Antidiabetic Efficacy of Citrullus colocynthis and Citrullus lanatus: A Review
DOI:
https://doi.org/10.48165/bpas.2023.39.1.6%20Keywords:
Anti-inflammatory, Antioxidant, Hypoglycemic, Cucurbitacins, Flavonoids, AlkaloidsAbstract
The present review is focused on the anti-diabetic potential of Citrullus colocynthis and Citrullus lanatus, commonly referred to as bitter apple and watermelon, respectively. The plants have a history of being employed for therapeutic uses and recent investigation has revealed their potential as antidiabetic agents owing to the presence of bioactive compounds, including cucurbitacins, flavonoids, and alkaloids. The present study examines the therapeutic potential of the plants, highlighting their antidiabetic, anti-inflammatory, antioxidant, and hypoglycemic properties. Additionally, the mechanisms responsible for the antidiabetic effects of these substances, and their effectiveness in the treatment of diabetes in animal and human subject. In addition to safety and toxicity, potential adverse effects were also discussed. In conclusion, these plants possess considerable potential as alternative therapies for diabetes. However, additional investigation is required to extensively comprehend their therapeutic efficacy and establish appropriate and safe dosages for clinical application.
References
Abu-Hiamed, H. A. A. (2017). Chemical Composition, Flavonoids and β-sitosterol Contents of Pulp and Rind of Watermelon (Citrullus lanatus) Fruit. Pakistan Journal of Nutrition, 16(7), 502–507. https://doi.org/10.3923/pjn.2017.502.507
Adebayo, A. (2014). Protective Properties of Citrullus lanatus on Carbon Tetrachloride Induced Liver Damage in Rats. European Journal of Medicinal Plants, 4(8), 979–989. https://doi.org/10.9734/ejmp/2014/9690
Agic, R., Bogoevska, Z., & Ibusoska, A. (2013). Comparison of Several Watermelon (Citrullus lanatus Thunb.) Hybrids in Republic of Macedonia. Агрознање, 14(3), 335.
https://doi.org/10.7251/agren1303335a 4. Ajiboye, B. O., Shonibare, M. T., &Oyinloye, B. E. (2020). Antidiabetic activity of watermelon (Citrullus lanatus) juice in alloxan-induced diabetic rats. Journal of Diabetes & Metabolic Disorders, 19, 343-352. 5. Al-Nablsi, S., El-Keblawy, A., Ali, M. A., Mosa, K. A., Hamoda, A. M., Shanableh, A., ... & Soliman, S. S. (2022). Phenolic contents and antioxidant activity of Citrullus Colocynthisfruits, growing in the hot arid desert of the UAE, influenced by the fruit parts, accessions, and seasons of fruit collection. Antioxidants, 11(4), 656.
American Diabetes Association. (2021). Standards of Medical Care in Diabetes— 2021. Diabetes Care, 44(Suppl. 1), S1–S232.
Anis Ben Hsouna. (2012). Gas chromatography-mass spectrometry (GC MS) analysis and in vitro evaluation of antioxidant and antimicrobial activities of various solvent extracts from Citrullus colocynthis (L.) roots to control pathogen and spoilage bacteria. African Journal of Biotechnology, 4(47). https://doi.org/10.5897/ajb12.417
Artana, I. W. (2020). Watermelon, Kalium, and Kidney Health: A Review Literature. Syst. Rev. Pharm, 11, 1001-1007.
Azizi, S., Mohamad, R., & Mahdavi Shahri, M. (2017). Green Microwave-Assisted Combustion Synthesis of Zinc Oxide Nanoparticles with Citrullus colocynthis (L.)
Schrad: Characterization and Biomedical Applications. Molecules, 22(2), 301. https://doi.org/10.3390/molecules22020301
Badmus, J. A., Oyelami, K. O., Adedeji, A. L., Adedosu, O. T., Bolarinwa, I. F., & Marnewick, J. L. (2021). Comparative study of physicochemical properties, fatty acid composition, antioxidant and toxicological potential of Citrullus lanatus and Citrullus colocynthis seeds oils. South African Journal of Botany, 142, 156–164. https://doi.org/10.1016/j.sajb.2021.06.019
Bande, Y., Adam, N., Jamarei, B., & Azmi, Y. (2012). Physical and Mechanical Properties of “Egusi” Melon (Citrullus colocynthislanatus var. lanatus) Fruit. International Journal of Agricultural Research, 7(10), 494–499.
https://doi.org/10.3923/ijar.2012.494.499 12. Bazabang, S. A., Makena, W., Onimisi, O. B., Rilwan, H. B., Buba, H. S., Jerome, V. K., & Yohana, A. (2023). Flavonoid-rich extract from Citrullus lanatus (Watermelon) seed attenuated Ethanol-Induced Kidney injury in Wistar Rats. Pharmacological Research Modern Chinese Medicine, 7, 100236.
