Spinosin Attenuates Alzheimer’s Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity

Cai, Mudan; Jung, Inhwa; Kwon, Huiyoung; Cho, Eunbi; Jeon, Justin Y.; Yun, Jeanho; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon

doi:10.4062/biomolther.2019.076

Cited by 12 publications

(8 citation statements)

References 42 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, previous studies have identi ed the potential biomedical function of Spinosin. It has been found that Spinosin inhibits Alzheimer's diseaserelated synaptic disorder by regulating plasmin activity (28). Spinosin is able to activate Nrf2/HO-1 signaling to inhibit the aggregation and production of Aβ 1-42 (20).…”

Section: Discussionmentioning

confidence: 99%

Spinosin Attenuates Osteoclastogenesis Through Suppressing NF-κB by the Activation of Nrf2/HO-1 Signaling in Osteoporosis

Liu

Zhang

2021

Preprint

View full text Add to dashboard Cite

ObjectiveOsteoporosis is a prevalent metabolic skeletal disorder featured by microarchitecture bone injury and excessive osteoclastic activity.Here, we aimed to explore the effect of Spinosin on osteoclastogenesis of osteoporosis.DesignThe receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis model was established in bone marrow macrophages (BMMs) in vitro. The ovariectomy (OVX)-induced bone loss mouse model was constructed in vivo, followed by micro-CT analysis, Histomorphometric analysis, Hematoxylin and Eosin (H&E) and TRAP staining.ResultsOur data showed that the treatment of Spinosin significantly inhibited the TRAP positive osteoclast and bone resorption induced by RANKL in the BMMs. Spinosin significantly reduced the expression of osteoclast-specific factors, including osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), cathepsin K (CTSK), TRAP, c-Fos and nuclear factor of activated T cells cytoplasm 1 (NFATc1)， in the RANKL-treated BMMs. Mechanically, Spinosin was able to inactivate NF-κB by stimulating Nrf2/HO-1 signaling in BMMs. The trabecular space (Tb.Sp), trabecular number (Tb.N), trabecular thickness (Tb.Th), and bone volume to total volume (BV/TV) were inhibited by OVX treatment, and Spinosin could reverse the effect in the bone resorption mouse model. The OVX-induced serum levels of tumor necrosis factor-α (TNF-α) and tartrate-resistant acid phosphatase 5 B (TRAcp5B) were blocked by Spinosin in the mice. Moreover, Spinosin was able to alleviate OVX-induced loss of femur bone and osteoclasts in vivo.ConclusionsIn conclusion, Spinosin attenuates osteoclastogenesis of osteoporosis through inhibiting NF-κB by activating Nrf2/HO-1 expression. Spinosin may serve as the potential candidate for the treatment of osteoporosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Spinosin Attenuates Osteoclastogenesis Through Suppressing NF-κB by the Activation of Nrf2/HO-1 Signaling in Osteoporosis

Liu

Zhang

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Another in vitro study using Neuro-2a cells (N2a/WT) and N2a/APP695 cells showed that spinosyn markedly reduced Aβ1-42 production by activating the Nrf2/HO-1 pathway [119]. In addition, spinosin might be beneficial to treat learning and memory deficits through the regulation of oxidative stress, inflammatory processes, apoptotic programs, and plasmin activity [120][121][122].…”

Section: Moas Of Ingredientsmentioning

confidence: 99%

Medicine-Food Herbs against Alzheimer’s Disease: A Review of Their Traditional Functional Features, Substance Basis, Clinical Practices and Mechanisms of Action

et al. 2022

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder that currently has reached epidemic proportions among elderly populations around the world. In China, available traditional Chinese medicines (TCMs) that organically combine functional foods with medicinal values are named “Medicine Food Homology (MFH)”. In this review, we focused on MFH varieties for their traditional functional features, substance bases, clinical uses, and mechanisms of action (MOAs) for AD prevention and treatment. We consider the antiAD active constituents from MFH species, their effects on in vitro/in vivo AD models, and their drug targets and signal pathways by summing up the literature via a systematic electronic search (SciFinder, PubMed, and Web of Science). In this paper, several MFH plant sources are discussed in detail from in vitro/in vivo models and methods, to MOAs. We found that most of the MFH varieties exert neuroprotective effects and ameliorate cognitive impairments by inhibiting neuropathological signs (Aβ-induced toxicity, amyloid precursor protein, and phosphorylated Tau immunoreactivity), including anti-inflammation, antioxidative stress, antiautophagy, and antiapoptosis, etc. Indeed, some MFH substances and their related phytochemicals have a broad spectrum of activities, so they are superior to simple single-target drugs in treating chronic diseases. This review can provide significant guidance for people’s healthy lifestyles and drug development for AD prevention and treatment.

show abstract

“…In the neocortex of AD patients, the levels of plasminogen (pro-type of plasmin) and plasmin were lower than healthy controls [ 35 ]. Cai et al reported that AD model mice showed a lower plasmin level in the hippocampus [ 36 ]. They also found that a treatment of spinosyn, a flavonoid isolated from Zizyphus jujuba var spinosa seeds, increased expression and activity of hippocampal plasmin and synaptic plasticity in AD model mice.…”

Section: Bdnf Signaling In Admentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimer’s Disease: Beneficial Effects of Flavonoids for Neuroprotection

Numakawa

Odaka

2021

IJMS

View full text Add to dashboard Cite

The function of the brain-derived neurotrophic factor (BDNF) via activation through its high-affinity receptor Tropomyosin receptor kinase B (TrkB) has a pivotal role in cell differentiation, cell survival, synaptic plasticity, and both embryonic and adult neurogenesis in central nervous system neurons. A number of studies have demonstrated the possible involvement of altered expression and action of the BDNF/TrkB signaling in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). In this review, we introduce an essential role of the BDNF and its downstream signaling in neural function. We also review the current evidence on the deregulated the BDNF signaling in the pathophysiology of AD at gene, mRNA, and protein levels. Further, we discuss a potential usefulness of small compounds, including flavonoids, which can stimulate BDNF-related signaling as a BDNF-targeting therapy.

show abstract

Spinosin Attenuates Alzheimer’s Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity

Cited by 12 publications

References 42 publications

Spinosin Attenuates Osteoclastogenesis Through Suppressing NF-κB by the Activation of Nrf2/HO-1 Signaling in Osteoporosis

Spinosin Attenuates Osteoclastogenesis Through Suppressing NF-κB by the Activation of Nrf2/HO-1 Signaling in Osteoporosis

Medicine-Food Herbs against Alzheimer’s Disease: A Review of Their Traditional Functional Features, Substance Basis, Clinical Practices and Mechanisms of Action

Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimer’s Disease: Beneficial Effects of Flavonoids for Neuroprotection

Contact Info

Product

Resources

About