A member of the Cucurbitaceae family, Coccinia grandis (L.) is a perennial climbing vine that grows quickly (2). Additionally, Coccinia grandis is an East African native plant that has spread by seed to various parts of tropical Asia and the Pacific region (3). Not only is this plant used in traditional medicine extensively but also as a nutritious vegetable. Almost any part of the plant has been used as a traditional medicine in Asian countries to treat skin diseases such as leprosy, acne, scabies, and wounds. It has also been used to treat poisoning, malaria, jaundice, and hepatitis, and it is now traditionally used to treat diabetes and obesity (4). Moreover, In Southeast Asia, the squashed fresh leaves of this plant are used as a traditional herbal treatment for bruises and itching from bug bites. This process is done by applying the crushed leaves directly to the lesion. So, it was also added as one of the traditional home remedies used to treat common illnesses (5). The whole plant of Coccinia grandis having pharmacological activities like analgesic, antipyretic, anti-inflammatory, antimicrobial, antiulcer, antidiabetic, antioxidant, hypoglycemic, hepatoprotective, antimalarial, antidyslipidemic, anticancer, antitussive, mutagenic and the present review gives botany, chemical constituents, and pharmacological activities of Coccinia grandis (6, 7). For individuals recently diagnosed with type 2 diabetes mellitus, an herbal medication made from Coccinia grandis extract showed promise as a helpful treatment. The medication was safe, well tolerated, and greatly improved glycemic and lipid profile parameters in randomized and controlled clinical trials (8). Evidences also suggest that the plant's ethanolic extract may be safely incorporated into herbal remedies for the clinical development of antibacterial activity against strains of bacteria that are resistant to many drugs (3). This review focuses on the pharmacological responses of the sections of the Coccinia grandis plant in this study, which include hepatoprotective, antioxidant, antihyperlipidemic, and antidiabetic activities.

2.1 Synonyms of Coccinia grandis

       Many names are associated with Coccinia grandis, including Staphylosyce, Physedra, Cephalandra indica, Coccinia indica, and Coccinia cordifolia. It is known by various names, including kundru (Urdu), tindoli (Oriya), ivy gourd (English), and scarlet gourd. (9-11) In Bangladesh, it is known as Telakucha (12).

2.2 Taxonomy and visual inspection

Kingdom: Plantae; Order: Cucurbitales; Family: Cucurbitaceae; Genus: Coccinia; Species: Coccinia grandis (L.) (13, 14)

Figure 1: Different parts of Coccinia grandis (L.) Voigt

2.3 Distribution of Coccinia grandis

In different subtropical and tropical places of the world, as garden vegetables, sometimes Coccinia grandis (Ivy gourd) is cultivated. In the case of Asia, India, and central Africa, it is native. In the case of its base, which humans have obscured, there are also some important aspects of the process that are available, such as transportation, cultivation, usage, and history. In the case of Southeast Asia, it is considered a common weed. In various countries, such as the Solomon Islands, Marshall Islands, Guam, Fiji, Vanuatu, Hawaii, Florida, and Texas, it is neutralized. While in India and Southeast Asia by the local people, it is known as a valuable wild vegetable (32).

2.4 Botanical description of Coccinia grandis

This plant is recognized for its significant morphological variation among wild accessions and cultivated varieties (33).

Table 1: Different parts of the plants with their description

Table 2: Different parts of Coccinia grandis plants, and their medicinal use

3.1 Phytochemical Composition of Coccinia grandis

The pharmacological properties of Coccinia grandis are attributed to its abundance of bioactive substances, such as triterpenes, amino acids, flavonoids, and phenolics(15, 16).

Table 3: Different parts of the plant Coccinia grandis and their compounds, with their properties

3.2 Nutrient composition of Coccinia grandis

Table 4: Parts of Coccinia grandis with their nutrient compositions

3.3 Chemical constituents of Coccinia grandis

 Table 5: Parts of Coccinia grandis with their phytochemical constituents 

4.1 Antidiabetic effect

To comprehend the antidiabetic action of Coccinia grandis, it is essential to understand the fundamental pharmacological mechanism of an animal model of diabetes. All of the data pertaining to beta cell malfunction, insulin resistance, and two major risk factors for diabetes mellitus have been compiled. The liver, muscle, and fat cells are less responsive to insulin, particularly in individuals with Type 2 diabetes mellitus (T2DM). This reduces the body's ability to absorb glucose, causing the liver to continually produce glucose even when the body doesn't need it. Insulin resistance is caused by a variety of factors, including genetics, obesity, chronic inflammation, excess fatty acids, and dysregulated adipokines (46, 47). The inability of the pancreatic beta cells to perform their intended tasks may result in the release of sufficient insulin to overcome resistance. Beta cells are further harmed by lipo-toxicity and glucose toxicity, which facilitate their degradation (47, 48). The normal insulin pathway is depicted in Figure 2 .

Figure 2: Normal Insulin Signaling Pathway in this figure In this diagram, IR- Insulin Receptor, IRS- Insulin Receptor Substrate, PKc- Protein Kinase C, ROS- Reactive Oxygen Species, Ps- Phosphorylation, DAG Diacylglycerols, PI3K-Phosphoinositide-3-kinase (1).

Table 5: The key factors in insulin resistance and beta-cell dysfunction

Figure 3: Antidiabetic effect of Coccinia grandis

4.2 Antihyperlipidemic effect

The term ‘hyperlipidemia’ refers to the condition characterized by abnormally high levels of lipids in the human systemic circulation, primarily triglycerides (TG) and cholesterol. The body produces, absorbs, transports, and eliminates lipoproteins, which include chylomicrons, VLDL, LDL, and HDL, in an imbalanced way. High dietary fat intake, heredity, and insulin resistance are among the variables that influence cholesterol homeostasis. This imbalance may promote cardiovascular disease and result in the development of atherosclerosis (62-65). After eating a high-fat meal that has a lot of TGs, chylomicrons, and VLDL, the amount of lipoprotein goes up. In hyperlipidemic situations, these lipoproteins take longer to clear, which leads to a persistent rise in the number of particles in the blood(62, 65). VLDL and chylomicron residual balance depend on lipoprotein lipase activity. The primary role of lipoprotein lipase activity is compromised in cases of metabolic syndrome development, such as obesity and type 2 diabetes. Therefore, hyperlipidemia is a possibility (62, 63). Chronic inflammation and oxidative stress lead to the disruption of lipid metabolism and the development of endothelial dysfunction (64, 66-68).