Benariba, N., Bellakdhar, W., Djaziri, R., Hupkens, E., Louchami, K., & Malaisse, W. J. (2012). Protective action of Citrullus colocynthis seed extracts against the deleterious effect of streptozotocin on both in vitro glucose-stimulated insulin release from rat pancreatic islets and in vivo glucose homeostasis. Biomedical Reports, 1(1), 119– 121. https://doi.org/10.3892/br.2012.5
Bharath, R., Priya, A. J., Jayaraman, S., & Devi, R. G. (2021). Induction of Bax and Activation of Caspases by Hydro Ethanolic Leaf Extract of Citrullus colocynthis (L)- mediated Apoptosis in Breast Cancer Cell Line (MCF-7). Journal of Pharmaceutical Research International, 173–180. https://doi.org/10.9734/jpri/2021/v33i62b
Bourhia, M., Bouothmany, K., Bakrim, H., Hadrach, S., Salamatullah, A. M., Alzahrani, A., & Benbacer, L. (2021). Chemical profiling, antioxidant, antiproliferative, and antibacterial potentials of chemically characterized extract of Citrullus colocynthis L. seeds. Separations, 8(8), 114.
Burrows, G. E., & Shaik, R. S. (2014). Comparative developmental anatomy of the taproot of the cucurbitaceous vines Citrullus colocynthis (perennial), Citrullus lanatus (annual) and Cucumis myriocarpus (annual). Australian Journal of Botany, 62(7), 537. https://doi.org/10.1071/bt14124
Buryukova, E. V., Jabbar, A., & Elizarova, S. V. (2017). When basal insulin is not enough: successful strategies for insulin intensification in patients with type 2 diabetes mellitus. Diabetes Mellitus, 20(5), 363–373. https://doi.org/10.14341/dm8824
Chawech, R., Jarraya, R., Girardi, C., Vansteelandt, M., Marti, G., Nasri, I., Fabre, N. (2015). Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad. Molecules,
(10), 18001–18015. https://doi.org/10.3390/molecules20101800 1
Choukem, S. P., &Dimala, C. A. (2021). BMI and diabetes risk in low-income and middle income countries. The Lancet, 398(10296), 190–192. https://doi.org/10.1016/s0140- 6736(21)01425-2
Della, D. A., Soetjipto, H., & Aminu, N. R. (2022). Linoleic Acid Isolation from Watermelon Seeds Oil (Citrullus lanatus L) with Urea Inclusion Method. EduChemia (Jurnal Kimia Dan Pendidikan), 7(2), 250. https://doi.org/10.30870/educhemia.v7i2.1
Duran Barón, R., Valle-Vargas, M. F., Quintero-Gamero, G., Quintanilla-Carvajal, M. X., & Alean, J. (2021). Encapsulation of citrulline extract from watermelon (Citrullus lanatus) by-product using spray drying. Powder Technology, 385, 455–465. https://doi.org/10.1016/j.powtec.2021.03.0
Ellahi Elltayeib, A. A. (2020). Chemical properties and antibacterial effect of the oil from seeds of Citrullus colocynthis. Insights in Chemistry and Biochemistry, 1(3). https://doi.org/10.33552/icbc.2020.01.0005
Erhirhie, E. O., & Ekene, N. E. (2013). Medicinal values on Citrullus lanatus (watermelon): pharmacological review. International Journal of Research in Pharmaceutical and Biomedical Sciences, 4(4), 1305-1312.
