Medicinal and edible plant Allium macrostemon Bunge for the treatment of testosterone-induced androgenetic alopecia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Allium macrostemon Bunge (AMB), a widely distributed wild garlic plant, possesses a variety of health-promoting properties. Androgenetic alopecia (AGA) is a common disorder that affects quality of life. AIM OF THE STUDY: We sought to investigate whether AMB stimulates hair regrowth in AGA mouse model, and clarify the underlying molecular mechanisms. MATERIALS AND METHODS: The chemical constituents of AMB water extract were identified by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q/TOF-MS) analysis. Cell viability assay and Ki-67 immunostaining were undertaken to evaluate the impacts of AMB on human hair dermal papilla cell (HDPC) proliferation. Wound-healing assay was undertaken to assess cell migration. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were performed to examine cell apoptosis. Western blotting, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays were undertaken to determine the impacts of AMB on Wnt/ß-catenin signaling and growth factors expression in HDPC cells. AGA mouse model was induced by testosterone treatment. The effects of AMB on hair regeneration in AGA mice were demonstrated by hair growth measuring and histological scoring. The levels of ß-catenin, p-GSK-3ß, and Cyclin D1 in dorsal skin were measured. RESULTS: AMB promoted proliferation and migration, as well as the expression of growth factors in cultured HDPC cells. Meanwhile, AMB restrained apoptosis of HDPC cells by increasing the ratio of anti-apoptotic Bcl-2/pro-apoptotic Bax. Besides, AMB activated Wnt/ß-catenin signaling and thereby enhancing growth factors expression as well as proliferation of HDPC cells, which was abolished by Wnt signaling inhibitor ICG-001. In addition, an increase of hair shaft elongation was observed in mice suffering from testosterone-induced AGA upon the treatment of AMB extract (1% and 3%). Consistent with the in vitro assays, AMB upregulated the Wnt/ß-catenin signaling molecules in dorsal skin of AGA mice. CONCLUSION: This study demonstrated that AMB promoted HDPC cell proliferation and stimulated hair regrowth in AGA mice. Wnt/ß-catenin signaling activation, which induced production of growth factors in hair follicles and, eventually, contributed to the influence of AMB on the hair regrowth. Our findings may contribute to effective utilization of AMB in alopecia treatment.

Functionalized Prussian Blue Nanozyme as Dual-Responsive Drug Therapeutic Nanoplatform Against Maxillofacial Infection via Macrophage Polarization.

Purpose: Maxillofacial infection is a common disease in stomatology and is difficult to treat owing to its high potential to spread to vital anatomical structures. Excessive levels of reactive oxygen species (ROS) in infected tissues lead to cellular damage and impede tissue regeneration. However, uncontrollable strategies to remove ROS have limited therapeutic efficacy. Nanoparticle systems for scavenging ROS and remodeling the inflammatory microenvironment offer much promise in the treatment of maxillofacial inflammation. Methods: Here, a novel microenvironment-stimuli-responsive drug delivery nanoplatform (HMPB@Cur@PDA) based on a polydopamine (PDA)-functionalized hollow mesoporous Prussian blue (HMPB) nanozyme was developed for the delivery of curcumin (Cur) in the treatment of maxillofacial infection. Low pH and excess ROS in the inflammatory microenvironment cause degradation of the outer PDA layer of the nanocomplex, exposing the HMPB nanozyme and loaded Cur, which synergistically act as a ROS scavenger and anti-inflammatory agent, respectively, and induce macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. Results: Experiments in vitro provided strong evidence for the application of novel nanocomplexes in scavenging multiple ROS and inhibiting lipopolysaccharide-induced inflammation. In addition, in vivo results obtained using a mouse maxillofacial infection model demonstrated that HMPB@Cur@PDA had excellent biocompatibility, significantly attenuated the inflammatory response in periodontal tissue, and improved the repair of damaged tissue. Conclusion: Our results indicate that HMPB@Cur@PDA nanocomposites have great potential for ROS regulation as well as having anti-inflammatory effects, providing new insights for the development of dual-response maxillofacial infection treatments.