Article Sidebar
Downloads
Main Article Content
Abstract
Background: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Metformin is the first-line therapy for type-2 diabetes mellitus. The combination of synthetic drugs with herbs was reported to be superior and popular compared to monotherapy. However, drug-herb interactions can have both beneficial and detrimental effects.
Objective: This review aimed to identify the interactions that occur between the antidiabetic drug metformin and herbs.
Methods: A literature search was done through ScienceDirect, ResearchGate, Pharmaceutics, and Genes by MDPI databases using the keywords metformin, antidiabetic, herb-drug, interaction, pharmacology, combination, pharmacokinetics, and pharmacodynamics.
Results: The combination of metformin and such herbs as Korean ginseng (Panax ginseng), Lonicera japonica, Houttuynia cordata, mulberry (Morus alba), banana (Musa sapientum), Momordica charantia, coconut (Cocos nucifera), and Scutellaria baicalensis showed pharmacokinetic interactions in the form of increasing plasma metformin uptake mediated by MATE1 inhibition and increased OCT1, as well as hOCT2 inhibition which caused decreased metformin uptake in the kidneys. The pharmacodynamic interactions showed a direct effect, both additive and synergistic effects, in reducing blood glucose levels.
Conclusion: Consuming metformin with herbs shows the potential for drug interactions in terms of both pharmacokinetics and pharmacodynamics.
Keywords: pharmacokinetic, pharmacodynamic, herb-drug, metformin
Intisari
Latar belakang: Diabetes melitus yaitu gangguan metabolisme yang ditandai dengan hiperglikemia. Metformin merupakan lini pertama pengobatan DM tipe 2. Kombinasi obat sintetis dengan herbal telah dilaporkan menjadi lebih unggul dan populer dibandingkan pengobatan monoterapi saja. Penggunaan obat sintetis dengan herbal dapat memicu interaksi obat yang dapat memberikan efek menguntungkan ataupun merugikan.
Tujuan: Review ini bertujuan untuk mengetahui interaksi yang terjadi antara obat antidiabetes metformin dengan herbal.
Metode: Penelusuran pustaka melalui database Sciencedirect, Researchgate, Pharmaceutics, dan Genes MDPI dengan penggunaan kata kunci seperti metformin, antidiabetic, herb-drug, interaction, pharmacology, combination, pharmacokinetic, dan pharmacodynamic.
Hasil: Kombinasi obat metformin dengan herbal seperti ginseng Korea (Panax ginseng), kamperfuli (Lonicera japonica), amis-amisan (Houttuynia cordata), murbei (Morus alba), pisang (Musa sapientum), pare (Momordica charantia), kelapa (Cocos nucifera), dan kopiah Cina (Scutellaria baicalensis) menunjukkan interaksi farmakokinetik berupa peningkatan penyerapan metformin dalam plasma yang diduga dimediasi oleh penghambatan MATE1 dan peningkatan OCT1, serta penghambatan hOCT2 yang menyebabkan penurunan penyerapan metformin di ginjal. Adapun interaksi farmakodinamiknya menunjukkan efek yang searah baik aditif maupun sinergis dalam penurunan kadar glukosa darah.
Kesimpulan: Konsumsi metformin dengan herbal menunjukkan adanya potensi interaksi obat baik secara farmakokinetik ataupun farmakodinamik.
Kata kunci: farmakokinetik, farmakodinamik, herbal-obat, metformin
Keywords
Article Details
Copyright (c) 2022 Jurnal Ilmiah Farmasi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish in the Jurnal Ilmiah Farmasi agree to the following terms:
- Authors retain copyright and grant Jurnal Ilmiah Farmasi right of first publication with the work simultaneously licensed under a Creative Commons Attribution Licence that allows others to adapt (remix, transform, and build) upon the work non-commercially with an acknowledgement of the work's authorship and initial publication in Jurnal Ilmiah Farmasi.
- Authors are permitted to share (copy and redistribute) the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in Jurnal Ilmiah Farmasi.
