Main Article Content
Abstract
The Sesquiterpene lactones, enhydrin and uvedalin, are the chemotype and subtype compounds of the yacon leaf. They are known to have anti-diabetic activity, but their mechanisms are not clear. One of the mechanisms of anti-diabetic agents is to inhibit the activity of the dipeptidyl peptidase 4 enzyme (DPP-4). The research aimed to determine the inhibition of the extract, enhydrin, and uvedalin isolated from the yacon leaf against the DPP-4 enzyme activity. Yakon leaves were extracted using 70% ethanol by the maceration method. Enhydrin and uvedalin were obtained from previous research. The inhibitory activity of the DPP-4 enzyme was then determined by the fluorescence assay method using a multi-well plate reader. Sitagliptin was used as standard inhibitor of DPP-4 enzyme. The ethanol extract of yacon leaves inhibits the DPP-4 enzyme with an IC50 of 856.9 ppm. The percentage inhibition of the DPP-4 enzyme by the enhydrin and uvedalin at a concentration of 250 ppm was 2.37 and 35.16%, respectively. The inhibitory potency of the pure isolated compounds was not substantially greater than that of the crude extract itself. This led us to the conclusion that the overall contribution of enhydrin and uvedalin to the extract's DPP-4 inhibitory activity is actually modest, suggesting the presence of other active compounds within the extract. However, it may provide a new approach to the treatment of type 2 diabetes.
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Copyright (c) 2025 Hady Anshory Tamhid, Triana Hertiani, Yosi Bayu Murti, Retno Murwanti
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References
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- Ahrén, B., & Foley, J. E. (2016). Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism. Diabetologia, 59(5), 907–917. https://doi.org/10.1007/s00125-016-3899-2
- Ansari, P., Hannon-Fletcher, M. P., Flatt, P. R., & Abdel-Wahab, Y. H. A. (2021). Effects of 22 traditional anti-diabetic medicinal plants on DPP-IV enzyme activity and glucose homeostasis in high-fat fed obese diabetic rats. Bioscience Reports, 41(1), BSR20203824. https://doi.org/10.1042/BSR20203824
- Contreras-Puentes, N., & Alvíz-Amador, A. (2021). Hypoglycaemic Property of Yacon (Smallanthus sonchifolius (Poepp. and Hendl.) H. Robinson): A Review. Pharmacognosy Reviews, 14(27), 37–44. https://doi.org/10.5530/phrev.2020.14.7
- de Andrade, E. F., Carpiné, D., Dagostin, J. L. A., Barison, A., Rüdiger, A. L., de Muñiz, G. I. B., & Masson, M. L. (2017). Identification and antimicrobial activity of the sesquiterpene lactone mixture extracted from Smallanthus sonchifolius dried leaves. European Food Research and Technology, 243(12). https://doi.org/10.1007/s00217-017-2918-y
- Honoré, S. M., Genta, S. B., Serafina Sánchez, S., & Sánchez, S. (2015). Smallanthus sonchifolius ( Yacon ) leaves : an emerging source of compounds for diabetes management. Journal of Research in Biology, 5((A)), 21–42. http://jresearchbiology.com/%0Adocuments/RA0502.pdf
- Khan, M. F., Rashid, R. Bin, & Rashid, M. A. (2022). Identification of Natural Compounds with Analgesic and Antiinflammatory Properties Using Machine Learning and Molecular Docking Studies. Letters in Drug Design & Discovery, 19(3), 256–262. https://doi.org/10.2174/1570180818666210728162055
- Mercado, M. I., Coll Aráoz, M. V., Manrique, I., Grau, A., & Catalán, C. A. N. (2014). Variability in sesquiterpene lactones from the leaves of yacon (Smallanthus sonchifolius) accessions of different geographic origin. Genetic Resources and Crop Evolution, 61(6), 1209–1217. https://doi.org/10.1007/s10722-014-0103-8
