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Abstract：
UNASSIGNED: Drug-induced liver injury (DILI), a type of acute inflammation, has sparked significant concern owing to its unpredictability and severity. Psoraleae Fructus (PF), an edible Chinese herb widely used in traditional Chinese medicine (TCM), causes liver injury. Therefore, the elucidation of the mechanism underlying PF-induced liver injury and the search for more effective means of detoxification using herbal compatibility has become an urgent issue. This study evaluated the hepatoprotective effects of Paeoniae Radix Alba (PRA), a hepatoprotective Chinese medicine, on PF-induced liver injury and explored the underlying mechanisms.
UNASSIGNED: A rat model of lipopolysaccharide (LPS)-induced immune stress was established to evaluate the hepatotoxicity of PF and the detoxifying effect of PRA. Subsequently, inflammatory pathways were identified using network pharmacology. Finally, the molecular mechanism by which PRA alleviates PF-induced liver injury was validated using an inflammasome activation model in bone marrow-derived macrophages (BMDMs).
UNASSIGNED: In vivo, hepatocytes in rats treated with LPS + PF exhibited massive inflammatory infiltration and apoptosis, and the expression of liver injury indicators and inflammatory factors was significantly upregulated, which was reversed by PRA pretreatment. Network pharmacology showed that PRA alleviated PF-induced liver injury and was associated with the NOD-like receptor signaling pathway. Moreover, PF directly induced inflammasome activation in LPS-primed BMDMs which in turn induced caspase-1 activation and the secretion of downstream effector cytokines such as IL-1β. PRA pretreatment inhibited PF-induced activation of the NLRP3 inflammasome by mitigating the accumulation of mitochondrial reactive oxygen species (mtROS).
UNASSIGNED: The present study demonstrates that PRA alleviated PF induced-liver injury by inhibiting NLRP3 inflammasome activation. The results of this study are expected to inform the prevention and control of PF-induced hepatotoxicity in clinical practice.
UNASSIGNED: A rat model of lipopolysaccharide (LPS)-induced immune stress was established to evaluate the hepatotoxicity of PF and the detoxifying effect of PRA. Subsequently, inflammatory pathways were identified using network pharmacology. Finally, the molecular mechanism by which PRA alleviates PF-induced liver injury was validated using an inflammasome activation model in bone marrow-derived macrophages (BMDMs).
UNASSIGNED: In vivo, hepatocytes in rats treated with LPS + PF exhibited massive inflammatory infiltration and apoptosis, and the expression of liver injury indicators and inflammatory factors was significantly upregulated, which was reversed by PRA pretreatment. Network pharmacology showed that PRA alleviated PF-induced liver injury and was associated with the NOD-like receptor signaling pathway. Moreover, PF directly induced inflammasome activation in LPS-primed BMDMs which in turn induced caspase-1 activation and the secretion of downstream effector cytokines such as IL-1β. PRA pretreatment inhibited PF-induced activation of the NLRP3 inflammasome by mitigating the accumulation of mitochondrial reactive oxygen species (mtROS).
UNASSIGNED: The present study demonstrates that PRA alleviated PF induced-liver injury by inhibiting NLRP3 inflammasome activation. The results of this study are expected to inform the prevention and control of PF-induced hepatotoxicity in clinical practice.
摘要：
■药物性肝损伤（DILI），一种急性炎症，由于其不可预测性和严重性，引发了重大关注。补骨脂（PF），一种广泛用于中药（TCM）的可食用中草药，导致肝损伤。因此,阐明PF诱导的肝损伤的潜在机制以及寻找使用草药配伍的更有效的解毒方法已成为当务之急。本研究评估了白芍（PRA）的保肝作用，一种保肝中药,并探讨了PF诱导的肝损伤的潜在机制。
■建立脂多糖（LPS）诱导的免疫应激大鼠模型，以评估PF的肝毒性和PRA的解毒作用。随后，使用网络药理学鉴定炎症途径.最后,使用骨髓源性巨噬细胞(BMDMs)炎症体激活模型验证了PRA减轻PF诱导的肝损伤的分子机制.
■体内，LPS+PF处理的大鼠肝细胞出现大量炎症浸润和凋亡,肝损伤指标和炎症因子的表达明显上调,通过PRA预处理逆转。网络药理学显示，PRA减轻了PF诱导的肝损伤，并与NOD样受体信号通路有关。此外，PF直接诱导LPS引发的BMDMs中的炎性小体激活，进而诱导caspase-1激活和下游效应细胞因子如IL-1β的分泌。PRA预处理通过减轻线粒体活性氧（mtROS）的积累来抑制PF诱导的NLRP3炎性体活化。
■本研究表明，PRA通过抑制NLRP3炎性体激活减轻PF诱导的肝损伤。这项研究的结果有望在临床实践中预防和控制PF引起的肝毒性。
■建立脂多糖（LPS）诱导的免疫应激大鼠模型，以评估PF的肝毒性和PRA的解毒作用。随后，使用网络药理学鉴定炎症途径.最后,使用骨髓源性巨噬细胞(BMDMs)炎症体激活模型验证了PRA减轻PF诱导的肝损伤的分子机制.
■体内，LPS+PF处理的大鼠肝细胞出现大量炎症浸润和凋亡,肝损伤指标和炎症因子的表达明显上调,通过PRA预处理逆转。网络药理学显示，PRA减轻了PF诱导的肝损伤，并与NOD样受体信号通路有关。此外，PF直接诱导LPS引发的BMDMs中的炎性小体激活，进而诱导caspase-1激活和下游效应细胞因子如IL-1β的分泌。PRA预处理通过减轻线粒体活性氧（mtROS）的积累来抑制PF诱导的NLRP3炎性体活化。
■本研究表明，PRA通过抑制NLRP3炎性体激活减轻PF诱导的肝损伤。这项研究的结果有望在临床实践中预防和控制PF引起的肝毒性。