References
- Abouzekry, S. S., Badawy, M. T., Ezzelarab, N. M., & Abdellatif, A. (2021). Phytotherapy for diabetes mellitus; A review of Middle Eastern and North African folk medicinal plants. J Herbmed Pharmacol, 10(1), 1-13. https://doi.org/10.34172/jhp.2021.01
- Adegoke, G. A., Onasanwo, S. A., Eyarefe, O. D., & Olaleye, S. B. (2016). Ameliorative effects of Musa sapientum peel extract on acetic acid-induced colitis in rats. The Journal of Basic & Applied Zoology, 77, 49-55. https://doi.org/https://doi.org/10.1016/j.jobaz.2016.06.004
- Choi, J., Kim, K.-J., Koh, E.-J., & Lee, B.-Y. (2018). Gelidium elegans Extract Ameliorates Type 2 Diabetes via Regulation of MAPK and PI3K/Akt Signaling. Nutrients, 10(1), 51. https://doi.org/10.3390/nu10010051
- Cortez-Navarrete, M., Martínez-Abundis, E., Pérez-Rubio, K. G., González-Ortiz, M., & Méndez-Del Villar, M. (2018). Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus. J Med Food, 21(7), 672-677. https://doi.org/10.1089/jmf.2017.0114
- Cusinato, D. A. C., Martinez, E. Z., Cintra, M. T. C., Filgueira, G. C. O., Berretta, A. A., Lanchote, V. L., & Coelho, E. B. (2019). Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF®) using an in vivo cocktail approach. J Ethnopharmacol, 245, 112174. https://doi.org/10.1016/j.jep.2019.112174
- da Silva, L. A., Pezzini, B. R., & Soares, L. (2015). Spectrophotometric Determination of The Total Flavonoid Content in Ocimum basilicum L. (Lamiaceae) Leaves. Pharmacogn Mag, 11(41), 96-101. https://doi.org/10.4103/0973-1296.149721
- Dai, S., Hong, Y., Xu, J., Lin, Y., Si, Q., & Gu, X. (2018). Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms. Biomed Pharmacother, 100, 93-100. https://doi.org/10.1016/j.biopha.2018.01.111
- Darvhekar, V., Tripathi, A. S., Jyotishi, S. G., Mazumder, P. M., & Shelke, P. G. (2016). Influence of Musa sapientum L. on Pharmacokinetic of Metformin in Diabetic Gastroparesis Chin. J. Integr. Med, 22, 783–788. https://doi.org/https://doi.org/10.1007/s11655-016-2520-3
- Dujic, T., Causevic, A., Bego, T., Malenica, M., Velija-Asimi, Z., Pearson, E. R., & Semiz, S. (2016). Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes. Diabet Med, 33(4), 511-514. https://doi.org/10.1111/dme.13040
- Elango, H., Ponnusankar, S., & Sundaram, S. (2015). Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats. Pharmacogn Mag, 11(Suppl 3), S423-426. https://doi.org/10.4103/0973-1296.168986
- Fan, W., Huang, Y., Zheng, H., Li, S., Li, Z., Yuan, L., Cheng, X., He, C., & Sun, J. (2020). Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms. Biomed Pharmacother, 132, 110915. https://doi.org/10.1016/j.biopha.2020.110915
- Fang, Y., & Wang, H.-y. (2017). Protective Effects and Underlying Mechanisms of Compound Herba Houttuyniae in db/db Mice. Chinese Herbal Medicines, 9, 381-387. https://doi.org/10.1016/S1674-6384(17)60119-9
- Gupta, R. C., Chang, D., Nammi, S., Bensoussan, A., Bilinski, K., & Roufogalis, B. D. (2017). Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetology & metabolic syndrome, 9, 59-59. https://doi.org/10.1186/s13098-017-0254-9
- Han, J. M., Kim, M. H., Choi, Y. Y., Lee, H., Hong, J., & Yang, W. M. (2015). Effects of Lonicera japonica Thunb. on Type 2 Diabetes via PPAR-γ Activation in Rats. Phytother Res, 29(10), 1616-1621. https://doi.org/10.1002/ptr.5413
- Han, K., Bose, S., Wang, J. H., Lim, S. K., Chin, Y. W., Kim, Y. M., Choi, H. S., & Kim, H. (2017). In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis. PLoS One, 12(9), e0182467. https://doi.org/10.1371/journal.pone.0182467
