RESUMO
BACKGROUND: Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage. AIMS: Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules. Therefore, the aim of this study was to investigate the anti-inflammatory effects and extracellular matrix (ECM) reconstructive activity of 23-HTA in UVA-irradiated normal human dermal fibroblasts (NHDFs). MATERIALS AND METHODS: The antioxidant capacity of 23-HTA was determined by examining its scavenging activities against hydrogen peroxide, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and diphenylpicrylhydrazyl in vitro. Its effect on cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide, and 2,7-dichlorofluorescin diacetate was used to investigate intracellular ROS scavenging activity. The mRNA levels of antioxidant enzymes and pro-inflammatory cytokines were detected using quantitative real-time polymerase chain reaction. A senescence-associated ß-galactosidase (SA-ß-gal) staining kit was used to assess senescent cells. RESULTS: 23-HTA showed antioxidant capacity mediated by ROS scavenging and regulation of antioxidant-related gene expression. Further, the SA-ß-gal analysis and mRNA expression of matrix metalloproteinases and type I procollagen suggested that 23-HTA regulates the gene expression of ECM proteins and cellular senescence under UVA-irradiated conditions. CONCLUSION: In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway.
Assuntos
Antioxidantes/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Triterpenos/farmacologia , Benzotiazóis/metabolismo , Compostos de Bifenilo/metabolismo , Catalase/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Derme/citologia , Fibroblastos/efeitos da radiação , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Glutationa Peroxidase/genética , Heme Oxigenase-1/genética , Humanos , Peróxido de Hidrogênio/metabolismo , Interleucina-1beta/genética , Interleucina-6/genética , Metaloproteinase 1 da Matriz/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos da radiação , Picratos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo , Fator de Necrose Tumoral alfa/genética , Raios Ultravioleta/efeitos adversosRESUMO
In the context of ethno botanical importance with no phytochemical investigations, Mussaenda roxburghii have been investigated to explore it's phytoconstituents and studies of their antibiofilm activity. Four compounds have been isolated from the aerial parts of this plant and were characterized as 2α,3ß,19α,23-tetrahydroxyurs-12-en-28-oic acid (1), ß-sitosterol glucoside (4), lupeol palmitate (5), and myoinositol (6). All these compounds were tested for antibacterial and antibiofilm activity against Pseudomonas aeruginosa. Compound 1 exhibited three times more antibiofilm activity with minimum inhibitory concentration (MIC) at 0.74 mm compared to that of streptomycin. Molecular docking studies exhibited a very high binding affinity of 1 with P. aeruginosa quorum sensing proteins and motility associated proteins viz. LasR and PilB, PilY1, PilT, respectively. Compound 1 was also found to be non-cytotoxic against sheep RBC and murine peritoneal macrophages at selected sub-MIC doses.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Rubiaceae/química , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Relação Dose-Resposta a Droga , Eritrócitos , Macrófagos , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ovinos , Relação Estrutura-AtividadeRESUMO
23-Hydroxytormentic acid (23-HTA) is an important herbal medicine purified from immature fruits of African Rubus aceae (Rosaceae). This study was carried out to examine the protection properties and potential mechanisms of 23-HTA against cerebral ischemia/reperfusion (I/R) damage. Rats underwent middle cerebral artery occlusion/reperfusion (MCAO/R) 2/24 h. All animals were euthanized 24 h after reperfusion. Rats were injected with various concentrations of 23-HTA intraperitoneally. Evaluations of infarct volumes, neurological deficit, and brain water contents were carried out to assess the outcome of 23-HTA treatment. The results showed that 23-HTA reduced infarct volumes, brain water content, and neurological deficit in a dosage-dependent manner. 23-HTA can also significantly reduce the numbers of TUNEL-positive cells, the expression levels of Bax, caspase-3, lipid peroxidation, Sod 1, Sod 2, catalase, and pro-inflammatory cytokines TNF and IL-1ß and increase the expression levels of Bcl-2 and p-Akt. 23-HTA has a neuroprotective effect due to its anti-apoptotic, antioxidant, and anti-inflammatory effects.