Sains Malaysiana 53(4)(2024): 795-805

http://doi.org/10.17576/jsm-2024-5304-06

Novel Blood Pressure-Lowering Effect of Spathulenol in Rats

(Kesan Penurunan Tekanan Darah Novel Spathulenol pada Tikus)

RASLAN AIN-FATIN¹, YEE YONG MEI¹, HOE SEE ZIAU², ONG HOOI TIN¹ & LAM SAU KUEN^1,*

¹Department of Pre-clinical Science, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Bandar Sungai Long, 43000 Kajang, Selangor, Malaysia

² Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

Diserahkan: 14 September 2023/Diterima: 27 Februari 2024

Abstract

In recent years, natural compounds from plant sources are sought after as alternative anti-hypertensive treatments. Spathulenol (Spa), a terpenoid plant metabolite obtained mainly from the Origanum species has shown anecdotal evidence of blood pressure (BP)-lowering properties probably through the effects on vasoreactivity. This study aimed to investigate the BP-lowering activities of Spa in vivo as well as to ascertain the mechanisms of action in vitro. Male Sprague-Dawley (SD) rats (n=16) and spontaneously hypertensive rats (SHR) (n=16) with their normotensive Wistar-Kyoto (WKY) rats (n=16) as controls were subjected to anaesthesia and administered intravenous boluses of Spa at 0.0, 0.045, 0.90, 0.18, 0.36, and 0.7 mg/kg or positive control losartan at 0.0, 0.6, 1.2, 1.8, 2.4 and 3.0 mg/kg. The BP and heart rate (HR) of the rats were recorded by a computerised physiographical system (Power Lab) through carotid arterial cannulation that was connected to a pressure transducer. The data were analysed by using the Lab Chart 6 software. Spathulenol was also tested for angiotensin-converting enzyme (ACE) inhibitory activity by using the ACE1 inhibitor screening kit (PromoKine). Spathulenol was able to decrease the BP of rats in a dose-dependent manner with the BP-lowering effect being significantly (p < 0.05) higher in the SHRs than in the WKY controls. Furthermore, Spa was able to inhibit the ACE activity suggesting the possibility that this could be one of the mechanisms underlying the observed BP-lowering effect.

Keywords: Angiotensin-converting enzyme inhibition; blood pressure; Spathulenol; spontaneously hypertensive rats; Wistar-Kyoto rats

Abstrak

Dalam beberapa tahun kebelakangan ini, sebatian semula jadi daripada sumber tumbuhan telah didekati sebagai salah satu bentuk untuk rawatan anti-hipertensif. Spathulenol (Spa), metabolit tumbuhan terpenoid yang diperoleh terutamanya daripada spesies Origanum telah menunjukkan bukti anekdot tentang sifat menurunkan tekanan darah mungkin melalui kesan ke atas vasoreaktiviti. Oleh itu, penyelidikan ini dilakukan untuk mengkaji aktiviti penurunan tekanan darah Spa secara in vivo serta memastikan mekanisme tindakan secara in vitro. Tikus jantan Sprague-Dawley (SD) (n=16), tikus hipertensi spontan (SHR) (n=16) dan tikus Wistar-Kyoto (WKY) (n=16) sebagai kawalan normotensif telah diletakkan di bawah anestesia dan diberikan bolus intravena Spa sebanyak 0.0, 0.045, 0.90, 0.18, 0.36 dan 0.7 mg/kg atau kontrol positif losartan sebanyak 0.0, 0.6, 1.2, 1.8, 2.4 dan 3.0 mg/kg. Tekanan darah dan kadar denyutan jantung tikus direkodkan oleh sistem fisiografi berkomputer (PowerLab) melalui kanulasi arteri karotid yang disambungkan kepada transduser tekanan. Data dianalisis menggunakan perisian LabChart 6. Spathulenol juga telah diuji untuk aktiviti perencatan enzim penukar angiotensin (ACE) menggunakan kit pemeriksaan perencat ACE1 (PromoKine). Spathulenol didapati dapat mengurangkan tekanan darah tikus dalam cara yang bergantung kepada dos dengan kesan penurunan tekanan darah secara signifikan (p < 0.05) lebih tinggi dalam SHR berbanding kawalan WKY. Tambahan pula, Spa dapat merencat aktiviti ACE yang menunjukkan kemungkinan bahawa ini boleh menjadi salah satu mekanisme yang mendasari kesan penurunan tekanan darah yang diperhatikan.

