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Objective To investigate the effect of baicalin(BA)regulating cyclic adenosine phosphate(cAMP)/protein kinase A(PKA)/cAMP response elemen-binding protein(CREB)pathway on skin barrier function in eczema rats.Methods SD rats were randomly divided into the control group(NC group),the model group,the low-dose BA group(BA-L group,25 mg/kg),the medium-dose BA group(BA-M group,50 mg/kg),the high-dose BA group(BA-H group,100 mg/kg),the prednisone group(PNS group,25 mg/kg),the BA-H+cAMP inhibitor(SQ22536)group(100 mg/kg+2.13 mg/kg)and the BA-H+PKA inhibitor(H-89)group(100 mg/kg+5 mg/kg),12 animals in each group.Except for the NC group,eczema rat model was constructed in the other groups.Two days after successful modeling,drug administration was performed in groups.Changes of eczema area and severity index(EASI)score,transcutaneous water loss(TEWL)and cuticle water content(WCSC)were detected.Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of immunoglobulin E(IgE),interferon-γ(IFN-γ)and interleukin-4(IL-4)in rat serum and the expression of cAMP protein in rat back lesions.HE staining was used to detect pathological changes of skin lesions on the back of rats.Western blot assay was used to detect aquaporin 3(AQP3),cathelicidin related antimicrobial peptide(CRAMP),p-PKA,p-CREB protein expression in rat back lesions.Results Compared with the NC group,rats had serious pathological lesions on the back of the tested area,increased EASI score,TEWL,IgE and IL-4 levels,and decreased WCSC,IFN-γ,AQP3,CRAMP,cAMP,p-PKA and p-CREB protein levels in the model group(P<0.05).Compared with the model group,pathological lesion of the tested area in the back of rats was relieved,and EASI score,TEWL,IgE and IL-4 levels were decreased,WCSC,IFN-γ levels,AQP3,CRAMP,cAMP,p-PKA and p-CREB protein were increased in the BA-L group,the BA-M group,the BA-H group and the PNS group(P＜0.05).Changes of above indexes in the BA-L group,the BA-M group,the BA-H group were dose-dependent.SQ22536 or H-89 attenuated the improvement effect of high dose BA on skin barrier function in eczema rats.Conclusion BA may improve skin barrier function in eczema rats by activating cAMP/PKA/CREB signaling pathway.
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Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]- 22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol- 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.
Résumé
Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]- 22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol- 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.
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Objective To investigate the susceptibility ofepidermal cells to ultraviolet A(UVA)-induced apoptosis in dopachrome tautomerase knockout Dct~(-/-) mice versus wildtype C57BL/6J mice.Methods High titer of anti-Ro/SSA-positive sera collected from three patients with SLE and typical cutaneous phntosensitivity were intraperitoneally injected into both Dct~(-/-) and wildtype mice,which were then chronically exposed to UVA irradiation at a single dose of 10 J/cm~2 three times a week for two weeks.Then,UVA-irradiated tail skin was excised from each mouse,embedded with paraffin,cut into 4 to 5-μm sections followed by hematoxylin/eosin staining and terminal deoxynucleotidyl transferase nick end labeling(TUNEL),respectively,for the counting of sunburn cells(SBC) and apoptotie cells.Results After chronic UVA exposure,the number of SBC and TUNEL-positive cells per 100 epithelial cells was significantly higher in serum-injected Dct~(-/-) mice than in serum-injected wildtype mice(14±1.0 vs 7±-0.6,62±2.7 vs 30 ±1.6,both P<0.05).A significant decrease was also observed in the number of SBC (6 ±0.9 per 1 00 epithelial cells)and TUNEL-positive cells (42±2.5 per 100 epithelial cells)in uninjected Dct~(-/-) mice compared with those of serum-injcoted Dct~(-/-) mice(both P<0.05).Conclusions The deficiency of Dct gene increases the susceptibility of epidermal cells to UVA-induced apoptosis under the presence of anti-Ro/SSA antibody,which potentially contributes to the develop-ment of anti-Ro/SSA antibody-mediated photosensitivity in SLE.
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< 0.05; 8.9% vs 0.1%, x2 = 8.23, P< 0.05). Conclusion Low concentration (0.1%) of DMSO could enhance the effect of ALA-PDT on HaCaT cells.