European journal of pharmacology · 2025
Icariside II ameliorates slow transit constipation by inhibiting macrophage polarization and suppressing the cGAS-STING pathway.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jiang Ziying, Yin Fangxu, Ping Yaqian, Ma Wenyue, Dou Xiaohui, Li Rui, Zheng Kai, Tong Yunbin, Han Lu, Fu Lang, Wu Bozhao, Sun Daqing
Аннотация
BACKGROUND: Slow transit constipation (STC) is a functional disorder characterized by slowed colonic peristalsis and delayed emptying. Its pathogenesis involves enteric nervous system damage and immune dysregulation, among other factors. Icariside II (ICS II) is a natural flavonoid glycoside from Herba Epimedii and is known for its anti-inflammatory, antioxidant, and neuroprotective effects. However, the effect of ICS II on STC and the underlying mechanisms remains unclear.
METHODS: In this study, the effects of ICS II on STC were assessed in a loperamide-induced STC animal model. Drug efficacy was evaluated by observing the general phenotype using hematoxylin and eosin staining, immunofluorescence, Western blotting, and flow cytometry. Additionally, the roles of intestinal macrophages and the cyclic guanosine monophosphate-adenosine synthase/stimulator of interferon genes (cGAS-STING) signaling pathway in STC were studied using clodronate liposomes and STING inhibitor.
RESULTS: ICS II treatment significantly increased fecal count, fecal moisture content, and intestinal propulsion rate, shortened first dark fecal defecation time, and improved colonic histopathology in the STC animal model. Notably, ICS II reduced intestinal M1-type macrophage proportion, downregulated proteins in the cGAS-STING signaling pathway, and lowered the release of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. ICS II also decreased intestinal neuronal damage and increased nerve fiber density in STC disease, demonstrating its anti-inflammatory and neuroprotective effects.
CONCLUSION: This study provides evidence that ICS II exerts significant anti-inflammatory and neuroprotective effects. This is achieved by inhibiting the cGAS-STING pathway and suppressing macrophage M1 polarization, suggesting its potential as a therapeutic agent for STC.
METHODS: In this study, the effects of ICS II on STC were assessed in a loperamide-induced STC animal model. Drug efficacy was evaluated by observing the general phenotype using hematoxylin and eosin staining, immunofluorescence, Western blotting, and flow cytometry. Additionally, the roles of intestinal macrophages and the cyclic guanosine monophosphate-adenosine synthase/stimulator of interferon genes (cGAS-STING) signaling pathway in STC were studied using clodronate liposomes and STING inhibitor.
RESULTS: ICS II treatment significantly increased fecal count, fecal moisture content, and intestinal propulsion rate, shortened first dark fecal defecation time, and improved colonic histopathology in the STC animal model. Notably, ICS II reduced intestinal M1-type macrophage proportion, downregulated proteins in the cGAS-STING signaling pathway, and lowered the release of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. ICS II also decreased intestinal neuronal damage and increased nerve fiber density in STC disease, demonstrating its anti-inflammatory and neuroprotective effects.
CONCLUSION: This study provides evidence that ICS II exerts significant anti-inflammatory and neuroprotective effects. This is achieved by inhibiting the cGAS-STING pathway and suppressing macrophage M1 polarization, suggesting its potential as a therapeutic agent for STC.