Kata kunci: Perencatan enzim penukar angiotensin; Spathulenol; tekanan darah; tikus hipertensi spontan; tikus Wistar-Kyoto

RUJUKAN

Al-Akwaa, A.A., Asmawi, M.Z., Dewa, A. & Mahmud, R. 2020. Antihypertensive activity and vascular reactivity mechanisms of Vitex pubescens leaf extracts in spontaneously hypertensive rats. Heliyon 6(7): e04588. https://doi.org/10.1016/j.heliyon.2020.e04588

Antlanger, M., Bernhofer, S., Kovarik, J.J., Kopecky, C., Kaltenecker, C.C., Domenig, O., Poglitsch, M. & Säemann, M.D. 2017. Effects of direct renin inhibition versus angiotensin II receptor blockade on angiotensin profiles in non-diabetic chronic kidney disease. Annals of Medicine 49(6): 525-533.

Dib, I., Fauconnier, M.L., Sindic, M., Belmekki, F., Assaidi, A., Berrabah, M., Mekhfi, H., Aziz, M., Legssyer, A., Bnouham, M. & Ziyyat, A. 2017. Chemical composition, vasorelaxant, antioxidant and antiplatelet effects of essential oil of Artemisia campestris L. from Oriental Morocco. BMC Complementary and Alternative Medicine 17(1): 82. https://doi.org/10.1186/s12906-017-1598-2

do Nascimento, K.F., Moreira, F.M.F., Alencar Santos, J., Kassuya, C.A.L., Croda, J.H.R., Cardoso, C.A.L., Vieira, M.D.C., Góis Ruiz, A.L.T., Ann Foglio, M., de Carvalho, J.E. & Formagio, A.S.N. 2018. Antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of Psidium guineense Sw. and spathulenol. Journal of Ethnopharmacology 210: 351-358. https://doi.org/10.1016/j.jep.2017.08.030

Jackson, R.E. & Bellamy, M.C. 2015. Antihypertensive drugs. BJA Education 15(6): 280-285.

Jamalzadeh, L., Ghafoori, H., Sariri, R., Rabuti, H., Nasirzade, J., Hasani, H. & Aghamaali, M.R. 2016. Cytotoxic effects of some common organic solvents on MCF-7, RAW-264.7 and human umbilical vein endothelial cells. Avicenna J. Med. Biochem. 4(1): e33453. https://doi.org/10.17795/ajmb-33453

Joshi, D.R. & Adhikari, N. 2019. An overview on common organic solvents and their toxicity. Journal of Pharmaceutical Research International 28(3): 1-18. https://doi.org/10.9734/jpri/2019/v28i330203

Khalil, H. & Zeltser, R. 2023. Antihypertensive medications. In StatPearls [Internet]. Treasure Island: (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554579/

Kollerup Madsen, B., Hilscher, M., Zetner, D. & Rosenberg, J. 2018. Adverse reactions of dimethyl sulfoxide in humans: A systematic review. F1000Research 7: 1746. https://doi.org/10.12688/f1000research.16642.2

Lareb. 2015. ACE inhibitor-associated hallucinations. Reactions Weekly 1543(1). doi:10.1007/s40278-015-8625-1

Lin, H.T., Shiou, Y.L., Jhuang, W.J. & Lee, H.C. 2019. Simultaneous electrocardiography recording and invasive blood pressure measurement in rats. Journal of Visualized Experiments (143). 10.3791/59115. https://doi.org/10.3791/59115

Malik, J.A., Siddiqui, W.A. & Zafar, S. 2016. Comparison between the effects of captopril and lisinopril on bradykinin-induced contraction in tracheal smooth muscle of guinea pig. Pakistan Journal of Medical and Health Sciences 10(3): 841-845.

Mulla, S. & Siddiqui, W.J. 2022. Losartan. In StatPearls [Internet]. Treasure Island: (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK526065/

Perez-Hernandez, N., Ponce-Monter, H., Medina, J.A. & Joseph-Nathan, P. 2008. Spasmolytic effect of constituents from Lepechinia caulescens on rat uterus. Journal of Ethnopharmacology 115(1): 30-35. https://doi.org/10.1016/j.jep.2007.08.044

Silverman, J., Macy, J. & Preisig, P.A. 2017. The role of the IACUC in ensuring research reproducibility. Lab Animal 46(4): 129-135.

Suručić, R., Kundaković, T., Lakušić, B., Drakul, D., Milovanović, S.R. & Kovačević, N. 2017. Variations in chemical composition, vasorelaxant and angiotensin I-converting enzyme inhibitory activities of essential oil from aerial parts of Seseli pallasii besser (Apiaceae). Chemistry & Biodiversity 14(5). https://doi.org/10.1002/cbdv.201600407

Whelton, P., Carey, R., Aronow, W. et al. 2017 ACC/ AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/ NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the Am erican College of Cardiology 71(19): e127–e248. https://doi.org/10.1016/j.jacc.2017.11.006

World Health Organization: WHO & World Health Organization: WHO. (2023 March 16). Hypertension. https://www.who.int/news-room/fact-sheets/detail/ hypertension

*Pengarang untuk surat-menyurat; email: lamsk@utar.edu.my