Figure 4: Mechanisms that are driving heart disease through the development of dyslipidemia.

According to research based on animal trials, Coccinia grandis extract exhibits antihyperlipidemic properties that can lower body weight and cholesterol levels (including triglycerides, VLDL, and LDL), while reducing the risk of vascular atherosclerosis.

Table 7: Evidence from animal studies is gathered to understand the effect of Coccinia grandis as an antidiabetic and antihyperlipidemic agent.

Figure 5: Antihyperlipidemic effect of Coccinia grandis.

4.3 Antioxidant effect

When the body produces more free radicals than it can counteract, primarily reactive oxygen species (ROS) and reactive nitrogen species (RNS), the state is known as oxidative stress. Both endogenous (normal physiological processes) and exogenous (external exposures) pathways may produce these free radicals. The mitochondrial electron transport chain generates highly reactive hydroxyl radicals (•OH) during the process of ATP synthesis. During the synthesis of ATP, superoxide (O2•) is first produced and then radicals (into hydrogen peroxide (H2O2). Extremely reactive hydroxyl free radicals are produced by the Fenton reaction.(79-81). Numerous studies indicate that several enzymes, including nitric oxide synthase, cytochrome P450, xanthine oxidase, and NADPH oxidase, may be involved in the production of ROS and RNS during immunological and metabolic processes (79-81). The generation of lipid radicals and peroxyl radicals can be produced due to the initiation of the chain reaction by abstracting hydrogen from polyunsaturated fatty acids in membranes(79, 80). During a respiratory burst can be produced a large number of ROS/RNS during the activation of immune cells, including macrophages and neutrophils, to destroy pathogens (79, 81-83). Several external environmental factors are responsible for stimulating the production of free radicals in the body, including Ultraviolet and ionizing radiation, pollution, cigarette smoke, certain drugs, and heavy metals. These factors can generate free radicals or stimulate their production in tissues. (79, 81, 82).

According to some research-based data, Coccinia grandis extract contains antioxidant properties that can help lower the body's oxidative stress levels by reducing the formation of highly reactive oxygen and nitrogen species.

Table 8: The antioxidant activity of C. grandis in multiple animal model studies:

Figure 6: Antioxidant effect of Coccinia grandis.

4.4 Hepatoprotective effect

Multiple mechanisms, including direct injury, inflammation, and metabolic stress, may cause damage to hepatocytes. The primary processes that harm hepatocytes and result in fibrosis and inflammation include apoptosis, necrosis, pyroptosis, and organelle dysfunctions. The most widely used biomarker for liver function is the measurement of serum enzyme levels; however, other specialized biomarkers are increasingly available. The damage in hepatocytes may occur due to apoptosis (regulated cell death), necrosis (uncontrolled lysis), and pyroptosis (inflammatory cell death). The release of inflammasome particles is able to activate hepatic stellate cells and further drive them to fibrosis in the case of pyroptosis (88, 89)The production of DAMPs, or damage-associated molecular patterns, may occur in hepatocytes when certain essential organelles, including the mitochondria, lysosomes, and endoplasmic reticulum, sustain damage. These DAMPs have the ability to cause hepatocyte inflammation and further damage(89, 90).Cytokines, chemokines, and extracellular vesicles are released by a damaged hepatocyte, increasing inflammation and attracting immune cells. Additionally, this may stimulate hepatic stellate cells, which could lead to fibrosis (88, 89, 91, 92).Hepatic cell damage is caused by a variety of factors, including autoimmune illnesses, metabolic abnormalities, ischemia/reperfusion, alcohol use, viral hepatitis, and medications like paracetamol (89, 91).

Table 9: Biomarkers to understand liver function are given below

Table 10: Hepatoprotective effects of Coccinia grandis in animal models

 According to research on animal models, extracts from various parts of Coccinia grandis can lower several indicators related to liver function, providing insight into the plant's hepatoprotective effects (Table 10). It has the capacity to lower hepatocyte inflammation and apoptosis, as well as oxidative indicators MDA and SOD, which are closely related to liver function. 

Figure 7: Hepatoprotective effect of Coccinia grandis.

 Conceptualization, MAA and NS; methodology, MAA, MMUR, ABJ, JA; formal analysis, MSH, SBZ, TA, HCG; investigation, MSH, SBZ, TA, MTH; resources, ABJ, HCG, JA; data curation, MMUR, HCG; writing—original draft preparation, MMUR, MSH, SBZ; writing—review and editing, MMUR, HCG, JA; visualization, MAA, NS; supervision, MAA, NS; project administration, NS; All authors have read and agreed to the published version of the manuscript. 

 This research did not receive any internal or external funding from profit and non-profit organization. 

Not Applicable (N/A)

Data used in this study will be available upon reasonable request from the corresponding author.

Authors are gratefully acknowledging the logistic support from the department of Pharmaceutical Sciences, North South University.