- Han, S. Y., Chae, H. S., You, B. H., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2019). Lonicera japonica extract increases metformin distribution in the liver without change of systemic exposed metformin in rats. J Ethnopharmacol, 238, 111892. https://doi.org/10.1016/j.jep.2019.111892
- Huh, H. W., Na, Y.-G., Bang, K.-H., Kim, S.-J., Kim, M., Kim, K.-T., Kang, J.-S., Kim, Y.-H., Baek, J.-S., Lee, H.-K., & Cho, C.-W. (2020). Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2. Pharmaceutics, 12(1), 49. https://doi.org/10.3390/pharmaceutics12010049
- IDF. (2019). IDF Diabetes Atlas Ninth edition 2019 Ninth ed., International Diabetes Federation
- Islam, M., Islam, M. S., Zannah, S., Sadik, M., & Rashid, M. (2018). Momordica charantia (Bitter melon) in Combination with Metformin Potentiates Hypoglycemic and Hypolipidemic Effects in Alloxan-induced Diabetic Rats. Bangladesh Pharmaceutical Journal, 21, 109. https://doi.org/10.3329/bpj.v21i2.37921
- Jin, S., Lee, S., Jeon, J. H., Kim, H., Choi, M. K., & Song, I. S. (2019). Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract. Pharmaceutics, 11(4). https://doi.org/10.3390/pharmaceutics11040189
- Jovanovski, E., Smircic-Duvnjak, L., Komishon, A., Au-Yeung, F. R., Sievenpiper, J. L., Zurbau, A., Jenkins, A. L., Sung, M.-K., Josse, R., Li, D., & Vuksan, V. (2021). Effect of coadministration of enriched Korean Red Ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L) on cardiometabolic outcomes in type-2 diabetes: A randomized controlled trial. Journal of ginseng research, 45(5), 546-554. https://doi.org/10.1016/j.jgr.2019.11.005
- Kaur, G., Sankrityayan, H., Dixit, D., & Jadhav, P. (2020). Cocos nucifera and metformin combination for modulation of diabetic symptoms in streptozotocin induced diabetic rats. J Ayurveda Integr Med, 11(1), 3-9. https://doi.org/10.1016/j.jaim.2017.02.006
- Kemenkes_RI. (2019). Pedoman Pelayanan Kefarmasian pada Diabetes Melitus Jakarta: Kemenkes RI
- Kennedy, M. S. N., & Masharani, U. (2018). Basic & Clinical Pharmacology Fourteenth ed., New York: McGraw-Hill Education.760
- Kim, S. K., Jung, J., Jung, J. H., Yoon, N., Kang, S. S., Roh, G. S., & Hahm, J. R. (2020). Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med, 52, 102524. https://doi.org/10.1016/j.ctim.2020.102524
- Liang, X., Chien, H. C., Yee, S. W., Giacomini, M. M., Chen, E. C., Piao, M., Hao, J., Twelves, J., Lepist, E. I., Ray, A. S., & Giacomini, K. M. (2015). Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm, 12(12), 4301-4310. https://doi.org/10.1021/acs.molpharmaceut.5b00501
- Liu, Z., Cheng, Z., He, Q., Lin, B., Gao, P., Li, L., Liu, Q., & Song, S. (2016). Secondary metabolites from the flower buds of Lonicera japonica and their in vitro anti-diabetic activities. Fitoterapia, 110, 44-51. https://doi.org/10.1016/j.fitote.2016.02.011
- Men, L.-H., Pi, Z.-F., Hu, M.-X., Liu, S., Liu, Z.-Q., Song, F.-R., Chen, X., & Liu, Z.-Y. (2021). Serum Metabolomics Coupled with Network Pharmacology Strategy to Explore Therapeutic Effects of Scutellaria Baicalensis Georgi on Diabetic Nephropathy. Chinese Journal of Analytical Chemistry, 49(1), e21001-e21013. https://doi.org/https://doi.org/10.1016/S1872-2040(20)60075-5
- Meng, F., Su, X., Li, W., & Zheng, Y. (2017). Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis. Exp Ther Med, 13(5), 2551-2557. https://doi.org/10.3892/etm.2017.4280
- Mouly, S., Lloret-Linares, C., Sellier, P. O., Sene, D., & Bergmann, J. F. (2017). Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res, 118, 82-92. https://doi.org/10.1016/j.phrs.2016.09.038
- Murthy, S. S. N., & Felicia, C. (2015). Antidiabetic Activity of Musa sapientum Fruit Peel on STZ Induced Diabetic Rats. Int J Pharm Bio Sci 6(1), 537-543.
