{"id":221,"title":"Leonurine microcomposite depots alleviate endometriosis and rheumatoid arthritis via shared anti-inflammatory cascades","title_zh":"益母草碱微晶长效储库通过共同抗炎级联缓解子宫内膜异位症与类风湿关节炎","url":"https://pubmed.ncbi.nlm.nih.gov/42991488","doi":"10.1016/j.ijpx.2026.100690","pmid":"42991488","journal":"Int J Pharm X","kind":"paper","lang":"en","published_at":"2026-10-17T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Meng S","Zhong J","Xiao Y","Zhang X","Tang Z","Song Z","Yang X","Zhu YZ","Wang X","Guo H"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":4.0,"hits":["endometriosis"]},{"slug":"repro-endo","score":1.0,"hits":["progesterone"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":66.0,"final_score":66.0,"score_dims":{"novelty":70,"rigor":65,"impact":55,"relevance":48,"translation":60},"recommend_reason":"以长效控释制剂同时干预内异症与类风湿关节炎，抗炎上游机制与自噬/凋亡下游通路衔接清晰，动物层面验证较完整；但以内异症与炎症为主、与胚胎与ART核心环节距离较远，且缺乏灵长类或临床数据，故定位为可浏览。","keywords":["益母草碱","长效控释储库","子宫内膜异位症","抗炎级联","自噬与凋亡","类风湿关节炎"],"selected":1,"story_id":382,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"研究开发了包载益母草碱微晶的微复合长效储库（Leo-micro@MD），载药量高、18天持续无突释释放。机制上该制剂抑制上游关键炎症因子，在子宫内膜异位症中减弱雌激素-ERα信号、恢复孕激素受体B表达，进而重启LC3B介导的自噬与Bax/Bcl-2依赖凋亡以清除异位病灶；在佐剂诱导关节炎大鼠模型中减轻滑膜增生、改善骨密度与骨小梁结构并恢复关节基质稳态（micro-CT与组织病理学验证），且未见肝、肾及免疫器官毒性。结论提示该控释平台可作为慢性炎症性疾病的转化治疗策略。","summary":"Chronic inflammatory diseases, such as endometriosis (EMS) and rheumatoid arthritis (RA), share a common pathogenic hallmark driven by a hyperinflammatory microenvironment. Nonetheless, long-acting therapeutic platforms capable of concurrently addressing these disparate disorders remain rarely explored. Herein, we developed a leonurine microcrystal-encapsulated microcomposite depot (Leo-micro@MD) capable of effectively mitigating inflammation, thereby reversing the progression of both EMS and RA. Systemic formulation optimization yielded an optimized Leo-micro@MD formulation with high drug loading and a sustained, burst-free release profile extending over 18 days, markedly reducing administration frequency. Mechanistically, Leo-micro@MD suppresses key upstream inflammatory cytokines, thereby branching into distinct downstream therapeutic pathways tailored to each disorder. In EMS, this reduction attenuated estrogen-ERα signaling and restored progesterone receptor B (PRB) expression, subsequently reactivating LC3B-mediated autophagy and Bax/Bcl-2-dependent apoptosis to eradicate ectopic lesions. Concurrently, in an adjuvant-induced arthritis rat model, this anti-inflammatory cascade attenuates synovial hyperplasia, rescues bone mineral density and trabecular architecture, and re-establishes articular matrix homeostasis, as confirmed by micro-CT and comprehensive histopathology. Importantly, these disease-modifying effects are achieved with an excellent systemic safety profile, with no detectable hepatotoxicity, nephrotoxicity, or immune organ damage. Collectively, this study provides a robust and translatable controlled-release strategy for the comprehensive management of chronic inflammatory diseases.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}