INTRODUCTION:

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia and high blood sugar levels in postprandial and fasting states. (Fattaheian-Dehkordi S, et.al, 2021).¹⁴

Diabetes is a rapidly growing global health issue that affects people worldwide. This condition is characterized by high blood glucose levels, which occur due to either insufficient insulin production or the body's ineffective use of insulin. Type 2 diabetes, also known as non-insulin-dependent diabetes mellitus, is the most common form, accounting for 90% - 95% of diabetes cases. It usually develops in adults, but more and more young people are being diagnosed. This type of diabetes is often linked to lifestyle factors such as poor diet, lack of exercise, and obesity.

According to the World Health Organization, the global diabetic population is projected to reach or exceed 300 million by 2025. (Patel DK.et.al, 2012).³⁹

The global incidence of diabetes is rapidly increasing. In 2019, the prevalence was estimated at 9.3%, affecting around 463 million people worldwide. This number is expected to rise to 10.2% (578million) by 2030 and further to 10.9% (700million) by 2045. Diabetes is more prevalent in urban areas, with a rate of 10.8% compared to 7.2% in rural areas. High-income countries also have a higher prevalence (10.4%) compared to low-income countries (4.0%). Alarmingly, half of the individuals with diabetes (50.1%) are unaware of their condition, indicating a significant lack of diagnosis and awareness. Additionally, the global prevalence of impaired glucose tolerance, a precursor to diabetes, was estimated to be 7.5% (374million) in 2019, with projections indicating an increase to 8.0% (454million) by 2030 and 8.6% (548 million) by 2045. These statistics highlight the urgent need for improved global health initiatives focused on education, screening, and management of diabetes to address its growing impact and enhance health outcomes worldwide. (Saeedi P, et.al, 2019)⁴⁵

Almost half a billion people worldwide have diabetes, with the number projected to increase by 25% in 2030 and 51% in 2045. (Saeedi P, et.al, 2019)⁴⁵

Diabetes is a condition characterized by high levels of blood sugar, or glucose, which is a critical source of energy for the body. Normally, the body regulates blood sugar through the production of insulin, a hormone that helps glucose enter cells to be used for energy. However, in diabetes, this process is disrupted. The body either does not produce enough insulin, fails to produce any insulin, or cannot effectively use the insulin it does produce. As a result, glucose remains in the bloodstream instead of being absorbed by the cells. This persistent high blood sugar can lead to various health complications. Additionally, diabetes has been linked to an increased risk of certain types of cancer, emphasizing the importance of managing this condition. Preventive measures and effective management strategies for diabetes, such as maintaining a healthy diet, engaging in regular physical activity, and monitoring blood sugar levels, are crucial in reducing the risk of developing diabetes and mitigating its associated health risks.

Epidemiology:

India is currently facing a major diabetes crisis, with over 74 million affected individuals, which represents more than 8.3% of the adult population. Alarmingly, about 57% of these cases are undiagnosed, posing a significant public health challenge. Among young and middle-aged adults, the prevalence of diabetes is 6.7%, with an additional 5.6% classified as prediabetic, according to the National Family Health Survey-4. The average age of onset is relatively young at 42.5 years, indicating a growing trend of earlier disease manifestation. Annually, nearly 1 million Indians succumb to diabetes-related complications.

Projections by the Indian Heart Association suggest that by 2035, India will be home to 109 million individuals with diabetes. Additionally, a study by the American Diabetes Association predicts that India will experience the most significant increase in diabetes diagnoses by 2030. This surge in incidence is primarily attributed to a combination of genetic predisposition and lifestyle changes, particularly among India's expanding middle class. The adoption of a high-calorie diet coupled with a sedentary lifestyle has exacerbated the genetic vulnerability, leading to a rapid increase in diabetes cases. This trend underscores the urgent need for public health interventions focused on lifestyle modifications, early detection, and effective management of diabetes to mitigate its impact on the Indian population. (Pradeepa R et.al., 2021)⁴¹

Pathophysiology of Diabetes:

