Geniposide Alleviates Nerve Injury in Rats with Cardiac Arrest by Inhibiting the c-Jun N-Terminal Kinases Pathway

Abstract

Context: Geniposide (GE) has a neuroprotective effect. Objective: Our study examines whether GE can alleviate nerve injury after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Materials and Methods: Male Sprague Dawley rats were randomly assigned to the following treatment groups by the random number table method: Sham, CA (CA model established by asphyxiation, and then CRP), CA + saline (same volume of normal saline, gavage), CA + GE (60 mg/kg, orally), CA + Aniso (5 mg/kg anisomycin (JNK agonist), intraperitoneal injection) and CA + Aniso + GE. The water maze test and neurological deficit scale were used to assess the neurological function of the rats. Western blot assays were used to quantify interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8, as well as c-Jun N-terminal kinase (JNK) pathway-associated protein expression levels. Results: The CA + GE group had higher neurological scores (61 vs 77) and better performance in the water maze test [longer escape latency (46 s vs 28 s), lower platform crossing time (1.8 vs 6.3), and a smaller percentage of time spent in target quadrant (13% vs 22%)] than the CA/CRP group. Furthermore, IL-6 (0.82 vs 0.61), TNF-α (1.35 vs 0.98), IL-8 (1.29 vs 1.01), p-JNK/JNK (1.14 vs 0.48), p-extracellular signal-regulated kinase (ERK)/ERK (1.22 vs 0.55), and p-p38/p38 (1.51 vs 1.03) protein expression levels were decreased in the hippocampus of GE-treated CA/CRP rats. Administration of the JNK agonist anisomycin aggravated the inflammatory response and neurological impairment in the CA/CRP rats. In contrast, GE treatment played a neuroprotective role by partially reversing the effect of anisomycin on CA/CRP rats. Conclusions: GE may have a neuroprotective role against CA/CRP-induced cognitive impairment and inflammatory responses in the brains of CA/CRP rats, which is mediated via the JNK pathway. Therefore, GE may be used as a novel potential therapeutic agent for CA/CRP.