	Vitamin B3 (Niacin)	Meat, Fish, Eggs, Milk, Cereals, Mushroom	Reduce blood sugar
4)	Vitamin B6 (Pyridoxine)	Chicken, Beans, Avocado, Sunflower seeds, Sesame seeds	Helps to produce essential proteins and maintain blood sugar level
5)	Vitamin C (Ascorbic acid)	Fresh fruits, Broccoli, Goat milk, Chestnuts, Black currant	Anti-oxidant (reduce damage cause by free radicals), Decrease hypertension
6)	Vitamin D	Fish liver oil, Egg, Beef, Chicken breast	Improve glucose tolerance and insulin resistance, Improve bone health
7)	Vitamin E	Potatoes, Pumpkin, Milk, Nuts, Seeds, Mango	Improve renal dysfunction, The rentinal blood flow

S. No.	Name of the plant	Reported mechanism of action
1	Annona squamosal L. Common name: Sugar apple [Family: Annonaceae]	Lowers blood glucose level.
2	Allium sativum L. Common name: garlic [Family: Alliaceae]	Has strong antioxidant activity and rapid reactivity with thiol containing proteins responsible for the hypoglycaemic property.
3	Biophytum sensitivum (L.) DC. Common name: Life Plant [Family: Oxalidaceae]	Stimulates pancreatic beta cells to release insulin.
4	Beta vulgaris L. Common name: Garden beet [Family: Chenopodiaceae]	Lowers blood glucose level.
5	Brassica juncea (L.) Czern. Common name: Brown Mustard [Family: Brassicaceae]	Increases the concentration of hepatic glycogen and glycogenesis and suppressed the activity of glycogen phosphorylase and gluconeogenic enzymes, lead to reduction in glycogenolysis and gluconeogenesis.
6	Cassia auriculata L. Common name: Tanner’s Cassia [Family: Leguminosae]	Suppresses enhanced gluconeogenesis during diabetes and enhance utilization of glucose through increased glycolysis in addition to pronounced alpha glucosidase inhibitory actions resulting in a significant and potent lowering of blood glycaemic response.
7	Boerhavia diffusa L. Common name: Tar vine [Family: Nyctaginaceae]	Increases plasma insulin levels and improves glucose tolerance, produces significant antioxidant activity.