- Nam, S. J., Han, Y. J., Lee, W., Kang, B., Choi, M. K., Han, Y. H., & Song, I. S. (2018). Effect of Red Ginseng Extract on the Pharmacokinetics and Efficacy of Metformin in Streptozotocin-Induced Diabetic Rats. Pharmaceutics, 10(3). https://doi.org/10.3390/pharmaceutics10030080
- Patcharee, P., Wilawan, P., & Chusri, T. (2017). Anti-hyperglycemic and Anti-hyperlipidemic Effects of Extract from Houttuynia cordata Thumb. in Streptozotocin-Induced Diabetic Rats. Pharmacognosy Journal, 9(3). /files/PJ-9-3/10.5530pj.2017.3.65
- Perkeni. (2019). Pedoman pengelolaan dan pencegahan diabetes melitus tipe 2 dewasa di Indonesia 2019 Perkumpulan Endokrinol. Indonesia.1–117
- Poonam, T., Prem Prakash, G., & Vijay Kumar, L. (2013). Interaction of Momordica Charantia with Metformin in Diabetic Rats. Am. J. Pharmacol. Toxicol 8, 102–106. https://doi.org/ https://doi.org/10.3844/ajptsp.2013.102.106
- Pramesthi, A., Ardana, M., & Indriyanti, N. (2019). Drug-Herb Interaction between Metformin and Momordica charantia in Diabetic Mice. Molecular and Cellular Biomedical Sciences, 3, 81. https://doi.org/10.21705/mcbs.v3i2.47
- Rajkapoor, B., & Pakkir Maideen, N. M. (2018). Pharmacologically relevant drug interactions of sulfonylurea antidiabetics with common herbs. Journal of HerbMed Pharmacology, 7. https://doi.org/10.15171/jhp.2018.32
- Ramachandran, A. (2014). Know the signs and symptoms of diabetes. The Indian journal of medical research, 140(5), 579-581. https://pubmed.ncbi.nlm.nih.gov/25579136
- Reddy, A. J., Dubey, A. K., Handu, S., Sachin, M., Mediratta, P. K., & Mushtaq, Q. A. (2017). Effects of Musa sapientum stem extract on experimental models of anxiety. Avicenna journal of phytomedicine, 7(6), 495-501. https://pubmed.ncbi.nlm.nih.gov/29299432
- Sease, J., & Shealy, K. (2016). Pharmacotherapy Principles & Practice Fourth ed., New York: McGraw-Hill Education Companies.651
- Shin, N. R., Gu, N., Choi, H. S., & Kim, H. (2020). Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation. Am J Physiol Endocrinol Metab, 318(1), E52-e61. https://doi.org/10.1152/ajpendo.00221.2019
- Singla, R. K., & Dubey, A. K. (2019). Phytochemical Profiling, GC-MS Analysis and α-Amylase Inhibitory Potential of Ethanolic Extract of Cocos nucifera Linn. Endocarp. Endocr Metab Immune Disord Drug Targets, 19(4), 419-442. https://doi.org/10.2174/1871530319666181128100206
- Thaipitakwong, T., Supasyndh, O., Rasmi, Y., & Aramwit, P. (2020). A randomized controlled study of dose-finding, efficacy, and safety of mulberry leaves on glycemic profiles in obese persons with borderline diabetes. Complement Ther Med, 49, 102292. https://doi.org/10.1016/j.ctim.2019.102292
- Trujillo, J., & Haines, S. (2020). Pharmacotherapy A Pathophysiologic Approach 11 ed., New York: Mc Graw-Hill.3573
- van den Berg, J. P., Vereecke, H. E., Proost, J. H., Eleveld, D. J., Wietasch, J. K., Absalom, A. R., & Struys, M. M. (2017). Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration. Br J Anaesth, 118(1), 44-57. https://doi.org/10.1093/bja/aew312
- Vijaya, K., Sunitha, S., Khan, P. A. H., Sandhya, P., Sujatha, D., & Reddy, G. G. (2014). Synergistic Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Momordica Charantia and Metformin in Streptozotocin Induced Diabetic Rats. World J. Pharm. Res, 3, 1890–1901.