Insulin, produced by the pancreas, is the primary hormone responsible for regulating blood sugar levels in the body. It primarily affects liver, fat tissue, and muscle cells. Insulin's main function is to facilitate the uptake and utilization of glucose by cells, thereby reducing blood glucose levels. It does this by inhibiting the breakdown of stored glycogen into glucose in the liver and promoting the uptake of glucose into fat and muscle cells. This helps in energy production and storage. Insulin also promotes the storage of glucose in the form of glycogen, primarily in the liver and muscle tissues. This glycogen serves as a readily accessible source of glucose when the body requires additional energy, such as during periods of fasting or physical exertion. Insulin additionally regulates blood sugar levels by suppressing the release of glucose from the liver into the bloodstream, contributing to glycemic control. Overall, insulin's actions contribute to the maintenance of optimal blood sugar levels, ensuring that cells receive an adequate supply of glucose for energy production and storage while preventing hyperglycemia. Dysfunction in insulin production or signaling pathways can lead to imbalances in blood sugar regulation, contributing to the development of various forms of diabetes and associated metabolic disorders. (Guthrie RA et al., 2004)

Insulin, produced by beta cells within the pancreatic islets of Langerhans, plays a crucial role in regulating blood sugar levels in the body. When blood glucose levels rise, beta cells release insulin into the bloodstream. Insulin helps cells throughout the body take up glucose, using it for energy or storing it for later use. Conversely, when blood sugar levels are low, beta cells release less insulin and convert stored glycogen into glucose to raise blood sugar levels. Insulin works in tandem with glucagon, another hormone produced by the pancreas, to keep blood sugar levels within a narrow range. If insulin is insufficient or not working properly, as in cases of insulin resistance or defective insulin production, cells cannot effectively take up glucose, leading to persistently high blood sugar levels, known as hyperglycemia. Without proper insulin action, cells cannot use glucose for energy or storage, resulting in various metabolic disturbances and complications associated with diabetes. In summary, the balance between insulin and glucagon is crucial for regulating blood sugar levels. When this balance is disrupted due to insulin deficiency or dysfunction, it leads to persistent high blood sugar levels and a range of metabolic disorders, highlighting the critical role of insulin in maintaining metabolic balance. (Plows JF et al.,2018)

When blood sugar remains high over time, the kidneys reach a point where they start excreting sugar through urine (glycosuria). This increases the osmotic pressure of the urine, preventing water from being reabsorbed by the kidneys, leading to increased urine production (polyuria) and increased fluid retention. The body tries to replace the lost fluids by drawing water from the brain and other parts of the body, causing dehydration and increased thirst (polydipsia). Furthermore, the lack of glucose in cells stimulates appetite, leading to overeating (polyphagia). (Guthrie RA et al. 2004).

Signs and Symptoms of Diabetes:

· Weight loss

· Increased hunger

· Raised thirst

· Extreme fatigue

· Blurry vision

· Frequent urination

· Cuts and wounds take longer to heal.

Diabetes and its complication:

Diabetes is a complex metabolic disorder that can have a profound impact on various organ systems in the body, leading to a wide range of complications. These complications can be broadly categorized into microvascular and macrovascular complications. Microvascular complications primarily affect small blood vessels and include neuropathy (nerve damage), nephropathy (kidney damage), and retinopathy (eye damage). Neuropathy can manifest as tingling, numbness, or pain in the extremities, while nephropathy can progress to kidney failure. Retinopathy can cause vision impairment or even blindness. On the other hand, macrovascular complications involve larger blood vessels and are associated with cardiovascular diseases such as coronary artery disease, stroke, and peripheral vascular disease. These conditions increase the risk of heart attacks, strokes, and circulation problems in the limbs. (Deshpande AD et.al 2008)

· Heart Disease and Stroke

· Peripheral Arterial Disease

· Retinopathy (Blindness)

· Nephropathy (renal disease)

· Macrovascular Complications of Diabetes

Treatment for Diabetes:

The treatment for type 1 diabetes includes insulin injections or the use of an insulin pump, frequent blood sugar checks, and carbohydrate counting. In some cases, a pancreas transplant or islet cell transplant may be an option.

The treatment of type 2 diabetes mostly involves lifestyle changes, blood sugar monitoring, and may include oral diabetes drugs, insulin, or both.

