Hongbo Xu’s research while affiliated with Innovative Drug Research Solutions and other places

Introduction Wuling capsule is a Chinese patent medicine mainly used for the treatment of chronic liver disease in clinical practice. Our previous work has revealed that Wuling capsule could inhibit liver fibrosis by regulating macrophage polarization, and firstly demonstrated its anti-gout effects on monosodium urate (MSU)- induced acute gouty arthritis (AGA) in rats. High uric acid (UA) levels are known to be the primary cause of gout. Therefore, this study investigated the UA lowering, kidney protection effects and underlying mechanisms of Wuling capsule in vivo and in vitro, and also determined its key bioactive constituents. Methods The efficacy of Wuling capsule for HUA symptoms in rats was evaluated. Histopathological analysis of liver and kidney tissues were detected by HE staining. The biochemical indices were measured using specific kits. The main constituents of Wuling capsule and its medicated serum were analyzed by UPLC-QTOF-MS/MS. Protective effects of saikosaponin A, tanshinone IIA, schisandrol B, and ganoderic acid A on UA-injured HK-2 cells were assessed via Hoechst 33342/PI staining and flow cytometry. Molecular docking and dynamics simulation predicted the binding energy and stability of these constituents to UA related transporters. The mRNA and protein expression levels of UA related transporters were examined using RT-qPCR and Western blotting. Results In HUA rats, Wuling capsule significantly reduced the serum UA level and xanthine oxidase (XOD) content in both serum and liver. Furthermore, it improved liver function markers (ALT, AST) and renal injury indicators (Cr, BUN), ameliorated renal tubule dilation and inflammatory infiltration in the kidney, and regulated the mRNA and protein expression of UA related transporters (URAT1, GLUT9, ABCG2 and OAT1). In vitro, the main constituents of Wuling capsule (saikosaponin A, tanshinone IIA, schisandrol B and ganoderic acid A) improved cell viability and inhibited cell apoptosis in UA-injured HK-2 cells. Subsequently, its four serum constituents also significantly regulated the mRNA and protein expression of URAT1, GLUT9, and ABCG2 selectively. Discussion This work demonstrated the therapeutic effect of Wuling capsule on HUA by protecting liver and kidney function and regulating UA related transporters. These findings provide novel support for the further clinical application of Wuling capsule.

To develop and refine an online activity detection system for in vitro screening of bioactivity and structure–activity relationship of Ziziphi Spinosae Semen (ZSS.). An online active detection system integrating ultrahigh performance liquid chromatography, photodiode array detection, mass spectrometry, and 5‐lipoxygenase fluorescence detection was established. Additionally, molecular docking were conducted to predict interactions between the potential active ingredients and 5‐lipoxygenase, facilitating the swift identification of antiinflammatory agents from the ZSS. The optimal conditions for the reaction system were identified as a temperature of 30°C, a flow rate of 0.2 mL/min, and a 0.1 mol/L phosphate‐buffered saline solution at pH 8.1, with an enzyme concentration of 1.5 × 10 ⁴ U/mL. Using this system, 10 constituents from the ZSS. exhibited potential binding affinity with 5‐lipoxygenase. Subsequent molecular docking of these 10 candidate bioactive molecules with 5‐lipoxygenase indicated that rutin, zivulgarin, sanjoine, 6‴‐feruloylspinosin, 6‴‐(3‴′,4‴′,5‴′‐trimethoxyl)‐( E )‐cinnamoylspinosin, nummularine B, vicenin II, 6‴‐ O ‐(3 R ‐1‐ N ‐β‐ d ‐glucopyranosyl‐2‐oxo‐3‐hydroxy‐indole‐3‐acetyl)spinosin, and apigenin displayed significant binding capabilities with 5‐lipoxygenase. This system offers a robust platform for screening 5‐lipoxygenase inhibitors, supporting the identification of premium ZSS. This methodology presents a novel approach for the rapid identification of potential antiinflammatory bioactive components in traditional Chinese medicine.

