Potential of Combined Insulin Leaf (Smallanthus sonchifolius) and Noni Fruit (Morinda citrifolia L.) Extracts in Reducing Blood Glucose Level and Spermatogenic Cells Improvement in Diabetic Mice

Authors

Sukarjati , Aldi Syahputra

DOI:

10.29303/jppipa.v11i5.11174

Published:

2025-05-25

Issue:

Vol. 11 No. 5 (2025): May

Keywords:

Diabetes Mellitus, Mice, Morinda citrifolia L, Smallanthus sonchifolius, Spermatogenic Cells

Research Articles

Downloads

How to Cite

Sukarjati, & Syahputra, A. (2025). Potential of Combined Insulin Leaf (Smallanthus sonchifolius) and Noni Fruit (Morinda citrifolia L.) Extracts in Reducing Blood Glucose Level and Spermatogenic Cells Improvement in Diabetic Mice. Jurnal Penelitian Pendidikan IPA, 11(5), 1089–1100. https://doi.org/10.29303/jppipa.v11i5.11174
Crossref
Scopus
Google Scholar
Europe PMC

Downloads

Metrics

PDF views
20
Jul 2025Jan 202612

Abstract

Elevated blood glucose levels are a hallmark of diabetes mellitus, which can lead to reproductive disorders, particularly affecting spermatogenic cells. This study aimed to evaluate the effectiveness of insulin leaf extract, noni fruit extract, and their combinations in reducing blood glucose levels and their impact on the number of spermatogenic cells in diabetic mice. A total of 36 male mice were divided into 12 treatment groups, including a normal control group, a negative control group (induced with alloxan 120 mg/KgBW), a positive control group (alloxan + metformin), and nine treatment groups with various doses of individual and combined extracts. Blood glucose levels were measured using Accu-Chek, and testicular histology was prepared following laboratory standards. Data were analyzed using the ANOVA test followed by the Duncan post hoc test. Results showed that the combination of insulin leaf extract at 150 mg/KgBW/day and noni fruit extract at 62.5 mg/KgBW/day was the most effective in reducing blood glucose levels. Additionally, the combination of 125 mg/KgBW insulin leaf extract and 50 mg/KgBW noni fruit extract significantly increased the number of spermatogenic cells. Thus, the combination of insulin leaf and noni fruit extracts shows potential as a natural antidiabetic therapy and for restoring spermatogenic cell function in diabetic conditions.

References

Aitken, R. J. (2017). Reactive oxygen species as mediators of sperm capacitation and pathological damage. Molecular Reproduction and Development, 84(10), 1039–1052. https://doi.org/10.1002/mrd.22871

Akhtar, M. F., Ahmad, E., Mustafa, S., Chen, Z., Shi, Z., & Shi, F. (2020). Spermiogenesis, stages of seminiferous epithelium and variations in seminiferous tubules during active states of spermatogenesis in Yangzhou goose ganders. Animals, 10(4), 570. https://doi.org/10.3390/ani10040570

Algenstaedt, P., Stumpenhagen, A., & Westendorf, J. (2018). The Effect of Morinda citrifolia L . Fruit Juice on the Blood Sugar Level and Other Serum Parameters in Patients with Diabetes Type 2. Hindawi, 2018, 1–10. https://doi.org/10.1155/2018/3565427

Aquila, S., Santoro, M., Amicis, F. De, & Guido, C. (2012). Red wine consumption may affect sperm biology : The effects of different concentrations of the phytoestrogen Myricetin on human male gamete function. Molecular Reproduction and Development, 80(2), 1–29. https://doi.org/10.1002/mrd.22145

Arambas, J., & Vidakovic, M. (2022). Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. Frontiers in Endocrinology, September, 1–20. https://doi.org/10.3389/fendo.2022.1006376

Arjadi, F., Mustofa, D. A. N., Anatomi, B., Kedokteran, F., & Soedirman, U. J. (2017). Ektrak Daging Buah Mahkota Dewa Meregenerasi Sel Pulau Langerhans Pada Tikus Putih Diabetes. Biogenesis, 5(1), 27–33. https://doi.org/10.24252/bio.v5i1.3430

Arruda, L. C. P., Silva, R. A. J. A., Mergulhão, F. C. C., Monteiro, M. M., Costa, J. A. S., Júnior, P. L. J. M., Seal, D. C. M., & Guerra, M. M. P. (2022). Quality of ram semen cryopreserved in egg yolk extender supplemented with myricetin. South African Journal of Animal Science, 52(1), 77–89. https://doi.org/10.4314/sajas.v52i1.10

