Sains Malaysiana 52(12)(2023): 3497-3509

http://doi.org/10.17576/jsm-2023-5212-12

Molecular Mechanism of DLBS3233 Bioactive Fraction in Type-2 Diabetes Mellitus: Network Pharmacology and Docking Study

(Mekanisme Molekul Pecahan Bioaktif DLBS3233 dalam Diabetes Mellitus Jenis-2: Farmakologi Rangkaian dan Kajian Dok)

SANTI TAN^1,2, RAYMOND RUBIANTO TJANDRAWINATA^1,* & VIVITRI DEWI PRASASTY³

¹Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, South Jakarta, DKI Jakarta 12930, Indonesia

²Bioinformatics and Computational Biology, Dexa Group, South Tangerang, Banten 15224, Indonesia

³Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, United States

Diserahkan: 5 April 2023/Diterima: 1 Disember 2023

Abstract

Although several antidiabetic agents are currently available, they commonly have undesirable effects and are not fully effective in reducing blood glucose. Therefore, since a long time ago, some Indonesians have preferred herbal medicine to cure and prevent diseases such as Lagerstroemia speciosa (L.) Pers. and Cinnamomum burmanni. (Nees & T.Nees) Blume, plants from Indonesia, are believed to be able to treat type 2 diabetes mellitus (T2DM). Both herbs are present in DLBS3233 bioactive fraction, a standardized herbal extract that acts as an insulin sensitizer like thiazolidinediones (TZDs). However, the molecular mechanisms, the bioactive compounds, and the target proteins involved remain unclear. To understand more about the potential molecular mechanism of DLBS3233 in treating T2DM, this network pharmacology study is conducted for the first time. Quercetin, kaempferol, and ellagic acid were discovered to have antidiabetic effects in this study as selected compounds of DLBS3233, primarily on eight core target proteins, including AKT1, EGFR, GSK3B, IL6, PTK2, RELA, SRC, and VEGFA. We also found that they exhibited ligand-receptor binding activity comparable to pioglitazone in the molecular docking study. Concisely, as a reference for furthering the development of this bioactive fraction, this study provides novel information on DLBS3233 in T2DM treatment that was not shown in prior studies.

Keywords: Cinnamomum burmanni. Blume; DLBS3233; Lagerstroemia speciosa; network pharmacology; type 2 diabetes mellitus

Abstrak

Walaupun beberapa agen antidiabetik kini tersedia, agen tersebut biasanya mempunyai kesan yang tidak diingini dan tidak berkesan sepenuhnya dalam mengurangkan glukosa darah. Oleh itu, sejak dahulu lagi, sebilangan masyarakat Indonesia lebih menggemari jamu bagi mengubati dan mencegah penyakit seperti Lagerstroemia speciosa (L.) Pers. dan Cinnamomum burmanni. (Nees & T.Nees) Blume, tumbuhan dari Indonesia, dipercayai mampu merawat diabetes mellitus jenis 2 (DMJ2). Kedua-dua herba hadir dalam pecahan bioaktif DLBS3233, ekstrak herba piawai yang bertindak sebagai pemeka insulin seperti thiazolidinediones (TZDs). Walau bagaimanapun, mekanisme molekul, sebatian bioaktif dan protein sasaran yang terlibat masih tidak jelas. Untuk memahami lebih lanjut mengenai potensi mekanisme molekul DLBS3233 dalam merawat DMJ2, kajian farmakologi rangkaian ini dijalankan buat kali pertama. Kuersetin, kaempferol dan asid elagik didapati mempunyai kesan antidiabetis dalam kajian ini sebagai sebatian terpilih DLBS3233, terutamanya pada lapan protein sasaran teras, termasuk AKT1, EGFR, GSK3B, IL6, PTK2, RELA, SRC dan VEGFA. Kami juga mendapati bahawa mereka menunjukkan aktiviti mengikat reseptor ligan yang setanding dengan pioglitazone dalam kajian dok molekul. Secara ringkas, sebagai rujukan untuk melanjutkan pembangunan pecahan bioaktif ini, kajian ini menyediakan maklumat baru mengenai DLBS3233 dalam rawatan DMJ2 yang tidak didedahkan dalam kajian terdahulu.

Kata kunci: Cinnamomum burmanni. Blume; diabetes mellitus jenis 2; DLBS3233; farmakologi rangkaian; Lagerstroemia speciosa

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*Pengarang untuk surat-menyurat; email: raymond@dexa-medica.com