ABSTRACT
Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and ß-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and ß-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and ß-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and ß-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and ß-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and ß-sitosterol produced similar outcomes. Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.
ABSTRACT
OBJECTIVE: We investigated the protective effect of the extract of the Camellia japonica L. flower on cerebral ischemia-reperfusion injury in rats. METHODS: The rat ischemia-reperfusion injury was induced by middle cerebral artery occlusion for 90 minutes and reperfusion for 48 hours. The animals received an intravenous injection once a day of 20, 40, 80 mg/kg extract of C. japonica for three consecutive days before the ischemia reperfusion. The learning and memory function, the infarct volume, serum malondialdehyde (MDA) level and lactate dehydrogenase activity, and extravasation of immunoglobulin G (IgG) into cerebral parenchyma were assessed as the cell damage index. RESULTS: Pretreatment with extract of C. japonica markedly reduced the infarct volume, serum malondialdehyde level and lactate dehydrogenase activity, and markedly inhibited the extravasation of IgG. Moreover, pretreatment with extract of C. japonica may also inhibit the learning and memory deficits induced by an ischemia-reperfusion injury. CONCLUSION: It was concluded that pretreatment with extract of C. japonica has a protective effect on cerebral ischemia-reperfusion injury in rats.
Subject(s)
Brain Ischemia/prevention & control , Camellia/chemistry , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Reperfusion Injury/prevention & control , Animals , Disease Models, Animal , Female , Immunoglobulin G/blood , L-Lactate Dehydrogenase/analysis , Male , Malondialdehyde/blood , Nimodipine/pharmacology , Random Allocation , Rats, Sprague-Dawley , Reproducibility of Results , Swimming/physiology , Time Factors , Treatment OutcomeABSTRACT
ABSTRACT Objective: We investigated the protective effect of the extract of the Camellia japonica L. flower on cerebral ischemia-reperfusion injury in rats. Methods: The rat ischemia-reperfusion injury was induced by middle cerebral artery occlusion for 90 minutes and reperfusion for 48 hours. The animals received an intravenous injection once a day of 20, 40, 80 mg/kg extract of C. japonica for three consecutive days before the ischemia reperfusion. The learning and memory function, the infarct volume, serum malondialdehyde (MDA) level and lactate dehydrogenase activity, and extravasation of immunoglobulin G (IgG) into cerebral parenchyma were assessed as the cell damage index. Results: Pretreatment with extract of C. japonica markedly reduced the infarct volume, serum malondialdehyde level and lactate dehydrogenase activity, and markedly inhibited the extravasation of IgG. Moreover, pretreatment with extract of C. japonica may also inhibit the learning and memory deficits induced by an ischemia-reperfusion injury. Conclusion: It was concluded that pretreatment with extract of C. japonica has a protective effect on cerebral ischemia-reperfusion injury in rats.
RESUMO Objetivo: Investigamos o efeito protetor do extrato da flor de Camellia japonica L. (ECJ) na lesão de reperfusão isquêmica cerebral (I/R) em ratos. Métodos: A lesão de I/R de rato foi induzida por uma oclusão da artéria cerebral média por 90 minutos e reperfusão por 48 horas. Os animais receberam uma injeção intravenosa uma vez ao dia de 20, 40, 80 mg/kg de ECJ por três dias consecutivos antes da I/R. A função de aprendizagem e memória, o volume do infarto, o nível sérico de malondialdeído (MDA), a atividade da desidrogenase láctica e o extravasamento de imunoglobulina (IgG) no parênquima cerebral foram avaliados como índices de dano celular. Resultados: O pré-tratamento com ECJ reduziu acentuadamente o volume do infarto, o nível sérico de MDA e a atividade da desidrogenase láctica, e inibiu marcadamente o extravasamento de IgG. Além disso, o pré-tratamento com ECJ também poderia inibir os déficits de aprendizado e memória induzidos pela lesão de I/R. Conclusão: O pré-tratamento com ECJ tem um efeito protetor contra lesão cerebral de I/R em ratos.