Type 1 Diabetes:

1) Short acting insulin (Type 1 diabetes, Mayo clinic):

· Regular Human Insulin (RHI): Humulin R and Novolin R

2) Rapid acting insulin:

· Insulin aspart (Novolog)

· Insulin Lispro (Humalog)

· Insulin Glulisine (Apidra)

3) Intermediate acting insulin:

· NPH Insulin Novolin N, Humulin N

4) Long-acting insulin (Type I diabetes, Mayo clinic):

· Insulin degludec (Tresiba)

· Insulin detemir (Levemir)

· Insulin glargine (Lantus. Toujeosolostar)

Type 2 Diabetes:

· Metformin (Fortamet, Glumetza)

· Sulfonylureas (glyburide glipizide, glimepiride)

· Glinides (Repaglinide, Nateglinide)

· Thiozolidindiones (Rosiglitazone, Pioglitazone)

· DPP-4 inhibitors (exenatide, liraglutide, semaglutide)

· SGLT2 inhibitors (canagliflozine, dapagliflozin)

Herbal medicine available for the treatment of diabetes:

· Allium sativum

· Eugenia jambolana

· MomordicacharantiaOcimum sanctum

· Phyllanthusamarus

· Pterocarpusmarsupium

· Tinosporacordifolia

· Trigonellafoenumgraecum

· Withaniasomnifera.

Different herbs used in diabetes

· Aeglemarmelos

· Abrus precatorius

· Allium sativum

· Annona squamosal

Models for Diabetic:

1. Streptozotocin:

2. Alloxan: -

3. Gold Thioglucose: -

PLANT PROFILE:

BOTANICAL NAME: Tricholepis glaberrima

FAMILY: Asteraceae

COMMON NAME

HINDI: Brahmadandi

KANNADA: Nati Brahmadande

BENGALI: Chhagaladandi

SANSKRIT: Ajadandi

Chemical constituents:

The petroleum ether extract of Tricholepis glaberrima on chromatography over alumina yielded a sterol fraction and a triterpenoid identified as betulin. The sterol fraction on GLC resolution was found to be a mixture of spinasterol, stigmasterol, and stigmast-7-enol. (Chawla AS, et.al, 1976)

DISTRIBUTION:

It is found around West Rajputana, Mount Abu, Central India, Konkan, Deccan, Western Ghats in Bombay Presidency, and the hills of Mysore. It often grows on cultivated fields and rocky soil in grasslands. (Modak M, et.al, 2007)

Pharmacological activitiy:

1. Anti-inflammatory activity: - The anti-inflammatory activity of Brahmadandi is linked to the inhibition of the cyclo-oxygenase enzyme. A study has shown that the presence of phytochemical constituents such as alkaloids, flavonoids, glycosides, and saponins may result in significant inhibitory action against prostaglandin. (Khare E, et.al,2020)

2. Antidepressant activity: -The ethnobotanical study showed that Tricholepis glaberrima has antidepressant properties in rodents due to the presence of phytochemical constituents such as alkaloids, flavonoids, and glycosides. The study used two different models of depression, the forced swimming test and the tail suspension test, and compared the results to a standard drug, imipramine, at a dose of 10mg/kg. (Khare E, et.al,2020)

Botanical description:

It is a stout, annual erect herb, quite smooth and grayish, with purple bracts erect. The leaves are sessile, 2.5-6.3 cm by 3-6 mm, and are linear oblong or lanceolate, with an acute, entire, spinous, bristly, three-toothed, or spinous-serrate edge. The leaves are punctate, and the base of cauline leaves is not or rarely auricled, with the midrib and nerves very prominent beneath. The heads are 6-8 mm long, ovoid, and glabrous, with small and slender flowers that are more or less penciled, and few purple florets in the terminal head. The corollas are 1.25-1.4 cm long and purple. The style-arms are slender, with a ring of hairs at the base of the lobes. The pappus is shorter than the achenes, copious, yellowish brown, rigid, and subpaleaceous. The achenes are oblong and faintly ribbed. (Priyadarshi,et.al, 2018)

Use:

· Treatment of various ailments such as neurological disorders, hepatic disorders, sexual dysfunction, and skin diseases.

· Plant: The plant exhibits activity against liver disorders, inflammation, and acts as an antidepressant.

AIM AND OBJECTIVES:

Aim: Pharmacological evalution of Tricholepis glaberrima for antidiabetic potential in animal model.

OBJECTIVES:

Many new drugs have developed after scientifically validating the traditional uses for a variety of plants that have been used to treat diabetic disease. However, there are still a large number of herbal and medicinal plants that need to be investigated and validated. As a result, this research planned with the objective to assess how well Tricholepis glaberrima plant extract reduced blood suger level.

