Mangiferin regulates cognitive deficits and heme oxygenase-1 induced by lipopolysaccharide in mice

Guo

et al. 2017

Sci Rep

Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation

Guo

et al. 2017

Sci Rep

“…Accumulating evidence has revealed that mangiferin is able to attenuate LPS-induced cognitive deficits caused by neuroinflammation (70). Oral mangiferin pre-treatment (50 mg/kg) and treatment (50 mg/kg) following LPS injection in mice demonstrated that mangiferin ameliorates cognitive deficits by decreasing LPS-induced IL-6 expression and increasing heme oxygenase-1 (HO-1) expression in mice hippocampi.…”

Section: The Neuroprotective Properties Of Mangiferinmentioning

confidence: 99%

Mangiferin: An effective therapeutic agent against several disorders (Review)

Liu

Lei

et al. 2018

Mol Med Report

Mangiferin (1,3,6,7-tetrahydroxyxanthone-C2-β-Dglucoside) is a bioactive ingredient predominantly isolated from the mango tree, with potent antioxidant activity and multifactorial pharmacological effects, including antidiabetic, antitumor, lipometabolism regulating, cardioprotective, anti-hyperuricemic, neuroprotective, antioxidant, anti-inflammatory, antipyretic, analgesic, antibacterial, antiviral and immunomodulatory effects. Therefore, it possesses several health-endorsing properties and is a promising candidate for further research and development. However, low solubility, mucosal permeability and bioavailability restrict the development of mangiferin as a clinical therapeutic, and chemical and physical modification is required to expand its application. This review comprehensively analyzed and collectively summarized the primary pharmacological actions of mangiferin that have been demonstrated in the literature, to support the potential future development of mangiferin as a novel therapeutic drug. Contents 1. Introduction 2. Potential application of mangiferin in antidiabetic therapy 3. Anti-tumor effects of mangiferin 4. The neuroprotective properties of mangiferin 5. Cardiovascular effects of mangiferin 6. Other properties of mangiferin 7. Conclusions

“…administered LPS can be used to prepare animal models of brain injury with inflammation. No reliable drugs are available for these neurodegenerative diseases (Fu et al 2015). Though it has been reported that HDAC6 may emerge as a promising therapeutic target, genetic and pharmacological inhibition of HDAC6 have been shown to suppress neurodegenerative disorders, enhance immunomodulatory activity and alleviate disorder behaviors in animal models (Jianhua et al 2017;Martin et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HDAC6 alleviating lipopolysaccharide-induced p38MAPK phosphorylation and neuroinflammation in mice

Song

Qin

Yang

et al. 2019

Pharmaceutical Biology

Self Cite

Context: Researchers in a variety of fields have extensively focused on histone deacetylase 6 (HDAC6) due to its aggravation of inflammatory reaction. However, relevant studies examining whether HDAC6 could exacerbate lipopolysaccharide (LPS)-induced inflammation are still lacking. Objective: We assessed the role of HDAC6 in LPS-induced brain inflammation and used the HDAC6selective inhibitor Tubastatin A (TBSA) to investigate the potential mechanisms further. Materials and methods: Brain inflammation was induced in Kunming (KM) mice via intraperitoneal (I.P.), injection of Lipopolysaccharide (LPS) (1 mg/kg), the TBSA (0.5 mg/kg) was delivered via intraperitoneal. The phosphorylated p38 (p-p38) Mitogen-activated protein kinases (MAPK) and expression of typical inflammatory mediators, including tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) in both the hippocampus and cortex, were examined by immunoblotting. Nissl staining was used to detect the neuronal damage in the hippocampus and the cortex. Results: About 1 mg/kg LPS via daily intraperitoneal (I.P.) injections for 12 days significantly increased p38 MAPK phosphorylation, TNF-a and IL-6 expression, and neuronal loss. However, 0.5 mg/kg TBSA (three days before LPS treatment) by I.P. injections for 15 days could reverse the above results. Conclusions: This present study provided evidence that TBSA significantly suppressed LPS-induced neuroinflammation and the expression of p-p38. Results derived from our study might help reveal the effective targeting strategies of LPS-induced brain inflammation through inhibiting HDAC6. ARTICLE HISTORY