Sains Malaysiana 51(4)(2022): 1143-1154
http://doi.org/10.17576/jsm-2022-5104-16
Drug-Herb Interactions: Selected
Antihypertensive Drugs with Moringa
oleifera Leaves Extract
(Interaksi Ubat-Herba: Ubat
Antihipertensi Terpilih dengan Ekstrak Daun Moringa oleifera)
ENDANG KUMOLOSASI, MANDY CHEONG LI
CHING, NURAINA ATHIRA AHMAD SALWANIZAM, NUR SHAMIZAH AINNA MUHAMMAD ESHAM,
QISTINA ALYANI AYOB, RAMAVISITHIRA RAMASAMY, HARISHANKARI GOVINDAN, ADYANI MD
REDZUAN & MALINA JASAMAI*
Drugs
& Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan
Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Federal Territory,
Malaysia
Received:
17 June 2021/Accepted: 27 August 2021
Abstract
Moringa oleifera is a local plant which is commonly
used in cooking and as a health supplement. It has been reported to possess
blood pressure (BP) lowering effect and little is known about its possible
interactions with cardiovascular drugs. This study looked into the possible
drug-herb interactions between M.
oleifera leaves extract and selected antihypertensive drugs. Ten groups of
spontaneously hypertensive rats (SHRs) and one group of normotensive rats (NTs)
were administered either M. oleifera extract alone, drugs alone or drugs in combination with M. oleifera extract for 14 days and BP of the rats were measured.
Angiotensin converting enzyme (ACE) activity was also determined in vitro and ex vivo. Treated groups were found to produce significant BP
reduction on day 15 when compared with the negative control but there was no
significance difference when compared with positive controls (drugs alone). M. oleifera extract administered alone
significantly reduced BP of SHRs on day 15 and this is comparable with the BP
reduction observed when antihypertensive drugs were administered alone.
However, no additive effect was observed when drugs were used in combination
with M. oleifera extract. Similar
results were seen in the in vitro and ex vivo ACE inhibitory activity of M. oleifera extract and enalapril. It
can be concluded that there is a possibility of drug-herb interaction between M. oleifera extract and the selected
antihypertensive drugs.
Keywords: ACE activity; antihypertensive drugs;
blood pressure; drug-herb interactions; Moringa
oleifera
Abstrak
Moringa oleifera ialah tumbuhan tempatan yang
biasanya digunakan dalam masakan dan sebagai makanan tambahan kesihatan. Ia
dilaporkan mempunyai kesan penurunan tekanan darah (TD), tetapi amat sedikit
yang diketahui jika ia mungkin berinteraksi dengan ubat kardiovaskular. Kajian
ini melihat jika terdapat interaksi antara ekstrak daun M. oleifera dengan ubat hipertensi terpilih. Sepuluh kumpulan tikus
hipertensi secara spontan (SHR) dan satu kumpulan tikus normotensif (NT) diberi
sama ada ekstrak M. oleifera sahaja,
ubat sahaja atau gabungan ubat dan ekstrak M.
oleifera selama 14 hari dan TD tikus tersebut diukur. Aktiviti enzim
pengubah-angiotensin (ACE) juga ditentukan secara in vitro dan ex vivo.
Kumpulan yang dirawat didapati menurunkan TD secara ketara pada hari ke-15 jika
dibandingkan dengan kawalan negatif tetapi tidak menunjukkan perbezaan yang
bererti jika dibandingkan dengan kawalan positif (ubat sahaja). Ekstrak M. oleifera sahaja dapat mengurangkan TD SHR secara bererti pada
hari ke-15 dan ini setanding dengan penurunan TD yang diperoleh daripada ubat
hipertensi sahaja. Walau bagaimanapun, tiada kesan tambahan yang diperoleh
apabila ubat diberi bersama ekstrak M.
oleifera. Hasil yang serupa dilihat dalam aktiviti perencatan ACE secara in vitro dan ex vivo oleh ekstrak M.
oleifera dan enalapril. Dengan ini dapat disimpulkan bahawa berkemungkinan
terdapat interaksi ubat-herba antara ekstrak M. oleifera dengan ubat antihipertensi terpilih. Mekanisme
terperinci mengenai interaksi yang berlaku perlu dikaji dengan lebih lanjut
untuk memastikan penggunaan ekstrak M.
oleifera bersama ubat antihipertensi adalah selamat.
