In silico analysis of antihypertensive and hepatotoxicity potential of the n-butanol fraction of the methanol extract of of cantaloupe (Cucumis melo var. cantalupensis)

  • Dian Laila Purwaningroom Faculty of Health Sciences, Universitas Muhammadiyah Ponorogo, Jawa Timur
  • Dianita Rifqia Putri Faculty of Health Sciences, Universitas Muhammadiyah Ponorogo, Jawa Timur
  • Galuh Wening Permatasari Indonesian Research Institute for Biotechnology and Bioindustry, Bogor
Keywords: in silico, antihypertensive, hepatotoxicity, cantaloupe

Abstract

Latar belakang: Hipertensi merupakan faktor risiko utama penyakit kardiovaskular. Penduduk Indonesia cenderung mengkonsumsi herbal dalam terapi hipertensi dalam mempertahankan kadar tekanan darah seperti buah blewah (Cucumis melo var. cantalupensis). Namun mekanisme kerja buah blewah dalam menurunkan tekanan darah, dan potensi toksisitasnya jika dikonsumsi dalam jangka panjang masih belum jelas. Tujuan studi ini adalah untuk menganalisis mekanisme antihipertensi dari buah blewah dan potensi toksiknya melalui pendekatan in silico.

Metode: Bubuk blewah kering dimaserasi menggunakan metanol absolut, difraksinasi menggunakan n-butanol. Uji fitokimia dilakukan dengan metode LC-MS, kemudian senyawa bioaktif ditelusuri hingga SMILESnya di PubChem. Analisis QSAR untuk analisis potensi antihipertensi dilakukan dengan PASS server. Kelas toksisitas dan potensi hepatotoksisitas dianalisis menggunakan ProTox-II, dilanjutkan dengan analisis networking menggunakan STITCH dan STRINGdb.

Hasil: Setidaknya terdapat 434 jenis senyawa yang terdapat pada fraksi n-butanol dari ekstrak metanol buah blewah (FBEMB). Berdasarkan analisis STITCH dan STRINGdb, FBEMB dapat bekerja dalam menurunkan tekanan darah melalui mekanisme aksi seperti senyawa amlodipine, yang menstabilkan saluran kalsium tipe-L yang terisi tegangan dalam konformasi tidak aktifnya. Dengan demikian, mencegah kontraksi myocyte yang bergantung pada kalsium dan vasokonstriksi. FBEMB mungkin berpotensi hepatotoksik melalui mekanisme kerja senyawa seperti itrakonazol yang menghambat enzim sitokrom P450 yang mempengaruhi gangguan pada sintesis ergosterol, dan efavirenz yang memiliki efek neurotoksik. Penghambatan sitokrom P450 dapat menyebabkan toksisitas obat dan kerusakan hati.

Kesimpulan: FBEMB dapat bekerja dalam menurunkan tekanan darah melalui mekanisme penstabilan saluran kalsium tipe-L yang terisi tegangan dalam konformasi tidak aktifnya.

Kata kunci: in silico, antihipertensi, hepatotoksisitas, blewah

 

Abstract

Background: Hypertension is a major cardiovascular disease risk factor. Indonesian people tend to consume herbal medicine to maintain hypertension therapy, i.e cantaloupe (Cucumis melo var. cantalupensis). However, the mechanism of action of cantaloupe in lowering blood pressure and toxicity potential for long term consumption is unclear. The study aimed to analyze the antihypertensive mechanism of cantaloupe and its toxic potential through the in silico.

Methods: The dried cantaloupe powder was macerated using absolute methanol, then fractionated using n-butanol. The phytochemical test was done by LC-MS method, then the bioactive compounds were traced to their SMILES in the PubChem. The QSAR analysis of the antihypertensive potential was done using the PASS server. The toxicity class and hepatotoxicity potential were analyzed using ProTox-II, followed by networking analysis using STITCH and STRINGdb.

Results: At least 434 types of compounds were shown in the n-butanol fraction of the methanol extract of cantaloupe (BFMEC). Based on the networking analysis, BFMEC may work in lowering blood pressure through the action mechanism of the amlodipine compound-like, which stabilizes voltage-gated L-type calcium channels in an inactive conformation, thus, prevents calcium-dependent myocyte contraction and vasoconstriction. BFMEC presumably has hepatotoxic through the action mechanism of itraconazole compound-like inhibited cytochrome P450-dependent enzymes, affecting the impairment of ergosterol synthesis, and efavirenz which has neurotoxic effects. The inhibition of cytochrome P450 may cause drug toxicity and liver damage.

Conclusion: BFMEC may work in lowering blood pressure through the action mechanism which stabilizes voltage-gated L-type calcium channels in an inactive conformation.

Keywords: in silico, antihypertensive, hepatotoxicity, cantaloupe

 

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Published
2020-12-23
How to Cite
Purwaningroom, D., Putri, D., & Permatasari, G. (2020). In silico analysis of antihypertensive and hepatotoxicity potential of the n-butanol fraction of the methanol extract of of cantaloupe (Cucumis melo var. cantalupensis). Health Science Journal of Indonesia, 11(2), 106-114. https://doi.org/10.22435/hsji.v11i2.3629
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Articles