Sains Malaysiana 52(6)(2023): 1795-1810

http://doi.org/10.17576/jsm-2023-5206-15

Exploring the Antidiabetic Effect of Lupenone in Rats with Type 1 Diabetes and Its Underlying Mechanism Based on Network Pharmacology

(Mengkaji Kesan Antidiabetes Lupenon pada Tikus dengan Diabetes Jenis 1 dan Mekanisme Asasnya Berdasarkan Farmakologi Rangkaian)

HONGMEI WU¹, XULONG HUANG¹, FENG XU¹, XIAOFEN LI¹, YUQING LIANG¹, LIUBO YANG¹ & XIANGPEI WANG^2,*

¹Department of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang City, Guizhou Province, Guiyang 550002, PR China

²School of Ethnic-Minority Medicine, Guizhou Minzu University, Guiyang City, Guizhou Province, Guiyang 550002, PR China

Received: 16 December 2021/Accepted: 16 March 2023

Abstract

Lupenone has been reported to possess numerous medicinal values and gives a positive antidiabetic effect. But the mechanism of preventing and treating type 1 diabetes has not been elucidated in type 1 diabetic rats. This study investigated the effects and mechanism of action of lupenone in preventing and treating type 1 diabetes by network pharmacology and diabetic rats. The blood glucose, glycosylated hemoglobin (HbA1c), insulin, and inflammatory factors in the pancreas of rats with type 1 diabetes were measured, and histopathological changes were observed after treatment with lupenone. The pharmacological network of ‘component-target-disease’ was constructed on diabetic rats. Gene function enrichment, the Kyoto Encyclopedia of Genes and Genomes pathway analysis, and molecular docking were performed. The results showed that lupenone can decrease fasting blood glucose and HbA1c levels, increase insulin content and interleukin (IL)-4, IL-10, and decrease IL-6, transforming growth factor β and tumor necrosis factor α levels in the pancreas. Furthermore, ten targets were identified, and 50 signal pathways closely related to type 1 diabetes and inflammation were screened by network pharmacology, including insulin resistance, type II diabetes, type I diabetes, insulin signal pathway, mitogen activated protein kinase (MAPK) signal pathway, and tumor necrosis factor (TNF) signal pathway. The docking affinity of potential targets and lupenone were between -3.3 and -9.8, among which caspase-3 (CASP3), cyclin-dependent kinase 4 (CDK4), inhibitor of kappaB kinase beta (IKBKB), transforming growth factor beta-1 (TGFB1), and TNF had high binding abilities. Thus, lupenone has the potential to be developed as a new drug for treating type 1 diabetes.

Keywords: Inflammatory factors; lupenone; mechanism; network pharmacology; type 1 diabetes

Abstrak

Lupenon telah dilaporkan mempunyai banyak nilai perubatan dan memberikan kesan antidiabetes yang positif. Tetapi mekanisme mencegah dan merawat diabetes jenis 1 belum dijelaskan dalam tikus diabetes jenis 1. Penyelidikan ini mengkaji kesan dan mekanisme tindakan lupenone dalam mencegah dan merawat diabetes jenis 1 oleh farmakologi rangkaian dan tikus diabetes. Glukosa darah, hemoglobin glikosilasi (HbA1c), insulin dan faktor keradangan dalam pankreas tikus dengan diabetes jenis 1 diukur dan perubahan histopatologi diperhatikan selepas rawatan dengan lupenon. Rangkaian farmakologi ‘komponen-sasaran-penyakit’ telah dibina pada tikus diabetes. Pengayaan fungsi gen, analisis laluan Ensiklopedia Gen dan Genom Kyoto serta dok molekul telah dilakukan. Keputusan menunjukkan bahawa lupenon boleh mengurangkan tahap glukosa darah puasa dan HbA1c, meningkatkan kandungan insulin dan interleukin (IL)-4, IL-10 serta mengurangkan IL-6, mengubah faktor pertumbuhan β dan tahap tumor nekrosis faktor α dalam pankreas. Tambahan pula, sepuluh sasaran telah dikenal pasti dan 50 laluan isyarat yang berkait rapat dengan diabetes jenis 1 dan keradangan telah disaring oleh farmakologi rangkaian, termasuk rintangan insulin, diabetes jenis II, diabetes jenis I, laluan isyarat insulin, laluan isyarat mitogen diaktifkan protein kinase (MAPK) dan laluan isyarat tumor nekrosis faktor (TNF). Perkaitan dok sasaran berpotensi dan lupenon adalah antara -3.3 dan -9.8, antaranya caspase-3 (CASP3), kinase 4 (CDK4 yang bergantung kepada cyclin), perencat kappaB kinase beta (IKBKB), mengubah faktor pertumbuhan beta-1 (TGFB1) dan TNF mempunyai kebolehan mengikat yang tinggi. Oleh itu, lupenone mempunyai potensi untuk dibangunkan sebagai ubat baharu untuk merawat diabetes jenis 1.

Kata kunci: Diabetes jenis 1; faktor keradangan; farmakologi rangkaian; lupenon; mekanisme

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*Corresponding author; email: wxp0123@126.com