The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

Chinese herbal injections plus Western Medicine on inflammatory factors for patients with acute exacerbation of chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

Background: Chinese herbal injections (CHIs) are commonly prescribed in China as adjuvant therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, evidence supporting the effect of CHIs on inflammatory factors for patients with AECOPD is insufficient, posing a challenge for clinicians to choose the optimal CHIs for AECOPD. This network meta-analysis (NMA) aimed to compare the effectiveness of several CHIs combined with Western Medicine (WM) and WM alone on the inflammatory factors in AECOPD. Methods: Randomized controlled trials (RCTs) on different CHIs for treating AECOPD were thoroughly searched from several electronic databases up to August 2022. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. Bayesian network meta-analyses were designed to assess the effectiveness of different CHIs. Systematic Review Registration CRD42022323996. Results: A total of 94 eligible RCTs involving 7,948 patients were enrolled in this study. The NMA results showed that using Xuebijing (XBJ), Reduning (RDN), Tanreqing (TRQ), and Xiyanping (XYP) injections combined with WM significantly improved treatment effects compared to using WM alone. XBJ + WM and TRQ + WM significantly changed the level of C-reactive protein (CRP), white blood cells, percentage of neutrophils, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). TRQ + WM showed the most significant effect in reducing the level of procalcitonin. XYP + WM and RDN + WM could reduce the level of white blood cells and the percentage of neutrophils. A total of 12 studies reported adverse reactions in detail, and 19 studies demonstrated no significant adverse reactions. Conclusions: This NMA showed that using CHIs combined with WM could significantly reduce the level of inflammatory factors in AECOPD. A combination of TRQ and WM may be a relatively prior adjuvant therapy option for AECOPD treatment considering its effects in reducing the levels of the anti-inflammatory mediators.

Depression Exacerbates Dextran Sulfate Sodium-Induced Colitis via IRF5-Mediated Macrophage Polarization.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and concurrent depression are predisposed to severer disease activity and a worse prognosis. Macrophage polarization toward the M1 phenotype may contribute to the exacerbation of IBD with comorbid depression. Moreover, interferon regulatory factor 5 (IRF5) is involved in the pathogenesis of IBD. The aim of this study was to explore the role of IRF5 in macrophage polarization in the impact of depression upon colitis. METHODS: Depressive-like behavior was induced by repeated forced swim stress. Colon length, disease activity index (DAI), colon morphology, histology, ultrastructure of epithelial barrier, lamina propria macrophage polarization, and expression of IRF5 were compared between DSS colitis rats with and without depressive-like behavior. IRF5 shRNA was constructed to affect the rat peritoneal macrophages polarization in vitro. After IRF5 shRNA lentivirus was introduced into colon by enema, the colitis severity, lamina propria macrophage polarization, and TNF-α, IL-1ß, and IL-10 of colon tissues were measured. RESULTS: The study found severer colonic inflammation in depressed versus non-depressed DSS-colitis rats. Depressed DSS-colitis rats exhibited smaller subepithelial macrophages size and reduced intracellular granule diversity compared with nondepressed DSS-colitis rats. Increased polarization toward the M1 phenotype, elevated expression of IRF5, and co-expression of IRF5 with CD86 were found in depressed versus nondepressed DSS-colitis rats. Lentivirus-mediated shRNA interference with IRF5 expression switched rat peritoneal macrophage polarization from the M1 to the M2 phenotype, downregulated TNF-α, IL-1ß expression to a greater extent in depressed versus nondepressed colitis rats. CONCLUSIONS: IRF5-mediated macrophage polarization may likely underlie the deterioration of DSS-induced colitis caused by depression.

Cang-Ai Volatile Oil Ameliorates Depressive Behavior Induced by Chronic Stress Through IDO-Mediated Tryptophan Degradation Pathway.

Background: Cang-ai volatile oil (CAVO) is a Chinese herbal volatile oil. Previous studies report that CAVO exhibits of anti-depressant and anti-inflammatory effects, and modulates activity of monoamine neurotransmitter. The current study sought to explore whether CAVO exhibits anti-depressant effects of CAVO through inhibition of inflammatory response and regulation of indoleamine 2 and 3-dioxygenase (IDO) mediated tryptophan degradation pathway. Methods: The study established chronic unpredictable mild stress (CUMS) depression-like model using rats. Body weight and food intake of animals were determined, and open field test (OFT), forced swim test (FST), and sucrose preference test (SPT) were performed to explored the behavioral changes of animals. Expression levels of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), kynurenine (KYN), quinolinic acid (QUIN), tryptophan (Trp), kynurenic acid (KYNA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) in the prefrontal cortex of CUMS rats were determined by ELISA. Co-localization of the microglia markers, Iba1 and IL-6 was determined by immunofluorescence. Western blotting was performed to determine the protein expression level of IDO1. Results: The findings of the current study showed that CAVO increased the body weight and food intake of rats and alleviated depression-like behaviors as shown in OFT, FST, and SPT analysis. ELISA assay showed that CAVO decreased IL-6, IL-1ß, TNF-α, and IFN-γ levels and increased levels of IL-4 and IL-10 in the prefrontal cortex of CUMS rats. Analysis showed that CAVO significantly reduced KYN and QUIN levels and the ratio of KYN/Trp, whereas it increased the levels of Trp, KYNA, 5-HT, and 5-HIAA. Immunofluorescence analysis showed that CAVO reduced the number of positive cells with co-localization of microglia markers, Iba1 and IL-6. Western blot analysis showed that CAVO decreased the protein expression level of IDO1 in rats. Conclusion: The findings show that the anti-depressant effects of CAVO are mainly attributed to inhibition of the activation of microglia and downregulation of IDO expression, thus inhibiting the kynurenine pathway and reversing the effects exerted on the 5-HT system.

