Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein-coupled estrogen receptor: Probing a possible target for allergic inflammation.

Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali, on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)-induced allergic asthma mouse model and TNF-α and Poly(I:C) co-stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein-coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E-cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans-epithelial electric resistance (TEER). Cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E-cadherin in vivo and in vitro. The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERß agonist), G1 (GPER agonist) significantly inhibited TSLP, up-regulated occludin, and restored E-cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation.

Synthesis, Anti-Varicella-Zoster Virus and Anti-Cytomegalovirus Activity of 4,5-Disubstituted 1,2,3-(1H)-Triazoles.

BACKGROUND: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required. OBJECTIVE: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs. METHODS: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro. RESULTS: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK- VZV strains. CONCLUSION: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs.

[Seasonal variation of Cyclobalanopsis glauca whole-tree transpiration in karst region].

By using Granier's sap-flow method, the variations of sap flux density and whole-tree transpiration of Cyclobalanopsis glauca (syn. Quercus glauca) on a hilly slope in the karst region of South China were studied, with their driving factors analyzed. The sap flux density (Js) of C. glauca varied randomly with the diameter of breast height of individual trees, and its maximum occurred at 13:30-14:30. In a seasonal course, the daily Js was the maximum (56.00 g H2O x m(-2) x s(-1)) in summer, and the minimum (35.86 g H2O x m(-2) x s(-1)) in spring. The daily whole-tree transpiration had a greater change with weather condition, representing a power functional relationship with vapor pressure deficit (VPD) and photosynthesically active radiation (PAR) (R = 0.97, P < 0.01). The average daily whole-tree transpiration tended to be high in summer and low in winter and spring, and decreased with the decrease of soil moisture content in autumn (drought season). However, comparing with that of the tree species in other regions, the daily whole-tree transpiration amount of C. glauca in study region was still higher, even though the weather was dry and the soil was thin. It was presumed that in the dry season in karst region, the water supply for C. glauca could be mainly depended on the water-rich epikarst.