PLAN OF WORK:

In order to fulfill above objective, the work were planned as follows: -

· Collection, Identification and Authentication of Tricholepis glaberrima, plant material.

· Extraction of plant material using methanol by maceration.

· Preliminary phytochemical screening of plant extract.

· Induction of diabetes in rats by using STZ.

· Confirmation of diabetes in rats by estimating blood glucose level.

· Evaluation of effect of Tricholepis glaberrima plant extract in diabetes and related complications.

MATERIALS AND METHODS:

Materials: -

Animals-Healthy Sprague Dawley Rats (8 week of age) of weighing 150-250 gm were selected for the study. The animals were housed in polypropylene cages with wire mesh and husk bedding and maintained under standard environmental conditions (temperature 22+ 2°C), relative humidity 55-60%, light dark cycle of 12 hours each and rats were fed with standard pellets diet (Amrut Feeds, Sangli) and distill water was given ad libitum during course of study. The animals were housed and treated according to the rules and regulation of CPCSEA and IAEC. The protocol for the study was approved by the Institutional Animal Ethical Committee (IAEC) with reference no. 650/PO/Re/S-2002/2024/CPCSEA/07.

Chemicals- glibenclamide, ethanol, methanol, streptozotocin

Method:

Collection and Authentication of Plant Materials

Tricholepis glaberrima, plant was collected from Thiruvalla, Kerala. The plant material was identified and authenticated by Mr. DR. B.G. Wankhade, principal of Shri Jagadamba Vinkar Shikshan Sanstha, Achalpur (Ref No.JMV/Sr/1728/2024)

Fig no.1Effect of Tricholepis glaberrima on blood glucose level of Streptozotocin induced diabetic rats

Extraction of Tricholepis gaberrima Leaves:

Leaves of Tricholepis gaberrima plant was collected, dried in shade and coarsely powdered and, then process of fat conducted in the glass jar with petrol then, the powdered leaves were extracted in methanol by Soxhlet apparatus. Then it was dried by evaporation.

-A small quantity of extract pressed between the filter papers. No formation of oil spot indicates the absence of fixed oil & Fats.

Experimental Design:

Rats were divided in five groups six in each for this study

Group I (Vehicle control)- Rats were received only saline solution.

Group II (Negative control) - Diabetes was induced using Streptozotocin in rat.

Group III (Low dose) - Diabetic rats were treated with low dose of plant extract.

Group IV (High dose) - Diabetic rats were treated with high dose of plant extract.

Group V (Standard) - Diabetic rat were treated with standard anti-diabetic drug Glibenclamid.

RESULT:

Table no.1 and Figure no.1 shows the Effect of Tricholepis glaberrima on blood glucose level of Streptozotocin induced diabetic rats. There was significant (p<0.01) increase in the blood glucose level in all the groups compared to Normal control group of rats on day 5 to day 20. After the confirmation of diabetes, rats were treated mithanolic extract of Tricholepis glaberrima for 20 days. After treatment, there was a significant (p<0.05) reduction in the blood glucose level in Streptozotocin extract (100mg/kg) and a significant (p<0.01) reduction in blood glucose level in Streptozotocin extract (200mg/kg) compared to diabetic control group on day 15 and day 20 day.

DISCUSSION:

Diabetes mellitus is a group of metabolic disorders in which a person has high blood glucose, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood glucose produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger). There are three main types of diabetes mellitus (DM). Type 1 DM results from the body's failure to produce insulin, and presently requires the person to inject insulin or wear an insulin pump. This form was previously referred to as "Insulin-Dependent Diabetes Mellitus" (IDDM) or "Juvenile Diabetes". Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. This form was previously referred to as Non-Insulin-Dependent Diabetes Mellitus (NIDDM) or "Adult-Onset Diabetes". The third main form, gestational diabetes, occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede the development of Type 2 DM. (Rajaei Eet.al.,2019)

The higher consumption of water and food, along with high blood glucose levels and urine output, indicates a diabetic state in animals resulting from STZ administration. This study showed that the aqueous extract of Tricholepis glaberrima has anti-diabetic activity comparable to glibenclamide, a standard hypoglycemic drug.( Mohan Y et.al.,2013)