- Padilla-González, G. F., Frey, M., Gómez-Zeledón, J., Da Costa, F. B., & Spring, O. (2019). Metabolomic and gene expression approaches reveal the developmental and environmental regulation of the secondary metabolism of yacón (Smallanthus sonchifolius, Asteraceae). Scientific Reports, 9(1), 13178. https://doi.org/10.1038/s41598-019-49246-2
- Riyanti, S., Suganda, A. G., & Sukandar, E. Y. (2016). Dipeptidyl peptidase-IV inhibitory activity of some Indonesian medicinal plants. Asian Journal of Pharmaceutical and Clinical Research, 9(2), 375–377. https://www.journals.innovareacademics.in/index.php/ajpcr/article/view/11019
- Santos, K. C. dos, Bueno, B. G., Pereira, L. F., Francisqueti, F. V., Braz, M. G., Bincoleto, L. F., Silva, L. X. da, Ferreira, A. L. A., Nakamune, A. C. de M. S., Chen, C.-Y. O., Blumberg, J. B., & Corrêa, C. R. (2017). Yacon ( Smallanthus sonchifolius ) Leaf Extract Attenuates Hyperglycemia and Skeletal Muscle Oxidative Stress and Inflammation in Diabetic Rats. Evidence-Based Complementary and Alternative Medicine, 2017(1), 6418048. https://doi.org/10.1155/2017/6418048
- Schmidt, T. J. (2018). Structure-Activity and Activity-Activity Relationships of Sesquiterpene Lactones. In Sesquiterpene Lactones (pp. 349–371). Springer International Publishing. https://doi.org/10.1007/978-3-319-78274-4_15
- Sesti, G., Avogaro, A., Belcastro, S., Bonora, B. M., Croci, M., Daniele, G., Dauriz, M., Dotta, F., Formichi, C., Frontoni, S., Invitti, C., Orsi, E., Picconi, F., Resi, V., Bonora, E., & Purrello, F. (2019). Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetologica, 56(6), 605–617. https://doi.org/10.1007/s00592-018-1271-3
- Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C. N., Mbanya, J. C., Pavkov, M. E., Ramachandaran, A., Wild, S. H., James, S., Herman, W. H., Zhang, P., Bommer, C., Kuo, S., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183, 109119. https://doi.org/10.1016/j.diabres.2021.109119
- Tamhid, H. A., Hertiani, T., Murti, Y. B., & Murwanti, R. (2023). Quantification of Enhydrin and Uvedalin in the Ethanolic Extract of Smallanthus sonchifolius Leaves Validated by the HPLC Method. Molecules, 28(4), 1913. https://doi.org/10.3390/molecules28041913
- Widowati, W., Tjokropranoto, R., Wahyudianingsih, R., Tih, F., Sadeli, L., Kusuma, H. S. W., Fuad, N. A., Girsang, E., & Agatha, F. 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 Reports in Pharmaceutical Sciences, 10(2), 247–255. https://doi.org/10.4103/jrptps.JRPTPS_3_21
References
Adianingsih, O. R., Khasanah, U., Anandhy, K. D., & Yurina, V. (2022). In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy. Journal of Pharmacy & Pharmacognosy Research, 10(4), 571–594. https://doi.org/10.56499/jppres22.1345.10.4.571
Ahrén, B., & Foley, J. E. (2016). Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism. Diabetologia, 59(5), 907–917. https://doi.org/10.1007/s00125-016-3899-2
Ansari, P., Hannon-Fletcher, M. P., Flatt, P. R., & Abdel-Wahab, Y. H. A. (2021). Effects of 22 traditional anti-diabetic medicinal plants on DPP-IV enzyme activity and glucose homeostasis in high-fat fed obese diabetic rats. Bioscience Reports, 41(1), BSR20203824. https://doi.org/10.1042/BSR20203824
Contreras-Puentes, N., & Alvíz-Amador, A. (2021). Hypoglycaemic Property of Yacon (Smallanthus sonchifolius (Poepp. and Hendl.) H. Robinson): A Review. Pharmacognosy Reviews, 14(27), 37–44. https://doi.org/10.5530/phrev.2020.14.7
