Background: Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH₂ cytokines, eotaxin, prostaglandin D₂ (PGD₂) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved. Methods: The effect of Ac2-26 on TH₂ cytokine release, eotaxin production, PGD₂ levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD₂ were examined. Results: Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD₂ and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD₂ significantly attenuated the biological effects of Ac2-26. Conclusion: These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD₂ reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD₂ production and its CRTH2 receptor expression in vivo.

Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11-5 [3-(3, 4-methylenedioxy-5-trifluoromethyl phenyl)-2Epropenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11-5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2-week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD-1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11-5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS-exposed mice, suggesting remarkable antidepressant effect. Moreover, G11-5 ameliorated the changes in mitophagy-related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11-5 exhibited an obvious antidepressant through TSPO-mediated mitophagy pathway.