Review Article
Antidiabetic Potential of Kalmegh (Andrographis paniculata): A Systematic Review
Shubham M Shende*, Gaurav Goyanar, Nirmal Dongre and Raghvendra Dubey
Corresponding Author: Shubham M Shende, Research Scholar, Department of Pharmacy, Sage University, Indore, Madhya Pradesh, India.
Received: December 26, 2024; Revised: January 06, 2025; Accepted: Janauary 09, 2025 Available Online: Janauary 24, 2025
Citation: Shende SM, Goyanar G, Dongre N & Dubey R. (2025) Antidiabetic Potential of Kalmegh (Andrographis paniculata): A Systematic Review. J Pharm Drug Res, 8(1): 893-901.
Copyrights: ©2025 Shende SM, Goyanar G, Dongre N & Dubey R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, which can lead to severe complications if left untreated. Andrographis paniculata, commonly known as Kalmegh or the "King of Bitters," is a medicinal plant with a rich history of use in traditional medicine. Recent research highlights its potential antidiabetic properties, attributed to its bioactive compounds, particularly andrographolide. This review summarizes the mechanisms, pharmacological studies, and clinical implications of Kalmegh in managing diabetes, providing insights for future therapeutic applications.

Keywords: Kalmegh, Antidiabetic, Andrographolide, Preclinical studies
INTRODUCTION

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both [1]. It has become a major global health concern, with increasing prevalence and a rising incidence of complications like cardiovascular diseases, kidney failure, and neuropathy [2]. While conventional therapies, such as insulin therapy and oral hypoglycemic agents, are effective in managing diabetes, the adverse effects and limitations of these treatments have prompted the exploration of alternative and complementary approaches. Herbal medicine, with its rich history in traditional healing systems, has gained significant attention in recent years for its potential in managing diabetes [3].

Kalmegh (Andrographis paniculata): A Profile

Kalmegh (Figure 1) scientifically known as Andrographis paniculata, is a medicinal herb that belongs to the Acanthaceae family [4]. It is a well-known plant in traditional Ayurvedic, Chinese, and Southeast Asian medicine, where it is commonly referred to as the "King of Bitters" due to its strong bitter taste [5]. The plant is native to the Indian subcontinent and parts of Southeast Asia but has been cultivated in various regions across the world due to its therapeutic properties. The aerial parts of Andrographis paniculata (Table 1) particularly the leaves and stems-are primarily used for medicinal purposes.

The plant is an erect herb, growing to a height of 30-110 cm (12-43 inches), thriving in moist and shady locations. Its slender, dark green stem is square in cross-section, featuring longitudinal furrows and wing-like angles. The lance-shaped leaves are hairless, with blades measuring up to 8 cm (3.1 inches) in length and 2.5 cm (0.98 inches) in width. Small, pink flowers appear solitary or in loose, spreading racemes or panicles. The fruit is a capsule approximately 2 cm (0.79 inches) long and a few millimeters wide, containing numerous yellow-brown seeds. These seeds are subquadrate, rugose, and glabrous. The plant typically flowers from September to December.

Kalmegh has been traditionally employed to treat a wide range of ailments, including fever, infections, inflammation, liver disorders, and digestive issues. It has a reputation for its immune-modulatory, hepatoprotective, anti-inflammatory, and antioxidant effects. In recent years, scientific research has also highlighted its antidiabetic potential, making it an exciting candidate for the management of diabetes.


Plant Description (Table 2)


Antidiabetic Activity of Kalmegh

The antidiabetic properties of Kalmegh have been widely studied in both preclinical and clinical settings. Its potential in regulating blood glucose levels and enhancing insulin sensitivity has been attributed to several bioactive compounds found in the plant [6]. Various studies have reported its ability to reduce blood sugar levels and improve insulin function in both type 1 and type 2 diabetes models.

Kalmegh exhibits antidiabetic activity through multiple mechanisms, including:

  1. Regulation of Insulin Secretion and Sensitivity: Kalmegh has been shown to enhance insulin secretion from the pancreas and improve insulin sensitivity in peripheral tissues [7]. This effect may help to increase glucose uptake by cells, thereby lowering blood sugar levels.
  2. Inhibition of α-glucosidase Activity: Several studies have suggested that Andrographis paniculata inhibits the activity of the enzyme α-glucosidase, which is involved in the breakdown of complex carbohydrates into simple sugars. By inhibiting this enzyme, Kalmegh reduces the rate of carbohydrate absorption from the intestines, leading to a slower and more controlled rise in blood glucose levels after meals [7].
  3. Reduction of Oxidative Stress and Inflammation: Chronic inflammation and oxidative stress play a critical role in the pathophysiology of diabetes. Kalmegh’s antioxidant and anti-inflammatory properties help in reducing the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines, which are often elevated in diabetic conditions [8].
  4. Improvement of Lipid Profile: Diabetic patients frequently suffer from dyslipidemia, characterized by high levels of triglycerides and low levels of HDL cholesterol. Kalmegh has shown potential in improving the lipid profile by lowering serum triglyceride and cholesterol levels, which can benefit overall cardiovascular health in diabetic patients [9].