de Andrade, E. F., Carpiné, D., Dagostin, J. L. A., Barison, A., Rüdiger, A. L., de Muñiz, G. I. B., & Masson, M. L. (2017). Identification and antimicrobial activity of the sesquiterpene lactone mixture extracted from Smallanthus sonchifolius dried leaves. European Food Research and Technology, 243(12). https://doi.org/10.1007/s00217-017-2918-y
Honoré, S. M., Genta, S. B., Serafina Sánchez, S., & Sánchez, S. (2015). Smallanthus sonchifolius ( Yacon ) leaves : an emerging source of compounds for diabetes management. Journal of Research in Biology, 5((A)), 21–42. http://jresearchbiology.com/%0Adocuments/RA0502.pdf
Khan, M. F., Rashid, R. Bin, & Rashid, M. A. (2022). Identification of Natural Compounds with Analgesic and Antiinflammatory Properties Using Machine Learning and Molecular Docking Studies. Letters in Drug Design & Discovery, 19(3), 256–262. https://doi.org/10.2174/1570180818666210728162055
Mercado, M. I., Coll Aráoz, M. V., Manrique, I., Grau, A., & Catalán, C. A. N. (2014). Variability in sesquiterpene lactones from the leaves of yacon (Smallanthus sonchifolius) accessions of different geographic origin. Genetic Resources and Crop Evolution, 61(6), 1209–1217. https://doi.org/10.1007/s10722-014-0103-8
Padilla-González, G. F., Frey, M., Gómez-Zeledón, J., Da Costa, F. B., & Spring, O. (2019). Metabolomic and gene expression approaches reveal the developmental and environmental regulation of the secondary metabolism of yacón (Smallanthus sonchifolius, Asteraceae). Scientific Reports, 9(1), 13178. https://doi.org/10.1038/s41598-019-49246-2
Riyanti, S., Suganda, A. G., & Sukandar, E. Y. (2016). Dipeptidyl peptidase-IV inhibitory activity of some Indonesian medicinal plants. Asian Journal of Pharmaceutical and Clinical Research, 9(2), 375–377. https://www.journals.innovareacademics.in/index.php/ajpcr/article/view/11019
Santos, K. C. dos, Bueno, B. G., Pereira, L. F., Francisqueti, F. V., Braz, M. G., Bincoleto, L. F., Silva, L. X. da, Ferreira, A. L. A., Nakamune, A. C. de M. S., Chen, C.-Y. O., Blumberg, J. B., & Corrêa, C. R. (2017). Yacon ( Smallanthus sonchifolius ) Leaf Extract Attenuates Hyperglycemia and Skeletal Muscle Oxidative Stress and Inflammation in Diabetic Rats. Evidence-Based Complementary and Alternative Medicine, 2017(1), 6418048. https://doi.org/10.1155/2017/6418048
Schmidt, T. J. (2018). Structure-Activity and Activity-Activity Relationships of Sesquiterpene Lactones. In Sesquiterpene Lactones (pp. 349–371). Springer International Publishing. https://doi.org/10.1007/978-3-319-78274-4_15
Sesti, G., Avogaro, A., Belcastro, S., Bonora, B. M., Croci, M., Daniele, G., Dauriz, M., Dotta, F., Formichi, C., Frontoni, S., Invitti, C., Orsi, E., Picconi, F., Resi, V., Bonora, E., & Purrello, F. (2019). Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetologica, 56(6), 605–617. https://doi.org/10.1007/s00592-018-1271-3
Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C. N., Mbanya, J. C., Pavkov, M. E., Ramachandaran, A., Wild, S. H., James, S., Herman, W. H., Zhang, P., Bommer, C., Kuo, S., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183, 109119. https://doi.org/10.1016/j.diabres.2021.109119
Tamhid, H. A., Hertiani, T., Murti, Y. B., & Murwanti, R. (2023). Quantification of Enhydrin and Uvedalin in the Ethanolic Extract of Smallanthus sonchifolius Leaves Validated by the HPLC Method. Molecules, 28(4), 1913. https://doi.org/10.3390/molecules28041913
Widowati, W., Tjokropranoto, R., Wahyudianingsih, R., Tih, F., Sadeli, L., Kusuma, H. S. W., Fuad, N. A., Girsang, E., & Agatha, F. 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 Reports in Pharmaceutical Sciences, 10(2), 247–255. https://doi.org/10.4103/jrptps.JRPTPS_3_21