The administration of the plant extract effectively prevented the conditions of excessive thirst (polydipsia) and excessive hunger (polyphagia). A similar observation was reported by Shetty et al. who used Momordica charantia in diabetic rats. Despite the untreated diabetic rats having high feed and water intake, they gained minimal body weight compared to the extract-treated groups. The increase in body weight in the Galinosaparviflora-treated rats could be attributed to the increase in metabolic activity of their body systems. This indicates that the plant extract increased glucose metabolism which enhanced body weight in the rats. This observation was also reported by Ravi et al., who found that Eugenia jambolana seed kernels increased the body weight of diabetic rats. Of particular interest is the fact that the effect of Tricholepis glaberrima at the dose of 200 mg/kg body weight compared favorably with glibenclamide..( Mohan Y et.al.,2013)

India has the second-highest number of people with diabetes. Currently, more than 74 million Indians, which is over 8.3% of the adult population, are affected by diabetes. An estimated 57% of the current diabetes cases are believed to be undiagnosed. The National Family Health Survey-4 found that among young and middle-aged adults, the prevalence of diabetes is 6.7% and prediabetes is 5.6%. The average age of onset is 42.5 years, and nearly 1 million Indians die due to diabetes every year. According to the Indian Heart Association, India is projected to be home to 109 million individuals with diabetes by 2035. A study by the American Diabetes Association reports that India will see the greatest increase in people diagnosed with diabetes by 2030. The high incidence is attributed to a combination of genetic susceptibility and the adoption of a high-calorie, low-activity lifestyle by India's growing middle class.(Pradeepa R et.al.,2021)⁴¹

The genetic model spontaneously develops diabetic rats. These models allow the evaluation of the effects of natural products on animals without the interference of side effects induced by chemical drugs like Alloxan and STZ. An example is the Goto-Kakizaki rat, which is a genetic lean model of type 1 diabetes resulting from selective breeding over many generations of glucose-intolerant nondiabetic Wistar rats. In terms of type 1 diabetes models, mice typically present hyperglycemia between 12 and 30 weeks of age, but the high cost of this model restricts its study in sophisticated protocols. The majority of studies published in the field of ethnopharmacology between 1996 and 2006 employed chemical models for diabetes induction. Streptozotocin (STZ) and Alloxan (ALX) are the most frequently used drugs, and this model has been useful for studying multiple aspects of the disease. Both drugs exert their diabetogenic action when they are administered parenterally (intravenously, intraperitoneally, or subcutaneously). (Kottaisamy CP et.al.,2021)27

Different agents are used to induce diabetes mellitus. Alloxan is the most prominent chemical compound used in diabetogenic research. In research, it is used to induce Type 1 diabetes. Alloxan is a urea derivative that causes selective necrosis of the β-cells of pancreatic islets. It has been widely used to induce experimental diabetes in animals such as rabbits, rats, mice, and dogs, with different grades of disease severity by varying the dose of alloxan used. However, the mortality rate is too high with alloxan. (Iranloye BO et al., (2011) Streptozotocin (STZ) is a naturally occurring chemical used to induce Type-1 diabetes in animal models and Type-2 diabetes with multiple low doses. It is also used in medicine to treat metastatic cancer of the islets of Langerhans. Streptozotocin has a lower mortality rate than other agents used to induce diabetes mellitus. (Brentjens R et al., (2011) Dithizone induced diabetes symptoms in cats, rabbits, golden hamsters, and mice. Diabetic animals showed higher serum zinc, iron, and potassium levels but unchanged copper and magnesium levels. (Halim D et al., (1997) Gold thioglucose is a diabetogenic compound that induces hyperphagia and severe obesity, leading to Type 2 diabetes. It causes obesity-induced diabetes in genetically normal mouse strains. When treated with gold thioglucose, DBA/2 (Dilute Brown Non-Agouti), C57BLKs, and BDF1 mice rapidly gained weight and showed a significant increase in non-fasting plasma glucose levels within 8-12 weeks. (Karasawa H et al., (2011)

Intraperitoneal injection of a 60 mg/kg dose of Streptozotocin in adult Wistar rats causes the pancreas to swell and eventually leads to degeneration in the Langerhans islet beta cells, inducing experimental diabetes mellitus within 2-4 days. This induction of experimental diabetes mellitus is the initial step in the purification of pancreatic Langerhans islet cells from normal rats. Streptozotocin induces a type of diabetes similar to diabetes mellitus with non-ketosis hyperglycemia in some animal species. In this study, diabetes was induced by injecting 60 mg/kg of Streptozotocin intravenously. Three days after the degeneration of beta cells, diabetes was induced in all animals. Blood sugar levels were then checked using a glucometer, and it was found that there was a significant increase (P < 0.0001) in the blood glucose level of the STZ-treated rats. (Akbarzadeh, A et al., (2007)