Kata
kunci: Aktiviti ACE; interaksi
ubat-herba; Moringa oleifera; tekanan
darah; ubat antihipertensi
REFERENCES
Abdulazeez,
M.A. & Kurfi, B.G. 2016. Isolation, partial purification and
characterization of angiotensin converting enzyme from rat (Rattus norvegicus) lungs. Bayero Journal of Pure and Applied Sciences 9(2):
24-29.
Agbabiaka, T.B., Spencer, N.H. &
Goodman, C. 2018. Prevalence of drug-herb and drug-supplement interactions in
older adults: A cross-sectional survey. British
Journal of
General Practice 68(675): e711-e717.
Al Disi, S.S., Anwar, M.A. &
Eid, A.H. 2016. Anti-hypertensive herbs and their mechanisms of action: part
i. Frontiers
in Pharmacology 6: 323.
Alnaqeeb,
M., Mansor, K.A., Mallah, E.M., Ghanim, B.Y., Idkaidek, N. & Qinna, N.A.
2019. Critical pharmacokinetic and pharmacodynamic drug-herb interactions in
rats between warfarin and pomegranate peel or guava leaves extracts. BMC Complementary and Alternative Medicine 19: 29.
Angell, S.Y., De Cock, K.M. &
Frieden, T.R. 2015. A public health approach to global management of
hypertension. Lancet 385(9970):
825-827.
Anwar, F., Latif, S., Ashraf, M.
& Gilani, A.H. 2007. Moringa oleifera:
A food plant with multiple medicinal uses. Phytotherapy
Research 21(1): 17-25.
Asdaq,
S.M.B. & Inamdar, M.N. 2009. Interaction of propranolol with garlic in
biochemical and histological changes in rat. Iranian Journal of Pharmaceutical Research 8(3): 201-207.
Baxter,
K. 2010. Stockley’s Drug Interactions.
London: Pharmaceutical Press.
Brantley, S.J., Argikar, A.A., Lin,
Y.S., Nagar, S. & Paine, M.F. 2014. Herb-drug interactions: Challenges and
opportunities for improved predictions. Drug
Metabolism and Disposition 42(3): 301.
CDER. 2005. Pharmacology and Toxicology Guidance for Industry Estimating the
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult
Healthy Volunteers. U.S. Department of Health and Human Services Food and
Drug Administration: Center for Drug Evaluation and Research (CDER).
Colalto, C. 2010. Herbal
interactions on absorption of drugs: Mechanisms of action and clinical risk
assessment. Pharmacological Research 62(3):
207-227.
Coria-Téllez, A.V.,
Montalvo-Gónzalez, E., Yahia, E.M. & Obledo-Vázquez, E.N. 2018. Annona muricata: A comprehensive review
on its traditional medicinal uses, phytochemicals, pharmacological activities,
mechanisms of action and toxicity. Arabian
Journal of Chemistry 11(5): 662-691.
Dangi, S.Y., Jolly, C.I. &
Narayanan, S. 2008. Antihypertensive activity of the total alkaloids from the leaves
of Moringa oleifera. Pharmaceutical Biology 40(2): 144-148.
D'arcy, P.F., Mcelnay, J.C. &
Welling, P.G. 2012. Mechanisms of Drug
Interactions. Berlin: Springer Science & Business Media.
Daugherty, A., Rateri, D., Hong, L.
& Balakrishnan, A. 2009. Measuring blood pressure in mice using volume
pressure recording, a tail-cuff method. Journal
of Visualized Experiments 27: 1291.