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

1. Chandrasekaran, P.; Weiskirchen, R. Cellular and Molecular Mechanisms of Insulin Resistance. Curr. Tissue         Microenviron. Rep. 2024, 5(3), 79-90. https://doi.org/10.1007/s43152-024-00056-3
2. Hossain, M. S.; Jahan, I.; Islam, M.; Nayeem, J.; Anzum, T. S.; Afrin, N. A.; Mim, F. K.; Hasan, M. K. Coccinia grandis: Phytochemistry, pharmacology and health benefits. Clin. Tradit. Med. Pharmacol. 2024, 5(2), 200150. https://doi.org/10.1016/j.ctmp.2024.200150
3. Alshahrani, M. Y.; Ibrahim, E. H.; Asiri, M.; Kilany, M.; Alshehri, A.; Alkhathami, A. G.; Alshahrani, M. Inhibition realization of multidrug resistant bacterial and fungal isolates using Coccinia indica extracts. Saudi J. Biol. Sci. 2022, 29(5), 3207-3212. https://doi.org/10.1016/j.sjbs.2022.01.045
4. Chuchote, C.; Somwong, P. Assessment of the ethanolic extract of Coccinia grandis on in vitro anti-tyrosinase and anti-inflammatory activities and its active chemical determination. Food Res. 2024, 8(4), 162-169. https://doi.org/10.26656/fr.2017.8(4).427
5. Namchaiw, P.; Jaisin, Y.; Niwaspragrit, C.; Malaniyom, K.; Auvuchanon, A.; Ratanachamnong, P. The Leaf Extract of Coccinia grandis (L.) Voigt Accelerated In Vitro Wound Healing by Reducing Oxidative Stress Injury. Oxid. Med. Cell. Longev. 2021, 2021(1), 3963510. https://doi.org/10.1155/2021/3963510
6. Siddiqua, S.; Jyoti, F. H.; Saffoon, N.; Miah, P.; Lasker, S.; Hossain, H.; Akter, R.; Ahmed, M. I.; Alam, M. A. Ethanolic extract of Coccinia grandis prevented glucose intolerance, hyperlipidemia and oxidative stress in high fat diet fed rats. Phytomed. Plus. 2021, 1(4), 100046. https://doi.org/10.1016/j.phyplu.2021.100046
7. Sakharkar, P.; Chauhan, B. Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits. Avicenna J. Phytomed. 2017, 7(4), 295-307.
8. Wasana, K. G. P.; Attanayake, A. P.; Weerarathna, T. P.; Jayatilaka, K. A. P. W. Efficacy and safety of a herbal drug of Coccinia grandis (Linn.) Voigt in patients with type 2 diabetes mellitus: A double blind randomized placebo controlled clinical trial. Phytomedicine. 2021, 81, 153431. https://doi.org/10.1016/j.phymed.2020.153431
9. Yadav, L. P.; Gangadhara, K.; Apparao, V. V.; Yadav, V.; Mishra, D. S.; Singh, A. K.; Rane, J.; Kaushik, P.; Janani, P.; Kumar, R.; Verma, A. K.; Kumar, S.; Malhotra, S. K.; Shekhawat, N. Genetic diversity, morphological traits, quality traits and antioxidants potentiality of Coccinia grandis germplasm under rainfed semi-arid region. Sci. Rep. 2024, 14(1), 868. https://doi.org/10.1038/s41598-023-49091-4
10. Sarkar, T.; Mukherjee, A.; Chatterjee, K.; Akhmetova, S. O.; Alipbekova, A. S.; Temerbayeva, M.; Rebezov, M.; Shariati, M. A.; Lorenzo, J. M. Quality Assessment of tindora (Coccinia indica) using poincare plot and cartesian quadrant analysis. Food Anal. Methods. 2022, 15(9), 2357-2371. https://doi.org/10.1007/s12161-022-02287-2
11. Saikia, J.; Phookan, D.; Talukdar, P. Studies on genetic variability in ivy gourd [Coccinia grandis (L.) Voigt.]. Indian J. Hortic. 2017, 74(1), 139-141. https://doi.org/10.5958/0974-0112.2017.00031.7
12. Sarkar, S. K.; Uddin, M. M.; Hossain, M. M.; Masum, M. A.; Islam, M. S. Hematobiochemical effects of Telakucha (Coccinia indica) in alloxan induced diabetic rats. Res. Agric. Livest. Fish. 2020, 7(3), 431-438. https://doi.org/10.3329/ralf.v7i3.51362
13. Rahman, M. S.; Asaduzzaman, M.; Munira, S.; Rahman, M. M.; Hasan, M.; Siddique, A. H.; Khatun, M.; Islam, M. A. Evaluation of phytochemical, antibacterial, antioxidant, and cytotoxic properties of Coccinia cordifolia leaves. Int. J. Adv. Res. 2015, 3(8), 384-394.
14. Bussmann, R. W.; Paniagua-Zambrana, N. Y.; Njoroge, G. N. Coccinia grandis (L.) Voigt Cucurbitaceae. Ethnobot. Mt. Reg. 2021, 309-311. https://doi.org/10.1007/978-3-030-38386-2_44
15. Putra, I. M. W. A.; Kusumawati, I. G. A. W.; Sumadewi, N. L. U. Physical Characteristics, Total Phenolic, and Flavonoid Content of Coccinia grandis (L.) Voigt Leaves Extract. Acta Chim. Asiana. 2021, 4(2), 114-119. https://doi.org/10.29303/aca.v4i2.66
16. Lee, I. Y.; Park, J. H.; Joo, N. Changes in free amino acid, phenolic, triterpene and biogenicamine contents in Coccinia grandis pickles during aging. J. Agric. Food Res. 2024, 15, 101000. https://doi.org/10.1016/j.jafr.2024.101000
17. Shanmuganathan, E.; Arawwawala, L. D. A. M.; Wasana, K. G. P.; Attanayake, A. P. Selection and optimisation of extraction technique for the preparation of phenolic- and flavonoid-rich extract of leafy vegetable, Coccinia grandis (Linn.) Voigt. Int. Food Res. J. 2022, 29(5), 1032-1042. https://doi.org/10.47836/ifrj.29.5.06
