Antidiabetic Activity of Extract Combination of Orthosiphon aristatus and Oryza sativa L. var glutinosa
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Submitted
22 February 2021
22 February 2021
Published
30 August 2021
30 August 2021
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Abstract
Traditionally and scientifically, research has shown that Orthosiphon aristatus and Oryza sativa L. var. glutinosa have antidiabetic activity. The combination of two medicinal plants can increase their biological activity. This study aimed to determine the antidiabetic activity of O. aristatus and O. sativa L. var. glutinosa on single and combined extracts. Phytochemical screening of the single extract was done qualitatively. The α-glucosidase inhibitory method was used as an antidiabetic activity. The results showed that every extract contained alkaloids, steroids/triterpenoids, flavonoids, tannins, quinones, and coumarins. A single extract of O. sativa L. var glutinosa, O. aristatus, and their combinations (1:1, 1:2, and 2:1) had an α-glucosidase enzyme inhibitory activity with an IC50 value of 67.82, 80.93, 73.81, 88.72, and 61.51 µg/ml, respectively. The combination shows that the ratio of 1:1 was nearly additive, 1:2 was slight to moderate antagonism, and 2:1 was moderate to slight synergism. The combination of 96% ethanol extract of O. sativa L. var. glutinosa and O. aristatus in a ratio of 2:1 was the most effective in increasing its inhibitory activity.
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References
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11. Marianne M, Patilaya P, Barus BT. Uji Aktivitas Antioksidan Kombinasi Ekstrak Etanol Rimpang Temu Giring (Curcuma Heyneana) dan Daun Pugun Tanoh (Curanga Fel-Terrae) Menggunakan Metode Diphenyl Picrylhydrazil(DPPH). Talenta Conf Ser Trop Med (TM). 2018;1(2):398-404.
12. Harborne JB, Niksoliin S, Padmawinata K, Sudiro I. Metode Fitokimia: Penuntun Cara Modern Menganalisis Tumbuhan. Bandung: ITB Press; 1996.
13. Saijyo J, Suzuki Y, Okuno Y, Yamaki H, Suzuki T, Miyazawa M. Alpha-glucosidase inhibitor from Bergenia ligulate. J Oleo Sci. 2008;57(8):431-5. doi:10.5650/jos.57.431
14. Mugaranja KP, Kulai A. Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study. Heliyon. 2020;6(7):e04392. doi:10.1016/j.heliyon.2020.e04392
15. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-81. doi:10.1124/pr.58.3.10
16. Reynolds CP, Maurer BJ. Evaluating response to antineoplastic drug combinations in tissue culture models. Methods Mol Med. 2005;110:173-83. doi:10.1385/1-59259-869-2:173
17. Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med. 2018l13:20. doi:10.1186/s13020-018-0177-x
18. Proença C, Freitas M, Ribeiro D, Oliveira EFT, Sousa JLC, Tomé SM, et al. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study. J Enzyme Inhib Med Chem. 2017;32(1):1216-28. doi:10.1080/14756366.2017.1368503
19. Pereira DF, Cazarolli LH, Lavado C, Mengatto V, Figueiredo MSRB, Guedes A, et al. Effects of flavonoids on α-glucosidase activity: potential targets for glucose homeostasis. Nutrition. 2011;27(11-12):1161-7. doi:10.1016/j.nut.2011.01.008
20. Gao H, Huang YN, Li P, Inagaki C, Kawabata J. Inhibitory effect on α-glucosidase by Adhatoda vasica Nees. Food Chem. 2008;108(3):965-72. doi:10.1016/j.foodchem.2007.12.002
21. Kim SD. α-Glucosidase inhibitor from Buthus martensi Karsch. Food Chem. 2013;136(2):297-300. doi:10.1016/j.foodchem.2012.08.063
