In Silico Study of Active Compounds and Protein Targets of Orthosiphon aristatus as Alternative Therapy for Hypertension: Network Pharmacology and Docking
Hypertension poses a significant global health burden, prompting exploration into alternative treatments. This study investigates the pharmacological network of Orthosiphon aristatus, aiming to uncover its therapeutic potential for hypertension. We compiled data on Orthosiphon aristatus chemical constituents and predicted potential targets for its key components. Through screening processes utilizing the Gencard database, active compounds and protein targets were identified. We examined protein target similarities between Orthosiphon aristatus and hypertension, constructing a network illustrating the relationships between active compounds and target genes. Additionally, we conducted GO function analysis and KEGG pathway enrichment to elucidate Orthosiphon aristatus role in hypertension. Notably, TP53 exhibited the highest degree of centrality, while Scutellarein and aurantiamide acetate displayed the highest affinities in molecular docking with TP53. These findings offer novel insights into Orthosiphon aristatus' potential as an adjunctive therapy for hypertension and contribute to the advancement of pharmacological interventions in this domain.
Abdullah, F. I., Chua, L. S., Mohd Bohari, S. P., & Sari, E. (2020). Rationale of Orthosiphon aristatus for Healing Diabetic Foot Ulcer. Natural Product Communications, 15(9), 1934578X2095330. https://doi.org/10.1177/1934578X20953308
Arafat, O. M., Tham, S. Y., Sadikun, A., Zhari, I., Haughton, P. J., & Asmawi, M. Z. (2008). Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats. Journal of Ethnopharmacology, 118(3), 354–360. https://doi.org/10.1016/j.jep.2008.04.015
Awale, S., Tezuka, Y., Kobayashi, M., Ueda, J., & Kadota, S. (2004). Neoorthosiphonone A; a nitric oxide (NO) inhibitory diterpene with new carbon skeleton from Orthosiphon stamineus. Tetrahedron Letters, 45(7), 1359–1362. https://doi.org/10.1016/j.tetlet.2003.12.054
Benetos, A., Petrovic, M., & Strandberg, T. (2019). Hypertension Management in Older and Frail Older Patients. Circulation Research, 124(7), 1045–1060. https://doi.org/10.1161/CIRCRESAHA.118.313236
Chan, P., Liu, I.-M., Li, Y.-X., Yu, W.-J., & Cheng, J.-T. (2011). Antihypertension Induced by Tanshinone IIA Isolated from the Roots of Salvia miltiorrhiza. Evidence-Based Complementary and Alternative Medicine : ECAM, 2011, 392627. https://doi.org/10.1093/ecam/nep056
Chassagne, F., Haddad, M., Amiel, A., Phakeovilay, C., Manithip, C., Bourdy, G., Deharo, E., & Marti, G. (2018). A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases. Fitoterapia, 127, 226–236. https://doi.org/10.1016/j.fitote.2018.02.021
Chi, C.-F., Tseng, L.-K., & Jang, Y. (2012). Pruning a Decision Tree for Selecting Computer-Related Assistive Devices for People With Disabilities. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 20(4), 564–573. https://doi.org/10.1109/TNSRE.2012.2193419
Corbett, K. M., Ford, L., Warren, D. B., Pouton, C. W., & Chalmers, D. K. (2021). Cyclosporin Structure and Permeability: From A to Z and Beyond. Journal of Medicinal Chemistry, 64(18), 13131–13151. https://doi.org/10.1021/acs.jmedchem.1c00580
Crosara, K. T. B., Moffa, E. B., Xiao, Y., & Siqueira, W. L. (2018). Merging in-silico and in vitro salivary protein complex partners using the STRING database: A tutorial. Journal of Proteomics, 171, 87–94. https://doi.org/10.1016/j.jprot.2017.08.002
Faramayuda, F., Mariani, T. S., Elfahmi, E., & Sukrasno, S. . (2021). Potential of Orthosiphon aristatus Blume Miq as Antiviral: A Review. Tropical Journal of Natural Product Research, 5(3), 410–419. https://doi.org/10.26538/tjnpr/v5i3.1
