Journal of ethnopharmacology · 2025
Osthole promotes skin flap survival by inhibiting ferroptosis and alleviating pyroptosis.
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.
Xu Panshen, Wang An, Xiao Zhixi, Song Weilong, Pan Hebin, Yang Jianlong, Deng Jianpeng, Wang Kaitao, Lin Dingsheng
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is documented in the Compendium of Materia Medica as a treatment for traumatic injury with blood stasis ('pusun yuxue'), rheumatic arthralgia ('fengshi bitong'), and tinea and sores ('xuan chuang'). Osthole (OST), a coumarin derivative extracted from its fruit, possesses antioxidant and anti-inflammatory properties. Although OST is widely used for treating skin damage, its effect on skin flap survival remains unclear.
AIM OF THE STUDY: This study aimed to investigate the effect of OST on promoting the survival of ischemic flaps and to elucidate its underlying mechanisms.
MATERIALS AND METHODS: Network pharmacology was utilized to identify potential pathways and targets of OST in preventing ischemia/reperfusion injury (IRI). To simulate skin flap IRI, the McFarlane skin flap model in rats and the oxygen-glucose deprivation/reperfusion (OGD/R) model in HUVECs were established. Blood perfusion was assessed using laser Doppler imaging, and histopathological changes in Area II flap tissues were evaluated by H&E staining. Oxidative stress was measured via MDA content, SOD activity, and ROS levels. Additionally, immunofluorescence was performed to examine the expression of TNF-α, IL-6, IL-1β, and CD31. Western blotting was used to assess the expression of proteins associated with angiogenesis, pyroptosis, and ferroptosis.
RESULTS: Network pharmacology analysis suggested that OST enhances skin flap survival through pathways associated with oxidative stress and NLRP3-mediated pyroptosis. OST administration promotes angiogenesis, increased blood perfusion, and improved skin flap viability. During the ischemia-reperfusion phase, OST attenuated oxidative stress and inflammatory responses. Mechanistically, OST inhibited ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway and alleviated pyroptosis by downregulating the TLR4/NF-κB/NLRP3 pathway. Notably, these protective effects were partially reversed by the Nrf2 inhibitor ML385. Furthermore, the use of the ferroptosis inhibitor ferrostatin-1 and the caspase-1 inhibitor VX-765 suggests a potential crosstalk between ferroptosis and pyroptosis.
CONCLUSION: OST mitigated IRI by inhibiting ferroptosis and alleviating pyroptosis, providing a new therapeutic direction for enhancing skin flap survival.
AIM OF THE STUDY: This study aimed to investigate the effect of OST on promoting the survival of ischemic flaps and to elucidate its underlying mechanisms.
MATERIALS AND METHODS: Network pharmacology was utilized to identify potential pathways and targets of OST in preventing ischemia/reperfusion injury (IRI). To simulate skin flap IRI, the McFarlane skin flap model in rats and the oxygen-glucose deprivation/reperfusion (OGD/R) model in HUVECs were established. Blood perfusion was assessed using laser Doppler imaging, and histopathological changes in Area II flap tissues were evaluated by H&E staining. Oxidative stress was measured via MDA content, SOD activity, and ROS levels. Additionally, immunofluorescence was performed to examine the expression of TNF-α, IL-6, IL-1β, and CD31. Western blotting was used to assess the expression of proteins associated with angiogenesis, pyroptosis, and ferroptosis.
RESULTS: Network pharmacology analysis suggested that OST enhances skin flap survival through pathways associated with oxidative stress and NLRP3-mediated pyroptosis. OST administration promotes angiogenesis, increased blood perfusion, and improved skin flap viability. During the ischemia-reperfusion phase, OST attenuated oxidative stress and inflammatory responses. Mechanistically, OST inhibited ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway and alleviated pyroptosis by downregulating the TLR4/NF-κB/NLRP3 pathway. Notably, these protective effects were partially reversed by the Nrf2 inhibitor ML385. Furthermore, the use of the ferroptosis inhibitor ferrostatin-1 and the caspase-1 inhibitor VX-765 suggests a potential crosstalk between ferroptosis and pyroptosis.
CONCLUSION: OST mitigated IRI by inhibiting ferroptosis and alleviating pyroptosis, providing a new therapeutic direction for enhancing skin flap survival.