- Wang, D., Zhao, X., & Liu, Y. (2017). Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of Lonicera japonica in streptozotocin-induced diabetic rats. Int J Biol Macromol, 102, 396-404. https://doi.org/10.1016/j.ijbiomac.2017.04.056
- Wang, J.-H., Bose, S., Lim, S.-K., Ansari, A., Chin, Y.-W., Choi, H. S., & Kim, H. (2017). Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats. Genes, 8(10), 239. https://doi.org/10.3390/genes8100239
- Wang, Q., Wu, X., Shi, F., & Liu, Y. (2019). Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomedicine & Pharmacotherapy, 109, 744-750. https://doi.org/10.1016/j.biopha.2018.09.098
- Xia, Y.-T., Chan, G. K.-L., Wang, H.-Y., Dong, T. T.-X., Duan, R., Hu, W.-H., Qin, Q.-W., Wang, W.-X., & Tsim, K. W.-K. (2020). The anti-bacterial effects of aerial parts of Scutellaria baicalensis [21_Publication in refereed journal]. Potential application as an additive in aquaculture feedings, 526. https://doi.org/10.1016/j.aquaculture.2020.735418
- Xiao, N., Lou, M. D., Lu, Y. T., Yang, L. L., Liu, Q., Liu, B., Qi, L. W., & Li, P. (2017). Ginsenoside Rg5 attenuates hepatic glucagon response via suppression of succinate-associated HIF-1α induction in HFD-fed mice. Diabetologia, 60(6), 1084-1093. https://doi.org/10.1007/s00125-017-4238-y
- Yim, S., You, B. H., Chae, H. S., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2017). Multidrug and toxin extrusion protein 1-mediated interaction of metformin and Scutellariae radix in rats. Xenobiotica, 47(11), 998-1007. https://doi.org/10.1080/00498254.2016.1257836
- Yoo, J. H., Yim, S. V., & Lee, B. C. (2018). Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients. Evidence-based Complementary and Alternative Medicine. https://doi.org/ https://doi.org/10.1155/2018/9727240
- You, B. H., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2018). Houttuynia cordata extract increased systemic exposure and liver concentrations of metformin through OCTs and MATEs in rats. Phytother Res, 32(6), 1004-1013. https://doi.org/10.1002/ptr.6036
- Zhang, L., Su, S., Zhu, Y., Guo, J., Guo, S., Qian, D., Ouyang, Z., & Duan, J. A. (2019). Mulberry leaf active components alleviate type 2 diabetes and its liver and kidney injury in db/db mice through insulin receptor and TGF-β/Smads signaling pathway. Biomed Pharmacother, 112, 108675. https://doi.org/10.1016/j.biopha.2019.108675
- Zhang, X. J., Liu, S., Xing, J. P., Liu, Z. Q., & Song, F. R. (2018). Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats. Chin J Nat Med, 16(6), 418-427. https://doi.org/10.1016/s1875-5364(18)30075-x
References
Abouzekry, S. S., Badawy, M. T., Ezzelarab, N. M., & Abdellatif, A. (2021). Phytotherapy for diabetes mellitus; A review of Middle Eastern and North African folk medicinal plants. J Herbmed Pharmacol, 10(1), 1-13. https://doi.org/10.34172/jhp.2021.01
Adegoke, G. A., Onasanwo, S. A., Eyarefe, O. D., & Olaleye, S. B. (2016). Ameliorative effects of Musa sapientum peel extract on acetic acid-induced colitis in rats. The Journal of Basic & Applied Zoology, 77, 49-55. https://doi.org/https://doi.org/10.1016/j.jobaz.2016.06.004
Choi, J., Kim, K.-J., Koh, E.-J., & Lee, B.-Y. (2018). Gelidium elegans Extract Ameliorates Type 2 Diabetes via Regulation of MAPK and PI3K/Akt Signaling. Nutrients, 10(1), 51. https://doi.org/10.3390/nu10010051
Cortez-Navarrete, M., Martínez-Abundis, E., Pérez-Rubio, K. G., González-Ortiz, M., & Méndez-Del Villar, M. (2018). Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus. J Med Food, 21(7), 672-677. https://doi.org/10.1089/jmf.2017.0114
Cusinato, D. A. C., Martinez, E. Z., Cintra, M. T. C., Filgueira, G. C. O., Berretta, A. A., Lanchote, V. L., & Coelho, E. B. (2019). Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF®) using an in vivo cocktail approach. J Ethnopharmacol, 245, 112174. https://doi.org/10.1016/j.jep.2019.112174
