Sarsasapogenin‐<scp>AA</scp>13 ameliorates Aβ‐induced cognitive deficits via improving neuroglial capacity on Aβ clearance and antiinflammation

Huang, Cui; Dong, Dong; Jiao, Qian; Pan, Hui; Ma, Lei; Wang, Rui

doi:10.1111/cns.12697

Cited by 33 publications

(18 citation statements)

References 44 publications

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“…Among microglia, M2 microglia reportedly express NEP and IDE and reduce Aβ plaques (Shimizu et al, ). Recently, there are a few known agents such as PF‐3845, sarsasapogenin‐AA13, and dihydromyricetin, which promoted M2 microglial and inhibited M1 microglial polarization, leading to the memory recovery in traumatic brain injury and AD models (Feng et al, ; C. Huang et al, ; Tchantchou et al, ). Furthermore, dihydromyricetin promoted the clearance of Aβ and expression of NEP in APP/PS1 transgenic mice brain (Tchantchou et al, ).…”

Section: Resultsmentioning

confidence: 99%

Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression

Yang

Kuboyama

Tohda

2019

Phytotherapy Research

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Two kinds of microglia are known, classical M1 and alternative M2 phenotypes. Amyloid β (Aβ), a critical cause of Alzheimer's disease (AD), promotes M1 microglial polarization, leading to neuroinflammation and neuronal death. M2 microglia play important roles in anti-inflammatory effects, Aβ clearance, and memory recovery in AD. Therefore, increasing of M2 microglia is expected to recover from AD. We previously found that naringenin, a blood-brain barrier penetrating compound, decreased Aβ deposits and recovers memory function in transgenic AD model mice. Naringenin reportedly showed anti-inflammatory properties. Here, we aim to investigate potential effects of naringenin on microglial polarization and to reveal the underlying mechanisms of Aβ reduction. Primary cultured cortical microglia were treated with Aβ 1-42 , following administration of naringenin. Naringenin remarkably promoted M2 microglia polarization and inhibited Aβ 1-42 -induced M1 microglia activation. Because microglia reportedly played a critical role in cerebral Aβ clearance through Aβ degradation enzymes after phagocytosis, we investigated the expression of Aβ degradation enzymes, such as neprilysin and insulin degradation enzyme. After naringenin treatment, these Aβ degradation enzymes were downregulated in M1 microglia and upregulated in M2 microglia. Taken together, our results showed that naringenin increased Aβ degradation enzymes in M2 microglia, probably leading to Aβ plaque reduction.

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Section: Resultsmentioning

confidence: 99%

Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression

Yang

Kuboyama

Tohda

2019

Phytotherapy Research

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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%

Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

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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“…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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Sarsasapogenin‐AA13 ameliorates Aβ‐induced cognitive deficits via improving neuroglial capacity on Aβ clearance and antiinflammation

Cited by 33 publications

References 44 publications

Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression

Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression

<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

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