Phytoconstituents Responsible for Antidiabetic Activity

The therapeutic properties of Kalmegh, including its antidiabetic effects, are attributed to a variety of phytochemicals present in the plant [10]. Some of the key bioactive constituents responsible for its antidiabetic activity include (Figure 2):


  1. Andrographolide: Andrographolide is the major diterpenoid lactone found in Andrographis paniculata, and it has been extensively studied for its biological activities. It is believed to be the primary compound responsible for Kalmegh's antidiabetic effects. Andrographolide has been shown to enhance insulin secretion, improve glucose tolerance, and exert anti-inflammatory and antioxidant activities. It also contributes to the inhibition of α-glucosidase activity [11].
  2. Flavonoids: Flavonoids such as quercetin, kaempferol, and rutin are also present in Kalmegh. These compounds have strong antioxidant and anti-inflammatory properties, which help in reducing oxidative stress and inflammation-key contributors to the development and progression of diabetes [12].
  3. Polyphenols: Kalmegh contains several polyphenolic compounds that have been linked to its antidiabetic potential [13]. These polyphenols possess antioxidant activity and may help in reducing the damage caused by oxidative stress in pancreatic beta cells, thus supporting insulin production.
  4. Steroidal Saponins: These compounds have been identified in Kalmegh and are known to possess hypoglycemic effects. Steroidal saponins contribute to improved insulin sensitivity and glucose metabolism [14].
  5. Tannins and Alkaloids: Other bioactive compounds such as tannins and alkaloids present in Kalmegh may also contribute to its blood glucose-lowering effects. These compounds are known for their antioxidant and anti-inflammatory properties, which can indirectly support the body’s ability to regulate blood sugar [15].

Procedure for Kalmegh Extraction [16]

  1. Collection and Preparation of Plant Material
  • Source: Collect fresh Kalmegh leaves from a reliable source.
  • Drying:
    • Wash the leaves to remove dirt and impurities.
    • Shade-dry the leaves at room temperature to preserve phytochemicals.
    • Ensure complete dryness by checking for crispness (moisture content <10%).
  • Powdering: Grind the dried leaves into a fine powder using a grinder.
  1. Extraction Process

Solvent Selection:

  • Use polar solvents like ethanol, methanol, or water for extraction, as they efficiently extract active compounds like andrographolide.

Methods:

  1. Soxhlet Extraction:
  • Place 50-100 g of powdered Kalmegh in a thimble inside the Soxhlet apparatus.
  • Add ethanol or methanol as the solvent (1:10 plant material-to-solvent ratio).
  • Heat the system to allow solvent evaporation and continuous reflux for 6-8 h.
  • Collect the extract in a round-bottom flask.
  1. Cold Maceration (alternative method):
  • Mix the powdered material with the solvent in a glass container.
  • Stir occasionally and allow it to soak for 24-72 h at room temperature.
  • Filter the mixture using muslin cloth or filter paper.
  1. Filtration and Concentration
  • Filtration: Use Whatman filter paper to remove plant debris and obtain a clear filtrate.
  • Concentration:
  1. Use a rotary evaporator to remove the solvent under reduced pressure at 40-50°C.
  2. Obtain a thick, concentrated extract.
  3. Fractionation and Purification
  • If necessary, fractionate the extract using solvents like hexane or ethyl acetate to isolate specific compounds.
  • Purify the active components using chromatography techniques like HPLC.
  1. Storage
  • Store the concentrated extract in amber-colored vials at -20°C to prevent degradation.

Preclinical Studies:

Animal studies have demonstrated the efficacy of Kalmegh in managing diabetes (Table 3)


Clinical Studies: Although limited, clinical trials have shown promising results (Table 4):

  • Randomized Controlled Trials: Kalmegh supplementation improved glycemic control in patients with type 2 diabetes, with minimal adverse effects [19].
  • Combination Therapy: Kalmegh enhanced the efficacy of standard antidiabetic drugs when used as an adjuvant [20].

Safety and Toxicity: Kalmegh is generally considered safe at therapeutic doses. However, excessive consumption may cause gastrointestinal disturbances [21-22]. Toxicological studies indicate a high margin of safety, supporting its use in clinical settings.