22. Zafar M, Khan H, Rauf A, Khan A, Lodhi MA. In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds. Front Endocrinol. 2016;7:153. doi:10.3389/fendo.2016.00153
23. Abuelizz HA, Anouar EH, Ahmad R, Azman NIIN, Marzouk M, Al-Salahi R. Triazoloquinazolines as a new class of potent α-glucosidase inhibitors: in vitro evaluation and docking study. PLoS One. 2019;14(8):e0220379. doi:10.1371/journal.pone.0220379
24. Ur Rehman N, Rafiq K, Khan A, Halim SA, Ali L, Al-Saady N, et al. α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii. Mar Drugs. 2019;17(12):666. doi:10.3390/md17120666
25. Elsbaey M, Mwakalukwa R, Shimizu K, Miyamoto T. Pentacylic triterpenes from Lavandula coronopifolia: structure related inhibitory activity on α-glucosidase. Nat Prod Res. 2021;35(9):1436-444. doi:10.1080/14786419.2019.1655017
26. Hossain U, Das AK, Ghosh S, Sil PC. An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food Chem Toxicol. 2020;145:111738. doi:10.1016/j.fct.2020.111738
27. Abdelli I, Benariba N, Adjdir S, Fekhiker Z, Daoud I, Terki M, et al. In silico evaluation of phenolic compounds as inhibitors of Α-amylase and Α-glucosidase. J Biomol Struct Dyn. 2021;39(3):816-22. doi:10.1080/07391102.2020.1718553
28. Wang G, Wang J, He D, Li X, Li J, Peng Z. Synthesis, in vitro evaluation and molecular docking studies of novel coumarin-isatin derivatives as α-glucosidase inhibitors. Chem Biol Drug Des. 2017;89(3):456-63. doi:10.1111/cbdd.12867
29. Jung HA, Ali MY, Choi JS. Promising Inhibitory Effects of Anthraquinones, Naphthopyrone, and Naphthalene Glycosides, from Cassia obtusifolia on α-Glucosidase and Human Protein Tyrosine Phosphatases 1B. Molecules. 2016;22(1):28. doi:10.3390/molecules22010028
30. Sasenya S, Nanok K. α-glucosidase, α-amylase inhibitory potential and antioxidant activity of fragrant black rice (Thai coloured rice). Flavour Fragr J. 2020;35(4):376-86. doi:10.1002/ffj.3572
31. Rafi M, Purwakusumah ED, Ridwan T, Barus B, Sutandi A, Darusman, LK. Geographical classification of Java Tea (Orthosiphon stamineus) from Java Island by FTIR Spectroscopy Combined with Canonical Variate Analysis. MIPA. 2015;23(1):25-31.
32. Akowuah GA, Ismail Z, Norhayati I, Sadikun A. The effects of different extraction solvents of varying polarities on polyphenols of Orthosiphon stamineus and evaluation of the free radical-scavenging activity. Food Chem. 2005;93(2):311-7. doi:10.1016/j.foodchem.2004.09.028
33. Bhat M, Zinjarde SS, Bhargava SY, Kumar AR, Joshi BN. Antidiabetic Indian plants: a good source of potent amylase inhibitors. Evid Based Complement Alternat Med. 2011;2011:810207. doi:10.1093/ecam/nen040
34. Kwon YI, Apostolidis E, Shetty K. Evaluation of Pepper (Capsicum annuum) For Management of Diabetes and Hypertension. J Food Biochem. 2007;31(3):370-85. doi:10.1111/j.1745-4514.2007.00120.x
35. Djamil R, Winarti W, Simanjuntak P, Syamsudin. Standardization and α-glycosidase inhibition of extracts of Vatica pauciflora Blume stem barks and Smallanthus sonchifolius leaves. J Pharm Phytochem. 2014;3(4):42-6.
36. Argo BD, Wardani AK, Zubaidah E, Winarsih S. Endoglucanase, Exo-glucanase and Alpha-glucosidase Activity the Combination of Crude Enzyme from Trichoderma reesei and Aspergillus niger at Different Temperatures and pH. Res Rev Biosci. 2014;9(2):45-8.
37. Kesavanarayanan KS, Sathiya S, Ranju V, Sunil AG, Ilavarasan R, Babu CS, et al. In vitro cytotoxic, antioxidative and alpha-glucosidase inhibitory potential of a herbal mixture comprised of Allium sativum and Lagerstroemia speciose. Eur Rev Med Pharmacol Sci. 2012;16(Suppl 3):58-68.
