protopanaxadiol and Inflammation

Ulcerative colitis (UC) has emerged as a global healthcare issue due to high prevalence and unsatisfying therapeutic measures. 20(S)- Protopanaxadiol saponins (PDS) from Panax notoginseng with anti-inflammatory properties is a potential anti-colitis agent. Herein, we explored the effects and mechanisms of PDS administration on experimental murine UC. Dextran sulfate sodium-induced murine UC model was employed to investigate anti-colitis effects of PDS, and associated mechanisms were further verified in HMGB1-exposed THP-1 macrophages. Results indicated that PDS administration exerted ameliorative effects against experimental UC. Moreover, PDS administration remarkably downregulated mRNA expressions and productions of related pro-inflammatory mediators, and reversed elevated expressions of proteins related to NLRP3 inflammasome after colitis induction. Furthermore, administration with PDS also suppressed the expression and translocation of HMGB1, interrupting the downstream TLR4/NF-κB pathway. In vitro, ginsenoside CK and 20(S)-protopanaxadiol, the metabolites of PDS, exhibited greater potential in anti-inflammation, and intervened with the TLR4-binding domain of HMGB1 predictably. Expectedly, ginsenoside CK and 20(S)-protopanaxadiol administrations inhibited the activation of TLR4/NF-κB/NLRP3 inflammasome pathway in HMGB1-exposed THP-1 macrophages. Summarily, PDS administration attenuated inflammatory injury in experimental colitis by blocking the binding of HMGB1 to TLR4, majorly attributed to the antagonistic efficacies of ginsenoside CK and 20(S)-protopanaxadiol.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Dextran Sulfate; HMGB1 Protein; Inflammasomes; Inflammation; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Panax notoginseng; Saponins; Toll-Like Receptor 4

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Movement; Cell Survival; Cells, Cultured; Diabetic Foot; Drug Carriers; Drug Liberation; Gels; Humans; Inflammation; Lipids; Lipopolysaccharides; Male; Mice; Nanostructures; Neovascularization, Pathologic; Nitric Oxide; Particle Size; RAW 264.7 Cells; Sapogenins; Silicone Elastomers; Surface Properties; Wound Healing