Bibov, M. Y., Kuzmin, A. V, Alexandrova, A. A., Chistyakov, V. A., Natalia, M., & Kundupyan, O. L. (2018). Role of the reactive oxygen species induced DNA damage in human spermatozoa dysfunction. AME:Medical Journal, 3(19), 1–12. https://doi.org/10.21037/amj.2018.01.06

Cahyana, Y., & Adiyanti, T. (2021). Flavonoids as Antidiabetic Agents. Indonesian Journal of Chemistry, 21(2), 512-526. https://doi.org/10.22146/ijc.58439

Castleton, P. E., Deluao, J. C., Sharkey, D. J., & Mcpherson, N. O. (2022). Measuring Reactive Oxygen Species in Semen for Male Preconception Care : A Scientist Perspective. Antioxidants, 11(2), 264. https://doi.org/10.3390/antiox11020264

Cormier, M., Ghouili, F., Roumaud, P., Luc, J., & Touaibia, M. (2017). influence of flavonol and quecertin derivative compound on MA 10-leydig cell steroidogenic gene expression. In Toxicology in Vitro. Elsevier Ltd. https://doi.org/10.1016/j.tiv.2017.06.027

Delazari, S., & Barbalho, S. M. (2014). Antidiabetic and antilipidemic Effects of manilkara zapota. Journal of Medical Food, 00(0), 1–7. https://doi.org/10.1089/jmf.2013.0170

Farmaki, P., Damaskos, C., Garmpis, N., Garmpi, A., Savvanis, S., & Diamantis, E. (2020). Complications of the Type 2 Diabetes Mellitus. Current Cardiology Review, 16(4), 249–251. https://doi.org/10.2174/1573403X1604201229115531

Fontes, R. F., Karla, J., Andrade, S., Rajan, M., & Narain, N. (2023). Chemical characterization of different parts of noni ( Morinda citrifolia ) fruit and its freeze-dried pulp powder with emphasis on its bioactive compounds and antioxidant activities. Food Science and Technology, 2061, 1–8. https://doi.org/10.1590/fst.103722

Gerwen, J. Van, & Shun-shion, A. S. (2023). Insulin signalling and GLUT4 trafficking in insulin resistance. Biomedical Society Transaction, 0(May), 1057–1069. https://doi.org/10.1042/BST20221066

Ghorbani, A. (2017). Mechanisms of antidiabetic eff ects of flavonoid rutin. Biomedicine & Pharmacotheraphy, 96(8), 305–312. https://doi.org/10.1016/j.biopha.2017.10.001

Goyal, A., Gupta, Y., Singla, R., Kalra, S., & Tandon, N. (2020). American Diabetes Association ‘“ Standards of Medical Care — 2020 for Gestational Diabetes Mellitus ”’: A Critical Appraisal. Diabetes Therapy, 11(8), 1639–1644. https://doi.org/10.1007/s13300-020-00865-3

Grande, G., Barrachina, F., Soler-ventura, A., Jodar, M., Mancini, F., Marana, R., Chiloiro, S., Pontecorvi, A., Oliva, R., & Milardi, D. (2022). The role of testosterone in spermatogenesis: lessons from proteome profiling of human spermatozoa in testosterone deficiency. Frontiers in Endocrinology, 13, 852661. https://doi.org/10.3389/fendo.2022.852661

Guerriero, G., Trocchia, S., Abdel-gawad, F. K., & Ciarcia, G. (2014). Roles of reactive oxygen species in the spermatogenesis regulation. Frontiers in endocrinology, 5, 56, 10–13. https://doi.org/10.3389/fendo.2014.00056

Haryanto, H., Sutandi, A., Kusumawati, E., Nurhayati, S., Fitri, F. M., Nafsi, G., & Nuraeni, S. W. (2023). Potential of Therapeutic Curculigo latifolia Extracts on Alloxan-induced Diabetes in a Male Mus muscullus. Biosaintifika, 15(3), 370–377. https://doi.org/10.15294/biosaintifika.v15i3.40498

He, Z., Yin, G., Li, Q. Q., Zeng, Q., & Duan, J. (2021). Diabetes mellitus causes male reproductive dysfunction: A review of the evidence and mechanisms. In vivo, 35(5), 2503-2511. https://doi.org/10.21873/invivo.12531

Kotian, S. R., Kumar, A., & Souza, A. D. (2019). Effect of Diabetes on the Male Reproductive System — A Histomorphological Study. Journal of Morphological Sciences, 36(1), 17–23. Retrieved from https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0039-1683405

Liu, F., Liao, B., Ling, Y., Meng, X., Wang, J., Hu, L., Luo, X., & Yang, F. (2024). Icariin protects testicular damage in streptozotocin-induced diabetic rats through regulation of glycolysis pathway. International Journal of Imunopathology and Pharmacology, 38, 1–15. https://doi.org/10.1177/03946320241279525

