The international journal of biochemistry & cell biology · 2026
Ligustilide alleviates sepsis-associated acute kidney injury by activating Nrf2/HO-1 and PI3K/Akt signaling pathways.
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Huang Min, Xu Bo, Qi Hang, Xu Hongzhou, Cai Liang
Аннотация
OBJECTIVE: Sepsis-associated acute kidney injury (AKI) is a life-threatening complication among hospitalized and critically ill patients, markedly by a swift decline in renal function. This study aimed to investigate the role of ligustilide, a lipophilic compound derived from Ligusticum chuanxiong, in septic AKI.
METHODS: A septic AKI mouse model was established via cecal ligation and puncture (CLP) surgery, followed by oral administration of ligustilide. RT-qPCR was performed to measure the mRNA expression of kidney injury molecule 1 (KIM-1) in mouse renal tissues. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured using a biochemical analyzer. The effect of ligustilide on CLP-induced renal pathological damage in AKI mice was evaluated by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Reactive oxygen species (ROS) production and renal cell apoptosis were measured using immunofluorescence assay and TdT-mediated dUTP nick-end labeling staining, respectively. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in mouse renal tissues were assessed using corresponding biochemical kit. Immunoblotting was conducted to analyze protein levels of apoptotic markers (cleaved caspase-9, Bax, Bcl-2) and key factors involved in the nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways.
RESULTS: Ligustilide treatment ameliorated kidney dysfunction in septic AKI mice, as evidenced by reduced KIM-1, Scr and BUN levels in CLP + Ligustilide group relative to the CLP group. Histopathological analysis showed that ligustilide attenuated renal tissue damage in CLP mice, as reflected by reduced neutrophil infiltration and tubular injury. Moreover, ligustilide suppressed oxidative stress in CLP mice by inhibiting ROS production and MDA content while increasing SOD levels. Additionally, ligustilide administration suppressed renal cell apoptosis in septic AKI mice by downregulating Bax and cleaved caspase-9 expression and upregulating Bcl-2 expression. Importantly, ligustilide activated the Nrf2/HO-1 and PI3K/Akt signaling pathways in the kidneys of CLP mice.
CONCLUSION: Ligustilide mitigates sepsis-induced AKI by suppressing oxidative stress and apoptosis through activation of the Nrf2/HO-1 and PI3K/Akt pathways.
METHODS: A septic AKI mouse model was established via cecal ligation and puncture (CLP) surgery, followed by oral administration of ligustilide. RT-qPCR was performed to measure the mRNA expression of kidney injury molecule 1 (KIM-1) in mouse renal tissues. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured using a biochemical analyzer. The effect of ligustilide on CLP-induced renal pathological damage in AKI mice was evaluated by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Reactive oxygen species (ROS) production and renal cell apoptosis were measured using immunofluorescence assay and TdT-mediated dUTP nick-end labeling staining, respectively. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in mouse renal tissues were assessed using corresponding biochemical kit. Immunoblotting was conducted to analyze protein levels of apoptotic markers (cleaved caspase-9, Bax, Bcl-2) and key factors involved in the nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways.
RESULTS: Ligustilide treatment ameliorated kidney dysfunction in septic AKI mice, as evidenced by reduced KIM-1, Scr and BUN levels in CLP + Ligustilide group relative to the CLP group. Histopathological analysis showed that ligustilide attenuated renal tissue damage in CLP mice, as reflected by reduced neutrophil infiltration and tubular injury. Moreover, ligustilide suppressed oxidative stress in CLP mice by inhibiting ROS production and MDA content while increasing SOD levels. Additionally, ligustilide administration suppressed renal cell apoptosis in septic AKI mice by downregulating Bax and cleaved caspase-9 expression and upregulating Bcl-2 expression. Importantly, ligustilide activated the Nrf2/HO-1 and PI3K/Akt signaling pathways in the kidneys of CLP mice.
CONCLUSION: Ligustilide mitigates sepsis-induced AKI by suppressing oxidative stress and apoptosis through activation of the Nrf2/HO-1 and PI3K/Akt pathways.