A Pharmacokinetic-Pharmacodynamic Study of Protosappanoside D, a Component Derived from Biancaea decapetala Extracts, for Its Anti-Inflammatory Effects

Abstract

Biancaea decapetala (Roth) O. Deg. (Fabaceae), traditionally used by the Hmong people to treat rheumatoid arthritis (RA), has not been extensively studied for the correlation between its anti-inflammatory activity and its active components. Protosappanoside D (PTD), a new component, has been isolated for the first time from the extract of Biancaea decapetala. This study focused on the anti-arthritic and anti-inflammatory effects of Biancaea decapetala extracts (BDE) and PTD, along with their pharmacokinetic-pharmacodynamic (PK-PD) analysis. In the adjuvant-induced arthritis (AA) rat model, HE staining and cytokine assays showed that BDE alleviated joint damage and reduced inflammatory cytokines, similar to the positive control. In the LPS-induced inflammatory cell model, both BDE and PTD demonstrated anti-inflammatory effects by inhibiting the secretion of inflammatory factors. A PK-PD analysis of BDE in AA rats and inflammatory cells, as well as an analysis of PTD as a monomer, was conducted. The results indicated that PTD had different regulatory effects on cytokines like TNF-α, with a certain lag and sustained effects. These findings suggest the potential of BDE and PTD as treatments for rheumatoid arthritis, though further in vivo studies and clinical trials are needed.

Keywords: Biancaea decapetala; Protosappanoside D; pharmacokinetics–pharmacodynamics model; rheumatoid arthritis.

Figure 1

Total ion chromatograms of the Biancaea decapetala extracts and plasma samples collected after drug administration in model rats: (A) positive ion mode; (B) negative ion mode, and chemical structure of (C) PTD and (D) Puerarin.

Figure 1

Total ion chromatograms of the Biancaea decapetala extracts and plasma samples collected after drug administration in model rats: (A) positive ion mode; (B) negative ion mode, and chemical structure of (C) PTD and (D) Puerarin.

Figure 2

Extracted-ion chromatograms (EICs) and primary and secondary mass spectra of Protosappanoside D in (A) reference substances, (B) BDE, and (C) plasma samples. MS¹ refers to primary fragment ions, MS² refers to secondary fragment ions.

Figure 3

Results of in vivo AA model validation and the effects of BDE (4.5 g/kg, twice daily) and POS (102 mg/kg, twice daily) on it. Hematoxylin–eosin staining of ankle joints in rats of different groups with different magnification (A). Comparison of HE scores among groups was conducted using nonparametric test (B). Levels of TNF-α, IL-1β, IL-6, and RF in plasma of rats in each group (C). Comparison between groups was conducted using one-way analysis of variance (ANOVA). Data were presented as mean ± SD (n = 6); * p < 0.05, ** p < 0.01, *** p < 0.001 compared with control group; ^## p < 0.01, ^### p < 0.001 compared with AA group.

Figure 4

Results of in vitro inflammation model validation. Survival rate of RAW264.7 cells of LPS (A), BDE (B), and PTD (C) at different concentrations for 24 h, and accumulation of NO (D), TNF-α (E), and IF-6 (F) in LPS-induced RAW264.7 cells for 24 h. Comparison between groups was conducted using ANOVA. Data were presented as mean ± SD (n = 6); ** p < 0.01, *** p < 0.001 compared with control group; ^## p < 0.01 compared with model group.

Figure 5

The concentration–time–effect curves (A) and concentration–effect curves (B) of PTD with TNF-α, IL-1β, IL-6, and RF in the plasma of AA model rats after the administration of BDE. The red lines represent the relationship between the drug concentration in vivo and the pharmacodynamic index concentration in vivo.

Figure 6

Concentration–time–effect curves (A) and concentration–effect curves (B) of PTD with NO, TNF-α, and IL-6 in inflammatory cells after administration of BDE. The red lines represent the relationship between the drug concentration and the pharmacodynamic index concentration.

Figure 7

Concentration–time–effect curves (A) and concentration–effect curves (B) of PTD with NO, TNF-α, and IL-6 in inflammatory cells. The red lines represent the relationship between the drug concentration and the pharmacodynamic index concentration.