Faisal, M. S., Ali, N., & Ali, K. (2018). Citrullus colocynthis. The Professional Medical Journal, 25(01), 96–103. https://doi.org/10.29309/tpmj/2018.25.01.5 45
Ghauri, A. O., Ahmad, S., & Rehman, T. (2020). In vitro and in vivo anti-diabetic activity of Citrullus colocynthis pulpy flesh with seeds hydro-ethanolic extract. Journal of Complementary and Integrative Medicine, 17(2). https://doi.org/10.1515/jcim-2018-0228
Htwe, T. N. (2021). Metabolic Risk Markers in Insulin Resistance and Non-Insulin Resistance Type 2 Diabetes Mellitus. SOJ Diabetes and Endocrinology Care, 1(2). https://doi.org/10.53902/sojdec.2021.01.00
Hussain, H., Green, I. R., Saleem, M., Khattak, K. F., Irshad, M., & Ali, M. (2019). Cucurbitacins as Anticancer Agents: A Patent Review. Recent Patents on Anti-Cancer Drug Discovery, 14(2), 133–143. https://doi.org/10.2174/1574892813666181
İMAMOĞLU, A. (2021). Oral Glucose Lowering Agent Treatments in Type 2 Diabetes Mellitus. Turkish Journal of Internal Medicine, 3(1), 1–5. https://doi.org/10.46310/tjim.815794
International Diabetes Federation. (2019). IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation.
Ishtiaq, M. (2020). Comprehensive Review of Phytochemistry and Bioactivities of Citrullus Colocynthis (L.) Schrad. Open Access Journal of Pharmaceutical Research, 4(4).
https://doi.org/10.23880/oajpr-16000218 31. Itoh, T., Ono, A., Kawaguchi, K., Teraoka, S., Harada, M., Sumi, K., ... & Hashizume, T. (2018). Phytol isolated from watermelon (Citrullus lanatus) sprouts induces cell death in human T-lymphoid cell line Jurkat cells via S-phase cell cycle arrest. Food and Chemical Toxicology, 115, 425-435.
Kamboj, A., & Dahiya, R. S. (2022). Citrullus colocynthis (L.) Schrad (Bitter Apple): An Overview of its Traditional Uses, Phytochemistry and Pharmacological Potential. Serbian Journal of Experimental and Clinical Research, 0(0). https://doi.org/10.2478/sjecr-2021-0073
Karakuş, F., Yılmaz, K., Eyol, E., & Ünüvar, S. (2019). Combination of 2 Bioactive Compounds for Treatment of Breast Cancer: Triterpenoid Cucurbitacin I and Phenolic CAPE. Natural Product Communications, 14(6), 1934578X1985749. https://doi.org/10.1177/1934578x19857492
Karunakaran, S., & Hari, R. (2022). Comparative Antioxidant and Anti-gout Activities of Citrullus colocynthis loaded Fruit Silver nanoparticles with its Ethanolic extract. Avicenna journal of medical biotechnology, 14(4), 303–309.
KhusnulKhotimah, D. D. S. R. A. K. W. (2019). The study of watermelon rind (Citrullus lanatus) and pinenapple fruit (Ananas comosus L.) proportion with caragenan addition on fruit leather physicochemical characteristics. Food Technology and Halal Science Journal, 1(1), 71. https://doi.org/10.22219/fths.v1i1.7552
Kim, M. G., Lee, S. E., Yang, J. Y., & Lee, H. S. (2014). Antimicrobial potentials of active component isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues against foodborne bacteria. Journal of the Science of Food and Agriculture, 94(12), 2529–2533. https://doi.org/10.1002/jsfa.6590
Kostecka-Mądalska, O., & Noculak, A. (2015). Próbyuprawy Citrullus colocynthis (L.) Schrad. iwstępnaocenaprzydatności nasion [An attempt at Citrullus colocynthis (L.) Schrad. Cultivation and the initial estimation of the seeds utility]. Acta Agrobotanica, 24(1), 111–119. https://doi.org/10.5586/aa.1971.006
Kumar, R. R. (2021). A Comparative Study on Diabetes (Diabetes Mellitus) (Metabolic Disease that occurs when an Individual Has Elevated Blood Glucose). Journal of Medical Science and Clinical Research, 09(06). https://doi.org/10.18535/jmscr/v9i6.08
Kumar, S., Kumar, D., Jusha, M., Saroha, K., Singh, N., & Vashishta, B. (2008). Antioxidant and free radical scavenging potential of Citrullus colocynthis (L.) Schrad. methanolic fruit extract. Acta Pharmaceutica, 58(2). https://doi.org/10.2478/v10007-008-0008-1
Levi, A., Thomas, C., Joobeur, T., Zhang, X., & Davis, A. (2002). A genetic linkage map
for watermelon derived from a testcross population: (Citrullus lanatus var. citroides × C. lanatus var. lanatus) × Citrullus colocynthis. Theoretical and Applied Genetics,
(4), 555–563.
