New compatible pair of TCM: Paeoniae Radix Alba effectively alleviate Psoraleae Fructus-induced liver injury by suppressing NLRP3 inflammasome activation
Yingjie Xu,
Xianling Wang,
Yan Wang,
Longxin Guo,
Xiaomei Zhao,
Ming Dong,
Jincai Wen,
Zhixin Wu,
Chenyi Li,
Wenqing Mu,
Yuming Guo,
Zhaofang Bai,
Xiaohe Xiao
Affiliations
Yingjie Xu
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Dali University, Dali, 671000, China
Xianling Wang
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Yan Wang
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Longxin Guo
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Dali University, Dali, 671000, China
Xiaomei Zhao
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Ming Dong
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Jincai Wen
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Zhixin Wu
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Chenyi Li
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Dali University, Dali, 671000, China
Wenqing Mu
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China
Yuming Guo
Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, 100039, China
Zhaofang Bai
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Dali University, Dali, 671000, China; National Key Laboratory of Kidney Diseases, Beijing, 100039, China; Corresponding author. Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
Xiaohe Xiao
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Dali University, Dali, 671000, China; National Key Laboratory of Kidney Diseases, Beijing, 100039, China; Corresponding author. Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
Objective: 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. Methods: 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). Results: 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). Conclusions: 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.