(-)-Epigallocatechin gallate alleviates chronic unpredictable mild stress-induced depressive symptoms in mice by regulating the mTOR autophagy pathway and inhibiting NLRP3 inflammasome activation.

Depression is a global public health issue that is widely studied due to the large number of people it affects and its serious consequences. Clinical studies have shown that regular tea consumption may reduce depression risk. (-)-Epigallocatechin gallate (EGCG), the main tea polyphenol, was observed to alleviate depression, but the underlying mechanism has not been elucidated. In this study, chronic unpredictable mild stress (CUMS) was used to induce depression-like behavior in mice, and behavioral tests, such as sucrose preference test and forced swim test, were performed. Then, ELISA, western blot and QT-PCR tests were used to assess the expression of the key components of the NLRP3 inflammasome and its downstream inflammatory effectors (e.g., IL-1ß, IL-18), autophagy markers (Beclin-1, LC3, P62) and apoptosis markers (Bax, Bcl-2) in mouse brain tissues. Changes in serum lipid levels were also assessed. EGCG alleviated CUMS-induced depression-like behavioral changes in mice, reduced activation of the NLRP3 inflammasome, inhibited the mTOR signaling pathway, restored autophagy levels, reduced apoptosis marker expression and attenuated abnormal changes in blood lipid levels. Our study demonstrates that EGCG exerts antidepressive effects through multiple mechanisms, providing new insight into the pathological mechanism of depression and laying the foundation for the development of new therapeutic measures.

Esketamine prevents propofol-induced injection pain: Randomized controlled trial.

Background: Propofol is widely used during anesthesia. However, propofol-induced injection pain (PIP) is considered an unpleasant perioperative outcome. This study aimed to investigate the efficacy of a mixture of esketamine and propofol in preventing propofol injection pain in patients undergoing general anesthesia. Methods: This was a prospective, double-blind, multicenter, and randomized controlled trial. We included 252 adult patients with the American Society of Anesthesiologists physical status I to II who underwent surgery under general anesthesia. Patients were randomly allocated in a 1:1:1:1 ratio to four groups (n = 63 per group). Group NS received a mixture of 1% propofol (20 ml) and 0.9% normal saline (1 ml), group ESK-4 received a mixture of 1% propofol (20 ml) and esketamine 4 mg (diluted with 0.9% normal saline, 1 ml), group ESK-12 received a mixture of 1% propofol (20 ml) and esketamine 12 mg (diluted with 0.9% normal saline, 1 ml), and group ESK-20 received a mixture of 1% propofol (20 ml) and esketamine 20 mg (diluted with 0.9% normal saline, 1 ml) as sedative drugs during anesthesia. The primary outcome was the incidence and distribution of different degrees of PIP. The secondary outcomes were vital signs, characteristics of surgery and anesthesia, and adverse events. Results: The incidence of PIP in group ESK-20 (33.3%) was significantly lower than that in groups NS, ESK-4, and ESK-12 (63.3%, 62.2%, and 49.1%, respectively; p < 0.01). The incidence of moderate PIP in group NS (33.3%) and group ESK-4 (22.6%) was higher than that in groups ESK-12 (7.5%) and ESK-20 (6.7%). The incidence of severe PIP in group NS (6.7%) and group ESK-4 (9.4%) was higher than that in groups ESK-12 (1.9%) and ESK-20 (0%). There were no differences in the vital signs, characteristics of surgery and anesthesia, or adverse events between the groups. Conclusion: Our results indicated that the esketamine-propofol admixture reduced the incidence of PIP in patients undergoing general anesthesia without severe side effects.