Ferreira, L. G., Evora, P. R. B., Capellini, V. K., Albuquerque, A. A., Carvalho, M. T. M., Gomes, R. A. da S., Parolini, M. T., & Celotto, A. C. (2018). Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE. Phytomedicine, 38, 158–165. https://doi.org/10.1016/j.phymed.2017.02.006
Ge, S. X., Jung, D., & Yao, R. (2020). ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics, 36(8), 2628–2629. https://doi.org/10.1093/bioinformatics/btz931
Guengerich, F. P. (2011). Mechanisms of Drug Toxicity and Relevance to Pharmaceutical Development. Drug Metabolism and Pharmacokinetics, 26(1), 3–14. https://doi.org/10.2133/dmpk.DMPK-10-RV-062
Guo, Q., Zhang, Y., & Wang, J. (2020). Asian management of hypertension: Current status, home blood pressure, and specific concerns in China. The Journal of Clinical Hypertension, 22(3), 475–478. https://doi.org/10.1111/jch.13687
Ha, J. M., Kim, Y. W., Lee, D. H., Yun, S. J., Kim, E. K., Hye Jin, I., Kim, J. H., Kim, C. D., Shin, H. K., & Bae, S. S. (2011). Regulation of arterial blood pressure by Akt1-dependent vascular relaxation. Journal of Molecular Medicine, 89(12), 1253–1260. https://doi.org/10.1007/s00109-011-0798-3
Han, Y., Zhang, J., Hu, C. Q., Zhang, X., Ma, B., & Zhang, P. (2019). In silico ADME and Toxicity Prediction of Ceftazidime and Its Impurities. Frontiers in Pharmacology, 10. https://doi.org/10.3389/fphar.2019.00434
Hollman, P. C. H., & Katan, M. B. (1999). Dietary Flavonoids: Intake, Health Effects and Bioavailability. Food and Chemical Toxicology, 37(9–10), 937–942. https://doi.org/10.1016/S0278-6915(99)00079-4
Lago, R. M., Singh, P. P., & Nesto, R. W. (2007). Diabetes and hypertension. Nature Clinical Practice Endocrinology & Metabolism, 3(10), 667–667. https://doi.org/10.1038/ncpendmet0638
Li QL, Li BG, Zhang Y, Gao XP, Li CQ, & Zhang GL. (2008). Three angiotensin-converting enzyme inhibitors from Rabdosia coetsa. Phytomedicine.
Lipinski, C. A. (2004). Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Advanced Drug Delivery Reviews, 46(1–3), 3–26. https://doi.org/10.1016/S0169-409X(00)00129-0
Mardianingrum, R., Endah, S. R. N., Suhardiana, E., Ruswanto, R., & Siswandono, S. (2021). Docking and molecular dynamic study of isoniazid derivatives as anti-tuberculosis drug candidate. Chemical Data Collections, 32, 100647. https://doi.org/10.1016/j.cdc.2021.100647
MATSUBARA, T., BOHGAKI, T., WATARAI, M., SUZUKI, H., OHASHI, K., & SHIBUYA, H. (1999). Antihypertensive Actions of Methylripariochromene A from Orthosiphon aristatus, an Indonesian Traditional Medicinal Plant. Biological and Pharmaceutical Bulletin, 22(10), 1083–1088. https://doi.org/10.1248/bpb.22.1083
Matusbara, T., BOHGAKI, T., WATARAI, M., SUZUKI, H., OHASHI, K., & SHIBUYA, H. (1999). Antihypertensive Actions of Methylripariochromene A from Orthosiphon aristatus, an Indonesian Traditional Medicinal Plant. Biological and Pharmaceutical Bulletin, 22(10), 1083–1088. https://doi.org/10.1248/bpb.22.1083
Molden, E., & Jukić, M. M. (2021). CYP2D6 Reduced Function Variants and Genotype/Phenotype Translations of CYP2D6 Intermediate Metabolizers: Implications for Personalized Drug Dosing in Psychiatry. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.650750
Motohashi, H., & Inui, K. (2013). Organic Cation Transporter OCTs (SLC22) and MATEs (SLC47) in the Human Kidney. The AAPS Journal, 15(2), 581–588. https://doi.org/10.1208/s12248-013-9465-7
Nguyen, M. T. T., Awale, S., Tezuka, Y., Chien-Hsiung, C., & Kadota, S. (2004). Staminane- and Isopimarane-Type Diterpenes from Orthosiphon stamineus of Taiwan and Their Nitric Oxide Inhibitory Activity. Journal of Natural Products.
