Yaobitong capsules reshape and rebalance the gut microbiota and metabolites of arthritic rats: An integrated study of microbiome and fecal metabolomics analysis.

Yaobitong capsule (YBTC), a Chinese medicine compound preparation, has been demonstrated to affect multiple pathways associated with inflammation and exhibit potential anti-arthritis effect. In this study, an integrated omic approach based on UHPLC-Q-TOF MS and 16S rRNA sequencing analyses was proposed to reveal the anti-arthritis effect and possible mechanism of YBTC. The AIA rat model showed that YBTC significantly alleviated the typical symptoms of AIA rats such as weight, spleen index and pro-inflammatory cytokines. Fecal metabolomics results identified 41 differential metabolites, which mainly referred to tryptophan, bile acid and fatty acid metabolism. The gut microbiota played a crucially important role in anti-inflammatory immunity, 16S rRNA results indicated that YBTC changed the community structure and alleviated the microecological imbalance caused by rheumatoid arthritis (RA). Further ROC curve analysis demonstrated that it was reliable to identify RA by using 5 metabolites and 3 microorganisms (AUC > 0.83). In summary, it was the first time that the preventive effect of YBTC in RA was confirmed. The secretion of the microbiota-mediated metabolites was significantly improved by YBTC, through its callback effect on the disturbed gut microbiota. Thus, we have indicated a potential novel strategy for the prevention of RA via evaluation of intervention effects of YBTC on AIA rat model.

Integrative serum metabolomic analysis for preventive effects of Yaobitong capsule in adjuvant-induced rheumatoid arthritis rat based on RP/HILIC-UHPLC-Q-TOF MS.

Yaobitong capsule (YBTC) has been used for the prevention and treatment of inflammation-related lumbago and leg pain. However, its intervention mechanism still remains unclear. This study was aimed to evaluate the control efficiency of YBTC on adjuvant-induced rheumatoid arthritis (RA) rats by metabonomic method and to explore its possible anti-arthritis mechanism. Taking into account the complexity of endogenous metabolites in serum samples, an integrated metabolomics method based on RP/HILIC-UHPLC-Q-TOF MS was developed, to overcome the limitations of a single chromatographic in this study. The results showed that 32 potential biomarkers of arthritis were identified, primarily related to amino acid metabolism, glucose metabolism, lipid metabolism and nucleotide metabolism. Further receiver operating characteristic analysis revealed that the area under the curve of two down-regulated metabolites (3-Hydroxy-hexadecanoic acid, 2-Oxoarginine) and one up-regulated metabolite (l-Glutamic acid) among 32 biomarkers were 0.906, 0.969 and 1.000, respectively, indicating that high predictive ability of this method for RA. In this study, an integrated serum metabolomics method based on high-resolution mass spectrometry was successfully established for the first time to study the intervention mechanism of YBTC in RA, providing evidence regarding the clinical application of YBTC and a new insight for the prevention of RA in the future.

Efficacy of simplified-cognitive behavioral therapy for insomnia(S-CBTI) among female COVID-19 patients with insomnia symptom in Wuhan mobile cabin hospital.

BACKGROUND: The outbreak of Coronavirus Disease-2019 (COVID-19) caused great psychological distress often with comorbid insomnia. Insomnia is common in patients with COVID-19 admitted to mobile cabin hospitals. Insomnia may lead to immune dysfunction, a condition not conducive to recovery from COVID-19. The use of sedative-hypnotic drugs is limited by their inhibitory effect on the respiratory system. A paucity of research is available regarding psychotherapy interventions to improve insomnia symptoms among  patients with COVID-19. In the general population, sleep problems are more common in women than in men; insomnia in women patients requires special attention. The aim of this study was to develop simplified-cognitive behavioral therapy for insomnia (S-CBTI) for patients with COVID-19 and comorbid insomnia symptoms and to verify its effectiveness through a self-control trial. A second aim was to compare the effectiveness of S-CBTI between acute and chronic insomnia among women with COVID-19 and comorbid insomnia symptoms in Wuhan Jianghan Cabin Hospital. METHODS: S-CBTI consisted of education on COVID-19 and sleep hygiene, stimulus control, sleep restriction, and self-suggestion relaxation training over a period of two consecutive weeks. Of 67 women, 66 completed psychological intervention and baseline and post-intervention assessments. There were 31 women with acute insomnia and 35 with chronic insomnia. The Insomnia Severity Index (ISI) score and self-compiled sleep data were assessed at baseline and post-intervention, and subjective sleep evaluations were assessed at days 4, 7, 12, and 14. RESULTS: The ISI score, sleep latency, night sleep time, and sleep efficiency were statistically significantlly improved from baseline to post-intervention by paired T-test. After the intervention, the mean ISI score of the acute insomnia group was lower than that of the chronic insomnia group. The reduction of the ISI score and the improvement of sleep time from baseline to post-intervention in the acute insomnia group were greater than those in the chronic insomnia group. Utilization of sedative-hypnotic drugs in the acute insomnia group was less than that in the chronic insomnia group, and the difference was statistically significant. CONCLUSIONS: S-CBTI can improve the insomnia symptoms of women with COVID-19 in mobile cabin hospitals, especially for stress-related acute insomnia.

