REVIEW: METABOLOMICS APPROACH IN EXPLORATION OF ANTIHYPERTENSIVE PLANTS: PROFILE OF BIOACTIVE COMPOUNDS AND CHANGES IN ENDOGENOUS METABOLITES
DOI:
https://doi.org/10.5614/api.v50i2.25029Keywords:
Biomarkers, Hypertension, Chemometrics, Metabolite Profiling, MetabolomicAbstract
Metabolomic techniques represent an analytical strategy that supports the discovery of natural product-based drugs, including antihypertensive agents. This article aims to review various metabolomic techniques and approaches used to identify and characterize bioactive compounds in medicinal plants, highlighting two primary strategies: (1) plant metabolite profiling to identify potential bioactive biomarkers, and (2) analysis of endogenous metabolite changes in biological samples from hypertensive models treated with plant-based interventions. Literature was searched through databases such as PubMed and Google Scholar using relevant keywords. This review focuses on analytical methods such as LC-MS, NMR, and HPLC, data processing strategies including PCA, PLS-DA, and OPLS, and the integration of metabolomic techniques in the validation and exploration of plant-derived antihypertensive compounds. The findings demonstrate that metabolomic approaches significantly contribute to accelerating natural drug discovery by identifying biomarkers and elucidating mechanisms of action through related endogenous metabolic pathways.
References
Abdelhafez OH, Othman EM, Fahim JR, Desoukey SY, Pimentel?Elardo SM, Nodwell JR, Schirmeister T, Tawfike A, Abdelmohsen UR, 2020, Metabolomics analysis and biological investigation of three Malvaceae plants. Phytochemical Analysis, 31(2) : 204?214, doi: 10.1002/pca.2883
El-Shiekh RA, Saber FR, Abdel-Sattar EA, 2020, In vitro anti-hypertensive activity of Jasminum grandiflorum subsp. floribundum (Oleaceae) in relation to its metabolite profile as revealed via UPLC-HRMS analysis. Journal of Chromatography B, 1158, 122334, doi: 10.1016/j.jchromb.2020.122334
Esteva-Socias M, Artiga MJ, Bahamonde O, Belar O, Bermudo R, Castro E, Escez T, Fraga M, Jauregui-Mosquera L, Novoa I, PeirChova L, Rej JD, Ruiz-MirM, Vieiro-Balo P, Villar-Campo V, Zazo S, Rano A, Villena C, 2019, In search of an evidence-based strategy for quality assessment of human tissue samples: report of the tissue Biospecimen Research Working Group of the Spanish Biobank Network. Journal of Translational Medicine, 17(1): 370, doi: 10.1186/s12967-019-2124-8
Feng Z, Hou J, Yu Y, Wu W, Deng Y, Wang X, Zhi H, Zhang L, Wu W, Guo, D, 2019, Dissecting the Metabolic Phenotype of the Antihypertensive Effects of Five Uncaria Species on Spontaneously Hypertensive Rats. Frontiers in Pharmacology 10, doi: 10.3389/fphar.2019.00845
Gao L, Kong X, Wu W, Feng Z, Zhi H, Zhang Z, Long H, Lei M, Hou J, Wu W, Guo D, 2022, Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking. Frontiers in Pharmacology 13, doi: 10.3389/fphar.2022.909631