https://doi.org/10.1007/s00122-001-0860-6 41. Li, W., Li, W., Xing, Q., Liu, Z., Hu, Y., Liu, X., & Zhang, J. (2022). Progress in Traditional Chinese Medicine on Treatment of Diabetic Retinopathy. Natural Product Communications, 17(8), 1934578X2211185. https://doi.org/10.1177/1934578x22111854 7
Marzouk, B., Mahjoub, M. A., Bouraoui, A., Fenina, N., Aouni, M., & Marzouk, Z. (2012). Anti-inflammatory and analgesic activities of a new cucurbitacin isolated from Citrullus colocynthis seeds. Medicinal Chemistry Research, 22(8), 3984–3990. https://doi.org/10.1007/s00044-012-0406-2
Mashilo, J., Shimelis, H., Ngwepe, R. M., & Thungo, Z. (2022). Genetic Analysis of Fruit Quality Traits in Sweet Watermelon (Citrullus lanatus var. lanatus): A Review. Frontiers in Plant Science, 13. https://doi.org/10.3389/fpls.2022.834696
Mehmood, T., Kousar, K., Arshad, H., Iqbal, M., & Zeshan. (2021). Effect of Solvents on Extraction of Bioactive Substances from Citrullus Colocynthis and Their Antioxidant, Antimicrobial and Antiglycation Activities. Pharmaceutical Chemistry Journal, 55(3), 275–283. https://doi.org/10.1007/s11094-021-02411-2
Mohammed, M. F., Kannan, H. B., Abdalqader, M., Alwan, M. R., Alhoot, M. A., & Ghazi, H. F. (2020). Antibacterial activities of watermelon (Citrullus lanatus) rind and seed extracts against selected gram-positive and gram-negative bacteria. International Journal of Medical Toxicology & Legal Medicine, 23(3and4), 95- 100.
Neglo, D., Tettey, C. O., Essuman, E. K., Kortei, N. K., Boakye, A. A., Hunkpe, G., ... & Devi, W. S. (2021). Comparative antioxidant and antimicrobial activities of the peels, rind, pulp and seeds of watermelon (Citrullus lanatus) fruit. Scientific African, 11, e00582.
Oberoi, D. P. S., Singh, T. P., &Sogi, D. S. (2020). In Vivo Bioavailability of Lycopene
from Watermelon (Citrullus lanatus Thunb) Coloring. Nutrition and Cancer, 73(8), 1365– 1370.
https://doi.org/10.1080/01635581.2020.180 1773
Obi, O. F., &Offorha, L. C. (2015). Moisture dependent physical properties of melon (Citrullus colocynthislanatus) seed and kernel relevant in bulk handling. Cogent Food & Agriculture, 1(1), 1020743. https://doi.org/10.1080/23311932.2015.102
Ogbuji, K., McCutcheon, G. S., Simmons, A. M., Snook, M. E., Harrison, H. F., & Levi, A. (2012). Partial Leaf Chemical Profiles of a Desert Watermelon Species (Citrullus colocynthis) and Heirloom Watermelon Cultivars (Citrullus lanatus var. lanatus). Hort Science, 47(5), 580–584. https://doi.org/10.21273/hortsci.47.5.580
Omigie, I. O., & Agoreyo, F. O. (2014). Effects of Watermelon (Citrullus lanatus) Seed on Blood Glucose and Electrolyte Parameters in Diabetic Wistar Rats. Journal of Applied Sciences and Environmental Management, 18(2), 231. https://doi.org/10.4314/jasem.v18i2.12
Parihar, A., Vaja, M. B., Dhruve, J. J., Rukhsar, & Kumar, S. (2020). Identification of useful recombinants from interspecific hybrids of Citrullus lanatus and C. colocynthis. Vegetos, 33(3), 475–482. https://doi.org/10.1007/s42535-020-00131-8
Patel, D. K., Prasad, S. K., Kumar, R., & Hemalatha, S. (2012). An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pacific journal of tropical biomedicine, 2(4), 320-330.
