Farong Lu

Shenyang Pharmaceutical University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Yingchao Li

Hebei Medical University

Qikun Jiang

Shenyang Pharmaceutical University

Tianhong Zhang

Shenyang Pharmaceutical University

Zhonggui He

Shenyang Pharmaceutical University

Yawei Zhang

Shanxi Medical University

Xiaoyu Liu

Beihang University

Yawei Zhang

Chinese Academy of Sciences

Tianhong Zhang

Shenyang Pharmaceutical University

Meiling Luo

The Seventh Affiliated Hospital of Sun Yat-sen University

Yingchao Li

Institute of Oceanology

Cooperative Institutions

Shenyang Pharmaceutical University

Chinese Academy of Sciences

Shandong University

Hebei Medical University

Sun Yat-sen University

Peking University

Shenyang Agricultural University

Zhejiang Chinese Medical University

Second Hospital of Hebei Medical University

Ministry of Agriculture and Rural Affairs

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

LC–MS/MS Analysis and Pharmacokinetics of Daidzein and its 7-O-Glucuronide in Rats After Oral Administration of 7-O-L-Valyl Carbamate Prodrug

Bioanalysis (2021)

Xiaolong Xu Yingchao Li Xiaochen Bai Farong Lu Yawei Zhang

Background: A valine carbamate prodrug (7-P) was designed to enhance the low bioavailability of daidzein due to its low water solubility and membrane permeability. Here, we developed a high-throughput HPLC–MS/MS method to measure daidzein and its 7-O-glucuronide after oral administration of daidzein or 7-P. Materials & methods: A HPLC–MS/MS method was validated and successfully applied to assess the pharmacokinetic behavior of daidzein and its 7-O-glucuronide after orally administrating daidzein or 7-P. The validated method on selectivity, linearity (r ≥ 0.995), precision (relative standard deviation <11.4%), accuracy (relative error <7.1%), extraction recovery (>92.4%), matrix effect (<8.2%) and stability were satisfied. Conclusion: The proposed economical, rapid and sensitive method will be an alternative analytical procedure for daidzein and its metabolite in biological samples.

Glucuronide

10.4155/bio-2020-0276

Cite

Citations (2)

Dual Strategy for Improving the Oral Bioavailability of Resveratrol: Enhancing Water Solubility and Inhibiting Glucuronidation

Journal of Agricultural and Food Chemistry (2021)

Yingchao Li Ran Zhang Qi Zhang Meiling Luo Farong Lu

Resveratrol (RES) suffers from poor water solubility and extensive metabolism, which lead to low bioavailability. A phospholipid complex (PC) containing RES and a UDP-glucuronosyltransferase (UGT) inhibitor was prepared to address these two limiting factors, thereby improving RES bioavailability. First, 11 natural active ingredients metabolized by similar enzyme subtypes to RES were screened in a glucuronidation assay in liver microsomes. Then, glycyrrhetinic acid (GA), the strongest inhibitor, was prepared with RES in a PC. RES-PC was prepared as a control. As expected, the water solubility and the cumulative dissolution of RES were significantly enhanced by RES-PC and RES/GA-PC. Compared with the RES group, the AUC0–10 of RES and resveratrol-3-glucuronide (R-3-G) in the RES/GA-PC group showed increases of 2.49- and 1.70-fold, respectively, with the proportion of RES absorption to total absorption increasing 1.45 times. These results demonstrated that RES/GA-PC could improve the bioavailability of RES by increasing its water solubility and inhibiting its glucuronidation.

Glucuronide

10.1021/acs.jafc.1c02602

Cite

Citations (23)

Simultaneous determination of daidzein, its prodrug and major conjugative metabolites in rat plasma and application in a pharmacokinetic study

New Journal of Chemistry (2022)

Yingchao Li Xiaoyu Liu Farong Lu Jiaming Zhang Yawei Zhang

The developed method successfully validated that the synthesized prodrug improved the bioavailability of DAN by reducing its phase II metabolites.

10.1039/d2nj02690b

Cite

Citations (2)

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability

Journal of Agricultural and Food Chemistry (2024)

Yingchao Li Xiaoyu Liu Farong Lu H.B. Li Jiaming Zhang

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4′-O-CO-N-isoleucine, D-4′-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4′-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4′-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4′-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Lipophilicity

Carbamate

10.1021/acs.jafc.4c01251

Cite

Citations (2)

A rapid ultra high performance liquid chromatography–tandem mass spectrometry method for the quantification of daidzein, its valine carbamate prodrug, and glucuronide in rat plasma samples: Comparison of the pharmacokinetic behavior of daidzine valine carbamate prodrugs

Journal of Separation Science (2021)

Yingchao Li Farong Lu Yawei Zhang Xiaoyu Liu Longyi Lin

Two valine carbamate prodrugs of daidzein were designed to improve its bioavailability. To compare the pharmacokinetic behavior of these prodrugs with different protected phenolic hydroxyl groups of daidzein, a rapid and sensitive method for simultaneous quantification of daidzein, its valine carbamate prodrug, and daidzein-7-O-glucuronide in rat plasma was developed and validated in this study. The samples were processed using a fast one-step protein precipitation method with methanol added to 50 μL of plasma and were analyzed by ultra-high performance liquid chromatography with tandem mass spectrometry. To improve the selectivity, peak shape, and peak elution, several key factors, especially stationary phase and the composition of the mobile phase, were tested, and the analysis was performed using the Kinetex® C18 column (100 × 2.1 mm, 2.6 μm) within only 2.6 min under optimal conditions. The established method exhibited good linearity over the concentration range of 2.0-1000 ng/mL for daidzein, and 8.0-4000 ng/mL for the prodrug and daidzein-7-O-glucuronide. The accuracy of the quality control samples was between 95.5 and 110.2% with satisfactory intra- and interday precision (relative standard deviation values < 10.85%), respectively. This sensitive, rapid, low-cost, and high-throughput method was successfully applied to compare the pharmacokinetic behavior of different daidzein carbamate prodrugs.

Glucuronide

Protein precipitation

Carbamate

10.1002/jssc.202100331

Cite

Citations (5)