Systematically characterized mechanism of treatment for lumbar disc herniation based on Yaobitong capsule ingredient analysis in rat plasma and its network pharmacology strategy by UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Yaobitong capsule (YBTC) was a traditional Chinese medicine (TCM) and it had clinically used to treat lumbar disc degeneration (LDH) for a long time. However, the active ingredients of YBTC absorption into the plasma and its pharmacological mechanism of treatment for LDH still remained unclear. AIM OF THE STUDY: In this study, our research committed to identify the absorbed active ingredients of YBTC in rat plasma, and it may be a potential mechanism of action on LDH by the biological targets regulating related pathways. MATERIALS AND METHODS: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to identify the absorption components and metabolites of YBTC in rat plasma, and the network pharmacology was further investigated to illuminate its potential mechanism of treatment for LDH by the biological targets regulating related pathways. RESULTS: The network analysis found that 56 components were identified as its main active ingredients including ginsenoside Rg1, ginsenoside Rb1, senkyunolide H, and tetrahydropalmatine, etc. Combining with biological process, cellular component and molecular functions of GO, and kyotoencyclopedia of genes and genomes pathway enrichment analysis to perform network topology analysis on core targets. These active ingredients regulated 29 mainly pathways by 87 direct target genes including MAPK, Ras, PI3K-Akt, and NF-kappa B signaling pathway, etc. CONCLUSION: In this study, the absorption active ingredients of YBTC in rat plasma were firstly combined with the network pharmacology investigation to elucidate its biological mechanism of treatment for LDH in vivo. It inhibited excessive inflammatory reactions, thereby reducing the sensitivity of the nerves to reduce pain and relieve LDH, and potential medicine targets could be identified to clarify the molecular mechanism of YBTCs' regulation of LDH.

UPLC-MS/MS simultaneous determination of seven active ingredients of Yaobitong capsule in rat plasma and its integrated pharmacokinetic application.

A reliable and sensitive UPLC-MS/MS method was first established and validated for the simultaneous determination of seven active ingredients of Yaobitong capsule in rat plasma: ginsenoside Rg1, ginsenoside Rb1, osthole, tetrahydropalmatine, paeoniflorin, albiflorin, and ferulic acid. And this method was further applied for the integrated pharmacokinetic study of Yaobitong capsule in rats after oral administration. Plasma samples (100 µL) were precipitated with 300 µL of methanol using carbamazepine as internal standard. Chromatographic separation was achieved using an Aquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with the mobile phase consisting of 0.1% formic acid and acetonitrile. The method was validated using a good linear relationship (r ≥ 0.991), and the lower limit of quantification of the analytes ranged from 0.5 to 40 ng/mL. In the integrated pharmacokinetic study, the weight coefficient was calculated by the ratio of AUC0-∞ of each component to the total AUC0-∞ of the seven active ingredients. The integrated pharmacokinetic parameters Cmax , Tmax , and t1/2 were 81.54 ± 9.62 ng/mL, 1.00 ± 0.21 h, and 3.26 ± 1.14 h, respectively. The integration of pharmacokinetic parameters showed a shorter t1/2 because of fully considering the contribution of the characteristics of each active ingredient to the overall pharmacokinetics.