Long, L., Qiu, H., Cai, B., Chen, N., Lu, X., & Zheng, S. (2018). Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K / Akt pathway. Oncotarget, 9(4), 5321–5336. https://doi.org/10.18632/oncotarget.23915

Macdonald, O., & Mohammed, A. (2018). ScienceDirect Alloxan-induced diabetes , a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina, 1–10. https://doi.org/10.1016/j.medici.2018.02.001

Maresch, C. C., Stute, D. C., Alves, M. G., Oliveira, F., Kretser, D. M. De, & Linn, T. (2018). Diabetes-induced hyperglycemia impairs male reproductive function : a systematic review. Human Reproduction Update, 24(1), 86–105. https://doi.org/10.1093/humupd/dmx033

Mazidda, S., Hikmawati, D., & Yulinarsari, A. P. (2022). The effect of addition of Allium cepa extract in diluent Ringer ’ s-Dextrose on Gallus domesticus sperm quality at 5 ° C. Jurnal Ilmu Peternakan Terapan, 6(1), 4–11. https://doi.org/10.25047/jipt.v6i1.3584

Mohammadi, Z., Alaee, S., & Namavar, M. R. (2023). The antioxidant properties of resveratrol on sperm parameters , testicular tissue , antioxidant capacity , and lipid peroxidation in iso fl urane-induced toxicity in mice. Human & Experimental Toxicology, 42, 1–11. https://doi.org/10.1177/09603271231215036

Monageng, E., Offor, U., Takalani, N. B., Mohlala, K., & Opuwari, C. S. (2023). A Review on the Impact of Oxidative Stress and Medicinal Plants on Leydig Cells. Antioxidant, 12(1559), 1–29. https://doi.org/10.3390/antiox12081559

Nadalin, P., Kim, J. K., & Park, S. U. (2023). Recent studies on berberine and its biological and pharmacological activities. EXCLI journal, 22, 315. https://doi.org/10.17179/excli2022-5898

Nurkarimah, D. A., Hestianah, E. P., & Wahjuni, R. S. (2017). Effect of Propolis on Spermatogenic Cells Number and Diameter of Seminiferous Tubules in Male Mice (Mus musculus). KnE Life Sciences, 677-683, 677–683. https://doi.org/10.18502/kls.v3i6.1197

Omar, N., Aishah, C., Ismail, N., & Long, I. (2022). Tannins in the Treatment of Diabetic Neuropathic Pain : Research Progress and Future Challenges. Frontiers in Pharmacology, 12(1), 1–9. https://doi.org/10.3389/fphar.2021.805854

Pakaya, M. S., Uno, W. Z., & Nurrohwinta, E. (2024). Aktivitas Metabolit Sekunder Bakteri Endofit Tanaman Insulin (Smallanthus sonchifolius ) Sebagai Anti Hiperglikemia Pada Mencit Jantan ( Mus musculus ). JSSCR, 6(2), 198–208. https://doi.org/10.37311/jsscr.v6i2.27586

Pang, G., Li, F., Yan, Y., Zhang, Y., Kong, L., Zhu, P., Wang, K., & Zhang, F. (2019). Herbal medicine in the treatment of patients with type 2 diabetes mellitus. Chinese medical journal, 132(1), 78-85. https://doi.org/10.1097/CM9.0000000000000006

Rusli, J. (2022). Antidiabetic Activity of Noni ( Morinda citrifolia ) Extract on Swiss Webster Male Glucagon-Induced Mice. Pharmaceutical and Biomedical Sciences Journal (PBSJ), 3(2), 67-74. https://doi.org/10.15408/pbsj.v3i2.20183

Setiadi, E., Peniati, E., & Susanti, R. (2020). Pengaruh Ekstrak Kulit Lidah Buaya Terhadap Kadar Gula Darah Dan Gambaran. Life Science, 9(2), 171–185. https://doi.org/10.15294/lifesci.v9i2.47160

Škorjanc, D. (2021). Effect of Hydrolyzable Tannins on Glucose-Transporter Cell Model. Molecules, 26(345), 1–17. https://doi.org/10.3390/molecules26020345

Smith, L. B., & Walker, W. H. (2014). The regulation of spermatogenesis by androgens. Seminars in Cell and Developmental Biology, 30(June), 2–13. https://doi.org/10.1016/j.semcdb.2014.02.012

Sopianti, D. S. (2020). Review, Gambaran Efek Samping Metforminpada Pasien Diabetes Melitus Tipe II. Jurnal Ilmiah Pharmacy, 7(2), 209-221. https://doi.org/10.52161/jiphar.v7i2.169