Ibrahim RS, El-Mezayen NS,El?Banna AA, 2022, Alleviation of liver cirrhosis and associated portal-hypertension by Astragalus species in relation to their UPLC-MS/MS metabolic profiles: a mechanistic study. Scientific Reports, 12(1): 11884, doi: 10.1038/s41598-022-15958-1
Kario K, Okura A, Hoshide S, Mogi M, 2024, The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy. Hypertension Research, 47(5), 1099?1102, doi: 10.1038/s41440-024-01622-w
Kordalewska M, Markuszewski MJ, 2015, Metabolomics in cardiovascular diseases. Journal of Pharmaceutical and Biomedical Analysis, 113: 121?136, doi: 10.1016/j.jpba.2015.04.021
Kumar N, Bharat JS, Kumar A, Jaitak V, 2024, Recent advancement in mass based plant metabolomics: techniques, tools, and analytical approaches, Phytochemistry Reviews, doi: 10.1007/s11101-024-10028-y
Lai Y, Koelmel JP, Walker DI, Price EJ, Papazian S, Manz KE, Castilla-Ferndez D, Bowden JA, Nikiforov V, David A, Bessonneau V, Amer B, Seethapathy S, Hu X, Lin EZ, Jbebli A, McNeil BR, Barupal D, Cerasa M, Miller GW, 2024, High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage. Environmental Science & Technology 58(29): 12784?12822, doi: 10.1021/acs.est.4c01156
Li C, Wen R, Liu DW, Liu Q, Yan LP, Wu JX, Guo YJ, Li SY, Gong QF, Yu H, 2020, Diuretic Effect and Metabolomics Analysis of Crude and Salt-Processed Plantaginis Semen. Frontiers in Pharmacology: 11, doi: 10.3389/fphar.2020.563157
Ma XF, Mao XM, Batur MM, Chen CL, Ma LN, Li LL, Ma XL, 2021, Investigation of Coreopsis tinctoria Nutt extracts in spontaneously hypertensive rats by an NMR-based metabolomic approach. In Int J Clin Exp Med 14(12).
Mancia G, Kreutz R, Brunstr M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca, A, Cornelissen, V, Cruickshank JK, Cunha PG, Kjeldsen SE, 2023, 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension. Journal of Hypertension 41(12): 1874?2071, doi: 10.1097/HJH.0000000000003480
Markley JL, Brchweiler R, Edison AS, Eghbalnia HR, Powers R, Raftery D,Wishart DS, 2017, The future of NMR-based metabolomics. Current Opinion in Biotechnology, 43: 34?40, doi: 10.1016/j.copbio.2016.08.001
Naz S, Vallejo M, Garc A, Barbas C, 2014, Method validation strategies involved in non-targeted metabolomics. Journal of Chromatography A 1353: 99?105, doi: 10.1016/j.chroma.2014.04.071
Nikolic SB, Sharman JE, Adams MJ, Edwards LM, 2014, Metabolomics in hypertension. Journal of Hypertension 32(6): 1159?1169, doi: 10.1097/HJH.0000000000000168
Pratami MP, Sujarwo W, Fendiyanto MH, Yuniati R, Kurniyanto IR, Widiayani N, Seleiman MF, Ali N, Anshori MF, 2025, Metabolite profiling of some organs and the potential of Mukia javanica as an antihypertension. Frontiers in Sustainable Food Systems 8, doi: 10.3389/fsufs.2024.1487446
Rad, Shayani M, Moohebati M, Mohajeri SA, 2022, Effect of celery (Apium graveolens) seed extract on hypertension: A randomized, triple-blind, placebo-controlled, cross-over, clinical trial. Phytother Res 36(7): 2889-2907, doi: 10.1002/ptr.7469.
