Yucca schidigera purpurea-sourced arabinogalactan polysaccharides augments antioxidant capacity facilitating intestinal antioxidant functions.

This study isolated and purified a novel homogeneous arabinogalactan polysaccharide from Yucca schidigera extract (YSE), unveiled its unique structure and explored its antioxidant function. Firstly, the antioxidant potential of YSE was demonstrated in piglet trials. A homogeneous polysaccharide with a molecular weight of 24.2 kDa, designated as Yucca schidigera polysaccharide B (YPB), was isolated and purified from YSE. The monosaccharide composition of YPB was Rha, Araf, Galp, and Glcp, whose molar percentages were 2.8 %, 11.6 %, 45.5 %, and 40.0 %, respectively. Methylation analysis combined with 1D and 2D nuclear magnetic resonance showed that YPB was a complex polysaccharide with a main glycosidic linkage pattern of →2)-α-ʟ-Rha-(1 â†’ 3)-ß-ᴅ-Galp-(1→3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Glcp-(1→, and branched Araf and Galp fragments were connected with the main chain through →3,6)-ß-ᴅ-Galp-(1→, →3,4)-ß-ᴅ-Glcp-(1→, and →2,4)-α-ʟ-Rha-(1→ linkages. Following the in vitro biochemical assays of bioactive components, YPB should be the contributor to the antioxidant activity in YSE. Based on the establishment of oxidative stress model, YPB exhibited strong antioxidant capacity and activated NRF2 pathway, and then provided protection against the damage induced oxidative stress in IPEC-J2 cells and rats. Further analysis with inhibitors found that this antioxidant effect was attributed to its interaction with epidermal growth factor receptor and mannose receptor, and stimulating PI3K/AKT pathway.

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway.

Purpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism. Methods: The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software. Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream. Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.

Pharmacokinetic study of eight bioactive components following oral administration of Zhiqiao Gancao decoction and observation of its clinical efficacy.

Zhiqiao Gancao (ZQGC) decoction is widely used in China due to its therapeutic effect on lumbar disc herniation (LDH). In this study, we compared the clinical therapeutic effects among oral ZQGC decoction treatment, bed rest, and oral anti-inflammatory drug celecoxib treatment using visual analog scale, Oswestry Disability Index, and MacNab scores. The results showed that ZQGC decoction can significantly improve the symptoms of patients with LDH. A selective, sensitive, and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of eight bioactive components in rat plasma. The plasma samples were extracted by simple protein precipitation with methanol. The protonated analytes were quantitated simultaneously in positive and negative ion modes by multiple reaction monitoring with a mass spectrometer. The calibration curve of eight components in plasma showed good linearity (r > .996) and the extraction recovery was 81.19% ± 2.15% - 100.39 ± 3.36 (relative standard deviation: 1.21%-10.70%). The accuracy of all the lower limit of quantitation values was quantified within 80%-120%, and the precision was less than 15%. This validated method was successfully applied to the pharmacokinetics study in rat plasma after ZQGC decoction oral treatment. Our research can provide experimental basis for the rational clinical application of ZQGC decoction in the treatment of LDH.