The use of herbal therapy for primary health care is sought after by about 75-80% of the global population. The synthesis of herbal medicine has been the foundation for the therapeutic practices of physicians for hundreds of years. Herbal medicines are in high demand in the developing world, not only because they are affordable, but also due to their strong cultural acceptance, compatibility with the human body, and minimal side effects.

Diabetes mellitus is the most common endocrine disorder, affecting over 300 million people worldwide. Therapies developed according to the principles of western medicine (allopathic) are often limited in efficacy, carry the risk of adverse effects, and are often too costly, especially for the developing world. Therefore, treating diabetes mellitus with plant-derived compounds, which are accessible and do not require laborious pharmaceutical synthesis, seems highly attractive. There are various herbal drugs such as Allium cepa Linn, Allium sativum Linn, Aloe vera, Bidens pilosa, Elephantopus scaber, Mangifera indica, Tricholepis glaberrima, etc., that have significant antidiabetic activity due to the presence of chemical constituents like alkaloids, glycosides, steroids, flavonoids, carbohydrates, proteins, amino acids, etc. As Tricholepis glaberrimaatalso contain alkaloids. Steroids, amino acids, flavonoids, proteins, carbohydrates and tannins. Hence this plant was selected for screening antidiabeticactivity.

We had five groups: group 1, which was the normal control; group 2, which was the negative control group; group 3, received a low dose of Tricholepis glaberrimaat (100mg/kg); group 4, received a high dose of Galinsoga parviflora (200mg/kg); and group 5, received the standard drug Glibenclamide (5 mg/kg).

Animals treated with the methanolic extract of Tricholepis glaberrima showed a significant (P<0.01) decrease in blood sugar at both low dose (100mg/kg, P<0.01) and high dose (200mg/kg, P<0.01) at different intervals of 5 days, 10 days, 15 days, and 20 days. Compared to the negative control, this anti-diabetic effect of Tricholepis glaberrima may be due to the presence of flavonoids.

CONCLUSION:

Oral administration of methanolic extract of Tricholepis glaberrima showed hypoglycemic activity in STZ-induced diabetes in experimental Wistar rats.

REFERENCES

1. Alam U, Asghar O, Azmi S, Malik RA. General aspects of diabetes mellitus. Handbook of Clinical Neurology. 2014 Jan 1; 126:211-22.

2. Alam U, Asghar O, Azmi S, Malik RA. General aspects of diabetes mellitus. Handbook of Clinical Neurology. 2014 Jan 1; 126:211-22.

3. Ali Asgar MD. Anti-diabetic potential of phenolic compounds: A review. International Journal of Food Properties. 2013 Jan 1; 16(1): 91-103.

4. Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019 Sep 1;9(9):430.

5. Al-Rowais NA. Herbal medicine in the treatment of diabetes mellitus. Saudi Medical Journal. 2002 Nov 1;23(11):1327-31.

6. Arumugam G, Manjula P, Paari N. A review: Anti diabetic medicinal plants used for diabetes mellitus. Journal of Acute Disease. 2013 Jan 1;2(3):196-200.

7. Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna Journal of Medicine. 2020 Oct;10(04):174-88.

8. Bhatia M, Siddiqui N, Gupta S. Abrusprecatorius (L.): An evaluation of traditional herb. J Pharm Res. 2013; 3: 3296-15.

9. Blech W, Bierwolf B, Weiss I, Ziegler M. In vitro and in vivo effect of gold thioglucose on the insulin-and glucagon-secretion of the isolated perfused rat pancreas. Biomedica Biochimica Acta. 1986 Jan 1; 45(4): 507-22.

10. Chawla AS, Kapoor VK, Sangal PK, Gupta AK, Evans FJ. Chemical constituents of Tricholepis glaberrima. Plantamedica. 1976 Oct; 30(6): 151-3.

11. Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Physical therapy. 2008 Nov 1; 88(11): 1254-64.

