Topical rhubarb charcoal-crosslinked chitosan/silk fibroin sponge scaffold for the repair of diabetic ulcers improves hepatic lipid deposition in db/db mice via the AMPK signalling pathway

作者全名："Tan, Qi; He, Qifeng; Peng, Ze; Zeng, Xin; Liu, Yuzhe; Li, Dong; Wang, Shang; Wang, Jianwei"

作者地址："[Tan, Qi; Peng, Ze; Zeng, Xin; Liu, Yuzhe; Li, Dong; Wang, Shang; Wang, Jianwei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [He, Qifeng] Chongqing Med Univ, Coll Basic Med Sci, Chongqing 400016, Peoples R China; [Zeng, Xin; Wang, Jianwei] Chongqing Coll Tradit Chinese Med, Chongqing 402760, Peoples R China"

通信作者："Wang, S; Wang, JW (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China.; Wang, JW (通讯作者)，Chongqing Coll Tradit Chinese Med, Chongqing 402760, Peoples R China."

来源：LIPIDS IN HEALTH AND DISEASE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001169116300001

JCR分区：Q2

影响因子：3.9

年份：2024

卷号：23

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Rhubarb charcoal; Type 2 diabetes; AMPK signalling pathway; Hepatic lipid deposition

摘要："BackgroundType 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated.Material and methodsThe silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting.ResultsThe use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN).ConclusionBy regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of ""external and internal reshaping""."

基金机构：Xinglin Program of Chongqing TCM/TCM-integrated Key Discipline

基金资助正文：We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.