Objective: In recent years, the lung-gut axis has received increasing attention. The oxidative stress and systemic hypoxia occurring in chronic obstructive pulmonary disease (COPD) are related to gut dysfunction. That suggests probiotics have a potential therapeutic role in COPD. In this study, we therefore evaluated the ameliorative effects of probiotics on COPD.Methods: Searches were conducted in four electronic databases, including PubMed, Cochrane Library, the NIH clinical registry Clinical Trials. Gov and EMBASE. The data extracted was analyzed statistically in this study using StataMP17 software, with mean difference (MD) chosen as the effect size for continuous variables, and the results expressed as effect sizes and their 95% confidence intervals (CIs). Standardized Mean Difference (SMD) was used if the data units were different.Results: We included three randomized, controlled, double-blind clinical trials and five randomized controlled animal studies. The results show that for lung function, probiotics improved %FEV1 in COPD patients (MD = 3.02, 95%CI: 1.10, 4.93). Additionally, in inflammation, probiotics increased IL-10 (SMD = 1.99, 95%CI: 1.02, 2.96) and decreased inflammatory markers such as TNF-α (SMD= -2.64, 95%Cl: -3.38, -1.90), IL-1β (SMD= -3.49, 95%Cl: -4.58, -2.40), and IL-6 (SMD= -6.54, 95%Cl: -8.36, -4.73) in COPD animals, while having no significant effect on C-reactive protein (MD = 0.30, 95%CI: -0.71, 1.32) in COPD patients. For lung structure, probiotics significantly reduced the degree of pulmonary collagen fibers deposition in COPD animals (SMD = -2.25, 95%CI: -3.08, -1.41).Conclusion: Overall, probiotics may be an additional approach that can improve COPD. Further clinical trials are needed to evaluate the efficacy, safety, and impact factors of probiotics for COPD.Systematic Review Registration: https://inplasy.com/inplasy-2023-4-0023/, identifier INPLASY202340023.

Background/Objectives: Insomnia is a prevalent clinical sleep disorder, with existing hypnotic therapies limited by safety concerns. There is an urgent clinical need for new safe, effective sleep-promoting candidates derived from natural products. Spinosin is one of the main active components of Semen Ziziphi Spinosae that exerts sedative and hypnotic effects. The adenosine receptor (AR) has been reported as a potential therapeutic target for insomnia; however, the hypnotic effect of spinosin through the A_2AR remains to be elucidated. Methods: In the study, the involvement of A_2ARs in spinosin’s hypnotic effect was investigated using caffeine and further elucidated in A_2AR-knockout (KO) mice. Diazepam was used as a positive control drug to validate the experimental model and evaluate the hypnotic effect of spinosin. Molecular docking and molecular dynamics (MDs) simulations were performed to validate the interaction of spinosin with the A_2AR. Results: The hypnotic effects of spinosin were effectively antagonized by caffeine. Compared with A_2AR-wild-type (WT) mice, spinosin-induced non-rapid eye movement (NREM) sleep and locomotor activity diminution were significantly reduced in A_2AR-KO mice. Spinosin significantly increased the activity of γ-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and significantly decreased the activity of orexin neurons in the lateral hypothalamus (LH), as revealed by c-Fos immunostaining. These effects were significantly reversed by caffeine pretreatment or in A_2AR-KO mice. Finally, the results of molecular docking showed that spinosin had a good binding potential with the A_2AR. MD simulations further demonstrated that spinosin had strong binding stability with the A_2AR. Conclusions: Our findings strongly suggest that spinosin exerts the hypnotic effects through the A_2AR, and thus may have therapeutic potential for insomnia. Our identification of spinosin’s direct molecular target supports its translational potential as a novel natural-origin candidate for clinical insomnia drug development.