Future Perspectives: Further research is needed to:

  • Explore the synergistic effects of Kalmegh with other antidiabetic agents.
  • Conduct large-scale clinical trials to confirm efficacy and safety.
  • Develop standardized extracts for consistent therapeutic outcomes.

RESULT & DISCUSSION

The results from both preclinical and clinical studies highlight the significant antidiabetic potential of Kalmegh. The pharmacological effects of Kalmegh are attributed to its bioactive compounds, particularly andrographolide, which has been shown to modulate multiple pathways involved in glucose metabolism, insulin sensitivity, and oxidative stress.

Animal models have provided robust evidence supporting the antidiabetic activity of Kalmegh. In studies using streptozotocin (STZ)-induced diabetic rats, Kalmegh administration led to a significant reduction in fasting blood glucose levels and improved lipid profiles, including a decrease in triglycerides, LDL, and total cholesterol. These findings align with the clinical manifestation of diabetes, which often includes dyslipidemia and hyperglycemia. The protective effect of Kalmegh on pancreatic β-cells is noteworthy, as β-cell dysfunction is a hallmark of both type 1 and type 2 diabetes. Moreover, Kalmegh’s ability to enhance insulin sensitivity and reduce oxidative stress markers, such as malondialdehyde (MDA), highlights its potential for managing the complications associated with diabetes, such as cardiovascular diseases and neuropathy.

The therapeutic efficacy of Kalmegh can be attributed to its rich array of bioactive constituents. Andrographolide, the most studied compound, is primarily responsible for the herb’s antidiabetic properties. This diterpenoid lactone has been shown to enhance insulin secretion, improve glucose tolerance, and exhibit potent anti-inflammatory and antioxidant effects. Additionally, flavonoids, polyphenols, steroidal saponins, tannins, and alkaloids found in Kalmegh contribute to its blood glucose-lowering effects through their respective antioxidant and anti-inflammatory actions.

Kalmegh is generally considered safe at therapeutic doses. However, excessive consumption may cause gastrointestinal disturbances, such as nausea or diarrhea. Toxicological studies indicate that Kalmegh has a high safety margin, with no significant adverse effects observed in preclinical studies at standard doses. Clinical trials have reported no serious adverse events, further supporting the safety of Kalmegh for long-term use.

CONCLUSION

Kalmegh (Andrographis paniculata) has demonstrated significant potential as a natural remedy for managing diabetes. Its multifaceted mechanisms of action, including the regulation of insulin secretion, inhibition of α-glucosidase, reduction of oxidative stress and inflammation, and improvement of lipid profiles, make it an attractive candidate for inclusion in modern therapeutic regimens. Despite the promising results from preclinical and clinical studies, further research is necessary to establish definitive clinical guidelines and fully harness the potential of Kalmegh in diabetes management. The herb's minimal side effects and its ability to complement conventional therapies underscore its promising future in the treatment of diabetes.

CONFLICT OF INTEREST

Nil

ACKNOWLEDGEMENTS

The authors are thankful to HOI, Institutes of Pharmaceutical Science, Sage University, Indore, for providing essential guidance and support to carry out this work.

AUTHOR CONTRIBUTIONS

Concept-Shubham Shende.; Gaurav Goyanar., Design-Shubham Shende.; Supervision-Gaurav Goyanar.; Literature Search-Shubham Shende.; Writing-Shubham Shende; Critical Reviews-Gaurav Goyanar, Nirmal Dongre, Raghvendra Dubey.