18. Ahmed, R. M.; Widdatallah, M. O.; Alrasheid, A. A.; Widatallah, H. A.; Alkhawad, A. O. Evaluation of the phytochemical composition, antioxidant properties, and in vivo antihyperglycemic effect of Coccinia grandis leaf extract in mice. Univers. J. Pharm. Res. 2024, 9(2). https://doi.org/10.22270/ujpr.v9i2.1091
19. Prabhakar, P.; Mukherjee, S.; Kumar, A.; Rout, R. K.; Kumar, S.; Verma, D. K.; Dhara, S.; Rao, P. S.; Maiti, M. K.; Banerjee, M. In silico, In vitro and Ex vivo Assessment of Antihyperglycemic, Antioxidant and Cytotoxic Properties of Ivy Gourd (Coccinia grandis L.) Leaf Extract. Food Technol. Biotechnol. 2024, 62(2), 188-204. https://doi.org/10.17113/ftb.62.02.24.8162
20. Lee, I. Y.; Lee, D. H.; Park, J. H.; Joo, N. UHPLC-HRMS/MS–Based Metabolic Profiling and Quantification of Phytochemicals in Different Parts of Coccinia grandis (L.) Voigt. Food Sci. Nutr. 2025, 13(2). https://doi.org/10.1002/fsn3.70004
21. Preetha, T. S. Heavy metal screening of Coccinia grandis (L). Voigt leaves using atomic absorption spectroscopy (AAS). Int. J. Sci. Res. 2020, 9(3), 33-35.
22. Moulick, S. P.; Jahan, F.; Mamun, M. Z. U. A.; Hossain, M. I. S.; Ahmed, K. S.; Kabir, M. A.; Rashid, M. M.; Sathee, R. A.; Hasan, M. M. Boerhavia diffusa and Coccinia grandis: Two Indigenous vegetables as a source of essential minerals, vitamins, amino acids, and fatty acids. Appl. Food Res. 2024, 4(2), 100494. https://doi.org/10.1016/j.afres.2024.100494
23. Neetu; Purwar, S.; Bisht, V.; Neeraj; Maurya, B. Nutritional and therapeutic values of Coccinea grandis: A review. Int. J. Chem. Stud. 2020, 8(4), 2528-2534. https://doi.org/10.22271/chemi.2020.v8.i4o.9832
24. Kondhare, D.; Lade, H. Phytochemical profile, aldose reductase inhibitory, and antioxidant activities of Indian traditional medicinal Coccinia grandis (L.) fruit extract. 3 Biotech. 2017, 7, 1-10. https://doi.org/10.1007/s13205-017-1013-1
25. National Center for Biotechnology Information. PubChem Compound Summary. PubChem. 2021.
26. Lee, I. Y.; Joo, N. Identification and Quantification of Key Phytochemicals, Phytohormones, and Antioxidant Properties in Coccinia grandis during Fruit Ripening. Antioxidants 2022, 11(11), 2218. https://doi.org/10.3390/antiox11112218
27. Al-Madhagy, S.; Mostafa, N.; Youssef, F.; Awad, G.; Eldahshan, O.; Singab, A. Isolation and structure elucidation of compounds from Coccinia grandis leaves extract. Egypt. J. Chem. 2019, 62(10), 1891-1903. https://doi.org/10.21608/ejchem.2019.10925.1700
28. Al-Madhagy, S.; Mostafa, N.; Youssef, F.; Awad, G.; Eldahshan, O.; Singab, A. Metabolic profiling of a polyphenolic-rich fraction of Coccinia grandis leaves using LC-ESI-MS/MS and in vivo validation of its antimicrobial and wound healing activities. Food Funct. 2019, 10(10), 6667-6674. https://doi.org/10.1039/C9FO01532A
29. Mohammed, S.; Vishwakarma, K.; Maheshwari, V. Evaluation of Larvicidal Activity of Essential Oil from Leaves of Coccinia grandis against Three Mosquito Species. J. Arthropod Borne Dis. 2017, 11(2), 226-235.
30. Momin, Y. H.; Yeligar, V. C.; Saralaya, M. G.; Dharmamoorthy, G.; Mallikarjuna, B. P.; Jadhav, S.; Das, K.; Almuqbil, M.; Ahmad, F.; Rabbani, S. I.; Asdaq, S. M. B . Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters. Comput. Biol. Chem. 2024, 110, 108087. https://doi.org/10.1016/j.compbiolchem.2024.108087
31. Trinh, P. T. P.; Nguyen, T. T.; Van Hau, N.; Hung, Q. T.; Du, C. V.; Tuan, N. T.; Thao, N. P. Chemical constituents of the stem of Coccinia grandis. IOP Conf. Ser. Mater. Sci. Eng. 2020, 736(2), 022080. https://doi.org/10.1088/1757-899X/736/2/022080
32. Wasantwisut, E.; Viriyapanich, T. Ivy gourd (Coccinia grandis Voigt, Coccinia cordifolia, Coccinia indica) in human nutrition and traditional applications. World Rev. Nutr. Diet. 2003, 91, 60-66. https://doi.org/10.1159/000069929
33. Shaina, T. J.; Beevy, S. S. Morphological variation and evolutionary significance of Coccinia grandis (L.) Voigt: an under-exploited cucurbitaceous vegetable crop. Plant Syst. Evol. 2012, 298(3), 653-659. https://doi.org/10.1007/s00606-011-0574-4
34. Devani, R. S.; Sinha, S.; Banerjee, J.; Sinha, R. K.; Bendahmane, A.; Banerjee, A. K. De novo transcriptome assembly from flower buds of dioecious, gynomonoecious and chemically masculinized female Coccinia grandis reveals genes associated with sex expression and modification. BMC Plant Biol. 2017, 17(1), 241. https://doi.org/10.1186/s12870-017-1187-z
