Penelusuran mekanisme aksi sambiloto (Andrographis paniculata (Burm.F) Nees) sebagai antidiabetes berdasarkan profil sidik jari kimiawi, network pharmacology dan molecular docking

IZATUNNAFIS, Dr. B.S. Ari Sudarmanto, M.Si.; Dr.rer.nat. apt. Yosi Bayu Murti, M.Si.

2023 | Tesis | S2 Ilmu Farmasi

Penelitian sebelumnya menyatakan bahwa herba sambiloto (Andrographis paniculata (Burm. F.) Nees) memiliki aktivitas anti diabetes, namun belum ada studi yang komprehensif mengenai zat aktif dan mekanismenya. Penelitian ini bertujuan untuk menelusuri mekanisme anti diabetes herba sambiloto. 

Analisis sidik jari kimiawi menggunakan UPLC-HRMS-Q-Orbitrap dilakukan untuk mengidentifikasi senyawa dalam ekstrak metanol herba sambiloto. Pada senyawa yang berhasil teridentifikasi, dilakukan analisis network pharmacology untuk memprediksi senyawa yang berpotensi aktif serta target dan jalur aksi potensial yang terkait dengan mekanisme antidabetes herba sambiloto. Selanjutnya, interaksi senyawa dengan targetnya diverifikasi dengan studi molecular docking. 

Senyawa asam klorogenat, andrografolid, dan 14-deoksiandrografolid berhasil diidentifikasi dari ekstrak metanol herba sambiloto. Selanjutnya, hasil analisis network pharmacology memprediksi mekanisme anti-diabetes herba sambiloto dipengaruhi oleh ketiga senyawa tersebut berdasarkan data interaksi dengan 17 target potensial utama (termasuk PTPN1), melalui berbagai jalur KEGG, diantaranya jalur ‘AGE-RAGE signaling pathway in diabetic complications’ dan jalur ‘insulin resistance’. Verifikasi molecular docking terkait interaksi senyawa dan target hasil prediksi network pharmacology menunjukkan bahwa senyawa 14-deoksiandrografolid mampu membentuk ikatan hidrogen dengan situs aktif PTPN1 (Ser216, Ala217 dan Arg221) dan berpotensi menjadi inhibitor kompetitif PTPN1 karena memiliki skor docking lebih baik (S= -5.803) dibanding substrat PTPN1 (S= -5.356). Dari hasil tersebut dapat diprediksi bahwa mekanisme anti-diabetes ekstrak metanol herba sambiloto dipengaruhi oleh multi senyawa, multi target dan multi jalur.

Antidiabetic activity of the aerial part of sambiloto (Andrographis paniculata (Burm. F.) Nees) has been stated in previous studies. However, its active molecule and its comprehensive antidiabetic mechanism have not been explained. This study aims to explore the anti-diabetic mechanism of methanolic extract of the aerial part of sambiloto.

Chemical fingerprinting analysis using UPLC-HRMS-Q-Orbitrap was conducted for compound identification. Moreover, network pharmacology was performed on these identified compounds to predict potential active compounds, targets, and KEGG pathways associated with the antidiabetic mechanism of the aerial part of Sambiloto. Compound-target interaction was verified by molecular docking.

As a result, chlorogenic acid, andrographolide, and 14-deoxyandrographolide were identified from the extract. According to network pharmacology analysis predictions, these compounds involve in the anti-diabetic mechanism by targeting 17 potential targets (including PTPN1) through various KEGG pathways, including the ‘AGE-RAGE signaling pathway in diabetic complications’ and the ‘insulin resistance' pathway. In accordance with the network pharmacology prediction, molecular docking verification showed that 14-deoxyandrographolide interacts with PTPN1 receptor by forming hydrogen bonds with site actives of PTPN1 (Ser216, Ala217, and Arg221) and has the potential to be a competitive inhibitor of PTPN1 because it has a better docking score (S = -5.803) than PTPN1 substrate (S = -5.356). From these results, it can be predicted that the anti-diabetic mechanism of methanolic extract of Sambiloto aerial part is influenced by multiple compounds, multiple targets, and multiple pathways.

Kata Kunci : network pharmacology, diabetes mellitus, bioinformatic, sambiloto, Andrographis paniculata