Moringa oleifera Lam leaves extract and its compounds effect on the intracellular calcium release in human aortic smooth muscle cells
Keywords:
amlodipine, caffeine, cytosolic Ca2 , intracellular Ca2 , K depolarisation, Moringa oleifera
Abstract
Moringa oleifera leaves have been scientifically shown lower blood pressure but the mechanism of action on this is achieved has not been fully explored. Intracellular calcium release is a fundamental cellular process linked to vascular function and modulation of this process can have significant implications for cardiovascular health. The blocking effects of calcium influx and release by Moringa oleifera Lam leaf extract and its compounds on the human aortic smooth muscle cells (HAoSMCs) were studied. The cell viability assay was carried out to determine the concentrations of M. oleifera Lam leaf extract and its compounds for the assay. Test compounds (amlodipine, chlorogenic acid, gallic acid, kaempferol, M. oleifera leaf extract, quercetin and vicenin-2) were incubated with Quin-2-AM in the presence and absence of extracellular calcium (Ca2+) and with the addition of caffeine and potassium (K+) in HAoSMCs. Following treatments with the test compounds, the influx of extracellular Ca2+ into the cytosol of HAoSMCs was significantly inhibited (p <0.001). The test compounds significantly (p <0.001) decreased the concentration of cytosolic Ca2+ induced by K+ depolarisation. The test compounds also significantly (p <0.001) affected the intracellular Ca2+metabolism, regulated by the caffeine-sensitive storage site in HAoSMCs. No synergistic effect on the decreasing of cytosolic Ca2+ level was observed when the test compounds were used in combination with amlodipine. M. oleifera Lam leaf extract and its compounds may act as Ca2+channel blockers (CCBs) and there is also a possibility of interactions between the test compounds and amlodipine.
References
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Kanaide, H., Kobayashi, S., Nishimura, J., Hasegawa, M., Shogakiuchi, Y., Matsumoto T. & Nakamura, M. (1988). Quin2 microfluorometry and effects of verapamil and diltiazem on calcium release from rat aorta smooth muscle cells in primary culture. Circ Res. 63(1), 16-26.
Kholodenko, B.N., Rauch, N., Kolch W. & Rukhlenko, O.S. (2021). A systematic analysis of signaling reactivation and drug resistance. Cell Rep. 35(8), 109157.
Kirschstein, T., Rehberg, M., Bajorat, R., Tokay, T., Porath K. & Kohling, R. (2009). High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle. Acta Pharm Sinic. 30, 1123-1131.
Koe, X.F., Tengku Muhammad, T.S., Chong, A.S.C., Abdul Wahab, H. & Mei, L.T. (2014). Cytochrome P450 induction properties of food and herbal-derived compounds using a novel multiplex RT-qPCR in vitro assay, a drug–food interaction prediction tool. Food Sci Nutri. 2(5), 500–520.
Kumolosasi, E., Ching, M.C.L., Salwanizam, N.A.A., Muhammad Esham, N.S.A., Ayob, Q.A., Ramasamy, R., Govindan, H., Md Redzuan, A. & Jasamai, M. (2022). Drug-herb interactions: selected antihypertensive drugs with Moringa oleifera leaves extract. Sains Malays. 51(4), 1143-1154.
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Maaliki, D., Shaito, A.A., Pintus, G., El-Yazbi A., & Eid, A.H. (2019). Flavonoids in hypertension: A brief review of the underlying mechanisms. Curr Opin Pharmacol. 45, 57-65.
Ministry of Agriculture (MOA) (2018). Retrieved from http://www.moa.gov.my/en/industri herba.
Ng, J.M., Kok, P.K. & Wen, S.H.L. (2020). Prescribing patterns of antihypertensive medications and blood pressure control among hypertensive patients in a primary care setting in Malaysia. Prog Drug Dis Biomed Sci. 3(1), a0000055.
Niazmand, S., Fereidouni, E., Mahmoudabady, M. & Mousavi, S.M. (2014). Endothelium-independent vasorelaxant effects of hydroalcoholic extract from Nigella sativa seed in rat aorta: The roles of Ca2+ and K+ channels. Biomed Research Int. 2014, 247054.
Stohs, S.J. & Hartman, M.J. (2015). Review of the safety and efficacy of Moringa oleifera. Phytother Res. 29(6), 796-804.
Rathi, B., Bodhankar, S. & Baheti, A. (2006). Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats. Indian J Exp Biol. 44(11), 898-901.
Vongsak, B., Sithisarn, P., Mangmool, S., Thongpradichote, S., Wongkrajang, Y. & Gritsanapan, W. (2013). Maximizing total phenolics, total flavonoids contents and antioxidant activity of Moringa oleifera leaf extract by the appropriate extraction method. Ind Crop Prod. 44, 566– 571.
