Xiaoyaosan promotes neurotransmitter transmission and alleviates CUMS-induced depression by regulating the expression of Oct1 and Oct3 in astrocytes of the prefrontal cortex.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription for the treatment of liver depression and qi stagnation, and pharmacological studies have shown that XYS has great potential to reverse depression. However, anti-depression targets and the mechanism of XYS are still not entirely clear. AIM OF THE STUDY: The present study aims to explore and verify the anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant effect of XYS was assessed in rats with depression induced by chronic unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in different brain regions were measured using ELISA. The expression of organic cation transporters (Octs) were detected by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the correlation between Octs and depression-like behavior. Then, the effects of XYS on the behavior, neurotransmitter concentration, and Octs expression in D22-induced rats were examined. Finally, primary astrocytes were used to verify the mechanism of XYS exerting anti-depressant activity by regulating Octs. RESULTS: The result showed that XYS had a significant positive impact on the behavior of depression rats induced by CUMS. XYS also improved the secretion of 5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 expression in the PFC. These results suggest that XYS has the potential to alleviate depression by enhancing the secretion of neurotransmitters. This may be related to XYS regulation of Oct's expression. When the expression of Octs was inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was able to reverse this behavior, indicating that Octs play a significant role in the development of depression and XYS may exert its antidepressant effects through the regulation of Octs. Furthermore, the study also found that dopamine uptake decreased after inhibiting the expression of Octs, and XYS-containing serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant effects by promoting dopamine uptake to improve neurotransmitter transport by regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: The antidepressant effect of XYS may be attributed to its ability to regulate the expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting neurotransmitter transport.

Investigation of the effective components of the flowers of Trollius chinensis from the perspectives of intestinal bacterial transformation and intestinal absorption.

CONTEXT: The flowers of Trollius chinensis Bunge (Ranunculaceae), used for respiratory tract infections, mainly contain flavonoids, phenolic acids, and alkaloids; however, the effective components are debatable because of their unclear in vivo activities. OBJECTIVE: This study investigates the effective components from the perspectives of biotransformation and absorption. MATERIALS AND METHODS: Both single person derived- and multiple people-derived intestinal florae were used to investigate the biotransformation of aqueous extract of the flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0 mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2) monolayers and everted gut sacs were employed to evaluate the intestinal absorption of the intestinal bacterial transformed AEOF at the concentrations of 10, 20, and 30 mg/mL, respectively, for 180 min. RESULTS: 2″-O-ß-l-Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid, proglobeflowery acid, and trolline in AEOF were not transformed by intestinal bacteria, while isoquercetin and trollioside were completely transformed. The Papp values of 2″-O-ß-l-galactopyranosylorientin, orientin, and vitexin calculated based on the experimental data of intestinal absorption were at the levels of 10-5, whereas those of veratric acid, proglobeflowery acid, and trolline were at 10-4. The mass ratio of flavonoids to phenolic acids to alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. DISCUSSION AND CONCLUSION: The dominant position of flavonoids was replaced by phenolic acids after absorption. In addition to flavonoids which are usually considered as the dominant effective ones, phenolic acids and alkaloids should be also very important for the efficacy of these flowers.

Shenqifuzheng injection combined with chemotherapy in the treatment of advanced gastric cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of Shenqifuzheng (SQFZ) injection combined with chemotherapy in the treatment of advanced gastric cancer. MATERIALS AND METHODS: We conducted an electronic search by using PubMed, EMBASE, ASCO, ESMO and Chinese National Knowledge Infratructure (CNKI), databases. The randomized controlled trials about Shenqifuzheng injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric cancer were reviewed and collected. Pooled odds ratio (OR) for the response rate and KPS improvement were calculated using the software MetaAnalyst 3.1. RESULTS: Fifteen trials met our inclusion criteria and finally included in this meta-analysis. The objective response rate (ORR) in patients treated with Shenqifuzheng injection combined with chemotherapy was much higher than that of chemotherapy only (OR = 1.66, 95% CI: 1.20-2.29) with statistical significance (P < 0.05). The pooled data showed the combined treatment can significant increase the Karnofsky score (KPS) compared with the chemotherapy only (OR = 3.74, 95% CI: 2.66-5.27 (P < 0.05). CONCLUSION: SQFZ injection combined with chemotherapy treatment regimen can improve the clinical efficacy and performance status in patients with advanced gastric cancer compared with chemotherapy alone.