38. Vinholes J, Vizzotto M. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts. Pharmacognosy Res. 2017;9(1):101-7. doi:10.4103/0974-8490.197797
39. Kuok CF, Hoi SO, Hoi CF, Chan CH, Fong IH, Ngok CK, et al. Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study. Exp Biol Med. 2017;242(7):731-43. doi:10.1177/1535370216689828
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2. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi:10.1016/j.diabres.2019.107843
3. Mahmoodnia L, Aghadavod E, Beigrezaei S, Rafieian-Kopaei M. An update on diabetic kidney disease, oxidative stress and antioxidant agents. J Renal Inj Prev. 2017;6(2):153-7. doi:10.15171/jrip.2017.30
4. Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes. 2016;7(17):354-95. doi:10.4239/wjd.v7.i17.354
5. Alqahtani AS, Hidayathulla S, Rehman MT, ElGamal AA, Al-Massarani S, Razmovski-Naumovski V, et al. Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia. Biomolecules. 2020;10(1):61. doi:10.3390/biom10010061
6. Tabatabaei-Malazy O, Larijani B, Abdollahi M. Targeting metabolic disorders by natural products. J Diabetes Metab Disord. 2015,14:57. doi:10.1186/s40200-015-0184-8
7. Iryani I, Iswendi I, Katrina IT. Uji Aktivitas Anti Diabetes Mellitus Senyawa Metabolit Sekunder Fraksi Air Dari Beras Ketan Hitam (Oryza satival. Var glutinosa) Pada Mencit Putih. Eksakta Berkala Ilmiah Bidang MIPA. 2017;18(1):54-60. doi:10.24036/eksakta/vol18-iss01/17
8. Mohamed EAH, Siddiqui MJA, Ang LF, Sadikun A, Chan SH, Tan SC, et al. Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism. BMC Complement Altern Med. 2012;12:176. doi:10.1186/1472-6882-12-176
9. Juliani, Yuliana ND, Budijanto S, Wijaya CH, Khatib A. Senyawa Inhibitor α-Glukosidase Dan Antioksidan Dari Kumis Kucing Dengan Pendekatan Metabolomik Berbasis FTIR. Jurnal Teknologi dan Industri Pangan. 2016;27(1):17-20. doi:10.6066/jtip.2016.27.1.17
10. Abdulmunem OK, Makky EA, Tawfiq AA, Mahendran K, Zamri N. Evaluating the Effect of Combined Plant Extracts on α-amylase and α-glucosidase Inhibition Activity as Antidiabetic Agents. Pak J Biol Sci. 2020;23(3):287-94. doi:10.3923/pjbs.2020.287.294
11. Marianne M, Patilaya P, Barus BT. Uji Aktivitas Antioksidan Kombinasi Ekstrak Etanol Rimpang Temu Giring (Curcuma Heyneana) dan Daun Pugun Tanoh (Curanga Fel-Terrae) Menggunakan Metode Diphenyl Picrylhydrazil(DPPH). Talenta Conf Ser Trop Med (TM). 2018;1(2):398-404.
12. Harborne JB, Niksoliin S, Padmawinata K, Sudiro I. Metode Fitokimia: Penuntun Cara Modern Menganalisis Tumbuhan. Bandung: ITB Press; 1996.
13. Saijyo J, Suzuki Y, Okuno Y, Yamaki H, Suzuki T, Miyazawa M. Alpha-glucosidase inhibitor from Bergenia ligulate. J Oleo Sci. 2008;57(8):431-5. doi:10.5650/jos.57.431
14. Mugaranja KP, Kulai A. Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study. Heliyon. 2020;6(7):e04392. doi:10.1016/j.heliyon.2020.e04392
15. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-81. doi:10.1124/pr.58.3.10
16. Reynolds CP, Maurer BJ. Evaluating response to antineoplastic drug combinations in tissue culture models. Methods Mol Med. 2005;110:173-83. doi:10.1385/1-59259-869-2:173
17. Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med. 2018l13:20. doi:10.1186/s13020-018-0177-x
18. Proença C, Freitas M, Ribeiro D, Oliveira EFT, Sousa JLC, Tomé SM, et al. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study. J Enzyme Inhib Med Chem. 2017;32(1):1216-28. doi:10.1080/14756366.2017.1368503
19. Pereira DF, Cazarolli LH, Lavado C, Mengatto V, Figueiredo MSRB, Guedes A, et al. Effects of flavonoids on α-glucosidase activity: potential targets for glucose homeostasis. Nutrition. 2011;27(11-12):1161-7. doi:10.1016/j.nut.2011.01.008
20. Gao H, Huang YN, Li P, Inagaki C, Kawabata J. Inhibitory effect on α-glucosidase by Adhatoda vasica Nees. Food Chem. 2008;108(3):965-72. doi:10.1016/j.foodchem.2007.12.002
21. Kim SD. α-Glucosidase inhibitor from Buthus martensi Karsch. Food Chem. 2013;136(2):297-300. doi:10.1016/j.foodchem.2012.08.063
22. Zafar M, Khan H, Rauf A, Khan A, Lodhi MA. In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds. Front Endocrinol. 2016;7:153. doi:10.3389/fendo.2016.00153
