RESUMEN

Psoriasis, a chronic inflammatory skin disease, is characterized by the excessive proliferation and impaired differentiation of epidermal keratinocytes and is accompanied by the increased infiltration of inflammatory cells. The condition requires long­term treatment and has no definitive cure. Hence, supplements and therapeutic agents have been intensely investigated. Gomisin M2 (GM2), a lignan extracted from Schisandra chinensis (Turcz). Baill. (Schisandraceae; S. chinensis), has demonstrated diverse pharmacological properties, including anticancer, anti­inflammatory and antiallergic effects. Based on these findings, the present study examined the effects of GM2 on an imiquimod (IMQ)­induced psoriasis mouse model and on keratinocytes stimulated by tumor necrosis factor (TNF)­α and interferon­Î³. IMQ was topically applied to the back skin of mice for 7 consecutive days, and the mice were orally administered CD. These results showed that the oral administration of GM2 suppressed the symptoms of psoriasis, as evidenced by reductions in skin thickness, psoriasis area severity index scores for psoriasis lesions, transepidermal water loss and myeloperoxidase (MPO)­associated cell infiltration. Furthermore, GM2 reduced the pathologically increased levels of immunoglobulin G2a, MPO and TNF­α in the serum and T helper (Th)1 and Th17 cell populations in the spleen. GM2 decreased the gene expression of inflammatory­related cytokines and chemokines and inhibited the expression of signal transducer and activator of transcription 1 and nuclear factor­κB in the activated keratinocytes. These results suggested that GM2 from S. chinensis is a potential therapeutic candidate to alleviate psoriasis­like skin inflammation.

Asunto(s)

Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lignanos/farmacología , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Imiquimod/toxicidad , Inflamación/inducido químicamente , Inflamación/genética , Interferón gamma/toxicidad , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Lignanos/uso terapéutico , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Psoriasis/inducido químicamente , Psoriasis/patología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Factor de Necrosis Tumoral alfa/toxicidad

RESUMEN

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1ß, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1ß, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.

Asunto(s)

Antiinflamatorios/farmacología , Ciclooctanos/farmacología , Dermatitis Atópica , Dermatophagoides farinae/inmunología , Dermis/inmunología , Dinitroclorobenceno/toxicidad , Epidermis/inmunología , FN-kappa B/inmunología , Factor de Transcripción STAT1/inmunología , Animales , Antiinflamatorios/química , Ciclooctanos/química , Citocinas/inmunología , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Ratones , Ratones Endogámicos BALB C

RESUMEN

Gomisin M2 isolated from Schisandra viridis A. C. Smith has potential anti-tumor effects on certain cancers, including breast cancer. However, only a few investigations have been conducted on the effects of Gomisin M2 on breast cancer stem cells (CSCs), which have the ability to self-renew and differentiate, as a possible strategy to resolve cancer cell resistance to apoptosis and to improve treatments. It is essential to investigate the effects of Gomisin M2 on breast cancer stem cells (BCSCs). In this study, we enriched breast cancer stem cells with CD44+/CD24- from MDA-MB-231 and HCC1806 cells through magnetic-activated cell sorting and cultured these in serum-free medium. The ability of Gomisin M2 to kill breast cancer stem cells was evaluated in vitro and in vivo. Gomisin M2 significantly inhibited the proliferation of the triple-negative breast cancer cell lines and mammosphere formation in breast CSCs and downregulated the Wnt/ß-catenin self-renewal pathway. Moreover, Gomisin M2 induced apoptosis and blocked the mitochondrial membrane potential of BCSCs. Gomisin M2 suppressed the proliferation of MDA-MB-231 and HCC1806 xenografts in zebrafish. Together, these findings suggest that the anti-BCSC activity of Gomisin M2 could become a promising starting point for the discovery of novel BCSC-targeting drugs.

Asunto(s)

Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Proliferación Celular/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Schisandra/química , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Pez Cebra

RESUMEN

Mast cells are effector cells that induce allergic inflammation by secreting inflammatory mediators. Gomisin M2 (G.M2) is a lignan isolated from Schisandra chinensis (Turcz). Baill. exhibiting anti-cancer activities. We aimed to investigate the anti-allergic effects and the underlying mechanism of G.M2 in mast cell-mediated allergic inflammation. For the in vitro study, we used mouse bone marrow-derived mast cells, RBL-2H3, and rat peritoneal mast cells. G.M2 inhibited mast cell degranulation upon immunoglobulin E (IgE) stimulation by suppressing the intracellular calcium. In addition, G.M2 inhibited the secretion of pro-inflammatory cytokines. These inhibitory effects were dependent on the suppression of FcεRI-mediated activation of signaling molecules. To confirm the anti-allergic effects of G.M2 in vivo, IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were utilized. Oral administration of G.M2 suppressed the PCA reactions in a dose-dependent manner. In addition, G.M2 reduced the ASA reactions, including hypothermia, histamine, interleukin-4, and IgE production. In conclusion, G.M2 exhibits anti-allergic effects through suppression of the Lyn and Fyn pathways in mast cells. According to these findings, we suggest that G.M2 has potential as a therapeutic agent for the treatment of allergic inflammatory diseases via suppression of mast cell activation.