Wang, R., Zhang, H., Sun, S., Wang, Y., Chai, Y. & Yuan, Y. (2016). Effect of ginkgo leaf tablets on the pharmacokinetics of amlodipine in rats. Eur J Drug Metab Ph. 41(6), 825-833.
Wellman G.C. & Nelson, M.T. (2003) Signaling between SR and plasmalemma in smooth muscle: Sparks and the activation of Ca2+-sensitive ion channels. Cell calcium 34(3), 211-229.
Zhao, Y., Wang, J., Ballevre, O., Luo, H. & Zhang, W. (2012). Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res. 35(4), 370-374.
Alam, M.A., Bin Jardan, Y.A., Alzenaidy, B., Raish, M., Al-Mohizea, A.M., Ahad, A. & Al-Jenoobi, F.I. (2021). Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine. J Pharm Pharmacol. 73(9), 1151-1160.
Alam, M.A., Bin Jardan, Y.A., Raish, M., Al-Mohizea, A.M., Ahad, A. & Al-Jenoobi, F.I. (2022). Herb-drug interaction: pharmacokinetics and pharmacodynamics of anti-hypertensive drug amlodipine besylate in presence of Lepidium sativum and Curcuma longa. Xenobiotica 52(2), 177-185.
Awortwe, C., Makiwane, M., Reuter, H., Muller, C., Louw, J. & Rosenkranz, B. (2018). Critical evaluation of causality assessment of herb–drug interactions in patients. Brit J Clin Pharmaco. 84(4), 679-693.
Basri, N.F., Ramli, A.S., Mohamad, M. & Kamaruddin, K.N. (2022). Traditional and complementary medicine (TCM) usage and its association with Patient Assessment of Chronic Illness Care (PACIC) among individuals with metabolic syndrome in primary care. BMC Complement Med Ther. 22(1), 14.
Chin, C.Y., Jalil, J., Ng, P.Y. & Ng, S.F. (2018). Development and formulation of Moringa oleifera standardised leaf extract film dressing for wound healing application. J Ethnopharmacol. 212(2018), 188-199.
de Oliveira, L.M., de Oliveira, T.S., da Costa, R.M., de Souza Gil, E., Costa, E.A., de Cassia Aleixo Tostes Passaglia, R., Filgueira, F.P. & Ghedini, P.S. (2016). The vasorelaxant effect of gallic acid involves endothelium-dependent and -independent mechanisms. Vasc Pharmacol. 81, 69-74.
Dib, I., Tits, M., Angenot, L., Wauters, J.N., Assaidi, A., Mekhfi, H., Aziz, M., Bnouham, M., Legssyer, A., Frederich, M. & Ziyyat, A. (2017). Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco. J Ethnopharmacol. 206, 224-235.
Echeverri, D., Montes, F.R., Cabrera, M., Galan A. & Prieto, A. (2010). Caffeine's vascular mechanisms of action. Int J Vasc Med. 2010, 834060.
El-Bardai, S., Wibo, M., Hamaide, M.C., Lyoussi, B., Joelle, Q.L. & Morel, N. (2004). Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker. Brit J Pharmaco. 140, 1211-1216.
Endo, M., Tanaka, M. & Ogawa, Y. (1970). Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres. Nature 228(5266), 34-36.
Ferrari, R., Pavasini, R., Censi, S., Squeri, A. & Rosana, G. (2021). The new ESC guidelines for the diagnosis and management of chronic coronary syndromes: the good and the not so good. Curr Prob Cardiology 46(3), 100554.
Ghayur, M.N. & Gilani, A.H. (2005). Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders. Dig Dis Sci. 50(10), 1889-1897.
Hussain Ali, M., Ibrahim I. & Jasamai, M. (2022). Anti-malarial effect of Momordica charantia involved modulation of cytokine mediated via GSK3 inhibition in Plasmodium berghei-infected mice. Jordan J Biol Sci. 15(3), 523-529.
Ithnain, N., Panting, A.J., Kassim, R., Amirudin N. & Krishnan, M. (2020). Perception of conventional medicine and herbal medicine usage amongst diabetic patients: a qualitative study in Negeri Sembilan, Malaysia. Glob Health Sci. 12(10), 122-132.
Imtiaz, M.S., Katnik, C.P., Smith D.W. & van Helden, D.F. (2006). Role of voltage-dependent modulation of store Ca2+ release in synchronization of Ca2+ oscillations. Biophys J. 90(1), 1-23.
Izzo, A.A., Hoon‐Kim, S., Radhakrishnan, R. & Williamson, E.M. (2016). A critical approach to evaluating clinical efficacy, adverse events and drug interactions of herbal remedies. Phytother Res. 30(5), 691-700.
