Integrated Strategy From In Vitro, In Situ, In Vivo to In Silico for Predicting Active Constituents and Exploring Molecular Mechanisms of Tongfengding Capsule for Treating Gout by Inhibiting Inflammatory Responses

Abstract

The study of screening active constituents from traditional Chinese medicine (TCM) is important for explicating the mechanism of action of TCM and further evaluating the safety and efficacy effectively. However, detecting and identifying the active constituents from complicated biological samples still remain a challenge. Here, a practical, quick, and novel integrated strategy from in vitro, in situ, in vivo to in silico for rapidly screening the active constituents was developed. Firstly, the chemical profile of TCM in vitro was identified using UPLC-Q Exactive-Orbitrap HRMS. Secondly, the in situ intestinal perfusion with venous sampling (IPVS) method was used to investigate the intestinal absorption components. Thirdly, after intragastric administration of the TCM extract, the in vivo absorbed prototype components were detected and identified. Finally, the target network pharmacology approach was applied to explore the potential targets and possible mechanisms of the absorbed components from TCM. The reliability and availability of this approach was demonstrated using Tongfengding capsule (TFDC) as an example of herbal medicine. A total of 141 compounds were detected and identified in TFDC, and among them, 64 components were absorbed into the plasma. Then, a total of 35 absorbed bioactive components and 50 related targets shared commonly by compounds and gout were integrated via target network pharmacology analysis. Ultimately, the effects of the absorbed components on metabolism pathways were verified by experiments. These results demonstrated that this original method may provide a practical tool for screening bioactive compounds from TCM treating particular diseases. Furthermore, it also can clarify the potential mechanism of action of TCM and rationalize the application of TFDC as an effective herbal therapy for gout.

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

“…Tongfengding capsule has been shown in studies to have an anti-gouty arthritis effect by inhibiting the secretion of the inflammatory factors TNF-α and IL-6. Furthermore, its mechanism may be linked to the inhibition of the arachidonic acid signaling pathway [151]. Xiaofeng granule is made from a new formula that has been improved from modified simiaowan and has heatclearing and dampness-drying properties.…”

Exploration of Q-Marker of Rhubarb Based on Intelligent Data Processing Techniques and the AUC Pooled Method

“…Based on different preparation methods, the 2020 Chinese Pharmacopoeia calculates the content of total anthraquinone and free anthraquinone (above 1.5 and 0.02%, respectively) as to control the quality of rhubarb, in terms of the total amount of aloe-emodin, rhein, emodin, chrysophanol, and physcion. It is generally believed that substances that produce curative effects are TCM prototype components or their metabolites, which enter systemic circulation to reach the target organs ( Li et al, 2018 ; Zhou et al, 2020 ; Zhu et al, 2020 ; Yang et al, 2021 ). Although anthraquinones show good pharmacological activities in vitro , including laxative, anticancer, hepatoprotective, anti-inflammatory, antibacterial, analgesic, and other effects ( Xiang et al, 2020 ).…”

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments

“…It can clear away heat and dampness, promote blood circulation, dredge collaterals, and calm pain, which is mainly used for treating gout. The study found that TFDC might inhibit the inflammatory response in treating gout by regulating the arachidonic acid metabolic pathway, especially its active compound apigenin could significantly inhibit the related targets of prostaglandin G/H synthase 2 (PTGS2), tumor necrosis factor- α (TNF- α ), and interleukin-6 (IL-6) in this pathway [ 9 ]. Clinically, TFDC could improve blood uric acid levels in patients and reduce adverse reactions such as stomach discomfort and mild diarrhea, so as to better treat GA [ 10 ].…”