Protective effect of isoliquiritigenin against cerebral injury in septic mice via attenuation of NF-κB

Zou, Peng; Ji, Hongming; Zhao, Jianwei; Ding, Xiaoyan; Zhen, Zigang; Zhang, Xuan; Nie, Xiaoqi; Xue, Li-Xiong

doi:10.1007/s10787-018-0503-z

Cited by 23 publications

(12 citation statements)

References 32 publications

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“…Further, ISL maintained antioxidant enzyme expression during LPS-induced neuroinflammation. Consistent with these findings, ISL also restored the oxidant–antioxidant balance in rodent models of brain injury induced by cocaine [27], sepsis [28], ICH [11], and middle cerebral artery occlusion [29]. Oxidative stress is a key contributor to neuronal injury and death, and cognitive capacity is reduced by neuronal cell loss.…”

Section: Discussionmentioning

confidence: 63%

Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity

et al. 2019

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Background Oxidative stress and neuroinflammation are central pathogenic mechanisms common to many neurological diseases. Isoliquiritigenin (ISL) is a flavonoid in licorice with multiple pharmacological properties, including anti-inflammatory activity, and has demonstrated protective efficacy against acute neural injury. However, potential actions against cognitive impairments have not been examined extensively. We established a rat model of cognitive impairment by intracerebroventricular injection of lipopolysaccharide (LPS), and examined the effects of ISL pretreatment on cognitive function, hippocampal injury, and hippocampal expression of various synaptic proteins, antioxidant enzymes, pro-inflammatory cytokines, and signaling factors controlling anti-oxidant and pro-inflammatory responses. Results Rats receiving LPS alone demonstrated spatial learning deficits in the Morris water maze test as evidenced by longer average escape latency, fewer platform crossings, and shorter average time in the target quadrant than untreated controls. ISL pretreatment reversed these deficits as well as LPS-induced decreases in the hippocampal expression levels of synaptophysin, postsynaptic density-95, brain-derived neurotrophic factor, superoxide dismutase, glutathione peroxidase, and BCL-2. ISL pretreatment also reversed LPS-induced increases in TUNEL-positive (apoptotic) cells, BAX/BCL-2 ratio, and expression levels of tumor necrosis factor-α, interleukin (IL)-1 β , IL-6, and C-C motif chemokine ligand 3. Pretreatment with ISL increased the expression levels of phosphorylated (p)-GSK-3 β , nuclear NRF2, HO-1 mRNA, and NQO1 mRNA, and reversed LPS-induced nuclear translocation of nuclear factor (NF)- κ B. Conclusions ISL protects against LPS-induced cognitive impairment and neuronal injury by promoting or maintaining antioxidant capacity and suppressing neuroinflammation, likely through phosphorylation-dependent inactivation of GSK-3 β , enhanced expression of NRF2-responsive antioxidant genes, and suppression of NF- κ B-responsive pro-inflammatory genes.

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Section: Discussionmentioning

confidence: 63%

Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity

et al. 2019

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“…Other studies have shown that ISL can reduce the expression of COX-2 and iNOS in septic mice [ 11 ] and HT-29 cells [ 22 ]. COX-2 is an inducible enzyme activated by cytokines and growth factors, such as IL-1 and IL-6, while iNOS is a nitric oxide synthetase activated by pathologic stimuli.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammation of isoliquiritigenin via the inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells

