Cao YF

References (5)

Title : Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations - Hou_2020_Int.J.Biol.Macromol_145_620
Author(s) : Hou XD , Guan XQ , Cao YF , Weng ZM , Hu Q , Liu HB , Jia SN , Zang SZ , Zhou Q , Yang L , Ge GB , Hou J
Ref : Int J Biol Macromol , 145 :620 , 2020
Abstract : Herbal medicines are frequently used for the prevention and treatment of obesity and obesity-related disorders. Our preliminary screening showed that St. John's Wort (SJW) displayed potent inhibition on pancreatic lipase (PL), a key hydrolase responsible for lipid digestion and absorption in mammals. Herein, the inhibition potentials and inhibitory mechanism of SJW extract and its major constituents on PL were fully investigated by a set of in vitro and in silico studies. The results clearly demonstrated that the naphthodianthrones, biflavones and most of flavonoids in SJW displayed strong to moderate inhibition on PL. Among all tested natural compounds, two naphthodianthrones (hypericin and pseudohypericin) and one biflavone (I3,II8-biapigenin) isolated from SJW exhibited potent PL inhibition activity, with the IC(50) values of <1 microM. Inhibition kinetics analyses showed that hypericin, pseudohypericin and I3,II8-biapigenin inhibited PL via a mixed manner, while molecular dynamics simulations revealed that three newly identified PL inhibitors could bind on PL at both the catalytic cavity and the interface between colipase and the C-terminal domain of PL. Collectively, our findings suggested that part of major constituents in SJW displayed potent PL inhibition activities, which could be used as lead compounds for the development of novel PL inhibitors.
ESTHER : Hou_2020_Int.J.Biol.Macromol_145_620
PubMedSearch : Hou_2020_Int.J.Biol.Macromol_145_620
PubMedID: 31883893

Title : Inhibition of human carboxylesterases by magnolol: Kinetic analyses and mechanism - Song_2019_Chem.Biol.Interact_13ChEPon_308_339
Author(s) : Song YQ , Weng ZM , Dou TY , Finel M , Wang YQ , Ding LL , Jin Q , Wang DD , Fang SQ , Cao YF , Hou J , Ge GB
Ref : Chemico-Biological Interactions , 308 :339 , 2019
Abstract : Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.
ESTHER : Song_2019_Chem.Biol.Interact_13ChEPon_308_339
PubMedSearch : Song_2019_Chem.Biol.Interact_13ChEPon_308_339
PubMedID: 31170387

Title : Discovery of a highly specific and efficacious inhibitor of human carboxylesterase 2 by large-scale screening - Song_2019_Int.J.Biol.Macromol_137_261
Author(s) : Song YQ , Guan XQ , Weng ZM , Wang YQ , Chen J , Jin Q , Fang SQ , Fan B , Cao YF , Hou J , Ge GB
Ref : Int J Biol Macromol , 137 :261 , 2019
Abstract : Human carboxylesterase 2 (CES2A), one of the most abundant hydrolases distributed in human small intestine and colon, play key roles in the hydrolysis of a wide range of prodrugs and other esters. Recent studies have demonstrated that CES2A inhibitors may ameliorate irinotecan-induced severe diarrhea, but the specific and efficacious inhibitors targeting intracellular CES2A are rarely reported. Herein, a large-scale screening campaign was conducted for discovery of potent and specific CES2A inhibitor(s). Following screening of more than one hundred of natural products, glabridin (a bioactive compound of Glycyrrhiza glabra L.) was found displaying potent inhibition on CES2A and high specificity over CES1A (>500-fold) and other serine hydrolases. Further investigation showed that glabridin was cell permeable and low cytotoxic, as well as capable of inhibiting intracellular CES2A in living cells, with the IC50 value of 0.52muM. Molecular dynamics simulations showed that glabridin formed strong and stable interactions with both the catalytic cavity and Z site of CES2A via hydrophobic interactions. In summary, glabridin was a potent and specific inhibitor targeting intracellular CES2A, which could be used as an ideal lead compound to develop more efficacious CES2A inhibitors for modulating the pharmacokinetic behaviors of CES2A-substrate drugs and alleviating irinotecan-induced diarrhea.
ESTHER : Song_2019_Int.J.Biol.Macromol_137_261
PubMedSearch : Song_2019_Int.J.Biol.Macromol_137_261
PubMedID: 31260759

Title : Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1) - Sun_2016_Xenobiotica_46_503
Author(s) : Sun DX , Ge GB , Dong PP , Cao YF , Fu ZW , Ran RX , Wu X , Zhang YY , Hua HM , Zhao Z , Fang ZZ
Ref : Xenobiotica , 46 :503 , 2016
Abstract : 1. Fructus psoraleae (FP) is the dried ripe seeds of Psoralea corylifolia L. (Fabaceae) widely used in Asia, and has been reported to exert important biochemical and pharmacological activities. The adverse effects of FP remain unclear. The present study aims to determine the inhibition of human carboxylesterase 1 (CES1) by FP's major ingredients, including neobavaisoflavone, corylifolinin, coryfolin, psoralidin, corylin and bavachinin. 2. The probe substrate of CES1 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) was derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT), and human liver microsomes (HLMs)-catalyzed BMBT metabolism was used to phenotype the activity of CES1. In silico docking method was employed to explain the inhibition mechanism. 3. All the tested compounds exerted strong inhibition towards the activity of CES1 in a concentration-dependent behavior. Furthermore, the inhibition kinetics was determined for the inhibition of neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin towards CES1. Both Dixon and Lineweaver-Burk plots showed that neobavaisoflavone, corylifolinin, coryfolin and corylin noncompetitively inhibited the activity of CES1, and bavachinin competitively inhibited the activity of CES1. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 9.4, 1.9, 0.7 and 0.5 muM for neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin, respectively. In conclusion, the inhibition behavior of CES1 by the FP's constituents was given in this article, indicating the possible adverse effects of FP through the disrupting CES1-catalyzed metabolism of endogenous substances and xenobiotics.
ESTHER : Sun_2016_Xenobiotica_46_503
PubMedSearch : Sun_2016_Xenobiotica_46_503
PubMedID: 26560012

Title : A highly selective ratiometric fluorescent probe for in vitro monitoring and cellular imaging of human carboxylesterase 1 - Liu_2014_Biosens.Bioelectron_57C_30
Author(s) : Liu ZM , Feng L , Ge GB , Lv X , Hou J , Cao YF , Cui JN , Yang L
Ref : Biosensors & Bioelectronics , 57C :30 , 2014
Abstract : A new ratiometric fluorescent probe derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT) has been developed for selective monitoring of human carboxylesterase 1 (hCE1). The probe is designed by introducing benzoyl moiety to HMBT. The prepared latent spectroscopic probe 1 displays satisfying stability under physiological pH conditions with very low background signal. Both the reaction phynotyping and chemical inhibition assays demonstrated that hCE1 mediated the specific cleavage of the carboxylic ester bond of probe 1 in human biological samples. The release of HMBT leads to a remarkable red-shifted emission in fluorescence spectrum (120nm large emission shift). Furthermore, human cell-based assays show that probe 1 is cell membrane permeable, and it can be used for bioassay and cellular imaging of hCE1 activity in HepG2 cells. These findings lead to the development of a simple and sensitive fluorescent method for measurement of hCE1 activity in vitro or in living cells, in the presence of additional enzymes or endogenous compounds.
ESTHER : Liu_2014_Biosens.Bioelectron_57C_30
PubMedSearch : Liu_2014_Biosens.Bioelectron_57C_30
PubMedID: 24534577