Lung-protective effect of Punicalagin on LPS-induced acute lung injury in mice.

BACKGROUND: Punicalagin (Pun) is one of the main bioactive compounds in pomegranate peel, it possesses many properties, including antioxidant, anti-inflammation and immunosuppressive activities. The study was aimed to investigate the protective effect and mechanisms of Pun on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS AND RESULTS: Forty-eight BALB/c male mice were used to establish ALI by intratracheal-instilled 2.4 mg/kg LPS, the mice were randomly divided into model and Pun (10, 20, 40 mg/kg) groups. The other 12 mice were intratracheal-instilled same volume of water as control. After 2 h of receiving LPS, mice were administered drug through intraperitoneal injection. Lung index, histopathological changes, white blood cells and biomarkers in bronchoalveolar lavage fluid (BALF) were analyzed. The protein expression of total and phosphor p65, IκBα, ERK1/2, JNK and p38 in lung tissue was detected. The result showed that Pun could reduce the lung index and wet/dry weight (W/D) ratio, improve lung histopathological injury. In addition, Pun decreased the inflammation cells and regulated the biomarkers in BALF. Furthermore, Pun dose-dependently reduced the phosphor protein levels of p65, IκBα, ERK1/2, JNK and p38 in lung tissue, which exhibited that the effect of Pun related to mitogen-activated protein kinases (MAPKs) pathway. More importantly, there was no toxicity was observed in the acute toxicity study of Pun. CONCLUSION: Pun improves LPS-induced ALI mainly through its anti-inflammatory properties, which is associated with nuclear factor-κB (NF-κB) and MAPKs signaling pathways. The study implied that Pun maybe a potent agent against ALI in future clinic.

Pathogenic Characteristics of Th17 Cells Based on the IL-17 Signaling Pathway in the Regulation of Sebaceous Gland Lipoprotein Metabolism in an Acne Rat Model.

BACKGROUND: Acne is a common and chronic inflammatory dermatosis of sebaceous gland units of the human hair follicle. Acne is closely related to immune cytokines and cells including T helper 17cells (Th17 cells). Mis-regulated glycolipid metabolism also plays a vital role in the process. OBJECTIVE: This investigation aimed to explore the role of IL-17 in signaling pathways controlling sebaceous gland lipoprotein metabolism in a rat model of acne. METHODS: We generated the rat ear acne model, and investigated the pathological changes of acne skin tissue by histological analysis and the changes in the critical factors including DEFB1, GPR65, FADS1, and FADS2 by Western Blot in this model. RESULTS: There were more Th17 cells in the rat ear acne model than in the control mice. The expression levels of DEFB1, GPR65, FADS1, FADS2 and MOGAT1 were significantly upregulated in serum and tissue from rat acne model, which could be concluded that the Th17 cells play a major role in the pathogenesis of acne based. CONCLUSION: Although acne is associated with immune effects and glycolipid metabolism, inhibition of IL-17 signaling pathway might be a novel way for acne therapy. Our findings also suggest a new strategy for targeted therapy of acne.

Curcumin against imiquimod-induced psoriasis of mice through IL-6/STAT3 signaling pathway.

BACKGROUND: To explore the possible mechanism of Curcumin (Cur) for protecting imiquimod-induced psoriasis in mice. METHODS AND RESULTS: Sixty BALB/c mice were removal the back hair about 2 cm × 3 cm and divided into five groups. The control group was used Vaseline, the model and the drug group used 5% imiquimod in the back skin for 7 days, once time a day (62.5 mg/day/mice). At the same time, control and model mice were intragastric administration of normal saline, while the drug group were orally administrated with 50, 100 and 200 mg/kg Cur, respectively. The morphology, histopathological changes were observed. The serum levels of tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) were analyzed by ELISA. The protein expression levels of phosphorylation STAT 3 and its down-stream protein expression in lesion skin were detected by western blot. The protein expression of TNF-α and IL-6 in lesion skin were analyzed by immunohistochemistry. The result showed that Cur could improve the lesion skin pathological, decrease the levels of TNF-α and IL-6 in serum and in lesion skin of psoriasis mice. In addition, Cur also reduced the protein levels of phosphorylation STAT 3 and its down-stream protein levels of Cyclin D1, Bcl-2 and Pim 1 in lesion skin of psoriasis mice. CONCLUSION: Cur could effectivly improve the pathological characteristics of psoriasis mice, which may be through the regulation of IL-6/STAT3 signaling pathway.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.