12. Eidi A, Eidi M, Esmaeili E. Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine. 2006 Nov 24; 13(9-10): 624-9.

13. Eisenbarth GS. Type I diabetes mellitus. New England journal of medicine. 1986 May 22;314(21):1360-8.

14. Fattaheian-Dehkordi S, Hojjatifard R, Saeedi M, Khanavi M. A review on antidiabetic activity of Centaurea spp.: A new approach for developing herbal remedies. Evidence-based Complementary and Alternative Medicine. 2021 Jul 5; 2021.

15. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences. 2020 Aug 30; 21(17): 6275.

16. Ghasemi A, Jeddi S. Streptozotocin as a tool for induction of rat models of diabetes: A practical guide. EXCLI Journal. 2023; 22: 274.

17. Gound SS, Thakare VN, Khan S, Wadekar RR, Naik SR. Ameliorative effects of Tricholepis glaberrima in experimentally induced hepatic damage in rats: modulation of cytokines functions. Journal of Ethnopharmacology. 2015 Feb 3; 160: 164-72.

18. Gound SS, Thakare VN, Khan S, Wadekar RR, Naik SR. Ameliorative effects of Tricholepis glaberrima in experimentally induced hepatic damage in rats: modulation of cytokines functions. Journal of Ethnopharmacology. 2015 Feb 3; 160: 164-72.

19. Guthrie RA, Guthrie DW. Pathophysiology of diabetes mellitus. Critical Care Nursing Quarterly. 2004 Apr 1; 27(2): 113-25.

20. Jan SohilAhmad, Habib N, Shinwari ZK, Ali M, Ali N. The anti-diabetic activities of natural sweetener plant Stevia: an updated review. SN Applied Sciences. 2021 Apr; 3: 1-6.

21. Jodh R, Tawar M, Kachewar A. Evaluation of Antidepressant activity of I DC using various Paradigms. Research Journal of Pharmacy and Technology. 2022; 15(12): 5610-6.

22. Kamalakkannan N, Prince PS. Hypoglycaemic effect of water extracts of Aeglemarmelos fruits in streptozotocin diabetic rats. Journal of Ethnopharmacology. 2003 Aug 1; 87(2-3): 207-10.

23. Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Diabetes: An Old Disease, a New Insight. 2013:1-1.

24. Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. The Australasian Medical Journal. 2014; 7(1): 45.

25. Khare E, Sharma A, Nayanika K. The versatility of Tricholepis glaberrima (Brahmadandi): An Overview. Environment Conservation Journal. 2020 Dec 17; 21(3): 149-54.

26. Khare E, Sharma A, Nayanika K. The versatility of Tricholepis glaberrima (Brahmadandi): An Overview. Environment Conservation Journal. 2020 Dec 17; 21(3): 149-54.

27. Kottaisamy CP, Raj DS, Prasanth Kumar V, Sankaran U. Experimental animal models for diabetes and its related complications—a review. Laboratory Animal Research. 2021 Aug 24; 37(1): 23.

28. Li F, Li Q, Gao D, Peng Y. The optimal extraction parameters and anti-diabetic activity of flavonoids from Ipomoea batatas leaf. African Journal of Traditional, Complementary and Alternative Medicines. 2009; 6(2).

29. Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. Journal of Clinical Biochemistry and Nutrition. 2007; 40(3): 163-73.

30. Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. Journal of Clinical Biochemistry and Nutrition. 2007; 40(3): 163-73.

31. Mohan Y, Jesuthankaraj GN, RamasamyThangavelu N. Antidiabetic and antioxidant properties of Triticumaestivum in streptozotocin-induced diabetic rats. Advances in Pharmacological and Pharmaceutical Sciences. 2013 Jan 1; 2013.

32. Mukhopadhyay N, Lobo R. Antidiabetic medicinal plants: a review. International Research Journal of Pharmacy. 2019; 10(2): 31-7.

33. Naphade SS, Khadabadi SS, Deore SL, Jagtap NS, Hadke SP. Antioxidant activity of different extracts of plant I DC (Asteraceae). International Journal of Pharm Tech Research. 2009 Jul; 1(3): 502-5.

34. Neetha CS, Prathima C. Evaluation of the antidepressant activity of Tricholepis glaberrima bark alone and in combination with Mimosa pudica root extract. National Journal of Physiology, Pharmacy and Pharmacology. 2019 Jul 31; 9(8): 775.

