Omics-based pharmacological evaluation reveals Yuanhu Zhitong oral liquid ameliorates arthritis by regulating PKC/ERK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Successful use of herbal medicine in the treatment of rheumatoid arthritis (RA) creates opportunities for alternative therapies. Yuanhu Zhitong oral liquid (YZOL) is an herbal preparation known for its potent analgesic and anti-inflammatory properties in traditional use. However, the pharmacological mechanism of YZOL for treating RA remains unclear. AIM OF THE STUDY: The aim of this study was to evaluate the efficacy of YZOL in the treatment of RA and to explore its potential mechanisms through omics analysis. MATERIALS AND METHODS: Type II collagen was used to induce an arthritis rat model. The effects of YZOL on paw swelling, inflammatory cytokines, oxidative stress, and histopathological changes were systematically investigated. A pathway-driven transcriptomic analysis was performed to identify key signaling pathways associated with YZOL therapy. The key alterations were validated by qRT-PCR, Western blot, and immunohistochemistry assays. RESULTS: YZOL significantly attenuated arthritis progression, reduced paw swelling rate, and lowered arthritis score in CIA rats. YZOL also inhibited systemic inflammation and associated oxidative stress during RA. Transcriptomic analysis identified 341 genes with significantly altered expression following YZOL treatment. These genes were enriched in inflammation-related pathways, particularly in the NF-κB and MAPK signaling pathways. In addition, we discovered that YZOL can alleviate inflammation in the local synovial tissue. The effect of YZOL was confirmed by the suppression of PKC/ERK/NF-κB p65 signaling at systemic and local levels. CONCLUSIONS: This study provides novel evidence that YZOL treatment ameliorates RA by suppressing the PKC/ERK/NF-κB pathway, suggesting its potential as an alternative therapy for RA.

Integrated Metabolomics and Gut Microbiome Analysis Reveals the Efficacy of a Phytochemical Constituent in the Management of Ulcerative Colitis.

SCOPE: Cinnamaldehyde (CAH), a phytochemical constituent isolated from cinnamon, is gaining attention due to its nutritional and medicinal benefits. This study aimed to investigate the potential role of CAH in the treatment of ulcerative colitis (UC). METHODS AND RESULTS: Integrated metabolomics and gut microbiome analysis are performed for 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced UC rats. The effect of CAH on colonic inflammation, lipid peroxidation, metabolic profiles, and gut microbiota is systematically explored. It finds that CAH improves the colitis-related symptoms, decreases disease activity index, increases the colon length and body weight, and alleviates histologic inflammation of UC rats. These therapeutic effects of CAH are due to suppression of inflammation and lipid peroxidation. Moreover, multi-omics analysis reveals that CAH treatment cause changes in plasma metabolome and gut microbiome in UC rats. CAH regulates lipid metabolic processes, especially phosphatidylcholines, lysophosphatidylcholines, and polyunsaturated fatty acids. Meanwhile, CAH modulates the gut microbial structure by restraining pathogenic bacteria (such as Helicobacter) and increasing probiotic bacteria (such as Bifidobacterium and Lactobacillus). CONCLUSIONS: These results indicate that CAH exerts a beneficial role in UC by synergistic modulating the balance in gut microbiota and the associated metabolites, and highlights the nutritional and medicinal value of CAH in UC management.

Coupling antecedent rainfall for improving the performance of rainfall thresholds for suspended sediment simulation of semiarid catchments.

Suspended sediment transport is one of the essential processes in the geochemical cycle. This study investigated the role of rainfall thresholds in suspended sediment modeling in semiarid catchments. The results showed that rainfall-sediment in the study catchment (HMTC) could be grouped into two patterns on the basis of rainfall threshold 10 mm. The sediment modeling based on LSTM model with the rainfall threshold (C-LSTM scheme) and without threshold (LSTM scheme) were evaluated and compared. The results showed that the C-LSTM scheme had much better performances than LSTM scheme, especially for the low sediment conditions. It was observed that in the study catchment, the mean NSE was marginally improved from 0.925 to 0.934 for calibration and 0.911 to 0.924 for validation for medium and high sediment (Pattern 1); while for low sediment (Pattern 2), the mean NSE was significantly improved from -0.375 to 0.738 for calibration and 0.171 to 0.797 for validation. Results of this study indicated rainfall thresholds were very effective in improving suspended sediment simulation. It was suggested that the incorporation of more information such as rainfall intensity, land use, and land cover may lead to further improvement of sediment prediction in the future.

The Current Application of LC-MS/MS in Pharmacokinetics of Traditional Chinese Medicines (Recent Three Years): A Systematic Review.

BACKGROUND: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world's scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). METHODS: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. RESULTS: The vast majority of literature on preclinical PK of TCM uses single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK study of TCM.

Pharmacokinetic Comparisons of Different Combinations of Yigan Jiangzhi Formula in Rats: Simultaneous Determination of Fourteen Components by UPLC-MS/MS.

A rapid, specific, and sensitive analysis for simultaneous determination of fourteen components (daidzein, fermononetin, apigenin, luteolin, puerarin, ononin, calycosin-7-O-ß-D-glucoside, tanshinol, rosmarinic acid, alkanoic acid, salvianolic acid B, berberine, jatrorrhizin, and palmatine) of Yigan Jiangzhi formula (YGJZF, a clinical experienced formula for damp-heat syndrome) in rat plasma was developed and validated using ultraperformance liquid chromatography coupled with mass spectrometry. Lower limit of quantitation ranged from 0.2-10.0 ng/mL, and the calibration curves showed good linearity over 500 times of measuring range. The validated method was successfully applied to the pharmacokinetics investigation of the fourteen compounds in rat plasma after oral administration of two different doses of YGJZF. Compared with the low-dose group of YGJZF, the high-dose group showed significant increase (P < 0.01 or P < 0.05) in maximum plasma concentration, maximum concentration time, and area under the plasma concentration-time curve and decrease (P < 0.01 or P < 0.05) in clearance of most of the fourteen analytes, which suggested that the bioavailability of these components could be enhanced by increasing dosage. The above results may provide useful information for cognizing the relationship between in vitro and in vivo data of the fourteen bioactive ingredients of YGJZF and further guiding rational clinical drug prescription.