Isochlorogenic acid A attenuates progression of liver fibrosis through regulating HMGB1/TLR4/NF-κB signaling pathways

OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlorogenic acid A(ICQA)on liver fibrosis induced by carbon tetrachloride(CCl4)and clarify the underlying mechanism.METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10,20 and 40 mg·kg-1).RESULTS ICQA had significant protective effect on liver injury,inflammation,and fibrosis in rats.Meanwhile,ICQA prevented the activation of hepatic stellate cells(HSC)as indicated by inhibiting the overexpres⁃sion of a-smooth muscle actin(a-SMA).In addition,reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1)and toll like receptor(TLR)4.Moreover,ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver.Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB)p65 and inhibited degradation of IkBa expression in the liver of rats with liver fibrosis.CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.

Isochlorogenic acid A affects P450 and UGT enzymes in vitro and in vivo

Isochlorogenic acid A(ICQA), which has anti-inflammatory, hepatoprotective, and antiviral properties, is commonly presented in fruits, vegetables, coffee, plant-based food products, and herbal medicines. These herbal medicines are usually used in combination with other medicines in the clinic. However, little is known about the regulatory effects of ICQA on drug-metabolizing enzymes and the herb-drug interactions. In the present study, we evaluated the inhibitory potentials of ICQA on CYP1A2, CYP2C9,CYP2C19, CYP3A4, CYP2D6, and CYP2E1 in vitro based on a cocktail approach. The P450 and UGT activities in mice treated with ICQA for a prolonged period were also determined. Our results demonstrated that ICQA exhibited a weak inhibitory effect on CYP2C9 in human liver microsomes with IC_(50) being 57.25 μmol·L^(-1) and Ki being 26.77 μmol·L^(-1). In addition, ICQA inhibited UGT1A6 activity by 25%, in the mice treated with ICQA(i.p.) at 30 mg·kg^(-1)for 14 d, compared with the control group. Moreover, ICQA showed no mechanism-based inhibition on CYP2C9 or UGT1A6. In conclusion, our results further confirm a safe use of ICQA in clinical practice.

Isochlorogenic acid(ICGA): natural medicine with potentials in pharmaceutical developments

Natural products have attracted a great deal of attention as significant resources in traditional Chinese medicine(TCM)and in chemical medicine, as well as in cosmetic ingredients, nutraceuticals and food products. Isochlorogenic acid(ICGA), which has medicinal value, has been discovered in various plants. As a widespread natural medicine, ICGA should be the subject of further research and development. However, there have been no systematic analyses of ICGA. According to our investigation, ICGA was initially isolated from green coffee extracts by Barnes et al. in 1950. To date, it has been discovered in a variety of tea, vegetables, medicinal diet and TCM materials. ICGA is used as a chemical marker for the quality control of these TCM materials. The metabolic process of ICGA has been studied in detail, conforming to be linear dynamics. Thus, the clear pharmacokinetics of ICGA offers a solid foundation for its research and development. ICGA has multiple biological and pharmacological effects, and studies have mainly focused on its antioxidant, anti-inflammatory, antimicrobial, hypoglycemic, neuroprotective, and cardiovascular protective effects, and hepatoprotective properties. The mechanisms underlying these effects are summarized in this review to provide scientific support and inspiration for the future research and development of ICGA and ICGA-rich natural products.

Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study

A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.

Difference analysis of different parts of chicory based on HPLC fingerprint and multi-component content determination

Objective:To establish HPLC fingerprints of different parts of chicory stems,leaves,roots,flowers and seeds,and compare the similarities and differences of chemical components in different parts,so as to provide a scientific basis for the comprehensive utilization of chicory.Methods:To establish the HPLC fingerprint of chicory,the chromatographic column was chosen with Agilent ZORBAX Eclipse XDB-C_(18),the mobile phase was methanol(A)-0.2%formic acid(B),the flow rate was 1 mL/min,the column temperature was 30℃,and the detection wavelength was 254 nm.The Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition)was used to evaluate the similarity of different parts of decoction pieces,and the determination method of multi-component content was established based on fingerprint identification chromatographic peaks,and the determination results were analyzed.Results:The HPLC fingerprinting method of chicory was established.Sixteen chromatographic peaks were identified and 10 of them were identified as:caftaric acid(1),esculin(2),chlorogenic acid(3),esculetin(4),caffeic acid(5),cichoric acid(8),hyperoside(11),rutin(12),isochlorogenic acid C(14)and luteolin(16).The similarity of different parts was 0.084–0.701.At the same time,the total content of detected chemical components was ranked as flower>leaf>stem>root>seed.Roots did not contain caftaric acid,rutin,and luteolin,flowers did not contain luteolin,and seeds did not contain caftaric acid,cichoric acid,and luteolin.The content of cichoric acid in leaves was the most,and esculin in flowers was the most.Conclusion:The results of HPLC fingerprint and multi-component content determination revealed the similarity and difference of different parts of chicory from chemical composition,indicating that there were certain differences in different parts of chicory.The established HPLC fingerprinting method can provide a reference for quality control and evaluation of different parts of the chicory.