Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect via the NF-κB signaling pathway

Qian Sun; Xiangjian Zhang; Jingyi Fan; Lan Zhang; Hui Ji; Jing Xue; Cong Zhang; Rong Chen; Jing Zhao; Junmin Chen; Xiaoxia Liu; Degang Song

doi:10.1515/tnsci-2022-0273

Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect via the NF-κB signaling pathway

Transl Neurosci. 2023 Jun 9;14(1):20220273. doi: 10.1515/tnsci-2022-0273. eCollection 2023 Jan 1.

Authors

Qian Sun^{1

2}, Xiangjian Zhang^{1

2}, Jingyi Fan^{1

2}, Lan Zhang^{1

2}, Hui Ji^{1

2}, Jing Xue^{1

2}, Cong Zhang^{1

2}, Rong Chen^{1

2}, Jing Zhao^{1

2}, Junmin Chen^{1

2}, Xiaoxia Liu^{1

2}, Degang Song^{1

2

3}

Affiliations

¹ Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
² Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, Hebei, China.
³ Department of Neurology, First Hospital of Qinhuangdao, Hebei, China.

Abstract

Context: Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.

Objective: We explore the potential targets of geniposide in ischemic stroke.

Materials and methods: Adult male C57BL/6 mice were subjected to the middle cerebral artery occlusion (MCAO) model. Mice were randomly divided into five groups: Sham, MCAO, and geniposide-treated (i.p. twice daily for 3 days before MCAO) at doses of 25, 75, or 150 mg/kg. We first examined the neuroprotective effects of geniposide. Then, we further explored via biological information analysis and verified the underlying mechanism in vivo and in vitro.

Results: In the current study, geniposide had no toxicity at concentrations of up to 150 mg/kg. Compared with the MCAO group, the 150 mg/kg group of geniposide significantly (P < 0.05) improved neurological deficits, brain edema (79.00 ± 0.57% vs 82.28 ± 0.53%), and infarct volume (45.10 ± 0.24% vs 54.73 ± 2.87%) at 24 h after MCAO. Biological information analysis showed that the protective effect was closely related to the inflammatory response. Geniposide suppressed interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression in the brain homogenate, as measured by enzyme-linked immunosorbent assay (ELISA). Geniposide upregulated A20 and downregulated TNF receptor-associated factor-6 and nuclear factor kappa-B phosphorylation in the MCAO model and lipopolysaccharide-treated BV2 cells at 100 μM.

Conclusions: Geniposide exhibited a neuroprotective effect via attenuating inflammatory response, as indicated by biological information analysis, in vivo and in vitro experiments, which may provide a potential direction for the application of geniposide in the treatment of ischemic stroke.

Keywords: A20; MCAO; NF-Kb; TRAF6; neuroinflammation.