35. Ramachandran, K.; Subramaniam, B. Scarlet gourd Coccinia grandis little-known tropical drug plant. Econ. Bot. 1983, 37(4), 380-383. https://doi.org/10.1007/BF02904197
36. Jebadurai, S. G.; Raj, R. E.; Sreenivasan, V. S.; Binoj, J. S. Comprehensive characterization of natural cellulosic fiber from Coccinia grandis stem. Carbohydr. Polym. 2019, 207, 675-683. https://doi.org/10.1016/j.carbpol.2018.12.027
37. Prombanchong, T.; Suriyawong, A.; Srisongkram, P.; Suwanpayak, N. Anatomical and physical properties of tendril perversion of Coccinia grandis (L.) Voigt. IOP Conf. Ser. Mater. Sci. Eng. 2020, 965(1), 012011. https://doi.org/10.1088/1757-899X/965/1/012011
38. Jebadurai, S. G.; Raj, R. D. E.; Sreenivasan, V. S. Characterization of Natural Cellulosic Fiber from Coccinia grandis Root. J. Nat. Fibers 2022, 19(14), 9444-9456. https://doi.org/10.1080/15440478.2021.1982833
39. Ghadge, A. G.; Karmakar, K.; Devani, R. S.; Banerjee, J.; Mohanasundaram, B.; Sinha, R. K.; Sinha, S.; Banerjee, A. K. Flower development, pollen fertility and sex expression analyses of three sexual phenotypes of Coccinia grandis. BMC Plant Biol. 2014, 14, 325. https://doi.org/10.1186/s12870-014-0325-0
40. Rahman, M.; Sarker, J.; Akter, S.; Mamun, A.; Azad, M.; Mohiuddin, M.; Shahid, I. Z. Comparative evaluation of antidiabetic activity of crude methanolic extract of leaves, fruits, roots and aerial parts of Coccinia grandis. J. Plant Sci. 2015, 2(6-1), 19-23.
41. Lobo, J. A.; Sowmya, S. Pharmacological Review on Coccinia grandis Leaves. Int. J. Pharm. Sci. Rev. Res. 2022, 74(2), 96-99. https://doi.org/10.47583/ijpsrr.2022.v74i02.014
42. Lee, I. Y.; Joo, N. Identification and Quantification of Key Phytochemicals, Phytohormones, and Antioxidant Properties in Coccinia grandis during Fruit Ripening. Antioxidants 2022, 11(11), 2218. https://doi.org/10.3390/antiox11112218
43. Mandal, D.; Majumder, S.; Shah, D. J.; Guha, S.; Das, M.; Karmakar, A.; Seal, R. Coccinia grandis a Potential Herb in Traditional Use and Recent Established Biological Activities with New Prospectives - A Review. Trop. J. Pharm. Life Sci. 2025, 12(3), 183. https://doi.org/10.61280/tjpls.v12i3.183
44. Hasanuzzaman, M.; Sayeed, M. S. B.; Islam, M. S.; Sarwar, M. S.; Moghal, M. M. R.; Ahmed, J. U.; Islam, M. A. Preliminary antimicrobial activity and cytotoxicity of plant extracts (roots) of Coccinia grandis (Family: Cucurbitaceae). Int. J. Pharm. Sci. Res. 2013, 4(4), 1466-1470.
45. Neetu; Purwar, S.; Bisht, V.; Neeraj; Maurya, B. K. R. Nutritional and therapeutic values of Coccinea grandis: A review. Int. J. Chem. Stud. 2020, 8(4), 1555-1561. https://doi.org/10.22271/chemi.2020.v8.i4o.9832
46. Kumari, N.; Radha; Kumar, M.; Mekhemar, M.; Lorenzo, J. M.; Pundir, A.; Devi, K. B.; Prakash, S.; Puri, S.; Thakur, M.; Rathour, S.; Rais, N.; Jamwal, R.; Kumar, A.; Dhumal, S.; Singh, S.; Senapathy, M.; Dey, A.; Chandran, D.; Andrade-Cetto, A. Therapeutic uses of wild plant species used by rural inhabitants of Kangra in the western Himalayan region. S. Afr. J. Bot. 2022, 148, 415-436. https://doi.org/10.1016/j.sajb.2022.05.004
47. Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K. B.; Ostolaza, H.; Martín, C. Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2020, 21(17), 6275. https://doi.org/10.3390/ijms21176275
48. Yang, Y.; Chen, Z.; Zhao, X.; Xie, H.; Du, L.; Gao, H.; Xie, C. Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review. Front. Endocrinol. 2022, 13, 990299. https://doi.org/10.3389/fendo.2022.990299
49. Cerf, M. Beta Cell Dysfunction and Insulin Resistance. Front. Endocrinol. 2013, 4, 37. https://doi.org/10.3389/fendo.2013.00037
50. Kahn, S. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003, 46, 3-19. https://doi.org/10.1007/s00125-002-1009-0
51. Khalid, M.; Alkaabi, J.; Khan, M.; Adem, A. Insulin Signal Transduction Perturbations in Insulin Resistance. Int. J. Mol. Sci. 2021, 22(16), 8590. https://doi.org/10.3390/ijms22168590
52. Oh, Y.; Bae, G.; Baek, D.; Park, E.-Y.; Jun, H. Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes. Front. Endocrinol. 2018, 9, 384. https://doi.org/10.3389/fendo.2018.00384
53. Rodríguez-Rodríguez, A.; Porrini, E.; Torres, A. Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes? Int. J. Mol. Sci. 2021, 22(19), 10311. https://doi.org/10.3390/ijms221910311