Effect and mechanism of ethanol extracts of muxiang (Radix Aucklandiae) on gastric ulcers in rats.

OBJECTIVE: To investigate the effect of ethanol extracts of Muxiang (Radix Aucklandiae) (RA) on gastric ulcers in rats and explore the potential mechanisms. METHODS: A model was established by ethanol (0.75 mL/kg). According to body weight, rats were pretreated with RA extracts (2.5 or 5 g/kg). The rats were administered 95% ethanol orally after 1 h. The effects of ethanol were evaluated by measuring the gastric secretion volume, pH, pepsin activity, and ulcer area. Histological analysis and immunohistochemistry were also conducted. Furthermore, the effect of the ethanol extract of RA on transiting activity of the gastrointestinal tract was observed in mice. RESULTS: Intragastric administration of RA extracts protected the gastric mucosa from ethanol-induced gastric ulcers, while reducing submucosal edema and preventing hemorrhagic damage. Moreover, the extracts increased the production of gastric mucus, upregulated Bcl-2, and downregulated Bax expression. Importantly, pretreated rats exhibited no significant change in the gastric secretion volume, gastric juice acidity, or pepsin. Furthermore, pretreatment prominently (P < 0.05) enhanced propulsive movement of the gastrointestinal tract in normal mice and mice with gastrointestinal motility disorders. CONCLUSION: Ethanol extracts of RA ameliorated gastric lesions in the gastric ulcer rat model. The mechanisms of action were related to improvement of gastrointestinal dynamics, maintenance of mucus integrity, and inhibition of apoptosis by downregulating proapoptotic Bax protein and upregulating anti-apoptotic Bcl-2 protein.

[Excretion of (-)-clausenamide in rats].

AIM: To study the excretion of (-)-clausenamide in rats. METHODS: The urine, feces and bile were collected at predetermined time points after (-)-clausenamide was orally administrated to 6 rats (30 mg x kg(-1)). The concentrations of (-)-clausenamide and its metabolite 6-OH-(-)-clausnamide were determined by HPLC-MS/MS method using glipzide as the internal reference, and the accumulative excretion amount of (-)-clausenamide and 6-OH-(-)-clausenamide was calculated in the urine, feces and bile, separately. RESULTS: (-)-Clausenamide was recovered mostly (44%) from feces in 112 hours, 7.1% was found from urine in 120 hours and 0.013% was detected from bile in 24 hours. The accumulative excretions of 6-OH-(-)-clausenamide were 0.92% , 0.46% and 0.0003% of the administered dose from feces, urine and bile, respectively. CONCLUSION: The major amount of (-)-clausenamide was recovered from feces after (-)-clausenamide was orally administrated to rats (30 mg kg(-1)).

Excretion of (-)-clausenamide in rats / 药学学报

<p><b>AIM</b>To study the excretion of (-)-clausenamide in rats.</p><p><b>METHODS</b>The urine, feces and bile were collected at predetermined time points after (-)-clausenamide was orally administrated to 6 rats (30 mg x kg(-1)). The concentrations of (-)-clausenamide and its metabolite 6-OH-(-)-clausnamide were determined by HPLC-MS/MS method using glipzide as the internal reference, and the accumulative excretion amount of (-)-clausenamide and 6-OH-(-)-clausenamide was calculated in the urine, feces and bile, separately.</p><p><b>RESULTS</b>(-)-Clausenamide was recovered mostly (44%) from feces in 112 hours, 7.1% was found from urine in 120 hours and 0.013% was detected from bile in 24 hours. The accumulative excretions of 6-OH-(-)-clausenamide were 0.92% , 0.46% and 0.0003% of the administered dose from feces, urine and bile, respectively.</p><p><b>CONCLUSION</b>The major amount of (-)-clausenamide was recovered from feces after (-)-clausenamide was orally administrated to rats (30 mg kg(-1)).</p>