da Silva, L. A., Pezzini, B. R., & Soares, L. (2015). Spectrophotometric Determination of The Total Flavonoid Content in Ocimum basilicum L. (Lamiaceae) Leaves. Pharmacogn Mag, 11(41), 96-101. https://doi.org/10.4103/0973-1296.149721
Dai, S., Hong, Y., Xu, J., Lin, Y., Si, Q., & Gu, X. (2018). Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms. Biomed Pharmacother, 100, 93-100. https://doi.org/10.1016/j.biopha.2018.01.111
Darvhekar, V., Tripathi, A. S., Jyotishi, S. G., Mazumder, P. M., & Shelke, P. G. (2016). Influence of Musa sapientum L. on Pharmacokinetic of Metformin in Diabetic Gastroparesis Chin. J. Integr. Med, 22, 783–788. https://doi.org/https://doi.org/10.1007/s11655-016-2520-3
Dujic, T., Causevic, A., Bego, T., Malenica, M., Velija-Asimi, Z., Pearson, E. R., & Semiz, S. (2016). Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes. Diabet Med, 33(4), 511-514. https://doi.org/10.1111/dme.13040
Elango, H., Ponnusankar, S., & Sundaram, S. (2015). Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats. Pharmacogn Mag, 11(Suppl 3), S423-426. https://doi.org/10.4103/0973-1296.168986
Fan, W., Huang, Y., Zheng, H., Li, S., Li, Z., Yuan, L., Cheng, X., He, C., & Sun, J. (2020). Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms. Biomed Pharmacother, 132, 110915. https://doi.org/10.1016/j.biopha.2020.110915
Fang, Y., & Wang, H.-y. (2017). Protective Effects and Underlying Mechanisms of Compound Herba Houttuyniae in db/db Mice. Chinese Herbal Medicines, 9, 381-387. https://doi.org/10.1016/S1674-6384(17)60119-9
Gupta, R. C., Chang, D., Nammi, S., Bensoussan, A., Bilinski, K., & Roufogalis, B. D. (2017). Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetology & metabolic syndrome, 9, 59-59. https://doi.org/10.1186/s13098-017-0254-9
Han, J. M., Kim, M. H., Choi, Y. Y., Lee, H., Hong, J., & Yang, W. M. (2015). Effects of Lonicera japonica Thunb. on Type 2 Diabetes via PPAR-γ Activation in Rats. Phytother Res, 29(10), 1616-1621. https://doi.org/10.1002/ptr.5413
Han, K., Bose, S., Wang, J. H., Lim, S. K., Chin, Y. W., Kim, Y. M., Choi, H. S., & Kim, H. (2017). In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis. PLoS One, 12(9), e0182467. https://doi.org/10.1371/journal.pone.0182467
Han, S. Y., Chae, H. S., You, B. H., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2019). Lonicera japonica extract increases metformin distribution in the liver without change of systemic exposed metformin in rats. J Ethnopharmacol, 238, 111892. https://doi.org/10.1016/j.jep.2019.111892
Huh, H. W., Na, Y.-G., Bang, K.-H., Kim, S.-J., Kim, M., Kim, K.-T., Kang, J.-S., Kim, Y.-H., Baek, J.-S., Lee, H.-K., & Cho, C.-W. (2020). Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2. Pharmaceutics, 12(1), 49. https://doi.org/10.3390/pharmaceutics12010049
IDF. (2019). IDF Diabetes Atlas Ninth edition 2019 Ninth ed., International Diabetes Federation
Islam, M., Islam, M. S., Zannah, S., Sadik, M., & Rashid, M. (2018). Momordica charantia (Bitter melon) in Combination with Metformin Potentiates Hypoglycemic and Hypolipidemic Effects in Alloxan-induced Diabetic Rats. Bangladesh Pharmaceutical Journal, 21, 109. https://doi.org/10.3329/bpj.v21i2.37921
Jin, S., Lee, S., Jeon, J. H., Kim, H., Choi, M. K., & Song, I. S. (2019). Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract. Pharmaceutics, 11(4). https://doi.org/10.3390/pharmaceutics11040189
Jovanovski, E., Smircic-Duvnjak, L., Komishon, A., Au-Yeung, F. R., Sievenpiper, J. L., Zurbau, A., Jenkins, A. L., Sung, M.-K., Josse, R., Li, D., & Vuksan, V. (2021). Effect of coadministration of enriched Korean Red Ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L) on cardiometabolic outcomes in type-2 diabetes: A randomized controlled trial. Journal of ginseng research, 45(5), 546-554. https://doi.org/10.1016/j.jgr.2019.11.005