54. Dinić, S.; Jovanović, J. A.; Uskoković, A.; Mihailović, M.; Grdović, N.; Tolić, A.; Rajić, J.; Đorđević, M.; Vidaković, M. Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. Front. Endocrinol. 2022, 13, 1006376. https://doi.org/10.3389/fendo.2022.1006376
55. Made, I.; Putra, W. A.; Fakhrudin, N.; Nurrochmad, A.; Wahyuono, S. Antidiabetic effect of combined extract of Coccinia grandis and Blumea balsamifera on streptozotocin-nicotinamide induced diabetic rats. J. Ayurveda Integr. Med. 2024, 15(4), 101021. https://doi.org/10.1016/j.jaim.2024.101021
56. Meher, N.; Panda, B.; Ray, B. In Vivo Antidiabetic Activity of fruit extract of Coccinia grandis Linn in Normoglycemic, Adrenaline Induced and Alloxan Induced Diabetic rat. Res. J. Pharm. Technol. 2019, 12(11), 5143-5147. https://doi.org/10.5958/0974-360X.2019.01026.6
57. Gobinath, R.; Parasuraman, S.; Sreeramanan, S.; Sumitha, S. Antidiabetic and Antihyperlipidemic Activities of Methanolic Extract of Leaves of Coccinia grandis in Diabetic Rats. Int. J. Res. Pharm. Sci. 2020, 11(2), 2374-2379.
58. Mohammed, S.; Chopda, M.; Patil, R.; Vishwakarma, K.; Maheshwari, V. In vivo antidiabetic and antioxidant activities of Coccinia grandis leaf extract against streptozotocin induced diabetes in experimental rats. Asian Pac. J. Trop. Dis. 2016, 6(4), 298-304. https://doi.org/10.1016/S2222-1808(15)61034-9
59. Meenatchi, P.; Maneemegalai, S. Antidiabetic effect of Coccinia grandis Linn. on streptozotocin induced diabetic rats and its role in regulating hepatic key enzymes. J. Herb. Med. Toxicol. 2018, 12(1), 1-7.
60. Attanayake, A. P.; Jayatilaka, K. A. P. W.; Pathirana, C.; Mudduwa, L. K. B. Antihyperglycemic activity of Coccinia grandis (L.) Voigt in streptozotocin induced diabetic rats. S. L. J. Med. 2015, 24(1), 25-32.
61. Rahman, M.; Sarker, J.; Akter, S.; Mamun, A.; Azad, M.; Mohiuddin, M.; Haque, A. Comparative Evaluation of Antidiabetic Activity of Crude Methanolic Extract of Leaves, Fruits, Roots and Aerial Parts of Coccinia grandis. J. Plant Sci. 2015, 2(1), 19-23.
62. Yanai, H.; Adachi, H.; Hakoshima, M.; Katsuyama, H. Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments. Int. J. Mol. Sci. 2023, 24(17), 13118. https://doi.org/10.3390/ijms241713118
63. Maulana, H.; Ridwan, A. High-Fat Diets-Induced Metabolic Disorders to Study Molecular Mechanism of Hyperlipidemia in Rats. 3BIO: J. Biol. Sci. Technol. Manag. 2021, 3(2), 105-115. https://doi.org/10.5614/3bio.2021.3.2.5
64. Jia, X.; Xu, W.; Zhang, L.; Li, X.; Wang, R.-R.; Wu, S. Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia. Front. Cell. Infect. Microbiol. 2021, 11, 634780. https://doi.org/10.3389/fcimb.2021.634780
65. Vergès, B. Intestinal lipid absorption and transport in type 2 diabetes. Diabetologia 2022, 65(10), 1587-1600. https://doi.org/10.1007/s00125-022-05765-8
66. Yao, Y.; Li, T.; Zeng, Z. Mechanisms underlying direct actions of hyperlipidemia on myocardium: an updated review. Lipids Health Dis. 2020, 19(1), 23. https://doi.org/10.1186/s12944-019-1171-8
67. Sun, J.; Du, B.; Chen, M.; Jia, J.; Wang, X.; Hong, J. FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses. J. Endocrinol. Invest. 2024, 47(10), 2445-2458. https://doi.org/10.1007/s40618-024-02376-5
68. Lai, M.; Peng, H.; Wu, X.; Chen, X.; Wang, B.; Su, X. IL-38 in modulating hyperlipidemia and its related cardiovascular diseases. Int. Immunopharmacol. 2022, 108, 108876. https://doi.org/10.1016/j.intimp.2022.108876
69. Feng, J.; Xu, R.; Dou, Z.; Hao, Y.; Xu, R.; Khoso, M. A.; Shi, Y.; Liu, L.; Sun, H.; Chen, C.; Li, X.; Liu, H.; Han, W.; Cheng, M.; Tang, P.; Li, J.; Zhang, Y.; Liu, X. Tetrahydroberberrubine improves hyperlipidemia by activating the AMPK/SREBP2/PCSK9/LDL receptor signaling pathway. Eur. J. Pharmacol. 2025, 988, 177228. https://doi.org/10.1016/j.ejphar.2024.177228
70. Hu, Y.; Xu, R.; Feng, J.; Zhang, Q.; Zhang, L.; Li, Y.; Chen, L. Identification of potential pathogenic hepatic super-enhancers regulatory network in high-fat diet induced hyperlipidemia. J. Nutr. Biochem. 2024, 127, 109584. https://doi.org/10.1016/j.jnutbio.2024.109584
    https://doi.org/10.1016/j.jnutbio.2024.109584
71. Liang, X.; Zhang, Z.; Zhou, X.; Lu, Y.; Li, R.; Yu, Z.; Tong, L.; Gong. P.; Yi, H.; Zhang, L. Probiotics improved hyperlipidemia in mice induced by a high cholesterol diet via downregulating FXR. Food Funct. 2020, 11(11), 10134-10145. https://doi.org/10.1039/D0FO02255A