Jiang, N., Zhang, M., Meng X. & Sun, B. (2020). Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism. Pharm Biol. 58(1), 465-468.
Kanaide, H., Kobayashi, S., Nishimura, J., Hasegawa, M., Shogakiuchi, Y., Matsumoto T. & Nakamura, M. (1988). Quin2 microfluorometry and effects of verapamil and diltiazem on calcium release from rat aorta smooth muscle cells in primary culture. Circ Res. 63(1), 16-26.
Kholodenko, B.N., Rauch, N., Kolch W. & Rukhlenko, O.S. (2021). A systematic analysis of signaling reactivation and drug resistance. Cell Rep. 35(8), 109157.
Kirschstein, T., Rehberg, M., Bajorat, R., Tokay, T., Porath K. & Kohling, R. (2009). High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle. Acta Pharm Sinic. 30, 1123-1131.
Koe, X.F., Tengku Muhammad, T.S., Chong, A.S.C., Abdul Wahab, H. & Mei, L.T. (2014). Cytochrome P450 induction properties of food and herbal-derived compounds using a novel multiplex RT-qPCR in vitro assay, a drug–food interaction prediction tool. Food Sci Nutri. 2(5), 500–520.
Kumolosasi, E., Ching, M.C.L., Salwanizam, N.A.A., Muhammad Esham, N.S.A., Ayob, Q.A., Ramasamy, R., Govindan, H., Md Redzuan, A. & Jasamai, M. (2022). Drug-herb interactions: selected antihypertensive drugs with Moringa oleifera leaves extract. Sains Malays. 51(4), 1143-1154.
Li, D.Q., Zhao, J., Xie J. & Li, S.P. (2014). A novel sample preparation and on-line HPLC–DAD–MS/MS–BCD analysis for rapid screening and characterization of specific enzyme inhibitors in herbal extracts: Case study of α-glucosidase. J Pharm Biomed Anal. 88, 130-135.
Lonza Corporation (2011). Cell Culture Protocol. Lonza Protocol Number AA-1002-1407/11. Retrieved from https://bioscience.lonza.com/lonza_bs/US/en/download/product/asset/28066.
Maaliki, D., Shaito, A.A., Pintus, G., El-Yazbi A., & Eid, A.H. (2019). Flavonoids in hypertension: A brief review of the underlying mechanisms. Curr Opin Pharmacol. 45, 57-65.
Ministry of Agriculture (MOA) (2018). Retrieved from http://www.moa.gov.my/en/industri herba.
Ng, J.M., Kok, P.K. & Wen, S.H.L. (2020). Prescribing patterns of antihypertensive medications and blood pressure control among hypertensive patients in a primary care setting in Malaysia. Prog Drug Dis Biomed Sci. 3(1), a0000055.
Niazmand, S., Fereidouni, E., Mahmoudabady, M. & Mousavi, S.M. (2014). Endothelium-independent vasorelaxant effects of hydroalcoholic extract from Nigella sativa seed in rat aorta: The roles of Ca2+ and K+ channels. Biomed Research Int. 2014, 247054.
Stohs, S.J. & Hartman, M.J. (2015). Review of the safety and efficacy of Moringa oleifera. Phytother Res. 29(6), 796-804.
Rathi, B., Bodhankar, S. & Baheti, A. (2006). Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats. Indian J Exp Biol. 44(11), 898-901.
Vongsak, B., Sithisarn, P., Mangmool, S., Thongpradichote, S., Wongkrajang, Y. & Gritsanapan, W. (2013). Maximizing total phenolics, total flavonoids contents and antioxidant activity of Moringa oleifera leaf extract by the appropriate extraction method. Ind Crop Prod. 44, 566– 571.
Wang, R., Zhang, H., Sun, S., Wang, Y., Chai, Y. & Yuan, Y. (2016). Effect of ginkgo leaf tablets on the pharmacokinetics of amlodipine in rats. Eur J Drug Metab Ph. 41(6), 825-833.
Wellman G.C. & Nelson, M.T. (2003) Signaling between SR and plasmalemma in smooth muscle: Sparks and the activation of Ca2+-sensitive ion channels. Cell calcium 34(3), 211-229.
Zhao, Y., Wang, J., Ballevre, O., Luo, H. & Zhang, W. (2012). Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res. 35(4), 370-374.
Published
2025-03-27
How to Cite
Jasamai, M., Shirdashtzadeh, Z., Kumolosasi, E., & Mohd Fauzi , N. (2025). Moringa oleifera Lam leaves extract and its compounds effect on the intracellular calcium release in human aortic smooth muscle cells. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.12526
Issue
Section
Research Article
