RSC Advances
·
2018
·Vol. 8
·期 45
·25519-25525
·
IF 2.936
Xiangyu Cao,Yonglin He,Dan Liu,Yin He,Xiao Hou,Ye Cheng,Jianli Liu
Scoparone is a major biological active substance derived from the traditional Chinese herbal medicine called Artemisia capillaris. It has been confirmed that scoparone has anti-inflammatory, anti-tumor, hepatoprotective and antioxidant effects. However, the binding interaction of scoparone with bovine serum albumin (BSA) still remains unknown. Therefore, the present study was conducted to clarify the binding interaction of scoparone with BSA under simulated physiological conditions (pH = 7.4) by utilizing spectroscopic and molecular docking methods. The formation of the scoparone–BSA complex was identified by UV-vis absorption spectroscopy experiment results. The fluorescence experiment results revealed that the quenching mechanism was static quenching and the binding procedure was spontaneous mainly driven by hydrophobic interaction. At 310 K, the number of binding sites was approximately equal to 1 and the binding constant was 6.79 × 105 mol L−1. The binding distance (4.81 nm) between scoparone and BSA was determined by Förster's non-radiative energy transfer theory. Molecular docking and site marker competitive experiment results verified that scoparone was more likely to be located in site I of BSA. In addition, the results of synchronous fluorescence spectroscopy and circular dichroism spectroscopy experiments proved that scoparone slightly changed the conformation of BSA by binding interaction with BSA. These findings would be useful for understanding the pharmacokinetics of scoparone in vivo, including scoparone transport, distribution, metabolism and excretion.
研究领域:
药理学
·
生物化学
✓ 已验证
DOI
高影响因子
CURRENT DRUG METABOLISM
·
2023
·Vol. 24
·期 4
·303-311
·
IF 2.3
Tian Qiru,Jin Huan,Huo Xiaokui,Zhao Yupu,Wu Wenhui,Xu Lei,Wang Yinan,Yang Xiaobo,Sun Chengpeng,Deng Sa,Shu Xiaohong
Background: Scoparone, the principal natural active ingredient of Artemisia capillaries (Yin Chen), can effectively treat cholestatic diseases, but the pharmacokinetic properties of scoparone are rarely studied in intrahepatic cholestatic rats. Objective: A sensitive
and rapid LC-MS/MS method was established to detect scoparone and its metabolite of scopoletin in rat plasma and then compare their plasma pharmacokinetic differences between the normal and ANITinduced cholestasis rats. Methods: Positive ionization was used to separate scoparone and scopoletin
using acetonitrile and 0.1 % formic acid water as the mobile phase on a Hypersil ODS-BP column. Results: The calibration curves presented good linearity (R=0.9983 and 0.9989) in the concentration range of 10- 10000 ng/mL and 0.5-500 ng/mL for scoparone and scopoletin, respectively. The
precision of ≤ 9.4% and the accuracy ranged from -6.4% to 6.8% were recorded over three validation runs, and the recovery was higher than 83.9%. Under different storage conditions, scoparone and scopoletin were stable. Therefore, we studied the pharmacokinetic properties of scoparone and
scopoletin in rats after a single oral administration with the above method. According to the results, the pharmacokinetic parameters of AUC, t1/2, and Cmax values of scoparone in the ANIT group were increased by 106%, 75%, and 44%, respectively,
while these values of scopoletin were increased by 142%, 62%, and 65%. Conclusion: The findings indicated that the pharmacokinetic properties of scoparone and scopoletin were significantly different between the normal and ANIT-induced cholestasis rats, which suggested that the clinical
application dosage of scoparone should be adjusted according to the liver function of patients.
研究领域:
药理学
·
肝病学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Chaozhong Wang,Yuran Sun,Le Yang,Junling Ren,Heng Fang,Ye Sun,Guangli Yan,Ling Kong,Ying Han,Xijun Wang,Hui Sun
Ethnopharmacological relevance Artemisia capillaris Thunb. is a traditional Chinese medicinal herb commonly used in clinical practice for chronic alcoholic liver disease (CALD).Scoparone, one of the major active components of Artemisia capillaris Thunb., has emerged as a promising candidate for CALD intervention, yet its mechanism remains unclear. Aim of the study This study aimed to systematically elucidate the pharmacological effects of scoparone and its molecular mechanisms in CALD via multi-omics combined with targeted validation. Materials and methods The National Institute on Alcohol Abuse and Alcoholism (NIAAA) animal model was established. The NIAAA-established CALD mouse model (chronic ethanol feeding + acute binge, mimicking acute-on-chronic liver injury) was diagnosed via classic clinical methods (liver function biomarkers + histopathology). After validation, scoparone exhibited significant efficacy across different doses. Metabolomics and transcriptomics analyzed urine/tissue samples, with integrated analysis identifying core hubs. Meanwhile, primary hepatocytes were cultured and treated with scoparone. Potential targets were validated via gene knockdown, CETSA, CHX chase, and ubiquitination assays. We used the Seahorse XF Mito Stress Test to evaluate CALD-associated mitochondrial damage and elucidate the key interrelationships. Results Scoparone normalized serum biochemical indices and liver pathology to near-healthy levels. Urinary metabolomics identified 9 biomarkers, and liver transcriptomics detected 3665 differentially expressed genes.Integrated omics pinpointed the phenylalanine pathway, with TAT/AST co-regulation identified as key. In vitro, primary hepatocytes were cultured with 100 mmol/L ethanol ±25 μmol/L scoparone; CETSA and CHX chase assays confirmed scoparone enhances TAT stability via inhibiting the Ubiquitin-Proteasome pathway. Seahorse analysis showed TAT knockdown-induced hepatocyte apoptosis, oxidative stress, lipid accumulation, and mitochondrial damage were reversed by scoparone or TAT level restoration. Conclusions This study first reveals scoparone’s novel mechanism in treating CALD: it directly binds tyrosine aminotransferase (TAT), stabilizes its level by inhibiting Ubiquitin-Proteasome-mediated degradation, restores TAT’s regulation of phenylalanine to prevent tyrosinemia and associated liver injury or jaundice, and normalizes tyrosine regulation to recover mitochondrial tricarboxylic acid cycle-related pyruvate, reversing oxidative stress and mitochondrial dysfunction.This study validates scoparone as a potential CALD therapeutic and provides robust preclinical data for TAT-targeted therapy.
✓ 已验证
DOI
PubMed
高影响因子
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