Sparstolonin B improves neurological outcomes following intracerebral hemorrhage in mice

Abstract

Abstract. Inflammation serves an important role in inducing secondary injury following intracerebral hemorrhage (ICH).It has been demonstrated that sparstolonin B (SsnB) is able to attenuate the lipopolysaccharide-induced inflammatory response in sepsis. Mouse ICH models were used to explore the efficacy of SsnB on the ICH-induced inflammatory response. Mice underwent a working memory version of Morris water maze (MWM) test. They underwent 5 successive days of training consisting of 4 trials each day. The ICH model was established on the last training day. Mice were injected intraperitoneally either with vehicle or SsnB once a day for 3 consecutive days following the establishment of the ICH model. The MWM was used to determine the effect of SsnB on short-term memory following ICH. Neurological deficit scores and brain water content were measured following the MWM. Furthermore, the expression of inflammatory factors and signaling molecules downstream of TLR4 were measured. The results demonstrated that 5 mg/kg SsnB significantly improved the MWM path and time latency (P<0.05). Furthermore, neurological deficit scores were decreased in SsnB-treated mice compared with vehicle-treated mice (P<0.01). Brain water content, levels of inflammatory cytokines and the expression of inflammation-associated proteins were also significantly reduced in the SsnB-treated group (P<0.05). These results indicate that SsnB treatment stimulates short-term neurobehavioral recovery and reduces neurological deficits and this may inhibit the inflammatory response. Therefore, SsnB may attenuate the inflammatory response following ICH.

Microglia Phenotype and Intracerebral Hemorrhage: A Balance of Yin and Yang

“…Of course, increasing the M2/M1 phenotypic proportion of microglia usually brings more satisfactory results (Wang J. et al, 2018 ; Bai et al, 2020 ), and it has become the most frequently studied therapeutic method. Relying on the aforementioned targets, experimental therapeutic studies on the precise regulation on microglia phenotype are developing rapidly, and relevant drugs are summarized in Table 3 (Hu et al, 2011 ; Ohnishi et al, 2013 , 2019 ; Yang et al, 2014a , b , 2018 ; Iniaghe et al, 2015 ; Zhao et al, 2015a , b , 2018 ; Flores et al, 2016 ; Shi et al, 2016 ; Sukumari-Ramesh and Alleyne, 2016 ; Zhang et al, 2016 ; Anan et al, 2017 ; Chen-Roetling and Regan, 2017 ; Lan et al, 2017a ; Wang J. et al, 2017 ; Wei et al, 2017 ; Xu et al, 2017 ; Zeng et al, 2017 ; Chen C. et al, 2018 ; Chen S. et al, 2018 ; Fu et al, 2018 ; Han et al, 2018 ; Li X. et al, 2018 ; Qiao et al, 2018 ; Ren et al, 2018 ; Wang et al, 2018b ; Liang et al, 2019 ; Song and Zhang, 2019 ; Xi et al, 2019 ; Zhou F. et al, 2019 ; Cheng et al, 2020 ; Ding et al, 2020 ).…”

Emerging therapeutic targets associated with the immune system in patients with intracerebral haemorrhage (ICH): From mechanisms to translation

“…SsnB ameliorates brain oedema and neurological deficits in mice with ICH by inhibiting the formation of the TLR2-TLR4 heterodimer. SsnB exhibits high liposolubility and has a low molecular weight, which allows it to cross the BBB and attain a high concentration in the brain [41]. TAK-242 is a TLR4 antagonist.…”

Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1

“…Moreover, in a dose-dependent way, SsnB represses NF-κB activity regulated by toll-like receptor (TLR)4, swarms myeloid differentiation primary response gene 88 (MyD88) around TLR4, and reasonably diminishes LPS-caused inflammatory reaction in animal models [ 8 , 9 ]. As a selective TLR antagonist, SsnB showed significant pharmacological activities such as anti-tumour, anti-obesity, and anti-inflammatory effects in various inflammatory disorders [ 7 , 9 , 10 , 11 , 12 , 13 , 14 ]. Likewise, SsnB improved mouse survival when SsnB was injected before and after LPS treatment.…”