Ohashi, K., Bohgaki, T., Matsubara, T., & Shibuya, H. (2000). Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae). Chemical & Pharmaceutical Bulletin, 48(3), 433–435. https://doi.org/10.1248/cpb.48.433
Ohashi, K., BOHGAKI, T., & SHIBUYA, H. (2000). Antihypertensive Substance in the Leaves of Kumis Kucing (Orthosiphon aristatus) in Java Island. YAKUGAKU ZASSHI, 120(5), 474–482. https://doi.org/10.1248/yakushi1947.120.5_474
Ohashi, K., Bohgaki, T., & Shibuya, H. (2000). [Antihypertensive substance in the leaves of kumis kucing (Orthosiphon aristatus) in Java Island]. Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, 120(5), 474–482. https://doi.org/10.1248/yakushi1947.120.5_474
Oliveros, J. C. (2007). Venny. An interactive tool for comparing lists with Venn’s diagrams. Https://Bioinfogp.Cnb.Csic.Es/Tools/Venny/Index.Html.
Oparil, S., Acelajado, M. C., Bakris, G. L., Berlowitz, D. R., Cífková, R., Dominiczak, A. F., Grassi, G., Jordan, J., Poulter, N. R., Rodgers, A., & Whelton, P. K. (2018). Hypertension. Nature Reviews Disease Primers, 4(1), 18014. https://doi.org/10.1038/nrdp.2018.14
Peixoto-Neves, D., Leal-Cardoso, J. H., & Jaggar, J. H. (2014). Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels. Journal of Cardiovascular Pharmacology, 64(5), 401–406. https://doi.org/10.1097/FJC.0000000000000131
Peixoto-Neves, D., Wang, Q., Leal-Cardoso, J. H., Rossoni, L. V, & Jaggar, J. H. (2015). Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels. British Journal of Pharmacology, 172(14), 3484–3494. https://doi.org/10.1111/bph.13156
Prasannarong, M., Saengsirisuwan, V., Surapongchai, J., Buniam, J., Chukijrungroat, N., & Rattanavichit, Y. (2019). Rosmarinic acid improves hypertension and skeletal muscle glucose transport in angiotensin II-treated rats. BMC Complementary and Alternative Medicine, 19(1), 165. https://doi.org/10.1186/s12906-019-2579-4
Pullamsetti, S. S., Berghausen, E. M., Dabral, S., Tretyn, A., Butrous, E., Savai, R., Butrous, G., Dahal, B. K., Brandes, R. P., Ghofrani, H. A., Weissmann, N., Grimminger, F., Seeger, W., Rosenkranz, S., & Schermuly, R. T. (2012). Role of Src Tyrosine Kinases in Experimental Pulmonary Hypertension. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(6), 1354–1365. https://doi.org/10.1161/ATVBAHA.112.248500
Sajeev, A., Hegde, M., Girisa, S., Devanarayanan, T. N., Alqahtani, M. S., Abbas, M., Sil, S. K., Sethi, G., Chen, J.-T., & Kunnumakkara, A. B. (2022). Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases. Biomolecules, 12(9), 1185. https://doi.org/10.3390/biom12091185
Samidurai, D., Pandurangan, A. K., Krishnamoorthi, S. K., Perumal, M. K., & Nanjian, R. (2020). Sinensetin isolated from Orthosiphon aristatus inhibits cell proliferation and induces apoptosis in hepatocellular carcinoma cells. Process Biochemistry, 88, 213–221. https://doi.org/10.1016/j.procbio.2019.09.031
