Pharmacokinetic–pharmacodynamic modeling analysis and anti‐inflammatory effect of Wangbi capsule in the treatment of adjuvant‐induced arthritis

Abstract

Clinically, Wangbi Capsule (WBC) is widely used in the treatment of Rheumatoid arthritis (RA) because of its remarkable therapeutic effect. To reveal the mechanism, a pharmacokinetic-pharmacodynamic (PK-PD) model was developed for the first time to assess the relationship between time-concentration (dose)-effect. Freund's Complete Adjuvant was used to induce the adjuvant-induced arthritis model. Multiindices were used to evaluate the therapeutic effect and an S-I max PK-PD model was established based on the concentrations of osthole, 5-O-methylvisamminoside, cimifugin, albiflorin, paeoniflorin and icariin and the levels of interleukin-1β and prostaglandin E 2 using a two-compartment PK model together with a PD model with an effect-site compartment. The results suggest that WBC can treat RA by regulating the levels of prostaglandin E 2 and interleukin-1β. For the PK-PD model, the parameters indicated that WBC had a large safety margin and all six bioactive ingredients of WBC have therapeutic effects on RA. Among them icariin, osthole and 5-Omethylvisamminoside may be the main effective substances. This study provided a scientific basis for further study of population pharmacokinetics / population pharmacodynamics (PPK/PPD), to develop a reasonable administration plan and improve individualized drug therapy.

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

“…Previous studies reported the potential anti‐RA effect of OS 25,26 . In addition, OS has an inhibitory impact on cell proliferation, migration, and invasion 27,28 .…”

“…Previous studies reported the potential anti‐RA effect of OS. 25 , 26 In addition, OS has an inhibitory impact on cell proliferation, migration, and invasion. 27 , 28 In the present investigation, we found that OS not only inhibited RA‐FLS proliferation, migration, and invasion but also showed an additive effect with MTX.…”

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis

“…Quercetin and kaempferol remarkably suppressed production of PGE2 in human rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), and the mechanism might be related to the inhibition of COX1 and COX2 expression ( Lee and Kim, 2010 ; Sung et al, 2012 ; Yoon et al, 2013 ). PGE2 and COX2 were suppressed by quercetin, emodin and icariin in RA mice ( Zhu et al, 2013 ; Yang et al, 2018b ; Guazelli et al, 2018 ; Liu T et al, 2021 ). Apigenin, isoliquiritigenin and luteolin treatment had an inhibitory effect on the expression of COX2 in lipopolysaccharide (LPS) induced RAW 264.7 macrophage cells ( Kim et al, 2008 ; Lee and Kim, 2010 ).…”

“…The expression of VEGF, VEGFR1 and VEGFR2 in synovial tissues of CIA mice and vascular cell adhesion molecule (VCAM) in human umbilical vein endothelial cells (HUVECs) were significantly inhibited by apigenin ( Li et al, 2019 ; Zhou et al, 2021 ). A recent study showed that luteolin suppressed the expression of VEGF and HIF-1α in CIA mice and HUVECs ( Liu T et al, 2021 ; Zhou et al, 2021 ). In vivo and in vitro studies showed that β -sitosterol significantly inhibited the expression and phosphorylation of VEGFR2 ( Qian et al, 2021 ).…”

Separation of three chromones fromSaposhnikovia divaricatausing macroporous resins followed by preparative high‐performance liquid chromatography

“…It has been reported that CN could inhibit the inflammatory responses of RAW264.7 cells, ameliorate imiquimod‐induced psoriasis, and suppress allergic inflammation [15–17]. Recently, it was found that MV might be one of the main effective substances of Wangbi capsules in the treatment of rheumatoid arthritis [18]. Due to their various pharmacological activities, PG and MV are used as quality control indicators of SD in the Chinese Pharmacopoeia.…”