Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway / 中国天然药物

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity / 医学前沿

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

Simultaneous determination of 16 chemical components in Psoraleae Fructus based on quantitative analysis of multi-component with single-marker / 中草药

Objective: The purpose of this study was to establish a QAMS analytical method for 16 compounds in Psoraleae Fructus, and attempt to evaluate the quality difference among different batches of Psoralen Fructus by chemometrics. Methods: All experiments were performed on three different HPLC instruments. Isopsoralen was used as the internal reference substance to determine the relative correction factors of the other 15 compounds. The robustness and durability of the measured relative correction factors of the 15 compounds were evaluated on different chromatograph instruments and columns; And the measurement result deviation was compared between QAMS method and the external standard method. Results: Under the established chromatographic conditions, the relative correction factors of 15 compounds in Psoraleae Fructus had high accuracy, good durability, and good reproducibility under different experimental conditions. The results obtained from two analysis methods showed no significant deviation. The results obtained by the new established QAMS analytical method showed that the consistency of compound types among different batches of Psoraleae Fructus were better, but the content of different componounds was relatively different. Conclusion: The newly established QAMS analytical method for simultaneous determination of 16 compounds in Psoraleae Fructus provides a more efficient method to evaluate the comprehensive quality of Psoraleae Fructus from different sources.

Simultaneous Determination of Bavachin and Bakuchiol in Psorslea corylifolia by HPLC / 中国药房

OBJECTIVE:To establish a method for content determination of bavachin and bakuchiol in Psoralea corylifolia.METHODS:HPLC method was adopted.The determination was performed on Shim-Pack VP-ODS column with mobile phase consisted of acetonitrile-water (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 246 nm,the column temperature was 30 ℃,and the sample size was 10 μL.RESULTS:The linear ranges of bavachin and bakuchiol were 48.9-489 ng(r=0.999 8),784-7 840 ng(r=0.999 9).RSDs of precision,stability and reproducibility tests were all lower than 2.0％.Average recoveries ranged 95.30％-99.63％ (RSD=1.45％,n=9),96.89％-100.82％ (RSD=1.36％,n=9).CONCLUSIONS:The method is simple,accurate,stable and reproducible,and can be used for the simultaneous determination of bavachin and bakuchiol in P corylifolia.

Simultaneous Determination of 7 Kinds of Components in Qing'e Pills by HPLC / 中国药房

OBJECTIVE:To develop a method for simultaneous determination of psoralen,isopsoralen,bergapten,imperato-rin,trimethylpsorale,neobavaisoflavone and bavachin in Qing'e pills. METHODS:HPLC method was adopted. The separation was performed on Kinetex-C18 column with mobile phase consisted of methanol-0.1% glacial acetic (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 248 nm. The column temperature was 30 ℃. The sample size was 20 μL. RESULTS:The linear ranges were 1.012-101.2 μg/mL for psoralen(r=0.9999),1.007-100.7 μg/mL for isopsoralen(r=0.9997), 1.010-101.0μg/mL for bergapten(r=0.9999),1.021-102.1μg/mL for imperatorin(r=0.9999),1.002-100.2μg/mL for trimethyl-psorale(r=0.9996),1.008-100.8 μg/mL for neobavaisoflavone(r=0.9999),1.025-102.5 μg/mL for bavachin(r=0.9998),re-spectively. The limits of quantitation were 0.15,0.15,0.30,0.30,0.15,0.30,0.30 μg/mL,and the limits of detection were 0.05, 0.05,0.10,0.10,0.05,0.10,0.10 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were lower than 2.0%. The recoveries were 95.3%-99.6%(RSD=1.9%,n=6),96.1%-99.3%(RSD=1.2%,n=6),95.2%-98.4%(RSD=1.4%,n=6),95.4%-99.2%(RSD=1.5%,n=6),96.1%-99.3%(RSD=1.5%,n=6),95.6%-98.9%(RSD=1.4%,n=6), 95.2%-99.6%(RSD=1.6%,n=6),respectively. CONCLUSIONS:The method is simple and accurate,can be used for simultane-ous determination of 7 kinds of components in Qing'e pills.

Optimization of processing technology for Psoraleae Fructus by D-optimal response surface methodology with UHPLC / 中草药

Objective: To optimize the processing technology for Psoraleae Fructus by D-optimal response surface methodology with UHPLC. Methods: Based on the content variations of nine main constituents (psoralen, isopsoralen, neobavaisoflavone, bavachin, psoralidin, corylifolinin, corylin, bavachalcone, and bakuchiol) determined by UHPLC, the D-optimal response surface methodology combined with single factor experiment was used to optimize the moistened time, stir-fried temperature, salted dosage, and stir-fried time in the processing technology for Psoraleae Fructus. Results: The optimal processing technology for Psoraleae Fructus was as follows: 100 g Psoraleae Fructus was mixed with 2.10 g salt, moistened for 12 h, and stir-fried for 30 min at 80℃. Conclusion: The processing technology for Psoraleae Fructus optimized by D-optimal response surface methodology with UHPLC could be used to optimize the process parameters, to promote the stability and repeatability of the processing technology, which provides the technique support for improving the quality uniformity of Psoraleae Fructus and safety in clinic application.

Simultaneous Determination of the Content of 4 Psoralen Compounds in Buwu Tincture by HPLC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of 4 psoralen compounds in Buwu tincture. METHODS:HPLC was performed on the column of Dikma Diamonsil C18 with mobile phase of acetonitrile-0.2% Acetic acid by gradient elution at flow rate of 1 ml/min,detection wavelength was 246 nm,column temperature was 30 ℃,and the injection vol-ume was 15 μl. RESULTS:The linear range was 13.00-208 μg/ml for angelicin,26.00-416 μg/ml for bavachin,24.50-392 μg/ml for psoralidin and 37.88-606 μg/ml for isobavachalcone,respectively(r≥0.999 6);RSDs of precision,stability and reproducibility tests were less than 2.00%;recoveries were 95.22%-97.23%(RSD=0.87%,n=6),100.24%-104.64%(RSD=1.62%,n=6), 102.28%-104.39%(RSD=1.47%,n=6)and 97.68%-100.17%(RSD=0.97%,n=6),respectively. CONCLUSIONS:The method is simple and reproducible,and can be used for the quality control of Buwu tincture.