  1. Stefano GB, Challenger S, Kream RM (2016). Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. Eur J Nutr 55(8): 2339-2345.
  2. Marcovecchio ML, Lucantoni M, Chiarelli F (2011) Role of chronic and acute hyperglycemia in the development of diabetes complications. Diabetes Technol Ther 13(3): 389-394.
  3. Ngan T, Pham B, Le L (2020) Bioactive compounds in anti-diabetic plants: From herbal medicine to modern drug discovery. Biology 9(9): 252.
  4. Verma H, Negi MS, Mahapatra BS, Shukla A, Paul J (2019) Evaluation of an emerging medicinal crop Kalmegh (Andrographis paniculata (Burm. F.) Wall. Ex. Nees) for commercial cultivation and pharmaceutical & industrial uses: A review. J Pharmacogn Phytochem 8(4): 835-848.
  5. Nyeem MAB, Mannan MdA, Nuruzzaman M, Kamrujjaman KM, Das SK (2017) Indigenous king of bitter (Andrographis paniculata): A review. J Med Plants Stud 5(2): 318-324.
  6. Tomar A (2019) Antidiabetic activity of Andrographis paniculata (Burm. f.) Wall. ex Nees (Kalmegh). J Non-Timber Forest Prod 26(4): 207-209.
  7. Arya SS, Sonia NS, Nair DS (2021) Functional potential of anti-diabetic medicinal plants. J Pharmacogn Phytochem 10(2): 1177-1181.
  8. Hidayat R, Patricia W (2022) Effect of Andrographis paniculata on Blood Sugar Levels Through Regulation of Alpha-Glucosidase Enzyme Expression: An In Vivo Eureka Herba Indonesia 3(1): 136-139.
  9. Lim V, Jun JT, Yoke KY (2023) Kalmegh (Andrographis paniculata) and Cardioprotective Mechanisms. Ancient and Traditional Foods, Plants, Herbs and Spices used in Cardiovascular Health and Disease pp: 193-213.
  10. Kumar S, Ratha KK, Jaiswal S, Rao MM, Acharya R (2024) Exploring the potential of andrographis paniculata and its bioactive compounds in the management of liver diseases: A comprehensive food chemistry perspective. Food Chem Adv 4: 100674.
  11. Bhushan MS, Rao Ch V, Ojha SK, Kumar MV, Verma A (2010) An analytical review of plants for antidiabetic activity with their phytoconstituent & mechanism of action. Int J Pharm Sci Res 1(1): 29-46.
  12. Islam, MT, Ali ES, Uddin SJ, Islam MdA, Shaw S, et al. (2018) Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. Cancer Lett 420: 129-145.
  13. Praveen N (2014) Polyphenol composition and antioxidant activity of Andrographis paniculata Nees. Mapana J Sci 13(4): 33.
  14. Das P, Srivastav AK (2014) Phytochemical extraction and characterization of the leaves of Andrographis paniculata for its anti-bacterial, anti-oxidant, anti-pyretic and anti-diabetic activity. Int J Innov Res Sci Eng Technol 3: 15176-15184.
  15. Elekofehinti OO, Omotuyi IO, Kamdem JP, Ejelonu OC, Alve GV, et al. (2014) Saponin as regulator of biofuel: Implication for ethnobotanical management of diabetes. J Physiol Biochem 70: 555-567.
  16. Das B, Saha P (2024) A Review on Antidiabetic Potential of Plant Flavonoids in Acanthaceae Family Edible Plants of West Bengal. Indian J Pharm Sci 86 (3): 805-817.
  17. Venkata CN, Neelima S, Anupam MK, Prabhu R, Naraynam S, et al. (2019) Evaluation of the Procurement Time of Kalmegh (Andrographis paniculata (Burm. f.) Nees), through HPLC, Macro-and Microscopic Studies. J Drug Res Ayur Sci 4(2): 47-55.
  18. Wu KK, Huan Y (2008) Streptozotocin‐induced diabetic models in mice and rats. Curr Protoc Pharmacol 40(1): 5-47.
  19. Ankur R, Ali S (2012) Alloxan induced diabetes: Mechanisms and effects. Int J Res Pharm Biomed Sci 3(2): 819-823.
  20. Widjajakusuma EC, Jonosewojo A, Hendriati L, Ferawati SW, Surjadhana A, et al. (2019) Phytochemical screening and preliminary clinical trials of the aqueous extract mixture of Andrographis paniculata (Burm. f.) Wall. ex Nees and Syzygium polyanthum (Wight.) Walp leaves in metformin treated patients with type 2 diabetes. Phytomedicine 55: 137-147.
  21. Thikekar AK, Thomas AB, Chitlange SS (2021) Herb‐drug interactions in diabetes mellitus: A review based on pre‐clinical and clinical data. Phytother Res 35(9): 4763-4781.
  22. Abhishek N, Tewari SK, Lehri A (2010) Biological activities of kalmegh (Andrographis paniculata Nees) and its active principles- A Review. Indian J Nat Prod Resour 1(2): 125-135.
  23. Mishra SK, Sangwan NS, Sangwan RS (2007) Plant review Andrographis paniculata (Kalmegh): A review. Pharmacogn Rev 1(2): 283-298.
  24. Dwivedi K, Kumar K, Kumar G (2021) Studies on gamma rays induced cyto-morphological variations and procurement of some induced novel mutants in Kalmegh (Andrographis paniculata (Burm. f) nees). Cytol Genet 55(4): 379-387.
  25. Switu J, Rudrappa HC (2014) Morphological, structural and micrometric study of cystolith of family Acanthaeceae WSR to Kalmegh. Int J Green Pharm 8(1): 13.