et al. 2022

BMC Vet Res

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Background The application of plant extracts has received great interest for the treatment of bovine mastitis. Isoliquiritigenin (ISL) is a rich dietary flavonoid that has significant antioxidative, anti-inflammatory and anticancer activities. This study was conducted to explore the protective efficacy and related mechanism of ISL against lipopolysaccharide (LPS)-stimulated oxidation and inflammation in bovine mammary epithelial cells (MAC-T) by in vitro experiments. Results Real-time PCR and ELISA assays indicated that ISL treatment at 2.5, 5 and 10 μg/mL significantly reduced the mRNA and protein expression of the oxidative indicators cyclooxygenase-2 and inducible nitric oxide synthase (P < 0.01), and of the inflammatory cytokines interleukin-6 (P < 0.05), interleukin-1β (P < 0.01) and tumor necrosis factor-α (P < 0.01) in LPS-stimulated MAC-T cells. Moreover, Western blotting and immunofluorescence tests indicated that the phosphorylation levels of nuclear factor kappa (NF-κB) p65 and the inhibitor of NF-κB were significantly decreased by ISL treatment, thus blocking the nuclear transfer of NF-κB p65. In addition, ISL attenuated the phosphorylation levels of p38, extracellular signal-regulated kinase and c-jun NH2 terminal kinase. Conclusions Our data demonstrated that ISL downregulated the LPS-induced inflammatory response in MAC-T cells. The anti-inflammatory and antioxidative activity of ISL involves the NF-κB and MAPK cascades.

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“…A flavonoid with a chalcone structure, ISL, readily passes through the blood-brain barrier to exert its central actions [31]. Peripherally injected ISL is metabolized to liquiritigenin Evidence-Based Complementary and Alternative Medicine (another important bioactive flavonoid in G. radix) and other glucuronidated metabolites via cytochrome P450 2C19 and UDP-glucuronosyltransferases in the liver [32,33].…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin Attenuates Anxiety‐Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine

Wang

Kim

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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As important components of positive and negative reinforcement, locomotor sensitization and withdrawal anxiety following repeated exposure to nicotine (NIC) constitute crucial risk factors for relapse to NIC use after abstinence. Glycyrrhiza radix (G. radix), an important tonic used in traditional Oriental medicine, has not only anxiolytic effects but also reduces NIC-induced locomotor sensitization. Isoliquiritigenin (ISL), a bioactive ingredient of G. radix, also exhibits neuropharmacological effects, including anxiolytic action. Previously, we reported that ISL suppressed cocaine-induced extracellular dopamine release in the nucleus accumbens shell (NaccSh) and attenuated methamphetamine-induced neurotoxicity. e present study was performed to evaluate the effects of ISL on both NIC withdrawal anxiety and locomotor sensitization. Adult male rats received subcutaneous administration of NIC hydrogen tartrate (0.4 mg/kg, twice a day) for 7 days followed by 4 days of withdrawal. During the period of NIC withdrawal, the rats received four intragastric treatments with ISL (3, 10, or 30 mg/kg/day). All three doses of ISL significantly inhibited NIC withdrawal-induced anxiety-like behaviors in the elevated plus maze (EPM) test, but only the 10 mg/kg/day and 30 mg/kg/day ISL doses attenuated locomotor sensitization induced by a challenge dose of NIC. Intracerebroventricular ISL also inhibited both NIC-induced withdrawal anxiety and locomotor sensitization, but intra-NaccSh injection of ISL blocked only NIC locomotor sensitization, which was abolished by post-ISL infusion of tert-butyl hydroperoxide (an oxidant) or N-methyl-Daspartate (NMDA) into the NaccSh. Moreover, there was increased protein expression of phosphorylated Erk1/2 in the NICsensitized NaccSh, which was suppressed by ISL. Taken together, these results suggest that ISL can inhibit repeated NIC-induced withdrawal anxiety and locomotor sensitization, and the latter is mediated by antagonizing accumbal reactive oxygen species and NMDA receptor signaling.

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Protective effect of isoliquiritigenin against cerebral injury in septic mice via attenuation of NF-κB

Abstract: These results demonstrate that ISL causes protection of CLP-induced sepsis in experimental mice via multiple pathways.

Cited by 23 publications

References 32 publications

Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity

Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity

Anti-inflammation of isoliquiritigenin via the inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells

Isoliquiritigenin Attenuates Anxiety‐Like Behavior and Locomotor Sensitization in Rats after Repeated Exposure to Nicotine

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