Antihypertensive Activity Profile of Bangkirai Leaves (Shorea laevis Ridl.) Ethanol Extract on Angiotensin II (4ZUD) and β-Adrenergic (6PS5) Receptors

Penulis

DOI:

https://doi.org/10.32382/mf.v20i2.994

Kata Kunci:

Bangkirai leaves, Antihypertensive Activity, Angiotensin II Receptors, β-Adrenergic Receptors

Abstrak

Profil Aktivitas Antihipertensi Ekstrak Etanol Daun Bangkirai (Shorea laevis Ridl.) Pada Reseptor Angiotensin II (4ZUD) dan β-Adrenergic (6PS5)

Hipertensi merupakan gangguan sistem kardiovaskular yang ditandai dengan tekanan sistolik ≥ 140mmHg dan diastolik ≥ 90mmHg. Kenaikan tekanan darah tersebut dikarenakan adanya mekanisme dari reseptor angiotensin II dan β-adrenergik, sehingga dalam pengembangan obat untuk hipertensi diperlukan senyawa dalam penghambatan aktivasi angiotensin I menjadi angiotensin II, serta pada β-adrenergik. Kalimantan, Indonesia memiliki keanekaragaman hayati yang berpotensi sebagai obat seperti Bangkirai (Shorea laevis Ridl.). Berdasarkan penelitian sebelumnya mengenai metabolit sekunder telah teridentifikasi berbagai senyawa yang berpotensi sebagai calon obat baru, misalnya sebagai antihipertensi. Penelitian ini bertujuan untuk mengetahui profil farmakologi dan mekanisme inhibisi angiotensin I pada reseptor 4ZUD serta inhibisi β-adrenergik pada reseptor 6PS5, dari ekstrak etanol daun bangkirai dengan cara melakukan molecular docking yang diawali dengan beberapa tahapan antara lain preparasi dan optimasi struktur senyawa uji serta preparasi struktur 3D reseptor 4ZUD dan 6PS5. Untuk mengetahui kebenaran metode maka dilakukan validasi terhadap senyawa ligand olmesartan untuk 4ZUD dan ligand propranolol untuk 6PS5. Berdasarkan penelitian yang telah dilakukan pada kedua reseptor diperoleh hasil untuk senyawa uji berupa MolDockScore, profil farmakologi absorbsi, distribusi, metabolisme, ekskresi serta toksisitas. Hasil MolDockScore menunjukkan bahwa senyawa Colchicine,N-desacetyl-N-[4-hydroxy-3,5-dimethoxycinnamoyl] memiliki nilai paling rendah yakni -146.503 pada reseptor 4ZUD dan -129.718 pada reseptor 6PS5 yang mendekati nilai ligan alami dibandingkan senyawa metabolit lainnya. Selain itu juga memberikan hasil yang baik berdasarkan profil farmakologi pada reseptor 4ZUD & 6PS5 antara lain HIA (95,73%), Caco2 (35.14nm/detik) dan PPB (87.67%).  Hasil uji negatif juga ditunjukkan pada profil toksisitas mutagenik (Ames Test Method), non-mutagenik dan uji karsinogenik yang meliputi genotoksik dan nongenotoksik.

Hypertensive is a cardiovascular system disorder characterized by systolic pressure ≥ 140mmHg and diastolic ≥ 90mmHg. The increase in blod pressure is due to the mechanism of angiotensin II and β-adrenergic receptors, so in developing medicine for hypertension, compounds are needed to inhibit the activation of angiotensin II to angiotensin II, as well as β-adrenergic. Kalimantan, Indonesia has a biodiversity that has the potential as medicine such as Bangkirai (Shorea laevis Ridl.). Based on previous research on secondary metabolites, various compounds have been identified that have potential as new drug candidates, for example as antihypertensive. This study aims to determine the pharmacological profile and mechanism of angiotensin I inhibition at the 4ZUD and β-adrenergic receptors inhibition at the 6PS5 receptor, from ethanol extract of bangkirai leaves by carrying out molecular docking which begins with several stages including preparation and optimization of the structure of the test compound and structure preparation of 3D receptors 4ZUD and 6PS5. To find out the correctness of the method, validation was carried out on the Olmesartan ligand compound for 4ZUD and the propranolol ligand for 6PS5. Based on research carried out on both receptors, results were obtained for the test compounds in the form of MolDockScore, the pharmacological profile of absorption, distribution, metabolism, excretion, and toxicity. MolDockScore results show that the compound Colchicine, N-desacetyl-N-[4-hydroxy-3,5-dimethoxycinnamoyl] has the lowest values, namely -146.503 at the 4ZUD receptor dan -129.718 at the 6PS5 receptor, which is close to the natural ligand value compared to other metabolite compounds.  Apart from that, it also provides good results based on the pharmacological profile of the 4ZUD and 6PS5 receptors including HIA (95.73%), Caco2 (35.14nm/second), and PPB (87.67%). Negative test results are also shown in the mutagenic toxicity profile (Ames Test Method), non-mutagenic, and carcinogenic tests which include genotoxic and nongenotoxic.

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Unduhan

Diterbitkan

31-10-2024

Terbitan

Bagian

Terbitan Oktober 2024