Srinivasahan, V., & Durairaj, B. (2014). Antioxidant And Free Radical Scavenging Effect Of Morinda Citrifolia Fruit Extract. International Journal of Farmacy and Pharmaceutical Science, 6(4), 55–59. Retrieved from https://innovareacademics.in/journal/ijpps/Vol6Issue4/6824.pdf

Sogandi, S., & Rabima, R. (2019). Identifikasi Senyawa Aktif Ekstrak Buah Mengkudu (Morinda citrifolia L.) dan potensinya sebagai antioksidan. Jurnal Kimia Sains Dan Aplikasi, 22(5), 206–212. https://doi.org/10.14710/jksa.22.5.206-212

Sukarjati, Evarina, M. Y., & Andriani, V. (2023). Tepung labu kuning (Cucurbita moschata), Tepung porang (Amorphophallus muelleri Blume), dan Kombinasi Kedua Tepung sebagai Penurun Gula darah dan Peningkat Motilitas Spermatozoa Mencit (Mus musculus). Bioscientist, 11(2), 1135–1149. https://doi.org/10.33394/bioscientist.v11i2.8941

Sukarjati, Nurhayati, U., & Medistriani, D. (2024). Enhancing Spermatozoa Quality and Spermatogenic Cell in Hyperglycemic Mice ( Mus musculus L .) with Sambung Nyawa ( Gynura procumbens ) and Mahagany ( Swietenia mahagoni jacq ) extracts , Alone and in Combination. Jurnal PenelitianPendidikan IPA, 10(6), 3118–3131. https://doi.org/10.29303/jppipa.v10i6.7180

Timar, M., Salimnejad, R., Golmohammadi, M. G., & Banaei, S. (2024). Impact of saponin on cyclophosphamide -induced testicular damage. Phisiology and Pharmacoogy, 28(1), 3–9. Retrieved from https://ppj.phypha.ir/browse.php?a_id=2082&sid=1&slc_lang=en&ftxt=0

Wang, J., & Wang, H. (2017). Oxidative stress in pancreatic beta cell regeneration. Oxidative medicine and cellular longevity, 2017(1), 1930261. https://doi.org/10.1155/2017/1930261

Wang, Y., Fu, X., & Li, H. (2025). Mechanisms of oxidative stress- induced sperm dysfunction. Frontiers in Endocrinology, February, 1–15. https://doi.org/10.3389/fendo.2025.1520835

Wasik, A. A., & Lehtonen, S. (2018). Glucose Transporters in Diabetic Kidney Disease — Friends or Foes ? Frontiers in Endocrinology, 9(April), 1–12. https://doi.org/10.3389/fendo.2018.00155

Widowati, W., Sadeli, L., Widya, H. S., Fuad, A., & Agatha, A. (2021). Antidiabetic Potential Yacon ( Smallanthus sonchifolius ( Poepp .) H . Rob .) Leaf Extract via Antioxidant Activities , Inhibition of α -glucosidase , α - amylase , G-6-Pase by In Vitro Assay. Journal of Report in Pharmaceutical Sciences, 10(2), 247–255. https://doi.org/10.4103/jrptps.JRPTPS

Zhang, S., Wang, R., Zhao, Y., & Tareq, F. S. (2019). Biotransformation of Myricetin : A Novel Metabolic Pathway to Produce Aminated Products in Mice. Molecular Nutrition Food Research, 1900203(63), 1–9. https://doi.org/10.1002/mnfr.201900203

Zheng, X., & Gallot, G. (2020). Article Dynamics of Cell Membrane Permeabilization by Saponins Using Terahertz Attenuated Total Reflection. Biophysical Journal, 119(4), 749–755. https://doi.org/10.1016/j.bpj.2020.05.040

Zhou, Y., Zhang, H., Yan, H., Han, P., Zhang, J., & Liu, Y. (2025). Deciphering the Role of Oxidative Stress in Male Infertility : Insights from Reactive Oxygen Species to Antioxidant Therapeutics. Frontiers in Bioscience, 30(4), 1–21. https://doi.org/10.31083/FBL27046

Zirkin, B. R., & Papadopoulos, V. (2018). Leydig cells : formation , function , and regulation . Biology of Reproduction, 99(3), 101–111. https://doi.org/10.1093/biolre/ioy059

Author Biographies

Sukarjati, Universitas PGRI Adi Buana Surabaya

Aldi Syahputra, Universitas PGRI Adi Buana Surabaya

License

Copyright (c) 2025 Sukarjati, Aldi Syahputra

Creative Commons License

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

Authors who publish with Jurnal Penelitian Pendidikan IPA, agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC-BY License). This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Jurnal Penelitian Pendidikan IPA.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).