Kaur, G., Sankrityayan, H., Dixit, D., & Jadhav, P. (2020). Cocos nucifera and metformin combination for modulation of diabetic symptoms in streptozotocin induced diabetic rats. J Ayurveda Integr Med, 11(1), 3-9. https://doi.org/10.1016/j.jaim.2017.02.006
Kemenkes_RI. (2019). Pedoman Pelayanan Kefarmasian pada Diabetes Melitus Jakarta: Kemenkes RI
Kennedy, M. S. N., & Masharani, U. (2018). Basic & Clinical Pharmacology Fourteenth ed., New York: McGraw-Hill Education.760
Kim, S. K., Jung, J., Jung, J. H., Yoon, N., Kang, S. S., Roh, G. S., & Hahm, J. R. (2020). Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med, 52, 102524. https://doi.org/10.1016/j.ctim.2020.102524
Liang, X., Chien, H. C., Yee, S. W., Giacomini, M. M., Chen, E. C., Piao, M., Hao, J., Twelves, J., Lepist, E. I., Ray, A. S., & Giacomini, K. M. (2015). Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm, 12(12), 4301-4310. https://doi.org/10.1021/acs.molpharmaceut.5b00501
Liu, Z., Cheng, Z., He, Q., Lin, B., Gao, P., Li, L., Liu, Q., & Song, S. (2016). Secondary metabolites from the flower buds of Lonicera japonica and their in vitro anti-diabetic activities. Fitoterapia, 110, 44-51. https://doi.org/10.1016/j.fitote.2016.02.011
Men, L.-H., Pi, Z.-F., Hu, M.-X., Liu, S., Liu, Z.-Q., Song, F.-R., Chen, X., & Liu, Z.-Y. (2021). Serum Metabolomics Coupled with Network Pharmacology Strategy to Explore Therapeutic Effects of Scutellaria Baicalensis Georgi on Diabetic Nephropathy. Chinese Journal of Analytical Chemistry, 49(1), e21001-e21013. https://doi.org/https://doi.org/10.1016/S1872-2040(20)60075-5
Meng, F., Su, X., Li, W., & Zheng, Y. (2017). Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis. Exp Ther Med, 13(5), 2551-2557. https://doi.org/10.3892/etm.2017.4280
Mouly, S., Lloret-Linares, C., Sellier, P. O., Sene, D., & Bergmann, J. F. (2017). Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res, 118, 82-92. https://doi.org/10.1016/j.phrs.2016.09.038
Murthy, S. S. N., & Felicia, C. (2015). Antidiabetic Activity of Musa sapientum Fruit Peel on STZ Induced Diabetic Rats. Int J Pharm Bio Sci 6(1), 537-543.
Nam, S. J., Han, Y. J., Lee, W., Kang, B., Choi, M. K., Han, Y. H., & Song, I. S. (2018). Effect of Red Ginseng Extract on the Pharmacokinetics and Efficacy of Metformin in Streptozotocin-Induced Diabetic Rats. Pharmaceutics, 10(3). https://doi.org/10.3390/pharmaceutics10030080
Patcharee, P., Wilawan, P., & Chusri, T. (2017). Anti-hyperglycemic and Anti-hyperlipidemic Effects of Extract from Houttuynia cordata Thumb. in Streptozotocin-Induced Diabetic Rats. Pharmacognosy Journal, 9(3). /files/PJ-9-3/10.5530pj.2017.3.65
Perkeni. (2019). Pedoman pengelolaan dan pencegahan diabetes melitus tipe 2 dewasa di Indonesia 2019 Perkumpulan Endokrinol. Indonesia.1–117
Poonam, T., Prem Prakash, G., & Vijay Kumar, L. (2013). Interaction of Momordica Charantia with Metformin in Diabetic Rats. Am. J. Pharmacol. Toxicol 8, 102–106. https://doi.org/ https://doi.org/10.3844/ajptsp.2013.102.106
Pramesthi, A., Ardana, M., & Indriyanti, N. (2019). Drug-Herb Interaction between Metformin and Momordica charantia in Diabetic Mice. Molecular and Cellular Biomedical Sciences, 3, 81. https://doi.org/10.21705/mcbs.v3i2.47
Rajkapoor, B., & Pakkir Maideen, N. M. (2018). Pharmacologically relevant drug interactions of sulfonylurea antidiabetics with common herbs. Journal of HerbMed Pharmacology, 7. https://doi.org/10.15171/jhp.2018.32
Ramachandran, A. (2014). Know the signs and symptoms of diabetes. The Indian journal of medical research, 140(5), 579-581. https://pubmed.ncbi.nlm.nih.gov/25579136
Reddy, A. J., Dubey, A. K., Handu, S., Sachin, M., Mediratta, P. K., & Mushtaq, Q. A. (2017). Effects of Musa sapientum stem extract on experimental models of anxiety. Avicenna journal of phytomedicine, 7(6), 495-501. https://pubmed.ncbi.nlm.nih.gov/29299432
Sease, J., & Shealy, K. (2016). Pharmacotherapy Principles & Practice Fourth ed., New York: McGraw-Hill Education Companies.651
