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Objective: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. Methods: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. Results: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. Conclusion: Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions. [ABSTRACT FROM AUTHOR]

Context: Atorvastatin (ATV) and QiShenYiQi pills (QSYQ), a Chinese patent medicine, are often co-prescribed to Chinese cardiovascular patients. The effects of QSYQ on the pharmacokinetics of ATV have not been studied. Objective: We investigated the influence of QSYQ on the pharmacokinetics of ATV and its metabolites upon oral or intravenous administration of ATV to rats. Materials and methods: Sprague-Dawley rats (n = 5/group) were pre-treated with oral QSYQ (675 mg/kg) or vehicle control for 7 days and then orally administrated ATV (10 mg/kg) or intravenously administrated ATV (2 mg/kg). Serum concentrations of ATV and metabolites were determined by ultra-high performance liquid chromatography tandem mass spectrometry. Expression of metabolic enzymes and transporters in jejunum and ileum were measured by quantitative real-time PCR and Western blot. Results: QSYQ resulted in an increase of AUC0-12 h of ATV from 226.67 ± 42.11 to 408.70 ± 161.75 ng/mL/h and of Cmax of ATV from 101.46 ± 26.18 to 198.00 ± 51.69 ng/mL and in an increased of para-hydroxy atorvastatin from 9.07 ± 6.20 to 23.10 ± 8.70 ng/mL in rats administered ATV orally. No change was observed in rats treated intravenously. The expression of multidrug resistance-associated protein 2 mRNA and protein decreased in ileum, and the mRNA of P-glycoprotein decreased in jejunum, though no change in protein expression was found. Discussion and conclusions: QSYQ increased bioavailability of ATV administered orally through inhibiting the expression of Mrp2 in ileum. Clinicians should pay close attention to potential drug-drug interactions between ATV and QSYQ. [ABSTRACT FROM AUTHOR]

Xiao-Ai Jie-Du decoction (XAJDD) has been used in clinical practice to treat diffuse large B-cell lymphoma (DLBCL); its prescriptions vary based on the pathogenesis of patients. We aimed to determine the core formula of XAJDD and investigate its mechanism of action against DLBCL. Apriori data mining of 187 clinical cases (including 421 Traditional Chinese Medicines, TCMs) was conducted to retrieve the core formula of XAJDD. Comprehensive in silico modeling was used to identify potential active components and corresponding targets. The potential targets of 16 compounds were identified based on network pharmacology using in silico modeling. Thereafter, experimental determination of the active compounds and their mechanism of action in treating DLBCL was performed using different assays (including CCK-8, Annexin V-FITC/PI double-staining, Western blot, and flow cytometry assays). The core formula of XAJDD included six herbs: Astragalus mongholicus Bunge (Huangqi, family: Fabaceae), Scutellaria barbata D. Don (Banzhilian, family: Lamiaceae), Prunella vulgaris L. (Xiakucao, family: Lamiaceae), Smilax glabra Roxb. (Tufuling, family Smilacaceae) and Fritillaria thunbergii Miq. (Dabei, family: Liliaceae), and Curcuma zanthorrhiza Roxb. (Ezhu, family: Zingiberaceae); Databases including 62 druggable compounds and 38 DLBCL-related structural targets were constructed; ∼0.3 million data points produced by computational modeling based on potential compounds and targets six components from XAJDD, including astibin, folic acid, baicalin, kaempferol, quercetin, and luteolin, significantly inhibited DLBCL cell proliferation, induced apoptosis, and suppressed the expression of key oncogenes. This study provides an integrated strategy for determining the core formula of XAJDD and reveals the molecular mechanisms underlying the treatment of DLBCL, which were consistent with the principle of "monarch (Jun), minister (Chen), adjunctive (Zuo), and guide (Shi)", confirming that XAJDD may serve as a promising natural therapeutic agent against DLBCL. [Display omitted] • For the first time, we determined the core formula of XAJDD, which included six herbs, based on an analysis of 187 clinical cases (including 421 TCMs). • A database containing 62 druggable components of XAJDD and 38 targets related to DLBCL was constructed. • We constructed fingerprints indicating potentially active components and their corresponding targets using comprehensive in silico modeling, resulting in approximately 0.3 million data points. • Using network pharmacology, we predicted the potential targets of the 16 compounds identified by in silico modeling. • We experimentally determined the active components and their mechanisms of action for the treatment of DLBCL. [ABSTRACT FROM AUTHOR]

Huanglian Jiedu plaster (HJP) is a kind of Chinese patent medicine that contains four medicinal plants. It has been clinically proven to be beneficial for the treatment of tumor-associated radiation dermatitis. However, the underlying mechanism of HJP on radiation dermatitis remains unclear. This study aims to investigate the therapeutic effect of HJP on X-ray-induced radiation dermatitis, and how HJP improves the inflammatory response and skin damage of radiation dermatitis. In this study, We selected a case of esophageal cancer as a clinical demonstration of the efficacy of radiation dermatitis. The patient received a total radiation dose of 7000cGY, and treatment by HJP for 14 days.RD mouse models were established through continuous irradiation with X-ray (800cGY) on the right hind limb of mice for 5 days, and the treatment group mice was applied HJP to the irradiated skin for 15 days from modeling. An inflammatory cellular model was induced through irradiation with X-ray (100cGY) in JB6 cells and a co-culture system of JB6 cell and macrophage was established to examine the effect and mechanism of HJP on the inflammatory interaction of these two cells. The activation of HMGB1-TLR4-NF-κB signaling pathway, and the levels of epidermal injury related factors and inflammatory cytokins were subsequently detected. The results showed that HJP can significantly alleviate X-ray-induced skin injury, inhibiting skin inflammation and reducing the expression of inflammatory cytokins (IL-1β, IL-6, TNF-α) and epidermal damage related factors (Integrin β1, CXCL9 and Cytokeratin17), as well as significantly down-regulated the protein level of HMGB1 (a key DAMPs factor) in vivo and in vitro. Cell co-culture experiments demonstrated that HMGB1 released from X-ray-induced JB6 cells can promote inflammatory response of macrophage, which then feedback aggravate epithelial cell damage, notably, HJP can significantly improve radiation skin lesion by inhibiting HMGB1-mediated inflammatory interaction between epithelial cells and macrophages. In summary, these findings indicated the role of HJP in the treatment of RD by inhibiting the inflammatory interaction between macrophage and JB6 cells mediated by HMGB1, which may provide a reliable therapeutic method for RD. Furthermore, HMGB1 may be an effective target for HJP to inhibit inflammation and ameliorate skin damage in RD. [Display omitted] • HJP can alleviate X-ray-induced skin injury, inhibit skin inflammatory reaction. • HMGB1 can promote JB6's damages by mediating the inflammatory interaction with BMDM. • HJP can inhibit HMGB1-mediated inflammatory interaction. [ABSTRACT FROM AUTHOR]