RESUMO
Diabetic ulcer is a challenging complication of diabetes mellitus but current treatments cannot achieve satisfactory results. In this study, the effect of Huangbai liniment (HB) and berberine on the wound healing in high fat diet/streptozotocin injection induced diabetic rats was investigated by RNA-seq technology. HB topical treatment promoted wound healing in the diabetic patients and diabetic rats, and it affected multiple processes, of which IL-17 signalling pathway was of importance. Inhibiting IL-17a by its inhibitor or antibody remarkably facilitated wound healing and HB significantly repressed the high IL-17 expression and its downstream targets, including Cxcl1, Ccl2, Mmp3, Mmp9, G-CSF, IL1B and IL6, in diabetic wounds, promoted T-AOC, SOD activity and GSH levels; decreased the levels of nitrotyrosine and 8-OHdG; enhanced angiogenesis-related CD31, PDGF-BB and ANG1 expression; inhibited cleaved caspase-3 levels and promoted TIMP1 and TGFB1. Moreover, berberine (a major component in HB) repressed the IL-17 signalling pathway, and promoted wound healing in diabetes mellitus. This study highlights the strategy of targeting IL-17a in diabetic wounds, deepens the understanding of wound healing in diabetes mellitus in a dynamic way and reveals the characteristics of HB and berberine in promoting wound healing of type 2 diabetes mellitus.
Assuntos
Berberina , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Humanos , Interleucina-17/farmacologia , Linimentos/farmacologia , Ratos , Estreptozocina/farmacologia , CicatrizaçãoRESUMO
As a serious complication of diabetes, nonhealing skin ulcer leads to high mortality and disability in diabetic patients. However, limited therapy is available in managing diabetic wounds. In this study, RNA-seq technology was used to systematically investigate the effect of Huangbai (HB) liniment, a traditional Chinese medicine, on the streptozotocin- (STZ-) induced diabetic wound. HB liniment significantly accelerated the wound closure and enhanced the generation of extracellular matrix in diabetic rats, and oxidative stress was identified to play a vital role in HB-mediated wound healing. Importantly, HB liniment activated nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream antioxidant genes (e.g., genes involved in glutathione system, thioredoxin system, and GAPDH generation as well as other antioxidant genes), which inhibited oxidative damage and apoptosis. By associating drug targets of HB liniment with Nrf2 and its downstream genes, 54 components in HB liniment were screened out, and the majority was from Cortex Phellodendri and Forsythia suspensa. Additionally, HB liniment enhanced TGF-ß1 and reduced MMP9 level, accelerating wound healing in diabetes. The in vitro experiment showed HB facilitated cell proliferation and inhibited oxidative damage in high glucose-induced HaCaT cells. Our findings provided the experimental evidence for the treatment of diabetic wound with HB, clarified the potential mechanism of HB, and improved our understanding of diabetic wound healing.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Medicamentos de Ervas Chinesas/farmacologia , Linimentos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Cicatrização/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Diabetes Mellitus Experimental/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Glucose/toxicidade , Células HaCaT , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Ratos Sprague-Dawley , Estreptozocina , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização/genéticaRESUMO
In order to determine the anti-pathogenic clinical efficacy of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis, medical examination and treatment of these disorders have been carried out in a group of 80 patients. It is established that the use of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis decreases the infectious load in parodontal recess, reduces the manifestations of local inflammation, normalizes the immunity indices, and decreases the level of endogenous intoxication, which ensures the acceleration of recuperation processes and lowers the frequency of recurrences.
Assuntos
Acridinas/uso terapêutico , Inflamação/tratamento farmacológico , Linimentos/uso terapêutico , Boca/efeitos dos fármacos , Periodontite/tratamento farmacológico , Simplexvirus/efeitos dos fármacos , Estomatite Herpética/tratamento farmacológico , Acridinas/farmacologia , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Adulto , Candida albicans/efeitos dos fármacos , Candida albicans/imunologia , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/imunologia , Feminino , Humanos , Imunoensaio , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Inflamação/virologia , Indutores de Interferon/farmacologia , Indutores de Interferon/uso terapêutico , Interleucina-1beta/análise , Interleucina-1beta/imunologia , Linimentos/farmacologia , Masculino , Boca/imunologia , Boca/microbiologia , Boca/patologia , Boca/virologia , Periodontite/imunologia , Periodontite/microbiologia , Periodontite/patologia , Recidiva , Índice de Gravidade de Doença , Simplexvirus/imunologia , Estomatite Herpética/imunologia , Estomatite Herpética/patologia , Estomatite Herpética/virologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
AIM: To evaluate a specially developed photoplethysmographic (PPG) technique, using green and near-infrared light sources, for simultaneous non-invasive monitoring of skin and muscle perfusion. METHODS: Evaluation was based on assessments of changes in blood perfusion to various provocations, such as post-exercise hyperaemia and hyperaemia following the application of liniment. The deep penetrating feature of PPG was investigated by measurement of optical radiation inside the muscle. Simultaneous measurements using ultrasound Doppler and the new PPG application were performed to elucidate differences between the two methods. Specific problems related to the influence of skin temperature on blood flow were highlightened, as well. RESULTS: Following static and dynamic contractions an immediate increase in muscle perfusion was shown, without increase in skin perfusion. Liniment application to the skin induced a rapid increase in skin perfusion, but not in muscle. Both similarities and differences in blood flow measured by Ultrasound Doppler and PPG were demonstrated. The radiant power measured inside the muscle, by use of an optical fibre, showed that the near-infrared light penetrates down to the vascular depth inside the muscle. CONCLUSIONS: The results of this study indicate the potentiality of the method for non-invasive measurement of local muscle perfusion, although some considerations still have to be accounted for, such as influence of temperature on blood perfusion.