Shin, N. R., Gu, N., Choi, H. S., & Kim, H. (2020). Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation. Am J Physiol Endocrinol Metab, 318(1), E52-e61. https://doi.org/10.1152/ajpendo.00221.2019
Singla, R. K., & Dubey, A. K. (2019). Phytochemical Profiling, GC-MS Analysis and α-Amylase Inhibitory Potential of Ethanolic Extract of Cocos nucifera Linn. Endocarp. Endocr Metab Immune Disord Drug Targets, 19(4), 419-442. https://doi.org/10.2174/1871530319666181128100206
Thaipitakwong, T., Supasyndh, O., Rasmi, Y., & Aramwit, P. (2020). A randomized controlled study of dose-finding, efficacy, and safety of mulberry leaves on glycemic profiles in obese persons with borderline diabetes. Complement Ther Med, 49, 102292. https://doi.org/10.1016/j.ctim.2019.102292
Trujillo, J., & Haines, S. (2020). Pharmacotherapy A Pathophysiologic Approach 11 ed., New York: Mc Graw-Hill.3573
van den Berg, J. P., Vereecke, H. E., Proost, J. H., Eleveld, D. J., Wietasch, J. K., Absalom, A. R., & Struys, M. M. (2017). Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration. Br J Anaesth, 118(1), 44-57. https://doi.org/10.1093/bja/aew312
Vijaya, K., Sunitha, S., Khan, P. A. H., Sandhya, P., Sujatha, D., & Reddy, G. G. (2014). Synergistic Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Momordica Charantia and Metformin in Streptozotocin Induced Diabetic Rats. World J. Pharm. Res, 3, 1890–1901.
Wang, D., Zhao, X., & Liu, Y. (2017). Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of Lonicera japonica in streptozotocin-induced diabetic rats. Int J Biol Macromol, 102, 396-404. https://doi.org/10.1016/j.ijbiomac.2017.04.056
Wang, J.-H., Bose, S., Lim, S.-K., Ansari, A., Chin, Y.-W., Choi, H. S., & Kim, H. (2017). Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats. Genes, 8(10), 239. https://doi.org/10.3390/genes8100239
Wang, Q., Wu, X., Shi, F., & Liu, Y. (2019). Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomedicine & Pharmacotherapy, 109, 744-750. https://doi.org/10.1016/j.biopha.2018.09.098
Xia, Y.-T., Chan, G. K.-L., Wang, H.-Y., Dong, T. T.-X., Duan, R., Hu, W.-H., Qin, Q.-W., Wang, W.-X., & Tsim, K. W.-K. (2020). The anti-bacterial effects of aerial parts of Scutellaria baicalensis [21_Publication in refereed journal]. Potential application as an additive in aquaculture feedings, 526. https://doi.org/10.1016/j.aquaculture.2020.735418
Xiao, N., Lou, M. D., Lu, Y. T., Yang, L. L., Liu, Q., Liu, B., Qi, L. W., & Li, P. (2017). Ginsenoside Rg5 attenuates hepatic glucagon response via suppression of succinate-associated HIF-1α induction in HFD-fed mice. Diabetologia, 60(6), 1084-1093. https://doi.org/10.1007/s00125-017-4238-y
Yim, S., You, B. H., Chae, H. S., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2017). Multidrug and toxin extrusion protein 1-mediated interaction of metformin and Scutellariae radix in rats. Xenobiotica, 47(11), 998-1007. https://doi.org/10.1080/00498254.2016.1257836
Yoo, J. H., Yim, S. V., & Lee, B. C. (2018). Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients. Evidence-based Complementary and Alternative Medicine. https://doi.org/ https://doi.org/10.1155/2018/9727240
You, B. H., Chin, Y. W., Kim, H., Choi, H. S., & Choi, Y. H. (2018). Houttuynia cordata extract increased systemic exposure and liver concentrations of metformin through OCTs and MATEs in rats. Phytother Res, 32(6), 1004-1013. https://doi.org/10.1002/ptr.6036
Zhang, L., Su, S., Zhu, Y., Guo, J., Guo, S., Qian, D., Ouyang, Z., & Duan, J. A. (2019). Mulberry leaf active components alleviate type 2 diabetes and its liver and kidney injury in db/db mice through insulin receptor and TGF-β/Smads signaling pathway. Biomed Pharmacother, 112, 108675. https://doi.org/10.1016/j.biopha.2019.108675
Zhang, X. J., Liu, S., Xing, J. P., Liu, Z. Q., & Song, F. R. (2018). Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats. Chin J Nat Med, 16(6), 418-427. https://doi.org/10.1016/s1875-5364(18)30075-x