20(S)-Ginsenoside Rh2

Inhibiting inflammation in nervous system is a vital part of treating for spinal cord injury (SCI). Compounds originating from plants can decrease the damage in the spinal cord for recovering the function of nerve and interrupting the inflammatory reaction. 20(S)-Ginsenoside Rh2 (G-Rh2) from Panax ginseng is an anti-inflammatory property inhibiting the expression of MAPK14 protein by enabling the MAPK pathway. Therefore, this research explored the anti-inflammatory effects of G-Rh2 on SCI using cellular and animal models.

To explore G-Rh2's anti-inflammatory potential in SCI, we employed bioinformatics analysis to anticipate target proteins and signaling pathways associated with G-Rh2 and SCI. We utilized BV2 microglia cells to model inflammation induced by lipopolysaccharide (LPS), and a modified Allen's technique in a mouse SCI model. Our investigation utilized a range of methodologies including quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-Linked Immunosorbent Assay (ELISA), Immunofluorescence (IF) and Western Blot (WB).

Bioinformatics analysis and molecular docking identified MAPK14 as a key target of G-Rh2. In BV2 cells experiments, G-Rh2 reduced the expression and generation of inflammatory factors, reactive oxygen species (ROS), and transcription factors involved in the MAPK signaling pathway. G-Rh2 showed a decrease in inflammatory reaction and improvements in motor function in the mouse model using the modified Allen's approach for SCI.

G-Rh2 mitigates inflammatory responses and enhances motor function recovery in mice with SCI via the ROS/MAPK14 signaling pathway.

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development.