Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice

Dong, Dong; Zhou, Nannan; Liu, Rui-xuan; Xiong, Jia-wei; Pan, Hui; Sun, Shilei; Ma, Lei; Wang, Rui

doi:10.1038/aps.2016.180

Cited by 28 publications

(19 citation statements)

References 45 publications

(47 reference statements)

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“…17 More studies have also shown that its derivatives are effective in anti-inflammatory, neuroprotective, and memory impairment related to aging. 21,22 However, the role of sarsasapogenin in osteoclast formation and bone resorption has not been reported. Thus, the effects of sarsasapogenin on these areas remain to be studied.…”

Section: Introductionmentioning

confidence: 99%

<p>Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo</p>

Peng

Zhao

Zhu

et al. 2020

DDDT

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Introduction: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear. Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts. Results: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide. Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.

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Section: Introductionmentioning

confidence: 99%

<p>Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo</p>

Peng

Zhao

Zhu

et al. 2020

DDDT

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“…In our previous work, we synthesised several carbamate derivatives exhibiting neuroprotective and NO production inhibitory properties (Pan, Van Khang, Dong, Wang, & Ma, ). Among all the derivatives, AA13 has emerged as one of the most useful compounds to inhibit inflammatory reactions and ameliorate Aβ‐induced cognitive deficits (Dong et al, ; Huang et al, ). AA13 also shows neuroprotective effect on Alzheimers disease (AD) model by promoting Aβ clearance and shifting pro‐inflammatory M1 to anti‐inflammatory M2 phenotype.…”

Section: Introductionmentioning

confidence: 99%

A validated UPLC–MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin‐AA13 in rat plasma: Application to pharmacokinetic studies

Pei

Zhao

et al. 2020

Biomedical Chromatography

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Sarsasapogenin‐AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti‐inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid‐β‐injected mice. A sensitive UPLC–MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra‐day accuracy for AA13 was in the range of 90–114%, and inter‐day accuracy was in the range of 97–103 %. The relative standard deviation of intra‐day and inter‐day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, Cmax of AA13 was 1266.4 ± 316.1 ng/mL. AUC0–48 h was 6928.5 ± 1990.1 h·ng/mL, and t1/2 was 10.2 ± 0.8 h. Under intravenous administration of AA13 at a dosage of 250 μg/kg, AUC0–48 h was 785.7 ± 103.3 h⋅ng/mL, and t1/2 was 20.8 ± 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %.

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“…This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I) [3]. It results in activation of inflammatory processes that cause secondary tissue injury [4]. Anti-inflammatory Targets may be a promising therapeutic strategy to attenuate the progression of ischemic brain injury.…”

Section: Introductionmentioning

confidence: 99%

Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke

Gong

Chen

Wang

et al. 2020

Preprint

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Background: Microglia polarization plays an important role in poststroke recovery. Inhibition of proinflammatory (M1) polarization and promotion of anti-inflammatory (M2) polarization of microglia are potential therapeutic strategies for inflammation reduction and neuronal recovery after stroke. Analgecine (AGC), the extracts of Vaccin a variola-inoculated rabbit skin, is used to treat patients with chronic low back pain due to degenerative vertebral disorders. Here, we evaluated the neuroprotective effect of AGC in stroke and investigate anti-inflammatory mechanism of AGC on microglia-mediated neural damage.Methods: Sprague-Dawley (SD) rats underwent 120 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. We injected AGC intravenously into rats starting 3 h after the onset of MCAO. Then we investigated the effect of AGC on neurological impairment, neuronal loss and inflammatory cytokines. For in vitro study, we examined the effect of AGC on microglial polarization in oxygen-glucose deprivation/reperfusion (OGD/R) or LPS/IFN-γ induced microglia cells and further investigated neuroprotective effect of ACG in microglia-mediated neural damage based on the direct or indirect co-culture systems. Finally, TLR4/Myd88/ NF-κB pathway was detected in OGD/R-induced microglia cells with or without Myd88 siRNA transfection.Results: AGC treatment reduced the neurological deficits and suppressed neuronal loss. In terms of inflammatory cytokines, AGC inhibited the release of pro-inflammatory cytokines and elevated the content of anti-inflammatory cytokines in vivo (SD rats) and in vitro (microglia). We further showed that AGC promoted M1 to M2 phenotypic transition of microglia in OGD/R or LPS/IFN-γ induced microglia cells. Based on the direct or indirect co-culture systems, we found AGC indirectly inhibits LPS/IFN-γ-induced neuronal damage by modulating microglial polarization. Moreover, AGC suppressed the nuclear translocation of the phosphorylation of NF-κB p65 by inhibiting the TLR4/Myd88/TRAF6 but not TLR9 signaling. We also confirmed that AGC-regulated TLR4 inhibition partly dependent on Myd88 in a Myd88 depletion cell line.Conclusion: Our findings provide a new understanding of AGC in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing TLR4 MyD88-dependent and MyD88-independent pathways. Thus, AGC treatment may represent a novel approach in inflammation reduction or poststroke recovery.

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Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice

Cited by 28 publications

References 45 publications

<p>Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo</p>

<p>Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo</p>

A validated UPLC–MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin‐AA13 in rat plasma: Application to pharmacokinetic studies

Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke

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