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1.
Comput Biol Med ; 155: 106660, 2023 03.
Article in English | MEDLINE | ID: mdl-36809697

ABSTRACT

A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.


Subject(s)
Diabetes Mellitus , Drugs, Chinese Herbal , Humans , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Molecular Docking Simulation , Ointments , Class I Phosphatidylinositol 3-Kinases
2.
J Ethnopharmacol ; 274: 114041, 2021 Jun 28.
Article in English | MEDLINE | ID: mdl-33757812

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated. AIM OF THE STUDY: To assess the mechanism of QZLX mixture against psoriasis. MATERIALS AND METHODS: This study combines network pharmacology and experiments to study the mechanism of QZLX against psoriasis. First, construct the active compound-target network and PPI network. Secondly, determine possible drug targets through Molecular docking and KEGG. Thirdly, high-performance liquid chromatography (HPLC) was used for the quality control of QZLX. Finally, use a mouse model of psoriasis to further confirm the role of QZLX. RESULTS: (1) Network pharmacology analysis shows that QZLX alleviates psoriasis's epidermal inflammation, and neovascularization may be achieved by inhibiting the IL6/STAT3 signaling pathway. (2) QZLX improves the pathological characteristics of IMQ-induced skin damage in psoriasis-like mice. (3) QZLX inhibits the IL6/STAT3 signaling pathway and reduces the expression of IL-17, IL-23, and TNF-α related to inflammation in peripheral blood, as well as the expression of S100A7 in the lesion area. QZLX is better than MTX in inhibiting neovascularization by down-regulating the expression of HIF-1 and CD31 in the lesion area. Finally, inhibition of Ki67 alleviates the excessive proliferation of keratinocytes. CONCLUSION: In sum, this study clarifies the mechanism of QZLX against psoriasis and provides evidence to support its clinical use.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Psoriasis/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Proliferation/drug effects , Cytokines/genetics , Cytokines/immunology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/immunology , Imiquimod , Keratinocytes/drug effects , Male , Mice, Inbred C57BL , Molecular Docking Simulation , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Protein Interaction Maps , Psoriasis/chemically induced , Psoriasis/immunology , Psoriasis/pathology , STAT3 Transcription Factor/immunology , Skin/drug effects , Skin/immunology , Skin/pathology
3.
Chin J Integr Med ; 26(11): 867-872, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31385220

ABSTRACT

Research on the molecular mechanisms controlling circadian rhythm in Western medicine is comparable to the study of a day-night rhythm in Chinese medicine (CM), as also focus on the same life phenomenon. By comparing the two, this paper elaborates on the differences between them in their respective issues of consciousness, ways of thinking, research methods and research results. Relatively speaking, Nobel Prize research has a stronger sense of the problems and concerns about the essence of "what", while CM focuses on "how a thing functions". The former mainly adopts experimental and mathematical methods, while the latter primarily depends on observation and understanding. The natural philosophy and natural science eventually lead to the results and the inevitable, quantitative and qualitative differences. Research on the life rhythm in CM should be proposed, scientific problems should be fully grasped, and research should be carried out with the aid of multidisciplinary new knowledge and new achievements through cross-disciplinary studies. On the basis of clinical epidemiological research and experimental research, a systematic review should be made of the human physiology of CM and the pathological rhythm model to explore the regulatory mechanism of time rhythm and create a new theory of time medicine.


Subject(s)
Circadian Rhythm/physiology , Medicine, Chinese Traditional/history , Nobel Prize , History, 21st Century , Humans , Research Design
4.
Article in English | MEDLINE | ID: mdl-31975998

ABSTRACT

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common complications of diabetes mellitus, with the wound not healing as expected and healing slowly. Poor control can develop into gangrene and even amputation. Currently, the existing treatments are not satisfactory enough. In China, KangFuXin liquid (KFXL) has been clinically used to treat DFU and has shown good clinical efficacy. In order to provide more reference to clinicians and experts, evidence of efficacy for it needs to be further rigorously evaluated. METHODS: Eight electronic databases were searched to identify eligible randomized clinical trials (RCTs) published from construction of the library to April 2019. There is no language or data restriction; 11 trials involving 889 participants met the inclusion criteria. These RCTs compared the total effective rate, cure rate, cure time, and adverse events associated with KFXL. The Cochrane Handbook guidelines were used to assess the risk of bias and to evaluate the methodological quality of eligible studies. The methodological quality of included studies was generally low. Dichotomous and continuous data were presented using risk ratios (RRs) and mean differences (MDs), respectively. RESULTS: Compared with the basic treatment, meta-analyses showed that KFXL combined with basic treatment can improve the total effective rate (RR = 1.38; 95% CI = 1.23-1.54; P < 0.00001; fixed effect model: I 2 = 32%) and cure rate (RR = 1.67; 95% CI = 1.17-2.38; P=0.005; random effect model: I 2 = 65%), and shorten the healing time (MD = -5.73; 95% CI = -6.95 to -4.52; P < 0.00001; random effect model). Moreover, under the same basic treatment, KFXL had a better effect than external use of pharmaceutical medications (RR = 1.95; 95% CI = 1.30-2.93; P=0.001), but the cure rate was not significantly different. Also, KFXL had nothing to do with adverse reactions. CONCLUSION: The evidence confirms that KFXL is an effective treatment for DFU. However, further large-scale, rigorously designed trials and high-quality studies are needed to confirm the role of KFXL in the treatment of DFU.

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