AS-IV-HP-β-CD molecular capsules alleviated motor dysfunction and DA neuronal loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation in MPTP-induced PD mice

This study employed molecular simulation docking technology to identify the most suitable host molecules for encapsulating Astragaloside IV (AS-IV). AS-IV-HP-β-CD molecular capsules were prepared by encapsulating the hydrophobic groups of AS-IV in the inner cavity of HP-β-CD through the grinding method. The encapsulation behaviours were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and liquid nuclear magnetic resonance spectroscopy. It was found that AS-IV was encapsulated inside the HP-β-CD cavity and presented a layered structure after encapsulation. Content determination showed that the solubility and dissolution rate of AS-IV-HP-β-CD in vitro were significantly increased compared to AS-IV. Pharmacodynamic tests demonstrated that oral administration of AS-IV-HP-β-CD effectively ameliorated motor dysfunction, alleviated dopaminergic (DA) TH-positive neuronal loss, and reduced the expression of inflammatory cytokines IL-1β and IL-18 in the substantia nigra pars compacta of MPTP-induced Parkinson's disease mice. Simultaneously, the AS-IV-HP-β-CD intervention inhibited the expression of the NLRP3 inflammasome, accompanied by a decrease in the expression of TLR4/MyD88/NF-κB pathway proteins. This study addressed the issues of poor water solubility and dissolution rate, laying the groundwork for developing AS-IV formulations. Meanwhile, new data further support the potential of AS-IV as an effective dietary combination for adjuvant therapy of PD. • AS-IV-HP-β-CD protects TH + neurons by inhibiting NLRP3 inflammasome-mediated neuroinflammation in MPTP-induced PD mice.