Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases.

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE(-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.

Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear. AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases. MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored. RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia. CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.

Qi Gong Wan ameliorates adipocyte hypertrophy and inflammation in adipose tissue in a PCOS mouse model through the Nrf2/HO-1/Cyp1b1 pathway: Integrating network pharmacology and experimental validation in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.

Mindfulness-Based Movement Intervention to Improve Sleep Quality: A Meta-Analysis and Moderator Analysis of Randomized Clinical Trials.

(1) Background: Given that the most effective dose, optimal type, and most beneficial population for improving sleep with mindfulness-based movement (MBM) remains unknown, we conducted a systematic review and meta-analysis with moderator analysis of randomized controlled trials (RCTs) to assess these effects. (2) Methods: Three electronic databases (PubMed, Web of Science, and EBSCO) were systematically searched for RCTs published through August 2021 for analysis. The risk of bias of the included studies was assessed with Review Manager 5.3, and the meta-analysis was performed in Stata 16.0. (3) Results: A meta-analysis of 61 RCTs with 2697 participants showed that MBM significantly improved sleep quality compared to controls (SMD = −0.794; 95% CI: −0.794 to −0.994, p < 0.001, I2 = 90.7%). Moderator analysis showed that a long-term MBM (SMD = −0.829; 95% CI: 0.945 to 0.712; p < 0.001) had a larger effect size on sleep than a short-term MBM (SMD = −0.714; 95% CI: 0.784 to 0.644; p < 0.001). Practicing at least twice per week (SMD = −0.793; 95% CI: −0.868 to −0.718; p < 0.001) was more effective compared to practicing once per week (SMD = −0.687; 95% CI: −0.804 to −0.570; p < 0.001). Studies with a total intervention time of more than 24 h also revealed better sleep quality improvement (SMD = −0.759; 95% CI: −0.865 to −0.653; p < 0.001). In addition, the healthy population and older adults gained more from MBM than the patients and younger adults. (4) Conclusions: MBM can effectively improve subjective sleep quality, and the optimal intervention dose of MBM can be utilized in future intervention studies to treat or improve sleep disturbance (MBM more than twice a week for more than three months, with a total intervention time of more than 24 h).

Integrating Chronic Obstructive Pulmonary Disease Treatment With 8-Week Tai Chi Chuan Practice: An Exploration of Mind-Body Intervention and Neural Mechanism.

Objective: This study aims to explore the effect of integrating routine treatment with Tai Chi Chuan (TCC) intervention on the clinical symptom of patients with Chronic Obstructive Pulmonary Disease (COPD) from clinical and neurological perspectives. Methods: Twenty patients with COPD were recruited for regular treatment combined with 8-week TCC rehabilitative practice. Clinical symptoms were evaluated by Chronic Obstructive Pulmonary Symptom Assessment Scale (CAT) and Modified Dyspnea Scale (mMRC) at baseline and after treatment. Resting-state MRI scan was also performed with multiline T2-weighted echo-planar imaging (EPI) to acquire their functional images before and after the treatment. TCC rehabilitation involved a total of 8 weeks of practice with 90 min per session, three times a week. Results: After an 8-week integration routine treatment with TCC practice, the patient's clinical symptoms improved significantly. Imaging analysis showed that COPD patients exhibited decreased Degree of Centrality (DC) in the right inferior frontal gyrus (IFG), right middle frontal gyrus, bilateral cingulate cortex, bilateral precuneus, and right precentral gyrus. Moreover, correlation analysis found that the decreased DC in the right IFG was positively correlated with the CAT improvements. Conclusion: The routine treatment involving TCC rehabilitation practice could improve the clinical symptoms of patients with COPD. The right IFG might be a key brain region to contribute to the neural mechanism underlying integrative intervention on the clinical symptoms in COPD. These findings provide neurological evidence for treating COPD rehabilitation practice with mind-body practice based on Chinese culture to some extent, which also advances the understanding of the efficacy of TCC as the adjuvant technology from a neuroscience perspective. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?proj=45189], identifier [ChiCTR1900028335].

Self-triggered fluorescent metal-organic framework mimic enzyme for competitive immunoassay of hypoglycemic drug in functional tea.

Colorimetric or fluorescent biosensors based on mimic enzymes have come into the spotlight in virtue of their visual detection. In traditional visual sensors, fluorescent-changing or color-changing substances should be introduced for the catalytic reaction with mimic enzymes. Herein, a mimic enzyme (Au@Fe-MIL-88B) with self-triggered fluorescent property was prepared. By incorporating Au nanoparticles (Au NPs) in Fe-MIL-88B, a higher peroxidase activity of Au@Fe-MIL-88B was monitored due to the synergistic effect between Au NPs and Fe-MIL-88B. Besides, Au NPs can change the valence of Fe ion in metal organic framework (MOF), thus lower background fluorescence was discovered, but the addition of H2O2 can trigger the self-fluorescence of Au@Fe-MIL-88B. By using Au@Fe-MIL-88B as a label to anchor secondary antibody, a competitive immunosensor based on fluorescence and photoelectrochemistry was constructed for the immunoassay of rosiglitazone (RSG), a kind of hypoglycemic drug. Finally, a portable instrument was homemade for the on-site and convenient detection of RSG in functional tea. This self-triggered fluorescent MOF may provide a possible route to design biosensors for the detection of hazardous materials.

System optimisation quantitative model of on-line NIR: a case of Glycyrrhiza uralensis Fisch extraction process.

INTRODUCTION: The on-line analysis of active pharmaceutical ingredients (APIs) during the extraction process in herbal medicine is a challenge. Establishing a reliable and robust model is a critical procedure for the industrial application of on-line near-infrared (NIR) technology. OBJECTIVE: To evaluate the advantages of on-line NIR model development using system optimisation strategy, Glycyrrhiza uralensis Fisch was used as a case. The content of liquiritin and glycyrrhizic acid was monitored during pilot scale extraction process of Glycyrrhiza uralensis Fisch in three batches. METHODS: High-performance liquid chromatography (HPLC) was used as reference method for content determination of liquiritin and glycyrrhizic acid. The quantitative models of on-line NIR were developed by system optimisation of processing trajectory. For comparison, the models were simultaneously developed by stepwise optimisation. Moreover, the modelling parameters obtained through system optimisation and stepwise optimisation were reused in three batches. Root mean square error of prediction (RMSEP) and residual predictive deviation (RPD) were used to assess the model quality. RESULTS: The average values of RMSEP and RPD of systematic model for liquiritin in three batches were 0.0361, 4.1525 (first batch), 0.0348, 4.7286 (second batch) and 0.0311, 4.9686 (third batch), respectively. In addition, the modelling parameters of systematic model for glycyrrhizic acid in three batches were same, and the average values of RMSEP and RPD were 0.0665 and 5.2751, respectively. The predictive performance and robustness of systematic models for the three batches were better than the comparison models. CONCLUSION: The work demonstrated that system optimisation quantitative model of on-line NIR could be used to determine the contents of liquiritin and glycyrrhizic acid during Glycyrrhiza uralensis Fisch extraction process.

[Huaier aqueous extract inhibits proliferation of human hepatoma SK-HEP-1 cells through up-regulation of autophagy].

The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.