72. Duan, R.; Guan, X.; Huang, K.; Zhang, Y.; Li, S.; Xia, J.; Shen, M. Flavonoids from Whole-Grain Oat Alleviated High-Fat Diet-Induced Hyperlipidemia via Regulating Bile Acid Metabolism and Gut Microbiota in Mice. J. Agric. Food Chem. 2021, 69(27), 7618-7629. https://doi.org/10.1021/acs.jafc.1c01813
73. Hossain, M. F.; Rahaman, M. A.; Abdullah-Al-Mamun, H. K.; Islam, M. S.; Sumsuzzman, D. M. Antihyperlipidemic activity of Coccinia grandis on high fat diet induced wistar albino rats. Int. J. Res. Pharm. Biosci. 2017, 4(7), 15-20.
74. Toha, I. W.; Hasan, S. M. F.; Islam, S.; Ahmed, M. H.; Nobe, N.; Tasnim, S.; Shakil, F. S.; Chowdhury, M.M. Elucidation of Anti-hyperlipidemic Activity of 70% Ethanolic Extract of Coccinia grandis on High Fat-induced Hyperlipidaemic Wister Albino Rat Model. J. Complement. Altern. Med. Res. 2025, 26(3), 638. https://doi.org/10.9734/jocamr/2025/v26i3638
75. Nisu, R. A.; Nadvi, F. A.; Ankhi, A. A.; Suma, R. S.; Papiya, I. J.; Bose, A. An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Coccinia grandis Leaves in High Fat Induced Rodent Model. Cardiol. Angiol. Int. J. 2024, 13(1), 387. https://doi.org/10.9734/ca/2024/v13i1387
76. Singh, G.; Gupta, P.; Rawat, P.; Puri, A.; Bhatia, G.; Maurya, R. Antidyslipidemic activity of polyprenol from Coccinia grandis in high-fat diet-fed hamster model. Phytomedicine 2007, 14(12), 792-798. https://doi.org/10.1016/j.phymed.2007.06.008
77. Trang, D.; Linh, V. C.; Lan, N. T. P. Antihyperglycemic, antioxidant, and antihyperlipidemic activities of extract from Coccinia grandis (L.) Voigt. leaves by methanol on alloxan induced hyperglycemic mice. Vietnam J. Biotechnol. 2018, 16(3), 485-493.
78. Basini, J.; Kumar, K.; Swetha, A.; Roshini, P.; Prathima, N.; Chandana, D. In-vivo antihyperlipidemic activity of ethanolic fruit extract of Coccinia grandis Linn. against dexamethasone induced hyperlipidemia. World J. Pharm. Res. 2020, 9(7), 1297-1306.
79. Chandimali, N.; Bak, S. G.; Park, E. H.; Lim, H.; Won, Y.; Kim, E.; Park, S.; Lee, S. J. Free radicals and their impact on health and antioxidant defenses: a review. Cell Death Discovery 2025, 11(1), 2278. https://doi.org/10.1038/s41420-024-02278-8
80. Chaudhary, P.; Janmeda, P.; Docea, A. O.; Yeskaliyeva, B.; Razis, A. F. A.; Modu, B.; Calina, D.; Sharifi-Rad, J. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front. Chem. 2023, 11, 1158198. https://doi.org/10.3389/fchem.2023.1158198
81. Leyane, T. S.; Jere, S. W.; Houreld, N. N. Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation. Int. J. Mol. Sci. 2022, 23(13), 7273. https://doi.org/10.3390/ijms23137273
82. Jomová, K.; Raptová, R.; Alomar, S. Y.; Alwasel, S. H.; Nepovimova, E.; Kuča, K.; Valko, M. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch. Toxicol. 2023, 97(10), 2499-2574. https://doi.org/10.1007/s00204-023-03562-9
83. Tripathi, R.; Gupta, R.; Sahu, M.; Srivastava, D.; Das, A.; Ambasta, R. K.; Kumar, P. Free radical biology in neurological manifestations: mechanisms to therapeutics interventions. Environ. Sci. Pollut. Res. 2021, 29(41), 62160-62207. https://doi.org/10.1007/s11356-021-16693-2
84. Shankar, R.; Gnaneswari, K.; Devi, T.; Niharika, B. In-vitro anti-inflammatory, anti-oxidant and In-vivo anti-urolithiatic activities of Coccinia grandis fruit extract. GSC Adv. Res. Rev. 2024, 18(1), 124-132.
85. Banerjee, A.; Mukherjee, S.; Maji, B. Efficacy of Coccinia grandis against monosodium glutamate induced hepato-cardiac anomalies by inhibiting NF-kB and caspase 3 mediated signalling in rat model. Hum. Exp. Toxicol. 2021, 40(11), 1825-1851. https://doi.org/10.1177/09603271211010895
86. Umamaheswari, M.; Asokkumar, K.; Somasundaram, A.; Sivashanmugam, T.; Subhadradevi, V.; Ravi, T. k. Xanthine oxidase inhibitory activity of some Indian medical plants. J. Ethnopharmacol. 2007, 109(3), 547-551. https://doi.org/10.1016/j.jep.2006.08.020
87. Kumar, D.; Kumar, M. S. Evaluation of Anticonvulsant Activity of Hydro Ethanolic Extract of Coccinia grandis in Mice. Sch. Acad. J. Pharm. 2022, 11(9), 147-152. https://doi.org/10.36347/sajp.2022.v11i09.005
88. Gaul, S.; Leszczyńska, A.; Alegre, F.; Kaufmann, B.; Johnson, C. D.; Adams, L. A.; Wree, A.; Damm, G.; Seehofer, D.; Calvente, C. J.; povero,D.; Kisseleva, T.; Eguchi, A.; McGeough, M. D.; Hoffman, H. M.; pelegrin, P.; Laufs, U.; Feldstein, A. E. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J. Hepatol. 2021, 74(3), 674-686. https://doi.org/10.1016/j.jhep.2020.07.041
89. Gong, J.; Tu, W.; Liu, J.; Tian, D.-L. Hepatocytes: A key role in liver inflammation. Front. Immunol. 2023, 13, 1083780. https://doi.org/10.3389/fimmu.2022.1083780
