Effect of Ultrafine Powderization and Solid Dispersion Formation via Hot-Melt Extrusion on Antioxidant, Anti-Inflammatory, and the Human Kv1.3 Channel Inhibitory Activities of Angelica gigas Nakai

Angelica gigas Nakai (AGN) was first processed by ultrafine grinding technology and hot-melt extrusion (HME). The potential antioxidant and anti-inflammatory activities of AGN with a different process were compared, and the effect on the human Kv1.3 potassium channel was detected. The process of ultrafine powderization on AGN significantly increased the total phenolic and flavonoid contents, antioxidant activity, and DNA damage protective effect. On the contrary, AGN solid dispersion (AGN-SD) based on Soluplus® showed the highest inhibitory effect on NO production and the human Kv1.3 channel. In addition, AGN-SD inhibited the production of prostaglandin E2 and intracellular reactive oxygen species and the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1β, and interleukin 6. Taken together, these results suggest that ultrafine powderization and solid dispersion formation via HME can significantly improve the biological activities of AGN. The results also suggested that ultrafine powderization and HME may be developed and applied in the pharmaceutical industry

Size distribution of coarse and ultrafine AGN particles (F1 and F2).

<p>Size distribution of coarse and ultrafine AGN particles (F1 and F2).</p

Size distribution of the aqueous dispersion of formulations (F1-F8).

<p>Size distribution of the aqueous dispersion of formulations (F1-F8).</p

<i>In vivo</i> toxicity test in the intestinal epithelium after oral administration of AGN EtOH ext, F2, F5, and F8 in rats.

<p>Jejunum of rat was excised at 24 h post-administration of each formulation orally and the tissue was stained by H&E. The length of scale bar (green color) is 100 μm.</p

Released amounts (mg/g, w/w) of D and DA in DW (A), pH 1.2 (B), and pH 6.8 (C).

<p>Data are presented as mean ± SD (n = 3). ^#<i>p</i> < 0.05, compared to D or DA in AGN EtOH ext group. Two-tailed <i>t</i>-test is used for the statistical analysis.</p

Scheme of developing AGN-based solid formulations by HME technique.

<p>Scheme of developing AGN-based solid formulations by HME technique.</p

The influence of AGN EtOH ext and F8 on the scopolamine-induced memory impairment mice, evaluated by passive avoidance test.

<p>^#<i>p</i> < 0.05, compared to control group; *<i>p</i> < 0.05, compared to scopolamine-treated group; ⁺<i>p</i> < 0.05, compared to (scopolamine + AGN EtOH ext)-treated group. Two-tailed <i>t</i>-test is used for the statistical analysis. Each point represents mean ± SD (n = 6).</p

The compositions and processing conditions of developed formulations.

<p>The compositions and processing conditions of developed formulations.</p

Pharmacokinetic parameters of DOH after oral administration of AGN EtOH extract, F2, F5, and F8 in rats (n = 3–5).

<p>Data were expressed as means ± SD except for median (ranges) T_max.</p><p>^#<i>p</i> < 0.05, compared to AGN EtOH ext group.</p><p>*<i>p</i> < 0.05, compared to F2 group.</p><p>⁺<i>p</i> < 0.05, compared to F5 group.</p><p>ANOVA is used for the statistical analysis.</p><p>Pharmacokinetic parameters of DOH after oral administration of AGN EtOH extract, F2, F5, and F8 in rats (n = 3–5).</p

Pharmacokinetic profiles of DOH in plasma after oral administration of AGN EtOH ext, F2, F5, and F8 in rats.

<p>Each point indicates means ± SD (n = 3–5).</p