RESUMO
Growing evidence suggests that medicinal herbs have direct actions on endometrial cells. By screening multiple herbs using an in vitro model of endometriosis, we found that a commonly used herbal formula exerted considerable antiproliferative effects. Our purpose was to investigate the effects of this antiendometriosis herbal mixture on cell proliferation, apoptosis, and CCL5 expression and secretion in endometriotic stromal cells in vitro. Isolated normal endometrial, eutopic, and ectopic endometriotic stromal cells were cultured under established conditions. Cell proliferation, apoptosis, and CCL5 gene expression protein secretion was evaluated after incubation with different concentrations of an antiendometriosis herbal mixture extract. Cell proliferation was assessed by cell counting, (3)H-thymidine incorporation, and MTS assays. Apoptosis was determined by blotting using anti-cleaved caspase 3 antibodies and by a TUNEL assay. CCL5 gene expression and protein secretion were determined by transient transfection of gene promoter reporters and ELISAs in cell supernatants. Extracts of a traditional herbal mixture dose-dependently decreased cell proliferation in normal, eutopic, and ectopic endometriotic stromal cells. (3)H-Thymidine uptake and MTS confirmed these findings. The herbal extracts induced apoptosis, as evidenced by activation of caspase 3 and the presence of TUNEL-positive cells after treatment. The herbal extracts also suppressed CCL5 gene transcription and protein secretion in endometriotic stromal cells, even when corrected for cell number. Extracts from a medicinal herbal mixture have direct effects on cell proliferation, apoptosis, and CCL5 production in endometriotic stromal cells. Our findings support the further investigation of novel, potentially safe and well-tolerated botanical products as future endometriosis treatments.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL5/metabolismo , Endometriose/tratamento farmacológico , Magnoliopsida/metabolismo , Células Estromais/efeitos dos fármacos , Análise de Variância , Caspase 3/metabolismo , Células Cultivadas , Quimiocina CCL5/genética , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Endometriose/cirurgia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Mitose/efeitos dos fármacos , Fitoterapia , Plantas Medicinais/metabolismo , Estatísticas não Paramétricas , Células Estromais/enzimologia , Células Estromais/metabolismo , Transfecção , Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/farmacologiaRESUMO
Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.
Assuntos
Endometriose/tratamento farmacológico , Fitoterapia , Preparações de Plantas/uso terapêutico , Plantas Medicinais/química , Animais , Feminino , Interações Ervas-Drogas , Humanos , CamundongosRESUMO
Endometriosis is a disease that affects approximately 10% of all reproductive-aged women and the prevalence rises to 20-50% in infertile women. There is growing evidence that medicinal Chinese herbs with pain-alleviating and anti-inflammatory properties may be useful in the treatment of endometriosis and infertility, but the mechanisms of action of these herbs have yet to be investigated. In addition, studies of adequate design, sample size and appropriate control are lacking. Therefore, prospective randomized, controlled studies to evaluate the efficacy, mechanism of action and toxicities of Chinese herbs in the treatment endometriosis and infertility are needed.