Dzau, V.J., Bernstein, K.,
Celermajer, D., Cohen, J., Dahlöf, B., Deanfield, J., Diez, J. & Drexler,
H. 2002. Pathophysiologic and therapeutic importance of tissue ACE: Aconsensus
report. Cardiovascular Drugs and Therapy 16(2): 149-160.
Faizi, S., Siddiqui, B.S., Saleem,
R., Siddiqui, S., Aftab, K. & Gilani, A.U.H. 1995. Fully acetylated
carbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry 8(4): 957-963.
Forouzanfar, M.H., Liu, P., Roth,
G.A., Ng, M., Biryukov, S., Marczak, L., Lily Alexander, L., Estep, K., Hassen
Abate, K., Akinyemiju, T.F., Ali, R., Alvis-Guzman, N., Azzopardi, P.,
Banerjee, A., Bärnighausen, T., Basu, A., Bekele, T. & Bennett, D.A. 2017.
Global burden of hypertension and systolic blood pressure of at least 110 to
115 mm Hg. Journal of American Medical
Association 317(2): 165-182.
Gilani, A.H., Aftab, K., Suria, A.,
Siddiqui, S., Salem, R., Siddiqui, B.S. & Faizi, S. 1994. Pharmacological studies
on hypotensive and spasmolytic activities of pure compounds from Moringa oleifera. Phytotherapy Research 8(2): 87-91.
Izzo, A.A., Sung, H.K.,
Radhakrishnan, R. & Williamson, E.M. 2016. A critical approach to evaluating
clinical efficacy, adverse events and drug interactions of herbal remedies. Phytotherapy Research 30(5): 691-700.
Kearney, P.M., Whelton, M.,
Reynolds, K., Muntner, P., Whelton, P.K. & He, J. 2005. Global burden of hypertension:
Analysis of worldwide data. Lancet 365(9455): 217-223.
Koe, X.F., Tengku Muhammad, T.S.,
Chong, A.S.C., Abdul Wahab, H. & Tan, M.L. 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 Science
& Nutrition 2(5): 500-520.
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. Journal of Pharmaceutical and Biomedical Analysis 88: 130-135.
Li, Y., Revalde, J. & Paxton,
J.W. 2017. The effects of dietary and herbal phytochemicals on drug
transporters. Advanced Drug Delivery Reviews 116: 45-62.
Lima, C.C., Lemos, R.P.L. &
Conserva, L.M. 2014. Dilleniaceae family: An overview of its ethnomedicinal
uses, biological and phytochemical profile. Journal
of Pharmacognosy and Phytochemistry 3(2): 181-204.
Mamindla, S., Prasad, K.V.S.R.G.
& Koganti, B. 2016. Herb-drug interactions: An overview of mechanisms and
clinical aspects. International Journal
Pharmaceutical Sciences and Research 7(9): 3576-586.
Muhammad, S.A. & Fatima, N.
2015. In silico analysis and
molecular docking studies of potential angiotensin-converting enzyme inhibitor
using quercetin glycosides. Pharmacognosy
Magazine 11(1): S123-S126.
Nakamura, Y., Yamamoto, N., Sakai,
K., Okubo, A., Yamazaki, S. & Takano, T. 1995. Purification and
characterization of angiotensin I-converting enzyme inhibitors from sour milk. Journal of Dairy Science 78(4): 777-783.
Oboh, G., Ademosun, A., Oyetomi, O.
& Adewuni, T. 2018. Influence of Moringa (Moringa oleifera) leaf extracts
on the antioxidant and angiotensin-1 converting enzyme inhibitory properties of
lisinopril. Oriental Pharmacy and
Experimental Medicine 18(4): 317-324.
Oboh, G., Ademiluyi, A.O., Ademosun,
A.O., Olasehinde, T.A., Oyeleye, S.I., Boligon, A.A. & Athayde, M.L. 2015.
Phenolic extract from Moringa oleifera leaves inhibits key enzymes linked to erectile dysfunction and oxidative stress
in rats penile tissues. Biochemistry
Research International 2015: 175950.
