FASEB JOURNAL
·
2026
·Vol. 40
·期 5
·e71641
·
IF 4.3
Xiaoxue Wang,Zexin Zhu
Rosacea is a chronic inflammatory dermatological disorder involving the activation of various signaling pathways. Imperatorin (IMP), a coumarin compound, has been documented to exhibit anti‐inflammatory properties. Nevertheless, its therapeutic efficacy in managing rosacea remains unexplored. Bioinformatics and network pharmacology approaches were utilized to elucidate potential signaling pathways and molecular targets of IMP in the context of rosacea. Subsequently, to assess the in vivo therapeutic efficacy of IMP, murine models exhibiting rosacea‐like inflammatory responses were developed. Additionally, in vitro experiments were conducted to elucidate the molecular mechanisms underlying the anti‐rosacea effects of IMP. Our findings demonstrated that both intraperitoneal and topical administration of IMP significantly attenuated skin inflammation in mice with LL37‐induced rosacea models. Mechanistic investigations, guided by bioinformatics and network pharmacology analyses, revealed an interaction between JNK1 and STAT1. IMP was found to directly bind to JNK1 and STAT1, disrupting their interaction, thereby inhibiting STAT1 phosphorylation and nuclear translocation. This inhibition resulted in decreased production of STAT1‐mediated inflammatory mediators in keratinocytes. These results suggest that IMP may serve as a promising therapeutic agent for inflammatory skin diseases by targeting the crosstalk between JNK1 and STAT1. IMP treatment disrupts the interaction between JNK1 and STAT1, thereby attenuating STAT1 activity. This interference subsequently diminishes the phosphorylation and nuclear translocation of STAT1, which ultimately results in a reduced production of inflammatory cytokines and chemokines. Consequently, this process alleviates the symptoms of rosacea.
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FOOD CHEMISTRY
·
2026
·
IF 9.8
Xinye Shi,Hang Su,Jing Tang,Yajing Zhang,Songtao Li,Yanhui Zhong,Zian Lin
Furanocoumarins (FCMs) are a group of organic compounds abundantly found in citrus fruits. Excessive intake is closely associated with increased incidence of skin cancer. Consequently, the development of an efficient approach for in vivo determination of FCMs in citrus fruits is of critical importance. In this study, 1,3,5-tris (4-aminophenyl) benzene (TAPB) and 2,4-dihydroxybenzene-1,3,5-tricarbaldehyde (DHTA) were used to synthesize covalent organic framework (COF) as a solid phase microextraction (SPME) probe. The probe showed highly ordered porosity (1.49 nm), outstanding stability, and hydrophobicity. With respect to these superiorities, it was coupled with electrospray ionization mass spectrometry (ESI/MS) to achieve the detection of six FCMs with high enrichment factors (71.3–108.5), and low detection limits (0.003–0.160 μg L −1 ). The platform was used with great success for the in vivo analysis of FCMs in four citrus fruits, indicating that this platform had good prospects as a powerful instrument for in vivo monitoring fruits.
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Food Quality and Safety
·
2024
·
IF 3
Sun Yujing,Wang Yihua,Zhang Le,Ye Xingqian,Guo Jingtong
Furanocoumarins in citrus fruit can cause adverse drug interactions, however, there are few reports on furanocoumarins and drug interactions in common edible citrus cultivars except grapefruit. A UPLC-based method for ten furanocoumarins in citrus fruit was established and impacts on cytochrome P450 activity were investigated. Furanocoumarins were more abundant (2–43 times) in the peel than in the pulp. The pulp of Xiyou, Hongyou and Navel orange exhibited P450 inhibition with IC50 values of 0.63, 0.67 and 1.02 mg/mL, respectively. The peel of most varieties except Huyou and Satsuma exhibited P450 inhibition. Xiyou, Huangjinyou, Baiyou, Hongyou, Ponkan and Navel orange had IC50 values of 0.33, 0.38, 0.76, 0.35, 0.43 and 0.37 mg/mL, respectively. These findings indicate that the consumption of the pulp of popular Chinese varieties of citrus fruit except for Xiyou, Hongyou and Navel orange has a low risk of drug interactions, and use of citrus products including peel may carry a significant risk of adverse drug interactions.
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ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·Vol. 117
·期 3
·e70004
·
IF 1.5
Kai Tian,Jiang Zhu,Xinghui Qiu
Furanocoumarins are a class of chemical compounds with phototoxic properties. For herbivores, efficient detoxification of such defense compounds is the prerequisite to feed successfully on furanocoumarin-containing plants. The cotton bollworm Helicoverpa armigera is a very important polyphagous pest in agriculture, but how it copes with toxic furanocoumarins in some of its host plants is not well understood. Given that cytochrome P450s are well known for their capacity in xenobiotic metabolism, this study attempted to explore the potential roles of cytochrome P450s in furanocoumarin transformation in this pest. Our data showed that two linear structures (psoralen and xanthotoxin) could be metabolized by three recombinant CYP9A enzymes, but no detectable depletion was observed for the linear one with the 8-dimethylallyloxy substituent on the coumarin moiety (imperatorin) and the angular furanocoumarin (angelicin). Initial epoxidation of the double bond connecting C2' and C3' of the furano ring following by cleavage of the epoxidated furan ring, leading to the formation of more soluble, less reactive and nonphotosensitizing metabolites, was identified as a common mechanism of linear furanocoumarin metabolism using a quadrupole/time-of-flight (Q-TOF) mass spectrometry interfaced with a high performance liquid chromatography (HPLC) system. Our data demonstrated that multiple P450s were involved in the detoxification of linear furanocoumarins in the cotton bollworm. These findings contribute to a better understanding of the biochemical basis of adaptation to plant defense chemicals in this economically important pest. Summary CYP9A12, CYP9A14, and CYP9A17 are capable of metabolizing psoralen and xanthotoxin. Epoxidation of the C2'−C3' double bond of the furano ring is the common pathway. The three CYP9A enzymes exhibit no detectable activity against angelicin and imperatorin.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2025
·
IF 2.8
Huixiao Duo,Liyun Wang,Pei Lu,Xiaodan Zhang,Mingcong Zheng,Hanying Song,Juan Zhou,Wenzhuo Lei,Shushu Ding,Jie Jia Li,Junxu Li,Qing Zhu
Oxypeucedanin (OPD) is a linear furanocoumarin extracted from Chinese herbs, which has been reported to exhibit various pharmacological effects such as analgesia, antitussive, anticancer and anti-inflammatory activities. In this paper, the tissue distribution, excretion and metabolism characteristics of OPD in rat was conducted in order to better understand this compound and for potential development of OPD as a medicine. We first used the established HPLC/MS/MS method to examine the plasma protein binding rate and the tissue distribution of OPD in rats after oral administration. The excretion characteristics of OPD in urine, feces and bile, as well as its metabolic profiles in plasma, urine and bile were also investigated. The results demonstrated that after OPD administration, extensive metabolism occurred in rats, involving first-pass effect and enterohepatic circulation, with significant sex differences observed in the metabolic process. The study identified eight metabolites in rats, indicating that OPD metabolism primarily occurs through oxidation, reduction, and glucuronidation. In summary, this study systematically examined the basic process of OPD in vivo, providing a robust foundation for accurately predicting the behavior, efficacy and safety of OPD in humans.
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