23. Abuelizz HA, Anouar EH, Ahmad R, Azman NIIN, Marzouk M, Al-Salahi R. Triazoloquinazolines as a new class of potent α-glucosidase inhibitors: in vitro evaluation and docking study. PLoS One. 2019;14(8):e0220379. doi:10.1371/journal.pone.0220379
24. Ur Rehman N, Rafiq K, Khan A, Halim SA, Ali L, Al-Saady N, et al. α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii. Mar Drugs. 2019;17(12):666. doi:10.3390/md17120666
25. Elsbaey M, Mwakalukwa R, Shimizu K, Miyamoto T. Pentacylic triterpenes from Lavandula coronopifolia: structure related inhibitory activity on α-glucosidase. Nat Prod Res. 2021;35(9):1436-444. doi:10.1080/14786419.2019.1655017
26. Hossain U, Das AK, Ghosh S, Sil PC. An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food Chem Toxicol. 2020;145:111738. doi:10.1016/j.fct.2020.111738
27. Abdelli I, Benariba N, Adjdir S, Fekhiker Z, Daoud I, Terki M, et al. In silico evaluation of phenolic compounds as inhibitors of Α-amylase and Α-glucosidase. J Biomol Struct Dyn. 2021;39(3):816-22. doi:10.1080/07391102.2020.1718553
28. Wang G, Wang J, He D, Li X, Li J, Peng Z. Synthesis, in vitro evaluation and molecular docking studies of novel coumarin-isatin derivatives as α-glucosidase inhibitors. Chem Biol Drug Des. 2017;89(3):456-63. doi:10.1111/cbdd.12867
29. Jung HA, Ali MY, Choi JS. Promising Inhibitory Effects of Anthraquinones, Naphthopyrone, and Naphthalene Glycosides, from Cassia obtusifolia on α-Glucosidase and Human Protein Tyrosine Phosphatases 1B. Molecules. 2016;22(1):28. doi:10.3390/molecules22010028
30. Sasenya S, Nanok K. α-glucosidase, α-amylase inhibitory potential and antioxidant activity of fragrant black rice (Thai coloured rice). Flavour Fragr J. 2020;35(4):376-86. doi:10.1002/ffj.3572
31. Rafi M, Purwakusumah ED, Ridwan T, Barus B, Sutandi A, Darusman, LK. Geographical classification of Java Tea (Orthosiphon stamineus) from Java Island by FTIR Spectroscopy Combined with Canonical Variate Analysis. MIPA. 2015;23(1):25-31.
32. Akowuah GA, Ismail Z, Norhayati I, Sadikun A. The effects of different extraction solvents of varying polarities on polyphenols of Orthosiphon stamineus and evaluation of the free radical-scavenging activity. Food Chem. 2005;93(2):311-7. doi:10.1016/j.foodchem.2004.09.028
33. Bhat M, Zinjarde SS, Bhargava SY, Kumar AR, Joshi BN. Antidiabetic Indian plants: a good source of potent amylase inhibitors. Evid Based Complement Alternat Med. 2011;2011:810207. doi:10.1093/ecam/nen040
34. Kwon YI, Apostolidis E, Shetty K. Evaluation of Pepper (Capsicum annuum) For Management of Diabetes and Hypertension. J Food Biochem. 2007;31(3):370-85. doi:10.1111/j.1745-4514.2007.00120.x
35. Djamil R, Winarti W, Simanjuntak P, Syamsudin. Standardization and α-glycosidase inhibition of extracts of Vatica pauciflora Blume stem barks and Smallanthus sonchifolius leaves. J Pharm Phytochem. 2014;3(4):42-6.
36. Argo BD, Wardani AK, Zubaidah E, Winarsih S. Endoglucanase, Exo-glucanase and Alpha-glucosidase Activity the Combination of Crude Enzyme from Trichoderma reesei and Aspergillus niger at Different Temperatures and pH. Res Rev Biosci. 2014;9(2):45-8.
37. Kesavanarayanan KS, Sathiya S, Ranju V, Sunil AG, Ilavarasan R, Babu CS, et al. In vitro cytotoxic, antioxidative and alpha-glucosidase inhibitory potential of a herbal mixture comprised of Allium sativum and Lagerstroemia speciose. Eur Rev Med Pharmacol Sci. 2012;16(Suppl 3):58-68.
38. Vinholes J, Vizzotto M. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts. Pharmacognosy Res. 2017;9(1):101-7. doi:10.4103/0974-8490.197797
39. Kuok CF, Hoi SO, Hoi CF, Chan CH, Fong IH, Ngok CK, et al. Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study. Exp Biol Med. 2017;242(7):731-43. doi:10.1177/1535370216689828
Authors
1.
Septiana E, Rizka NM, Yadi Y, Simanjuntak P. Antidiabetic Activity of Extract Combination of Orthosiphon aristatus and Oryza sativa L. var glutinosa. Borneo J Pharm [Internet]. 2021Aug.30 [cited 2025Apr.16];4(3):202-9. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/2154
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