O'brien, E. 2017. The lancet
commission on hypertension: Addressing the global burden of raised blood
pressure on current and future generations. Journal
of Clinical Hypertension 19(6): 564-568.
Olawoye, O.S., Adeagbo, B.A. &
Bolaji, O.O. 2017. Effects of Moringa
oleifera leaf powder suspension on the pharmacokinetics of amodiaquine in
rats. Journal of Complementary and
Alternative Medical Research 3(4): 1-8.
Peng, C.C., Glassman, P.A., Trilli,
L.E., Hayes-Hunter, J. & Good, C.B. 2004. Incidence and severity of
potential drug–dietary supplement interactions in primary care patients an exploratory
study of 2 outpatient practices. Archives
of Internal Medicine 164(6): 630-636.
Posadzki, P., Watson, L. &
Ernst, E. 2013. Herb–drug interactions: An overview of systematic reviews. British Journal of Clinical Pharmacology 75(3): 603-618.
Rathi, B., Bodhankar, S. &
Baheti, A. 2006. Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats. Indian Journal of Experimental Biology 44(11):
898-901.
Ray, K., Hazra, R. & Guha, D.
2003. Central inhibitory effect of Moringa
oleifera root extract: Possible role of neurotransmitters. Indian Journal of Experimental Biology 41(11): 1279-1284.
Rodríguez-Fragoso, L.,
Martínez-Arismendi, J.L., Orozco-Bustos, D., Reyes-Esparza, J., Torres, E.
& Burchiel, S.W. 2011. Potential risks resulting from fruit/vegetable-drug interactions:
Effects on drug-metabolizing enzymes and drug transporters. Journal of Food Science 76(4):
R112-R124.
Saputri, F.C., Mun’im, A., Lukmanto,
D., Aisyah, S.N. & Rinandy, J.S 2015. Inhibition of angiotensin converting
enzyme (ACE) activity by some Indonesia edible plants. International Journal of Pharmaceutical Sciences and Research 6(3):
1054-1059.
Stohs, S.J. & Hartman, M.J.
2015. Review of the safety and efficacy of Moringa
oleifera. Phytotherapy Research 29(6): 796-804.
Tahkur, R.S., Soren, G., Pathapati,
R.M. & Buchineni, M. 2016. Diuretic activity of Moringa oleifera leaves extract in Swiss albino rats. The Pharma Innovation International Journal 5(3):
8-10.
Tarirai, C., Viljoen, A.M. &
Hamman, J.H. 2010. Herb–drug pharmacokinetic interactions reviewed. Expert Opinion in Drug Metabolism &
Toxicology 6(12): 1515-1538.
Teh,
X.R., Lim, M.T., Tong, S.F., Husin, M., Khamis, N. & Sivasampu, S. 2020.
Quality of hypertension management in public primary care clinics in Malaysia:
An update. PLoS ONE 15(8): 1-14.
Verbeeck, R.K., Kanfer, I.,
Löbenberg, R., Abrahamsson, B., Cristofoletti, R., Groot, D.W., Langguth, P.,
Polli, J.E., Parr, A., Shah, V.P., Mehta, M. & Dressman, J.B. 2017. Biowaiver
monographs for immediate release solid oral dosage forms: Enalapril. Journal of Pharmaceutical Sciences 106(8): 1933-1943.
Vij, T. & Prashar, Y. 2015. A
review on medicinal properties of Carica
papaya Linn. Asian Pacific Journal of
Tropical Diseases 5(1): 1-6.
Vongsak, B., Sithisarn, P.,
Mangmool, S., Thongpraditchote, 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. Industrial
Crops and Products 44: 566-571.
Wang,
X.D., Li, J.L., Lu, Y., Chen, X., Huang, M., Chowbay, B. & Zhou, S.F. 2007.
Rapid and simultaneous determination of nifedipine and dehydronifedipine in
human plasma by liquid chromatography–tandem mass spectrometry: Application to
a clinical herb-drug interaction study. Journal
of Chromatography B 852(1-2): 534-544.
*Corresponding
author; email: malina@ukm.edu.my
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