Studi In Silico Profil ADME dan Drug-Likeness Senyawa Bioaktif Pegagan (Centella asiatica L.) terhadap Potensi Terapi Alzheimer
DOI:
https://doi.org/10.29313/bcsp.v6i2.25682Keywords:
Alzheimer, Centella asiatica, Network pharmacologyAbstract
Abstract. Alzheimer’s disease is a complex neurodegenerative disorder involving several pathological mechanisms, including β-amyloid accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, neuronal apoptosis, and impaired signal transduction. Pegagan (Centella asiatica L.) contains bioactive compounds that are considered to have neuroprotective potential. This study aimed to analyze the potential of active compounds from Centella asiatica against Alzheimer’s disease using network pharmacology and molecular docking approaches. Compound data were collected from KNApSAcK, IMPPAT, and NPASS databases, followed by analysis using PubChem, SwissADME, SwissTargetPrediction, GeneCards, STRING, Cytoscape, CytoHubba, and molecular docking. A total of 160 bioactive compounds were obtained, and 31 compounds met the criteria for drug-likeness, bioavailability, and blood-brain barrier permeability. Target prediction of selected compounds identified 528 proteins, while Alzheimer’s disease-related targets from GeneCards consisted of 15,256 proteins, resulting in 431 overlapping targets. Further analysis identified PIK3CA, PIK3CB, PIK3CD, JAK2, and PTPN11 as the main protein targets. Molecular docking results showed that Mol29, namely Phaseollinisoflavan, had the best affinity toward PTPN11 with a binding affinity value of -9,13 kcal/mol. These results suggest that Centella asiatica has potential as an Alzheimer’s disease therapy candidate through multitarget and multipathway mechanisms based on in silico analysis.
Abstrak. Penyakit Alzheimer merupakan gangguan neurodegeneratif kompleks yang melibatkan berbagai mekanisme patologis, seperti akumulasi β-amiloid, hiperfosforilasi tau, stres oksidatif, neuroinflamasi, apoptosis neuron, dan gangguan transduksi sinyal. Pegagan (Centella asiatica L.) diketahui memiliki senyawa bioaktif yang berpotensi memberikan aktivitas neuroprotektif. Penelitian ini bertujuan untuk menganalisis potensi senyawa aktif Centella asiatica terhadap penyakit Alzheimer menggunakan pendekatan network pharmacology dan molecular docking. Data senyawa diperoleh dari basis data KNApSAcK, IMPPAT, dan NPASS, kemudian dianalisis menggunakan PubChem, SwissADME, SwissTargetPrediction, GeneCards, STRING, Cytoscape, CytoHubba, dan molecular docking. Hasil pengumpulan data memperoleh 160 senyawa bioaktif, dengan 31 senyawa yang memenuhi kriteria drug-likeness, bioavailabilitas, dan kemampuan menembus blood-brain barrier. Prediksi target senyawa menghasilkan 528 protein, sedangkan target Alzheimer dari GeneCards memperoleh 15.256 protein, dengan 431 protein irisan. Analisis lebih lanjut mengidentifikasi PIK3CA, PIK3CB, PIK3CD, JAK2, dan PTPN11 sebagai target utama. Hasil molecular docking menunjukkan bahwa Mol29, yaitu Phaseollinisoflavan, memiliki afinitas terbaik terhadap PTPN11 dengan nilai binding affinity -9,13 kcal/mol. Hasil penelitian menunjukkan bahwa Centella asiatica berpotensi sebagai kandidat terapi Alzheimer melalui mekanisme multitarget dan multipathway secara in silico.
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