Pathania, R., Chawla, P., Sharma, A., Kaushik, R., & Khan, M. A. (2022). GC-MS Characterization, In Vitro Antioxidant, Anti inflammatory and Potential Antidermatophytic Activity of Citrullus lanatus Seed Oil. Anti-Infective Agents, 20(1). https://doi.org/10.2174/2211352519666210 906151310
Rajamanickam, E., Gurudeeban, S., Ramanathan, T., & Satyavani, K. (2010). Evaluation of anti inflammatory activity of Citrullus colocynthis. International Journal of Current Research, 2(1), 67-69.
Rehman, R., & Mahmud, T. (2013). Sorptive elimination of alizarin Red-S dye from water using citrulluslanatus peels in environmentally benign way along with equilibrium data modeling. Asian Journal of Chemistry, 25(10), 5351.
Saeed, M. E., Boulos, J. C., Elhaboub, G., Rigano, D., Saab, A., Loizzo, M. R., ... & Efferth, T. (2019). Cytotoxicity of cucurbitacin E from Citrullus colocynthis against multidrug-resistant cancer cells. Phytomedicine, 62, 152945.
Sagar, R., & Dumka, V. (2019). Original article Evaluation of antipyretic, muscle relaxant and neurobehavioural activities of various leaf extracts of Citrullus colocynthis Schrad. Annals of Phytomedicine: An International Journal, 8(1), 88–93. https://doi.org/10.21276/ap.2019.8.1.10
Sansri, S., Kalbaza, A. Y., & Bairi, A. E. M. (2022). Treatment of Diabetes with a Medicinal Plant “Citrullus colocynthis” in Wistar Rats. Agricultural Science Digest - a Research Journal, (Of). https://doi.org/10.18805/ag.df-479
Shafaei, H. (2012). Citrullus colocynthis as a medicinal or poisonous plant: A revised fact. Journal of Medicinal Plants Research, 6(36). https://doi.org/10.5897/jmpr11.264
Siddiqui, W. A., Shahzad, M., Shabbir, A., & Ahmad, A. (2018). Evaluation of anti urolithiatic and diuretic activities of watermelon (Citrullus lanatus) using in vivo and in vitro experiments. Biomedicine & Pharmacotherapy, 97, 1212-1221.
Silva, J., & Hussain, A. (2017). Citrullus colocynthis (L.) Schrad. (colocynth): Biotechnological perspectives. Emirates Journal of Food and Agriculture, 29(2), 83. https://doi.org/10.9755/ejfa.2016-11-1764
Singh Gill, N., Sood, S., Muthuraman, A., Bali, M., & Dev Sharma, P. (2011). Evaluation of antioxidant and anti ulcerative potential of Citrullus lanatus seed extract in rats. Latin American journal of pharmacy, 30.
Tannin-Spitz, T., Grossman, S., Dovrat, S., Gottlieb, H. E., & Bergman, M. (2007). Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells.
Biochemical Pharmacology, 73(1), 56–67. https://doi.org/10.1016/j.bcp.2006.09.012 64. TO, A. (2017). Development and quality evaluation of Jam from Watermelon (Citrullus Lanatus) and Pawpaw (Carica Papaya) juice. Archive of Food and Nutritional Science, 1(2), 063–071. https://doi.org/10.29328/journal.afns.1001 010
Tripathy, D., & Chavez, A. O. (2010). Defects in Insulin Secretion and Action in the Pathogenesis of Type 2 Diabetes Mellitus. Current Diabetes Reports, 10(3), 184–191. https://doi.org/10.1007/s11892-010-0115-5
Varela, C., Melim, C., Neves, B. G., Sharifi Rad, J., Calina, D., Mamurova, A., & Cabral,
C. (2022). Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms. Journal of Translational Medicine, 20(1), 1-16.
Wahid, M., Saqib, F., Qamar, M., & Ziora, Z. M. (2022). Antispasmodic activity of the ethanol extract of Citrullus lanatus seeds: Justifying ethnomedicinal use in Pakistan to treat asthma and diarrhea. Journal of Ethnopharmacology, 295, 115314.
Wahyuni, I. (2019). Antifatigue Activity of Citrullus (Citrullus lanatus) Genus Plant: A Review. KnE Life Sciences, 4(10), 57. https://doi.org/10.18502/kls.v4i10.3829
