Effect of Nigella sativa and Fenugreek on the Pharmacokinetics and Pharmacodynamics of Amlodipine in Hypertensive Rats

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Abstract

Background: The present article is related to in-vitro and in-vivo herb-drug interaction studies.

Objectives: This study aimed to investigate the effect of Nigella sativa and fenugreek on the pharmacodynamics and pharmacokinetics of amlodipine.

Method: Hypertensive rats of group-I were treated with amlodipine and rats of group-II and III were treated with N. sativa, and N. sativa + amlodipine and fenugreek, and fenugreek + amlodipine, respectively. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of group-I, II and III rats were measured by the “tail-cuff system”.

Results: N. sativa, as well as fenugreek, reduced the SBP, DBP and MBP. Simultaneously, administration of fenugreek + amlodipine or N. sativa + amlodipine showed better control of BP. Individually, fenugreek, as well as N. sativa, showed a surprising reduction in the heart rate. There was no remarkable effect of any of these two herbs on Cmax, AUC0-t, Kel, and terminal elimination half-life of amlodipine, but fenugreek altered the Tmax of amlodipine significantly, from 2 ± 1.2h in control to 7.2 ± 1.7h in fenugreek treated group, probably by delaying the absorption.

Conclusion: Results of pharmacodynamics and pharmacokinetics studies suggested that simultaneous administration of fenugreek or N. sativa with amlodipine improved the pharmacological response of amlodipine in hypertensive rats, though there was no remarkable change in pharmacokinetic parameters (Cmax, Kel, elimination t1/2, and AUC0-t).

Keywords: Amlodipine, Nigella sativa, black seed, fenugreek, blood pressure, hypertension, herb-drug interaction.