35. Neetha CS, Prathima C. Evaluation of the antidepressant activity of I bark alone and in combination with Mimosa pudica root extract. National Journal of Physiology, Pharmacy and Pharmacology. 2019 Jul 31; 9(8): 775-.

36. Nguyen TT, Ta QT, Nguyen TK, Nguyen TT, Van Giau V. Type 3 diabetes and its role implications in Alzheimer’s disease. International Journal of Molecular Sciences. 2020 Apr 30; 21(9): 3165.

37. Padashetty SA, Mishra SH. Aphrodisiac studies of Tricholepis glaberrima. With supportive action from antioxidant enzymes. Pharmaceutical Biology. 2007 Jan 1; 45(7): 580-6.

38. Padashetty SA, Mishra SH. Aphrodisiac studies of Tricholepis glaberrima. With supportive action from antioxidant enzymes. Pharmaceutical Biology. 2007 Jan 1; 45(7): 580-6.

39. Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pacific Journal of Tropical Biomedicine. 2012 Apr 1; 2(4): 320-30.

40. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. International Journal of Molecular Sciences. 2018 Oct 26; 19(11): 3342.

41. Pradeepa R, Mohan V. Epidemiology of type 2 diabetes in India. Indian Journal of Ophthalmology. 2021 Nov 1; 69(11): 2932-8.

42. Priyadarshi, Apurva, Sadhana Singh, and Sushant Kumar. Review on ayurvedic, pharmacognostical, phytochemical and pharmacological insights of Brahmadandi (Tricholepis glaberrima DC). International Journal of Research and Analytical Reviews 2018; 5(2): 1738-1747.

43. Rajaei E, Jalali MT, Shahrabi S, Asnafi AA, Pezeshki SMS. HLAs in Autoimmune Diseases: Dependable Diagnostic Biomarkers? Curr Rheumatol Rev. 2019; 15(4): 269-276.

44. Rohilla A, Ali S. Alloxan induced diabetes: mechanisms and effects. International journal of research in pharmaceutical and biomedical sciences. 2012 Apr; 3(2): 819-23.

45. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and Clinical Practice. 2019 Nov 1; 157: 107843.

46. Samad MA, Uddin SZ. Evaluation of Acute Toxicity of Hydro-Ethanolic Extract of Tricholepis glaberrima. Journal of Drug Vigilance and Alternative Therapies. 2021 Mar 30;1(1):01-5.

47. Sarian MN, Ahmed QU, Mat So’ad SZ, Alhassan AM, Murugesu S, Perumal V, Syed Mohamad SN, Khatib A, Latip J. Antioxidant and antidiabetic effects of flavonoids: A structure-activity relationship-based study. BioMed Research International. 2017 Nov 28; 2017.

48. Shahbaz A, Iqbal J, Abbasi BA, Akhtar W, Fatima I, Zahra SA, Kanwal S, Sharifi-Rad J, Sher H, Mahmood T, Cho WC. Antioxidant, anticancer, and PXR-dependent CYP3A4 attributes of Schweinfurthiapapilionacea (Burm. f.) Boiss., Tricholepis glaberrima DC. and Viola stocksiiBoiss. Oxidative Medicine and Cellular Longevity. 2022; 2022.

Received on 06.06.2024 Revised on 30.07.2024

Accepted on 03.09.2024 Published on 07.12.2024

Available online on December 30, 2024

Res.J. Pharmacology and Pharmacodynamics.2024;16(4):283-290.

DOI: 10.52711/2321-5836.2024.00049

Groups	Blood glucose level (mg/dl)
	days
	0 days	5 days	10days	15 days	20 days
Normalcontrol	10283 +-4.13	101.83 ±4.579	101.83 ±4.579	101.83 ±4.579	101.83 ±4.579
Negativecontrol	104.3+-4.65^@	226.33±.4.579^@	232.5±4.637^@	239.33±4.320^@	248.5±4.370^@
Low dose (100mg/kg)	103.22+-3.66^*	209.166±5.811^*	197.166±2.639^**	181.83±2.858^**	171.16±3.545^**
high dose (200mg/kg)	102.8+-3.10^*	209.166±5.811^*	194.66±2.160^**	177.83±2.041^**	166±1.414^**
Standard dose	100.92+-3.05^*	206.83±3.710^*	195.33±3.327^**	178.66±2.582^**	161.16±2.639^**