Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-est...Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-established clinical history in effectively managing fever. However, the specific mechanisms underlying their efficacy remain unclear. Following the screening for lead compounds that inhibit PGE2from antipyretic herbs, alkynylated active molecule probes were designed and synthesized to track and identify potential targets. The target investigation revealed that three antipyretic compounds, namely cinnamaldehyde, 2,4-decadienal, and perillaldehyde, containing α,β-unsaturated aldehyde groups irreversibly targeted the microsomal PGES1-TM4 helix(m PGES1-TM4) at Ser139. This specific interaction effectually inhibited PGE2 production in the cerebral vasculature, leading to exert potent antipyretic effects.α,β-Unsaturated aldehydes targeting m PGES1-TM4 offer a new approach for antipyretic effects with significant potential for various applications.展开更多
Berberine(BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian(Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molec...Berberine(BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian(Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molecular mechanisms are not clear. In this paper, the BBR-affected energy metabolism pathway was screened by nontargeted metabolomics, and a BBR-derived photoaffinity labeled(PAL) probe was designed to identify potential targets via a chemical proteomics approach. NDUFV1, a subunit of complex Ⅰ on mitochondria, was identified as a potential target of BBR. In the respiratory chain, BBR suppressed the activity of complex Ⅰ, reduced the electrochemical potential in the mitochondrial intermembrane and inhibited the generation of ATP and heat via competitive binding with NDUFV1. The results illustrated the underlying mechanism of BBR in the downregulation of energy metabolism.展开更多
基金supported by the National Key R&D Program of China (Nos. 2022YFC3500800 and 2022YFC3500805)。
文摘Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-established clinical history in effectively managing fever. However, the specific mechanisms underlying their efficacy remain unclear. Following the screening for lead compounds that inhibit PGE2from antipyretic herbs, alkynylated active molecule probes were designed and synthesized to track and identify potential targets. The target investigation revealed that three antipyretic compounds, namely cinnamaldehyde, 2,4-decadienal, and perillaldehyde, containing α,β-unsaturated aldehyde groups irreversibly targeted the microsomal PGES1-TM4 helix(m PGES1-TM4) at Ser139. This specific interaction effectually inhibited PGE2 production in the cerebral vasculature, leading to exert potent antipyretic effects.α,β-Unsaturated aldehydes targeting m PGES1-TM4 offer a new approach for antipyretic effects with significant potential for various applications.
基金supported by the National Natural Science Foundation of China(No.81973449)the China Postdoctoral Science Foundation(No.2020M680871)。
文摘Berberine(BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian(Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molecular mechanisms are not clear. In this paper, the BBR-affected energy metabolism pathway was screened by nontargeted metabolomics, and a BBR-derived photoaffinity labeled(PAL) probe was designed to identify potential targets via a chemical proteomics approach. NDUFV1, a subunit of complex Ⅰ on mitochondria, was identified as a potential target of BBR. In the respiratory chain, BBR suppressed the activity of complex Ⅰ, reduced the electrochemical potential in the mitochondrial intermembrane and inhibited the generation of ATP and heat via competitive binding with NDUFV1. The results illustrated the underlying mechanism of BBR in the downregulation of energy metabolism.
