PPARγ mediates the anti-pulmonary fibrosis effect of icaritin.

BACKGROUND: Pulmonary fibrosis is a fatal lung disease with limited treatment options. Icaritin is the active ingredient derived from the traditional Chinese medical plant Epimedium and possesses many biomedical activities. This study aimed to investigate the effects and molecular mechanisms of icaritin on bleomycin-induced pulmonary fibrosis in mice. METHODS: To assess its preventative effects, bleomycin treated mice received 0, 0.04, 0.2, and 1 mg/kg of icaritin from day 1 onwards. To assess its therapeutic effects, bleomycin treated mice received 0 and 1 mg/kg of icaritin from day 15 onwards. Mice were sacrificed on day 21 and lung tissues were collected, stained with HE, Masson and immunohistochemistry. Q-PCR was used to measure Collagen I and Collagen III expression, western blotting was used to quantify α-SMA, Collagen I expression. Hydroxyproline content was measured using a biochemical method. NIH3T3 and HLF-1 cells were treated with TGF-ß1with or without icaritin, and α-SMA, Collagen I were tested. PPARγ antagonist GW9662 and PPARγ-targeted siRNA were used to investigate the mechanism of icaritin in inhibiting myofibroblast differentiation. RESULTS: Both preventative and therapeutic administration of icaritin improved the histopathological changes, decreased Collagen and α-SMA, lowered hydroxyproline content in bleomycin-treated lung tissues. Icaritin decreased α-SMA and Collagen I expression in TGF-ß1-stimulated NIH3T3 and HLF-1 cells. However, its effect in reducing α-SMA and Collagen I expression was suppressed when expression or activity of PPARγ was inhibited. CONCLUSIONS: Icaritin has therapeutic potential against pulmonary fibrosis via the inhibition of myofibroblast differentiation, which may be mediated by PPARγ.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

[The neuroprotective effects and its mechanisms of qingkailing injection on bacterial meningitis induced by E. coli in rabbits].

OBJECTIVE: To explore the neuro-protective effect and mechanism of qingkailing injection (QKL) against cerebral injury caused by E. coli-meningitis (CM). METHODS: The CM model rabbits were treated by ampicillin with QKL as adjuvant. The leukocyte count and protein content in cerebral spinal fluid (CSF), the contents of water, sodium, potassium and calcium in cerebral tissues were measured before, 16 h and 26 h after Bacillus coli injection respectively. The expression of matrix metalloproteinase-9 (MMP-9) was determined at the same time. RESULTS: Adjunctive treatment with QKL can not only inhibit the increase of leukocyte cells, protein content in CSF, and water, sodium, calcium content in cerebral tissues, but also the decrease of potassium content revealed during simple antibiotic treatment. It also can decrease the expression of MMP-9 in cerebral tissues of rabbits with CM. CONCLUSION: As an adjunctive treatment, QKL can prevent transient inflammatory reaction and aggravation of brain injury in CM induced by simple antibiotic treatment, its mechanisms might relate with calcium antagonism and attenuation of MMP-9 expression in brain tissues.

[Effect of shenfu injection on the synthesis of pulmonary surfactant in cultured lung explants].

OBJECTIVE: To explore the effect of shenfu injection on pulmonary surfactant synthesis. METHODS: Lung explants of adult rats were cultured in free serum DMEM. [3H] choline incorporated into lung tissue was determined by liquid scintillation system. The contents of total phospholipid (TPL) and phosphatidylcholine (PC) in lung tissue were measured by inorganic phosphorus quantitative analysis and thin-layer chromatography, respectively. RESULTS: Shenfu injection enhanced [3H] choline incorporation in a dose-dependent manner and increased the contents of TPL and PC as well as the ratio of PC/TPL. Both protein kinase C (PKC) antagonist H7 and calmodulin antagonist W7 inhibited the effects of Shenfu injection. The ginsenosides, ginsenoside Rb1, and ginsenoside Rg1 promoted the [3H] choline incorporation. CONCLUSION: Shenfu injection can enhance the synthesis of pulmonary surfactant through pathways mediated by PKC and calmodulin. The ginsenoside is an effective component in Shenfu injection.