Sains Malaysiana 50(9)(2021): 2687-2700

http://doi.org/10.17576/jsm-2021-5009-16

Cardiac Depressant and Vasodialatory Effect of Flaxseed - Basis for the Medicinal Use in Hypertension

(Tekanan Jantung dan Kesan Kevasokembangan Biji Rami - Asas untuk Penggunaan Ubatan dalam Tekanan Darah Tinggi)

AMBER HANIF PALLA^1,3, NAJEEB UR REHMAN*², HASAN SALMAN SIDDIQI³, ANWAR-UL-HASSAN GILANI⁴, BINA SHAHEEN SIDDIQUI⁵, MAIMOONA ILYAS⁵ & SOBIYA PERWAIZ^5,6

¹Faculty of Pharmacy, Department of Basic Medical Sciences, Salim Habib University (formerly Barrett Hodgson University), Karachi, Pakistan

²Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia

³Department of Biological and Biomedical Sciences, The Aga Khan University Hospital and Medical College, Karachi, Pakistan

⁴The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan

⁵H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, Sindh 75270, Pakistan

⁶Federal Urdu University, Karachi

Received: 4 October 2020/Accepted: 26 January 2021

ABSTRACT

Linum usitatissimum (Flaxseed) is known to be traditionally used for managing hypertension. In this study, we aim to provide a mechanistic basis for the medicinal use of Flaxseed in hypertension. The high-performance liquid chromatography (HPLC) analysis that we carried out during our study showed the presence of polar compounds (quercetin, nicotinic acid, and nicotinamide) in Flaxseed’s crude extract (Fs.Cr; aqueous methanolic). In anesthetized rats, Fs.Cr reduced arterial blood pressure (BP) dose-dependently (10-100 mg/kg). When tested for its mechanism of action ex vivo, Fs.Cr inhibited both the force and rate of spontaneous contractions in the dose range of 1-10 mg/mL in isolated guinea-pig atria, similar to how verapamil, a standard Ca⁺² channel blocker does it. Further, Fs.Cr showed vasodilator effect against the contractions induced by phenylephrine (PE, 1 μM) in rat aortic ring preparations (concentration range: 1-10 mg/mL), whereas no effect was observed against the contractions induced by low K⁺ (25 mM) as well as high K⁺ (80 mM). This selective inhibitory effect of Fs.Cr against PE was tested for endothelium-dependent nitric oxide (NO) and/or cholinergic component involvement. The vasodilator effect of Fs.Cr against PE was retested in the absence and presence of atropine in endothelium (E)-intact and E-denuded aorta, but no significant shift was observed in the inhibitory effect of Fs.Cr. Further, Fs.Cr shifted the PE-induced concentration-response curves (CRCs) to the right in a dose-dependent manner (1 and 3 mg/mL). This effect was similar to that of prazosin. All these findings indicate that Flaxseed may mediate its antihypertensive activity by the alpha-1 receptor antagonist and Ca⁺² channel blocking-like activity, which may account for its efficacy in hypertension.

Keywords: Alpha-1 Receptor antagonist; aorta; atria; Flaxseed; hypertension; vasodilator

ABSTRACT

Linum usitatissimum (Biji rami) diketahui secara tradisi digunakan untuk mengawal tekanan darah tinggi. Tujuan kajian ini adalah untuk memberikan dasar mekanistik penggunaan Biji rami dalam tekanan darah tinggi. Analisis kromatografi cecair berprestasi tinggi (HPLC) yang kami jalankan menunjukkan adanya sebatian polar (quersetin, asid nikotinik dan nikotinamida) dalam ekstrak kasar Biji rami (Fs.Cr; metanolik berair). Pada tikus yang dibius, Fs.Cr mengurangkan tekanan darah arteri (BP) bergantung pada dos (10-100 mg/kg). Semasa diuji untuk mekanisme tindakannya ex vivo, Fs.Cr menghalang kekuatan dan kadar kontraksi spontan dalam julat dos 1-10 mg/mL di atria tikus belanda yang terpencil, serupa dengan bagaimana verapamil, Ca⁺² standard penyekat saluran melakukannya. Selanjutnya, Fs.Cr menunjukkan kesan pemvasokembang terhadap kontraksi yang disebabkan oleh fenilefrina (PE, 1 μM) pada persiapan cincin aorta tikus (julat kepekatan: 1-10 mg/mL), sedangkan tidak ada kesan yang diamati terhadap kontraksi yang disebabkan oleh K⁺ rendah (25 mM) serta tinggi K⁺ (80 mM). Kesan penghambatan selektif Fs.Cr terhadap PE diuji untuk penglibatan komponen nitrat oksida (NO) dan/atau kolinergik yang bergantung pada endotelium. Kesan kevasokembangan Fs.Cr terhadap PE diuji semula dengan ketiadaan dan kehadiran atropin dalam aorta endotelium (E)-intact dan E-denuded, tetapi tidak ada perubahan yang ketara dalam kesan penghambatan Fs.Cr. Selanjutnya, Fs.Cr mengalihkan lengkung tindak balas kepekatan yang disebabkan oleh PE (CRC) ke kanan dengan cara yang bergantung pada dos (1 dan 3 mg/mL). Kesan ini serupa dengan prazosin. Semua penemuan ini menunjukkan bahawa Biji rami dapat memediasi aktiviti antihipertensi oleh antagonis reseptor alfa-1 dan aktiviti seperti penyekat saluran Ca⁺², yang mungkin menyumbang kepada keberkesanannya dalam hipertensi.

Kata kunci: Antagonis reseptor alfa-1; aorta; atria; Biji rami; kevasokembangan; tekanan darah tinggi

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*Corresponding author; email: n_rehman5@hotmail.com