Saeed A, Bashir K, Shah AJ, Qayyum R, Khan T, 2022, Antihypertensive Activity in High Salt-Induced Hypertensive Rats and LC-MS/MS-Based Phytochemical Profiling of Melia azedarach L. (Meliaceae) Leaves. BioMed Research International, 2022: 1?17. doi: 10.1155/2022/2791874
Salem MA, Ezzat SM, Ahmed KA, Alseekh S, Fernie AR,Essam RM, 2022, A Comparative Study of the Antihypertensive and Cardioprotective Potentials of Hot and Cold Aqueous Extracts of Hibiscus sabdariffa L. in Relation to Their Metabolic Profiles. Frontiers in Pharmacology 13, doi: 10.3389/fphar.2022.840478
Salem MA, Michel HE, Ezzat MI, Okba MM, EL-Desoky AM, Mohamed SO, Ezzat SM, 2020, Optimization of an Extraction Solvent for Angiotensin-Converting Enzyme Inhibitors from Hibiscus sabdariffa L. Based on Its UPLC-MS/MS Metabolic Profiling. Molecules, 25(10): 2307, doi: 10.3390/molecules25102307
Sun X, Wang S, Sheng H, Lv X, Li J, Han B, Wang S, Liu K, Zhang C, Zhang W, Guo, F, 2023a, Study on the mechanism of stir-fried Fructus Tribuli in enhancing the essential hypertension treatment by an integrated ?spectrum-effect relationship-network pharmacology-metabolomics? strategy. Biomedicine & Pharmacotherapy, 165: 115160, doi: 10.1016/j.biopha.2023.115160
Tian Z, Zhang S, Wang H, Chen Z, Sun M, Sun L, Gong L, Li Y, Jiang H, 2020a, Intervention of Uncaria and Its Components on Liver Lipid Metabolism in Spontaneously Hypertensive Rats. Frontiers in Pharmacology 11, doi: 10.3389/fphar.2020.00910
Vahedi M, Kabiri M, Salami SA, Rezadoost H, Mirzaie M, Kanani MR, 2018, Quantitative HPLC-based metabolomics of some Iranian saffron (Crocus sativus L.) accessions, Industrial Crops and Products, 118: 26?29, doi: 10.1016/j.indcrop.2018.03.024
Vera Y, Yanti S, 2020, Penyuluhan Pemanfaatan Tanaman Obat Dan Obat Tradisional Indonesia Untuk Pencegahan Dan Penanggulangan Penyakit Hipertensi Di Desa Salam Bue, Jurnal Education and Development, 8(1): 11?14.
Wahid M, Saqib F, Chicea L, Ahmedah HT, Sajer BH, Marc RA, Pop OL, Moga M, Gavris C, 2022, Metabolomics analysis delineates the therapeutic effects of hydroethanolic extract of Cucumis sativus L. seeds on hypertension and isoproterenol-induced myocardial infarction, Biomedicine & Pharmacotherapy, 148: 112704, doi: 10.1016/j.biopha.2022.112704
Wang ZB, Jiang SL, Liu SB, Peng JB, Hu S, Wang X, Zhuo W, Liu T, Guo JW, Zhou HH, Yang ZQ, Mao, XY, Liu ZQ, 2021, Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats, ACS Omega, 6(29): 18610?18622, doi: 10.1021/acsomega.1c01135
Xiao Q, Mu X, Liu J, Li B, Liu H, Zhang B, Xiao P, 2022, Plant metabolomics: a new strategy and tool for quality evaluation of Chinese medicinal materials, Chinese Medicine, 17(1): 45, doi: 10.1186/s13020-022-00601-y
Yuniarto A, Alviolita D, Kurniasukmawati I, Rasydy LOA, 2023, Antihypertension Activity of Averrhoa bilimbi Fruit Juice on Sodium Chloride and Prednisone-Induced Rats. MPI (Media Pharmaceutica Indonesiana) 5(2): 141-145.
Yoon D, Choi BR, Lee YS, Han KS, Kim D, Lee DY, 2020, Serum Metabonomic Research of the Anti-Hypertensive Effects of Ogaja on Spontaneously Hypertensive Rats, Metabolites, 10(10): 404, doi: 10.3390/metabo10100404
Zhang K, Liu Y, Liu L, Bai B, Shi L, Zhang Q, 2023, Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children, Nutrients, 15(4): 836, doi: 10.3390/nu15040836
Zhang Y, Yan P, He Y, Ren S, Wu D, Wang Y, Song S, Lu P, Li X, Li G, Jia W, Lyu Y, Dong H, Xiao D, Ding L, Lin S, Lin Y, 2024, Exploring synergistic effects of Achyranthes bidentata Blume and Paeonia lactiflora Pall. on hypertension with liver yang hyperactivity using the multidisciplinary integrative strategy. Heliyon, 10(21): e38649. doi: 10.1016/j.heliyon.2024.e38649