90. Zhang, X.; Wu, X.; Hu, Q.; Wu, J.; Wang, G.; Hong, Z.; Ren, J. Mitochondrial DNA in liver inflammation and oxidative stress. Life Sci. 2019, 236, 116464. https://doi.org/10.1016/j.lfs.2019.05.020
91. Konishi, T.; Lentsch, A. B. Hepatic Ischemia/Reperfusion: Mechanisms of Tissue Injury, Repair, and Regeneration. Gene Expr. 2017, 17(4), 277-287. https://doi.org/10.3727/105221617X15042750874156
92. An, P.; Wei, L. L.; Zhao, S.; Sverdlov, D. Y.; Vaid, K. A.; Miyamoto, M.; Kuramitsu, K.; Lai, M.; Popov, Y. V. Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis. Nat. Commun. 2020, 11(1), 2206. https://doi.org/10.1038/s41467-020-16092-0
93. Lehmann-Werman, R.; Magenheim, J.; Moss, J.; Neiman, D.; Abraham, O.; Piyanzin, S.; Zemmour, H.; Fox, I; Dor, T.; Grompe, M.; Landesberg, G.; Loza, B.; Shaked, A.; Olthoff, K.; Glaser, B.; Shemer, R.; Dor, Y. Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA. JCI Insight 2018, 3(12), e120687. https://doi.org/10.1172/jci.insight.120687
94. Akhtam, R.; Nuraliyevna, S. N.; Kadham, M. J.; Mirzakhamitovna, K. S.; Tursunaliyevna, R. M.; Shakhnoz, K.; Shakhzod. T.; Otabek, B.; Baxtiyorovich, M. I.; Shakhboskhanovna, A. F.; Zulxumoroxon, B.; Isroilovna, I. M.; Khodji-Akbarovna, N. R. Biomarkers in liver regeneration. Clin. Chim. Acta 2025, 576, 120413. https://doi.org/10.1016/j.cca.2025.120413
95. Wei, C.; Wu, L.; Wu, Y.; Xu, C.; Hu, H.; Wang, Z. Selection and evaluation of quality markers (Q-markers) of vladimiriae radix extract for cholestatic liver injury based on spectrum-effect relationship, pharmacokinetics, and molecular docking. J. Ethnopharmacol. 2024, 329, 118151. https://doi.org/10.1016/j.jep.2024.118151
96. Yuan, H.; Liu, Z.; Chen, M.; Xu, Q.; Jiang, Y.; Zhang, T.; Suo, C.; Chen, X. Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease. BMC Med. 2024, 22(1), 234. https://doi.org/10.1186/s12916-024-03466-0
97. Staufer, K.; Huber, H.; Zessner-Spitzenberg, J.; Stauber, R.; Finkenstedt, A.; Bantel, H.; Weiss, T. S.; huber, M.; Starlinger, P.; Gruenberger, T.; Reiberger, T.; Sebens, S.; Mclntyre, G.; Tabibiazar, R.; Giaccia, A.; Zoller, H.; Trauner, M.; Mikulits, W. Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis. Cell Death Discovery 2023, 9(1), 258. https://doi.org/10.1038/s41420-023-01551-6
98. Dallio, M.; Romeo, M.; Cipullo, M.; Ventriglia, L.; Scognamiglio, F.; Vaia, P.; Ladanza, G.; Coppola, A.; Federico, A. Systemic Oxidative Balance Reflects the Liver Disease Progression Status for Primary Biliary Cholangitis (Pbc): The Narcissus Fountain. Antioxidants 2024, 13(4), 387. https://doi.org/10.3390/antiox13040387
99. Wang, K.; Fang, Q.; He, P.; Tu, Y.; Liu, Z.; Li, B. Unveiling the potential of selenium-enriched tea: Compositional profiles, physiological activities, and health benefits. Trends Food Sci. Technol. 2024, 145, 104356. https://doi.org/10.1016/j.tifs.2024.104356
100. Vadivu, R.; Krithika, A.; Biplab, C.; Dedeepya, P.; Shoeb, N.; Lakshmi, K. S. Evaluation of Hepatoprotective Activity of the Fruits of Coccinia grandis Linn. Int. J. Health Res. 2008, 1(3), 163-168. https://doi.org/10.4314/ijhr.v1i3.55366
101. Yerramilli, V.; Singh, M.; Singh, I.; Nagar, L.; Singh, J. Hepato-restorative Activity of Methanolic Extracts of Coccinia grandis L. Voigt. in CCl4 - Intoxicated Rats. Pharmacogn. J. 2024, 16(5), 1165-1171. https://doi.org/10.5530/pj.2024.16.178
102. Kumar, P.; Sivaraj, A.; Elumalai, E. K.; Kumar, B. S. Carbon tetrachloride-induced hepatotoxicity in rats - protective role of aqueous leaf extracts of Coccinia grandis. Int. J. PharmTech Res. 2009, 1(4), 1612-1615.
103. Chidambaram, R.; Devi, R.; Selvi, R.; Alagendran, S.; Bhaskar, A. Protective effect of Coccinia grandis [L] against (Diethylnitrosamine) DEN-induced Hepatotoxicity in Wistar Albino Rats. Int. J. Pharm. Sci. Rev. Res. 2016, 38(1), 160-165.
104. Banerjee, A.; Mukherjee, S.; Maji, B. Coccinia grandis alleviates flavor-enhancing high-lipid diet induced hepatocellular inflammation and apoptosis. J. Food Biochem. 2022, 46(5), e14092. https://doi.org/10.1111/jfbc.14092
105. Kundu, M.; Mazumder, R.; Kushwaha, M. Evaluation of hepatoprotective activity of ethanol extract of Coccinia grandis (L.) Voigt. leaves on experimental rats by acute and chronic models. Orient. Pharm. Exp. Med. 2012, 12(2), 93-97. https://doi.org/10.1007/s13596-012-0057-3
106. Aljehany, B. M.; Abduljawad, E. A. Protective Effect of Coccinia grandis on Cyclophosphamide Induced Liver Damage. Am. J. Res. Commun. 2018, 6(2), 28-39.