RESUMEN
Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.
Asunto(s)
Isquemia Encefálica , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Medicina Tradicional China , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Cefalea/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi, has been shown to exert strong antitumor properties. The aim of the present study was to investigate the mechanisms underlying the proposed antitumor properties of PAB in the triplenegative breast cancer cells, MDAMB231. The cell processes evaluated included cell proliferation by Cell Counting Kit8 assay, colony formation and EdU assay, apoptosis by Annexin VFITC/PI apoptosis assay, cell migration by Transwell migration assay and invasion by Transwell invasion assay. PAB significantly inhibited the proliferation of MDAMB231 cells through a mechanism that was considered to be associated with cell cycle arrest at the G2/M phase. There was decreased protein expression levels of CDK1 and cyclin B1 and increased protein expression levels of p53 and p21. However, there were no welldefined inhibitory effects on the normal breast cell line MCF10A. PAB also triggered apoptosis in a concentrationdependent manner through the mitochondrial apoptosis pathway. It caused collapse of mitochondrial membrane potential, accumulation of reactive oxygen species and release of cytochrome c, as well as upregulation of cleaved caspase3, cleaved caspase9, cleaved PARP and Bax, and downregulation of Bcl2 and Bclxl. The migration and invasion ability of MDAMB231 cells were inhibited by decreasing the expression levels of the epithelialmesenchymal transitionrelated markers Ncadherin and vimentin and increasing the expression of Ecadherin. Moreover, the expression levels of PI3K (p110ß), phosphorylated (p)AKT (ser473) and pmTOR (ser2448) were downregulated and LY294002, a PI3K inhibitor, could interact additively with PAB to induce apoptosis of MDAMB231 cells. Overall, the present results demonstrated that PAB induced apoptosis via mitochondrial apoptosis and the PI3K/AKT/mTOR pathway in triplenegative breast cancer. It also inhibited cellular proliferation, migration and invasion, suggesting that PAB may be a useful phytomedicine for the treatment of triplenegative breast cancer.
Asunto(s)
Diterpenos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ApoptosisRESUMEN
Chinese materia medica( CMM) serves as an important cornerstone for the development of traditional Chinese medicine( TCM) culture and industry due to its unique ecological,medical,economic,scientific and technological,and cultural values. The supply shortage and unstable quality of some CMM resources have hindered the development of TCM. Ensuring the sustainable use of CMM resources has become essential for the development of TCM in China. Enriching CMM resources is the key to ensuring the sustainable utilization of TCM resources in China,which can be achieved via expanding the medicinal parts,developing the substitutes,seeking for analogues,exploring the ethnic and folk medicines,or introducing foreign medicinal materials. CMM efficacy or function positioning plays a very important role in the transformation of new CMM resources. The strategies and methods for efficacy or function positioning of new CMM resources,including analogy,plant genetic relationship exploration,medicinal property deduction,ethnobotanical investigation,text mining,network pharmacology,and structure-activity relationship exploration,were systematically proposed in this study based on CMM theory,textual research,and modern methodologies. This paper is expected to provide a theoretical reference for the continuous enrichment and development of CMM resources and the high-quality development of TCM culture and industry.