Graphical Abstract

[1]
Volpe, M.; Gallo, G.; Tocci, G. . New approach to blood pressure control: Triple combination pill. Trends. Cardiovasc. Med.,, 2019,, pii,S1050-1738(19)30031-3.
[2]
Salam, A.; Atkins, E.R.; Hsu, B.; Webster, R.; Patel, A.; Rodgers, A. Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials. J. Hypertens., 2019, 37(8), 1567-1573.
[http://dx.doi.org/10.1097/HJH.0000000000002089] [PMID: 31058799]
[3]
Lu, P.P.; Meng, X.; Zhang, Y.; Li, Y.Q.; Wang, S.; Liu, L.S.; Wang, W.; Li, Y.L.; Zhang, Y.Q.; Hu, A.H.; Zhou, X.L.; Ma, L.H. Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy. J. Geriatr. Cardiol., 2019, 16(4), 354-361.
[PMID: 31105756]
[4]
Simon, A.; Dézsi, C.A. Treatment of Hypertensive and hypercholesterolaemic patients with the triple fixed combination of atorvastatin, perindopril and amlodipine: The results of the CORAL study. Adv. Ther., 2019, 36(8), 2010-2020.
[http://dx.doi.org/10.1007/s12325-019-01002-8] [PMID: 31183780]
[5]
Alkaabi, M.S.; Rabbani, S.A.; Rao, P.G.M.; Ali, S.R. Prescription pattern of antihypertensive drugs: An experience from a secondary care hospital in the United Arab Emirates. J. Res. Pharm. Pract., 2019, 8(2), 92-100.
[http://dx.doi.org/10.4103/jrpp.JRPP_18_85] [PMID: 31367644]
[6]
He, H.; Zhao, W.; Xu, Y. [Clinical study on treatment of mild-middle degree congestive heart failure with integrated traditional Chinese and Western medicine]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2000, 20(5), 344-346.
[PMID: 11789244]
[7]
Gong, C.; Huang, S.L.; Huang, J.F.; Zhang, Z.F.; Luo, M.; Zhao, Y.; Jiang, X.J. Effects of combined therapy of Xuezhikang Capsule and Valsartan on hypertensive left ventricular hypertrophy and heart rate turbulence. Chin. J. Integr. Med., 2010, 16(2), 114-118.
[http://dx.doi.org/10.1007/s11655-010-0114-z] [PMID: 20473735]
[8]
Li, H.; Liu, L.T.; Zhao, W.M.; Liu, J.G.; Yao, M.J.; Han, Y.X.; Shen, Y.P.; Liu, X.D.; Liu, L.; Wang, X.M.; Cai, L.L.; Guan, J. Effect of traditional and integrative regimens on quality of life and early renal impairment in elderly patients with isolated systolic hypertension. Chin. J. Integr. Med., 2010, 16(3), 216-221.
[http://dx.doi.org/10.1007/s11655-010-0216-y] [PMID: 20694775]
[9]
Xu, Y.; Yan, H.; Yao, M.J.; Ma, J.; Jia, J.M.; Ruan, F.X.; Yao, Z.C.; Huang, H.M.; Zheng, J.; Chen, T.; Lv, H.; Endler, A.M. Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality. J. Cardiovasc. Pharmacol., 2013, 61(5), 355-360.
[http://dx.doi.org/10.1097/FJC.0b013e31827afddf] [PMID: 23188130]
[10]
Wu, S.X.; Dong, Z.Y. Diverse combination therapies of Chinese Medicine in treating Hypertension. Curr. Vasc. Pharmacol., 2015, 13(4), 504-519.
[http://dx.doi.org/10.2174/1570161112666141014152214] [PMID: 25360839]
[11]
Zhu, Y.; Wang, F.; Li, Q.; Zhu, M.; Du, A.; Tang, W.; Chen, W. Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab. Dispos., 2014, 42(2), 245-249.
[http://dx.doi.org/10.1124/dmd.113.055400] [PMID: 24301608]
[12]
Vaghela, M.; Sahu, N.; Kharkar, P.; Pandita, N. In vivo pharmacokinetic interaction by ethanolic extract of Gymnema sylvestre with CYP2C9 (Tolbutamide), CYP3A4 (Amlodipine) and CYP1A2 (Phenacetin) in rats. Chem. Biol. Interact., 2017, 278, 141-151.
[http://dx.doi.org/10.1016/j.cbi.2017.10.015] [PMID: 29042257]
[13]
Zhang, H.; Han, X.; Li, Y.; Li, H.; Guo, X. Effects of Danshen tablets on pharmacokinetics of amlodipine in rats. Pharm. Biol., 2019, 57(1), 306-309.
[http://dx.doi.org/10.1080/13880209.2019.1604768] [PMID: 31060428]
[14]
Han, X.; Zhang, H.; Hao, H.; Li, H.; Guo, X.; Zhang, D. Effect Of epigallocatechin-3-gallate on the pharmacokinetics of amlodipine in rats. Xenobiotica, 2019, 49(8), 970-974.
[http://dx.doi.org/10.1080/00498254.2018.1519732] [PMID: 30182817]
[15]
Zhang, C.; Gao, Z.; Niu, L.; Chen, X. Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC-MS/MS. Pharm. Biol., 2018, 56(1), 132-137.
[http://dx.doi.org/10.1080/13880209.2018.1430835] [PMID: 29385884]
[16]
Wang, R.; Zhang, H.; Sun, S.; Wang, Y.; Chai, Y.; Yuan, Y. Effect of Ginkgo leaf tablets on the pharmacokinetics of amlodipine in rats. Eur. J. Drug Metab. Pharmacokinet., 2016, 41(6), 825-833.
[http://dx.doi.org/10.1007/s13318-015-0312-3] [PMID: 26650374]
[17]
el Tahir, K.E.; Ashour, M.M.; al-Harbi, M.M. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen. Pharmacol., 1993, 24(5), 1123-1131.
[http://dx.doi.org/10.1016/0306-3623(93)90359-6] [PMID: 8270171]
[18]
Nagi, M.N.; Mansour, M.A. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol. Res., 2000, 41(3), 283-289.
[http://dx.doi.org/10.1006/phrs.1999.0585] [PMID: 10675279]
[19]
Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Damanhouri, Z.A.; Anwar, F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3(5), 337-352.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[20]
Mollazadeh, H.; Hosseinzadeh, H. The protective effect of Nigella sativa against liver injury: a review. Iran. J. Basic Med. Sci., 2014, 17(12), 958-966.
[PMID: 25859299]
