Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation

Qu, Keshen; Ru, Yi; Yang, Dan; Kuai, Le; Luo, Ying; Zhang, Pingan; Xing, Meng; Hua-fa, Que

doi:10.1016/j.compbiomed.2023.106660

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…In addition, we found that the mechanism of tendinopathy induced by T2DM may be related to the PI3K-Akt signaling pathway and AMPK signaling pathway. Previous literature has also confirmed that the PI3K-Akt signaling pathway is closely related to impaired wound healing related to diabetes, and the up-regulation of the PI3K/Akt signaling pathway may be a promising target for accelerating healing [ 40 ]. AMPK and PI3K/Akt signaling pathways may be involved in diabetes-induced cognitive decline, and DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling [ 41 ].AMPK may be a fundamental cellular pathway for metabolic disorders and diabetes [ 42 ].…”

Section: Discussionmentioning

confidence: 98%

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Xu,

Zhang,

Wang

et al. 2024

BMC Med Genomics

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Objective There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the “gene profile” of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. Methods A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups’ DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Results T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. Conclusions Transcriptomics reveals dynamic changes in the“gene profiles”of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

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Section: Discussionmentioning

confidence: 98%

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Xu,

Zhang,

Wang

et al. 2024

BMC Med Genomics

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“…Ointment stands as one of the commonplace topical preparations utilized in clinical practice, serving the treatment of various symptoms like burns, trauma, inflammation, and skin diseases [1][2][3][4]. Comprising two components, namely the drug and ointment base, the ratio of these constituents directly impacts the rheological properties of the ointment and subsequently influences its extrusion, extensibility, and stability [5].…”

Section: Introductionmentioning

confidence: 99%

Refining the rheological characteristics of high drug loading ointment via SDS and machine learning

Qian,

Wang,

et al. 2024

PLoS ONE

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This paper presents an optimized preparation process for external ointment using the Definitive Screening Design (DSD) method. The ointment is a Traditional Chinese Medicine (TCM) formula developed by Professor WYH, a renowned TCM practitioner in Jiangsu Province, China, known for its proven clinical efficacy. In this study, a stepwise regression model was employed to analyze the relationship between key process factors (such as mixing speed and time) and rheological parameters. Machine learning techniques, including Monte Carlo simulation, decision tree analysis, and Gaussian process, were used for parameter optimization. Through rigorous experimentation and verification, we have successfully identified the optimal preparation process for WYH ointment. The optimized parameters included drug ratio of 24.5%, mixing time of 8 min, mixing speed of 1175 rpm, petroleum dosage of 79 g, liquid paraffin dosage of 6.7 g. The final ointment formulation was prepared using method B. This research not only contributes to the optimization of the WYH ointment preparation process but also provides valuable insights and practical guidance for designing the preparation processes of other TCM ointments. This advanced DSD method enhances the screening approach for identifying the best preparation process, thereby improving the scientific rigor and quality of TCM ointment preparation processes.

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“…3 Hyperglycemia leads to vascular dysfunction in diabetic wounds, a large number of inflammatory factors and reactive oxygen species are produced, and tissue hypoxia and necrosis are also caused. 4 More and more studies have proved that promoting angiogenesis and improving vascular function can effectively promote wound healing. Therefore, it is necessary to develop new therapeutic drugs to actively improve the wound microenvironment and promote angiogenesis in order to effectively promote the healing of diabetic wounds.…”

Section: Introductionmentioning

confidence: 99%

“…Among them, inflammatory response and vascular disease are the main reasons leading to delayed wound healing, as well as one of the main reasons leading to increased wound infection and disease incidence . Hyperglycemia leads to vascular dysfunction in diabetic wounds, a large number of inflammatory factors and reactive oxygen species are produced, and tissue hypoxia and necrosis are also caused . More and more studies have proved that promoting angiogenesis and improving vascular function can effectively promote wound healing.…”

Section: Introductionmentioning

confidence: 99%

Curcumin-Loaded Macrophage-Derived Exosomes Effectively Improve Wound Healing

Zhang

Gao

et al. 2023

Mol. Pharmaceutics

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This study aims to investigate the potential therapeutic effect of exosomes derived from macrophages loaded with curcumin (Exos-cur) on the healing of diabetic wounds. As a new type of biomaterial, Exos-cur has better stability, antiinflammation, and antioxidation biological activity. In in vitro experiments, Exos-cur can promote the proliferation, migration, and angiogenesis of HUVECs (human umbilical vein endothelial cells) while reducing the ROS (reactive oxygen species) produced by HUVECs induced by high glucose, regulating the mitochondrial membrane potential, reducing cell oxidative damage, and inhibiting oxidative stress and inflammation. In the in vivo experiment, the Exos-cur treatment group had an increased percentage of wound closure and contraction compared with the diabetic wound control group. Hematoxylin−eosin staining (HE) and Masson staining showed that the Exos-cur treatment group had more advanced reepithelialization, and the generated mature granulation tissue was rich in a large number of capillaries and newly deposited collagen fibers. Western blot and immunofluorescence analyses showed that Exos-cur can inhibit inflammation by activating the Nrf2/ARE pathway, upregulate the expression of wound healing-related molecules, promote angiogenesis, and accelerate wound healing in diabetic rats. These results show that Exos-cur has a good therapeutic effect on diabetic skin defects and provide experimental evidence for the potential clinical benefits of Exos-cur.

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Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation

Cited by 5 publications

References 23 publications

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Refining the rheological characteristics of high drug loading ointment via SDS and machine learning

Curcumin-Loaded Macrophage-Derived Exosomes Effectively Improve Wound Healing

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