Paris polyphylla var. yunnanensis (PPY) is a traditional and valuable Chinese medicine in China, which is one of the important raw materials for many proprietary Chinese medicines, but its wild resources are scarce and the quality of cultivated products varies. Steroidal saponins are the main active components of PPY; in order to analyze the differences in the chemical constituents contained in different parts of PPY, the present study was conducted to characterize the steroidal constituents in different parts of PPY (axial roots, stems, and leaves) by ultrahigh‐performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry (UHPLC‐Q/TOF‐HRMS) coupled with molecular network technology and to determine the contents of the nine active components in PPY (tall and short stalk) by high‐performance liquid chromatography with photodiode array (HPLC‐PDA). The results showed that 62 chemical constituents were identified from different parts of PPY, and there were significant differences in composition types and contents in different parts, among which the composition types and contents of steroidal saponins in axial roots and leaves were higher, while those in stems were lower. The contents of three steroidal saponins specified in China Pharmacopoeia (2020 edition) are higher than 0.6% in the axial roots and leaves, indicating that the leaves of PPY can be used as one of the potential sources of steroidal saponins. The composition of PPY was similar in tall and short stalks, but higher total steroidal saponin content in taller stalk. In conclusion, this study points out the direction for resource conservation and rational development of PPY, and provides a basis for comprehensive evaluation of the quality of PPY medicinal herbs and screening of high‐quality PPY germplasm.

Introduction Targeted screening of inhibitors of key enzymes in the progression of diabetes from natural products is one of the effective methods for the treatment of diabetes. Polygala has been proved to reduce glucose levels; however, the bioactive compounds in Polygalae Radix (PR) that have anti‐diabetic properties are unknown. Objective The purpose of this study was to explore the material basis of the anti‐diabetic effect of PR by inhibiting α ‐amylase through an online detection system and molecular docking. Methods An online analysis platform was established and optimized for the screening of potent enzyme inhibitors from complex mixtures based on ultra‐performance liquid chromatography‐photodiode array‐quadrupole‐time‐of‐flight‐mass spectrometry‐ α ‐amylase‐fluorescence detector (UHPLC‐PDA‐Q‐TOF‐MS ⁿ ‐α‐amylase‐FLD) detection system and molecular docking, which could efficiently separate extracts, quickly detect α ‐amylase inhibitors, and determine their structures. Molecular docking confirms the inhibition of these compounds. The molecular interaction between α‐amylase and the active compound was evaluated. Results Among the 101 compounds identified, 28 compounds had a strong inhibitory effect on α ‐amylase. Molecular docking screening confirmed the inhibition of these compounds and evaluated the molecular interactions between α ‐amylase and 30 active compounds, which strongly supported the experimental results. Among the evaluated compounds, onjisaponin R ( 83 ) and polygalaxanthone III ( 11 ) have the strongest inhibitory activity to α ‐amylase (the binding energies were −9.639 and −8.972 kcal/mol, respectively) and are potential lead compounds against diabetes. Conclusion This study proved the feasibility of using the existing platform to screen the active ingredients in PR extract, and provided a practical method for the rapid screening of potential anti‐diabetic active ingredients in traditional Chinese medicine.

Macroporous resin is an efficient separation technology that plays a crucial role in the separation and purification of traditional Chinese medicine (TCM). However, the application of macroporous resins in TCM pharmaceuticals is hindered by serious fouling caused by the complex materials used in TCM. This study examines the impact of ultrafiltration (UF) membrane technology on the macroporous resin adsorption behavior of TCM extracts. In this paper, Bupleurum chinense DC. (B. chinense) water extracts were included as an example to study the effect of UF pretreatment on the macroporous resin adsorption of total saponins. The study results indicated that the adsorption of total saponins constituents from the water extracts of B. chinense on the macroporous resin followed the pseudo-second-order kinetic model and the Langmuir model. The thermodynamic parameters of adsorption, including enthalpy changes and Gibbs free energies, were negative, while entropy changes were positive. These results demonstrated that the total saponin components form a monolayer adsorption layer by spontaneous thermal adsorption on the macroporous resin, and that the adsorption rate is not determined by the rate of intraparticle diffusion. Following treatment with a UF membrane with an average molecular weight cut-off of 50 kDa, the protein, starch, pectin, tannin, and other impurities in the water extracts of B. chinense were reduced, while the total saponin content was retained at 82.32%. The adsorption kinetic model of the saponin constituents on the macroporous resin remained unchanged and was consistent with both the second-order kinetic model and the Langmuir model; the adsorption rate of the second-order kinetic model increased by 1.3 times and in the Langmuir model at 25 °C, the adsorption performance improved by 1.16 times compared to the original extracts. This study revealed that UF technology as a pretreatment method can reduce the fouling of macroporous resin by TCM extracts and improve the adsorption performance of macroporous resin.

Introduction Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. Objectives This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α‐amylase. Methodology An online analysis platform was established and optimized using an ultra‐performance liquid chromatography‐photo‐diode array‐quadrupole‐time‐of‐flight‐mass spectrometry‐α‐amylase‐fluorescence detector (UHPLC–PDA–Q‐TOF–MS–α‐amylase–FLD) system to screen α‐amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α‐amylase and active compounds were evaluated, which strongly supported the experimental results. Results Seventy‐eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α‐amylase binding activity. Conclusion This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.