[21]
Sahebkar, A.; Beccuti, G.; Simental-Mendía, L.E.; Nobili, V.; Bo, S. Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol. Res., 2016, 106, 37-50.
[http://dx.doi.org/10.1016/j.phrs.2016.02.008] [PMID: 26875640]
[22]
Beheshti, F.; Khazaei, M.; Hosseini, M. Neuropharmacological effects of Nigella sativa. Avicenna J. Phytomed., 2016, 6(1), 104-116.
[PMID: 27247928]
[23]
Koshak, A.; Koshak, E.; Heinrich, M. Medicinal benefits of Nigella sativa in bronchial asthma: A literature review. Saudi Pharm. J., 2017, 25(8), 1130-1136.
[http://dx.doi.org/10.1016/j.jsps.2017.07.002] [PMID: 30166900]
[24]
Gholamnezhad, Z.; Shakeri, F.; Saadat, S.; Ghorani, V.; Boskabady, M.H. Clinical and experimental effects of Nigella sativa and its constituents on respiratory and allergic disorders. Avicenna J. Phytomed., 2019, 9(3), 195-212.
[PMID: 31143688]
[25]
Kaleem, M.; Kirmani, D.; Asif, M.; Ahmed, Q.; Bano, B. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian J. Exp. Biol., 2006, 44(9), 745-748.
[PMID: 16999030]
[26]
Meddah, B.; Ducroc, R.; El Abbes Faouzi, M.; Eto, B.; Mahraoui, L.; Benhaddou-Andaloussi, A.; Martineau, L.C.; Cherrah, Y.; Haddad, P.S. Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats. J. Ethnopharmacol., 2009, 121(3), 419-424.
[http://dx.doi.org/10.1016/j.jep.2008.10.040] [PMID: 19061948]
[27]
Darakhshan, S.; Bidmeshki Pour, A.; Hosseinzadeh Colagar, A.; Sisakhtnezhad, S. Thymoquinone and its therapeutic potentials. Pharmacol. Res., 2015, 95-96, 138-158.
[http://dx.doi.org/10.1016/j.phrs.2015.03.011] [PMID: 25829334]
[28]
Khattab, M.M.; Nagi, M.N. Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytother. Res., 2007, 21(5), 410-414.
[http://dx.doi.org/10.1002/ptr.2083] [PMID: 17236176]
[29]
Fallah Huseini, H.; Amini, M.; Mohtashami, R.; Ghamarchehre, M.E.; Sadeqhi, Z.; Kianbakht, S.; Fallah Huseini, A. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2013, 27(12), 1849-1853.
[http://dx.doi.org/10.1002/ptr.4944] [PMID: 23436437]
[30]
Jaarin, K.; Foong, W.D.; Yeoh, M.H.; Kamarul, Z.Y.; Qodriyah, H.M.; Azman, A.; Zuhair, J.S.; Juliana, A.H.; Kamisah, Y. Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats. Clinics (São Paulo), 2015, 70(11), 751-757.
[http://dx.doi.org/10.6061/clinics/2015(11)07] [PMID: 26602523]
[31]
Bahmani, M.; Shirzad, H.; Mirhosseini, M.; Mesripour, A.; Rafieian-Kopaei, M. A Review on ethnobotanical and therapeutic uses of fenugreek (Trigonella foenum-graceum L). J. Evid. Based Complementary Altern. Med., 2016, 21(1), 53-62.
[http://dx.doi.org/10.1177/2156587215583405] [PMID: 25922446]
[32]
Basch, E.; Ulbricht, C.; Kuo, G.; Szapary, P.; Smith, M. Therapeutic applications of fenugreek. Altern. Med. Rev., 2003, 8(1), 20-27.
[PMID: 12611558]
[33]
Gong, J.; Fang, K.; Dong, H.; Wang, D.; Hu, M.; Lu, F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J. Ethnopharmacol., 2016, 194, 260-268.
[http://dx.doi.org/10.1016/j.jep.2016.08.003] [PMID: 27496582]
[34]
Balaraman, R.; Dangwal, S.; Mohan, M. Antihypertensive effect of Trigonella foenum-greacum. seeds in experimentally induced hypertension in rats. Pharm. Biol., 2008, 44(8), 568-575.
[http://dx.doi.org/10.1080/13880200600896538]
[35]
Korashy, H.M.; Al-Jenoobi, F.I.; Raish, M.; Ahad, A.; Al-Mohizea, A.M.; Alam, M.A.; Alkharfy, K.M.; Al-Suwayeh, S.A. Impact of herbal medicines like Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida, on cytochrome P450 2C11 gene expression in rat liver. Drug Res. (Stuttg.), 2015, 65(7), 366-372.
[PMID: 25099385]
[36]
Ahmmed, S.M.; Mukherjee, P.K.; Bahadur, S.; Kar, A.; Mukherjee, K.; Karmakar, S.; Bandyopadhyay, A. Interaction potential of Trigonella foenum graceum through cytochrome P450 mediated inhibition. Indian J. Pharmacol., 2015, 47(5), 530-534.
[http://dx.doi.org/10.4103/0253-7613.165179] [PMID: 26600643]
[37]
Al-Jenoobi, F.I.; Al-Thukair, A.A.; Alam, M.A.; Abbas, F.A.; Al-Mohizea, A.M.; Alkharfy, K.M.; Al-Suwayeh, S.A. Effect of Trigonella foenum-graecum L. on metabolic activity of CYP2D6 and CYP3A4. Forsch. Komplement. Med., 2015, 22(3), 180-184.
[PMID: 26335391]
[38]
Al-Jenoobi, F.I.; Alam, M.A.; Alkharfy, K.M.; Al-Suwayeh, S.A.; Korashy, H.M.; Al-Mohizea, A.M.; Iqbal, M.; Ahad, A.; Raish, M. Pharmacokinetic interaction studies of fenugreek with CYP3A substrates cyclosporine and carbamazepine. Eur. J. Drug Metab. Pharmacokinet., 2014, 39(2), 147-153.
[http://dx.doi.org/10.1007/s13318-013-0149-6] [PMID: 24022709]
[39]
Al-Jenoobi, F.I.; Ahad, A.; Mahrous, G.M.; Al-Mohizea, A.M.; AlKharfy, K.M.; Al-Suwayeh, S.A. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs. Pharm. Biol., 2015, 53(2), 296-300.
[http://dx.doi.org/10.3109/13880209.2014.916312] [PMID: 25243874]
[40]
Alkharfy, K.M.; Al-Jenoobi, F.I.; Al-Mohizea, A.M.; Al-Suwayeh, S.A.; Khan, R.M.; Ahmad, A. Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin pharmacokinetics in beagle dogs. Phytother. Res., 2013, 27(12), 1800-1804.
[http://dx.doi.org/10.1002/ptr.4947] [PMID: 23401262]