Objective To investigate the effects of curcumin on UVB-induced elevation of cellular ROS level and cell death and to explore the involvement of transcription factor Nrf2.Methods Mouse embryonic fibroblasts (MEFs) were pretreated with or without curcumin then irradiated with UVB.The cell viability,cellular ROS level and protein levels of Nrf2 and HO1 were determined by MTT assay,DCFH fluorescence and Western blotting,respectively.These measurements were also performed in Nrf2 (-/-) MEFs.Results UVB irradiation elevated cellular ROS level and decreased cell viability of MEFs(t =16.65,15.89,P ＜ 0.05),while the curcumin pretreatment significantly attenuated the deleterious effects of UVB(t =11.88,3.77,P ＜ 0.05).UVB irradiation moderately increased the protein levels of Nrf2 and HO1 and activated JNK and ERK.The curcumin pretreatment led to more remarked elevation of Nrf2 and HO1 proteins,while inhibited UVB-activated JNK and ERK,but it had little effect on p38MAPK.In contrast,Nrf2 (-/-) MEFs showed significantly decrease in Nrf2 and HO1 expressions and were more susceptible to UVB-induced damages.Interestingly,the protective effects of curcumin were also greatly compromised in Nrf2 (-/-) MEFs (t =16.73,-8.23,P ＜ 0.05).Conclusions Curcumin can attenuate UVB-induced oxidative damages in MEFs by activating Nrf2 signaling.

Orally inhaled drug products (OIDPs) play a great role in the pharmacological treatment of chronic obstructive pulmonary disease (COPD) and asthma. There is an unmet clinical need for OIDPs. Pharmacodynamics-Bioequivalence studies (PD-BE) are recommended by several national guidelines as important research methods for bioequivalence study of OIDPs. It can effectively bridge the gap between in vitro studies and PK-BE studies in evaluating the efficacy and safety consistency of generic drugs with the original drugs. There are two research methods for PD-BE, using a diastolic model or an excitation model. The different methods use different metrics to evaluate efficacy. The more commonly used metrics include Forced Expiratory Volume in the First Second (FEV1), Specific Airway Conductance (sGaw), Peripheral Airway Resistance (R5-20), and stimulant concentration/dose (PC20/PD20). PD-BE studies using FEV1 as an efficacy metric is also recommended by the FDA (Food and Drug Administration), EMA (European Medicines Agency) and NMPA (National Medical Products Administration) guidelines and is widely accepted by investigators. In such PD-BE studies, the trial protocols for different OIDPs drugs are relatively consistent in terms of trial design, trial data processing, and equivalence evaluation criteria, while there are detailed differences in terms of target population, single/multiple dosing, dose administration, and collection site design. This paper reviews the progress of PD-BE studies in the bioequivalence evaluation of OIDPs by combining national guidelines and PD-BE-related studies of OIDPs published in the last five years, with a view to providing important theoretical information for PD-BE studies of OIDPs.