Shafaei, A., Saeed, M. A. A., Hamil, M. S. R., & Ismail, Z. (2018). Application of high performance liquid chromatography and Fourier-transform infrared spectroscopy techniques for evaluating the stability of Orthosiphon aristatus ethanolic extract and its nano liposomes. Revista Brasileira de Farmacognosia, 28(6), 658–668. https://doi.org/10.1016/j.bjp.2018.07.005
Smith, D. A., Beaumont, K., Maurer, T. S., & Di, L. (2019). Clearance in Drug Design. Journal of Medicinal Chemistry, 62(5), 2245–2255. https://doi.org/10.1021/acs.jmedchem.8b01263
Tezuka, Y., STAMPOULIS, P., BANSKOTA, A. H., AWALE, S., TRAN, K. Q., SAIKI, I., & KADOTA, S. (2000). Constituents of the Vietnamese Medicinal Plant Orthosiphon stamineus. Chemical and Pharmaceutical Bulletin, 48(11), 1711–1719. https://doi.org/10.1248/cpb.48.1711
Tung, N. N., Tam, L. T., Anh, D. H., Hanh, T. T. H., Cuong, N. X., Cuong, N. T., & Quang, T. H. (2022). Antimicrobial phenolic metabolites from the aerial parts of Orthosiphon aristatus. Phytochemistry Letters, 52, 49–53. https://doi.org/10.1016/j.phytol.2022.09.004
Van de Waterbeemd, H. (2007). In Silico Models to Predict Oral Absorption. In Comprehensive Medicinal Chemistry II (pp. 669–697). Elsevier. https://doi.org/10.1016/B0-08-045044-X/00145-0
Wadanambi, P. M., & Mannapperuma, U. (2021). Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani. Heliyon, 7(6), e07178. https://doi.org/10.1016/j.heliyon.2021.e07178
Wakasugi, T., Shimizu, I., Yoshida, Y., Hayashi, Y., Ikegami, R., Suda, M., Katsuumi, G., Nakao, M., Hoyano, M., Kashimura, T., Nakamura, K., Ito, H., Nojiri, T., Soga, T., & Minamino, T. (2019). Role of smooth muscle cell p53 in pulmonary arterial hypertension. PloS One, 14(2), e0212889. https://doi.org/10.1371/journal.pone.0212889
Wang, T., Wu, Z., Sun, L., Li, W., Liu, G., & Tang, Y. (2018). A Computational Systems Pharmacology Approach to Investigate Molecular Mechanisms of Herbal Formula Tian-Ma-Gou-Teng-Yin for Treatment of Alzheimer’s Disease. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00668
Yang, Y.-F., Wu, S.-T., Liu, B., Xie, Z.-T., Xiong, W.-C., Hao, P.-F., Xiao, W.-P., Sun, Y., Ai, Z.-Z., You, P.-T., & Wu, H.-Z. (2019). A Novel Antiplatelet Aggregation Target of Justicidin B Obtained From Rostellularia Procumbens (L.) Nees. Frontiers in Pharmacology, 10. https://doi.org/10.3389/fphar.2019.00688
Yulianti, R. , N. D. A. , & N. L. (2015). Formulasi Sediaan Sabun Mandi Cair Ekstrak Daun Kumis Kucing (Orthosiphon Aristatus (Bl) Miq.). Kartika: Jurnal Ilmiah Farmasi, 3, 1–11.
Zouein, F. A., Zgheib, C., Hamza, S., Fuseler, J. W., Hall, J. E., Soljancic, A., Lopez-Ruiz, A., Kurdi, M., & Booz, G. W. (2013). Role of STAT3 in angiotensin II-induced hypertension and cardiac remodeling revealed by mice lacking STAT3 serine 727 phosphorylation. Hypertension Research, 36(6), 496–503. https://doi.org/10.1038/hr.2012.223
Copyright (c) 2024 Adha Dastu Illahi, Nur Hasanah, Gatot Fatwanto Hertono, Arry Yanuar
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
