Anemoside A3 rapidly reverses depression-like behaviors and weakening of excitatory synaptic transmission in mouse models of depression

Abstract

Background and aim: Developing fast-acting antidepressants attracts considerable attention. Anemoside A3, a natural triterpenoid glycoside isolated from Pulsatillae Radix, has been reported to produce antidepressant-like action in the forced swim test. We herein explore the fast-onset antidepressant-like potentials and antidepressant mechanisms of anemoside A3. Methods: The forced swim test and tail suspension test were used to determine the acute antidepressant-like action of anemoside A3. This action of anemoside A3 was confirmed in chronic mild stress and chronic social defeat stress models. In vitro extracellular field potential recordings were conducted to investigate the impact of anemoside A3 on chronic stress-induced alterations at temporoammonic-CA1 synapses. Western blot, whole-cell patch-clamp recordings, and microinjections of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonists into the stratum lacunosum-moleculare were performed to unravel the contribution of stratum lacunosum-moleculare α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors to anemoside A3’s antidepressant-like activity. In vivo microdialysis and pharmacological depletion of serotonin were implemented to examine the role of the serotonin system in the antidepressant-like effect of anemoside A3. Results: Anemoside A3 administered intraperitoneally displayed acute antidepressant-like effects in the mouse forced swim test and tail suspension test and anemoside A3 treatment (intraperitoneally) for five days was sufficient to reverse depression-related behaviors of mice subjected to chronic stress. Accordingly, chronic social defeat stress-induced weakening of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-mediated neurotransmission in the temporoammonic-CA1 pathway and downregulation of synaptic GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor expression in the stratum lacunosum-moleculare could both be normalized by five days of anemoside A3 treatment (intraperitoneally). Moreover, intra-stratum lacunosum-moleculare infusion of GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist abolished anemoside A3’s antidepressant-like effect. Lastly, serotonin system was not implicated in anemoside A3’s antidepressant-like effect. Conclusions: Our results suggest that anemoside A3 induces a rapid antidepressant-like response by a stratum lacunosum-moleculare GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-dependent mechanism. In view of this, anemoside A3 represents a promising agent for depression treatment.

Anemoside B4 alleviates DSS-induced colitis by inhibiting CD1d-dependent NLRP3 inflammasome activation in macrophages

“…It contains a large number of triterpenoids saponins and is considered to be its main active ingredient Ma et al, 2020;Zhang et al, 2021). Among them, the contents of AB4, AA3, and 23-HA are higher (Ip et al, 2017;Wang, Lin, Lin, Yao, & Zhang, 2019;Yao et al, 2018;Ye & Ji, 2012). In order to further clarify the main active ingredients of BTWT anti-colitis efficacy.…”

Anemoside B4 alleviates DSS-induced colitis by inhibiting CD1d-dependent NLRP3 inflammasome activation in macrophages

“…Among them, the content of AB4 is the highest, which can be used as the quality control index of BTWT. [34][35][36][37]. To evalute the anti-in ammatory activity of AB4, we investigated the role of AB4 in 3.0%DSS-induced colitis.…”

Role of Plant-Derived Natural Compounds in Experimental Autoimmune Encephalomyelitis: A Review of the Treatment Potential and Development Strategy

“…In mouse models, the mice were dosed with anemoside (AA3) at 30–300 mg/kg ( Ip et al, 2015 ; Ip et al, 2017 ; Wang C. et al, 2019 ). AA3 is usually administered intraperitoneally and orally ( Ip et al, 2015 ; Ip et al, 2017 ).…”