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 WANG2,*
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
Diserahkan:
16 Disember 2021/Diterima: 16 Mac 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 lupenone 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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