Cordycepin improved neuronal synaptic plasticity through CREB-induced NGF upregulation driven by MG-M2 polarization: a microglia-neuron symphony in AD

Jiao, Linchi; Yu, Zhihua; Zhong, Xin; Yao, Weifan; Xing, Lijuan; Ma, Guowei; Shen, Jiajia; Wu, Yuqiang; Du, Ke; Liu, Junxiu; Tong, Junhui; Jia, Fu; Liu, Mingyan

doi:10.1016/j.biopha.2022.114054

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…To assess the anti-inflammatory activity of compounds, BV-2 cells were divided into 21 groups: control (Con) group, model (Mod) group, compounds 1 -18 groups (5 µM), and Cordycepin (Cor, 1 µg/mL) group used as the positive control [44] . To further investigate the anti-inflammatory effect of compounds3 , 17 , and 18 , BV-2 cells were divided into 6 groups: control (Con) group, model (Mod) group, compound low, middle, high dose groups, and Cor group used as the positive control, respectively.…”

Section: Rt-qpcrmentioning

confidence: 99%

Discovery of sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.)K. F. Wu and their anti-inflammatory activity by suppression of the IKBα/NF-κB p65 signaling pathway

Liu,

Wang,

Wang

et al. 2024

Preprint

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The phytochemical investigation of the roots of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu led to the isolation and identification of 23 structurally diverse sesquiterpenes and their dimer, including a new eudesmane sesquiterpenoid dimer, nineteen new sesquiterpenoids and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer formed by assembling two highly rearranged eudesmane-type sesquiterpenes through a unique oxygen bridge (C-11–O–C-8′). It is worth noting that rearranged eudesmane type sesquiterpenoid dimers containing an oxygen bridge are rarely isolated from nature. (+)-2 and (−)-2 were a pair of new skeleton sesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction analysis, and quantum chemical calculation. Moreover, all the isolated compounds were evaluated for their potential anti-inflammatory activity using an LPS-induced BV-2 cell microglial. Among them, 18 suppressed TNF-α and IL-1β expression with EC50 values of 6.81 µM and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production. In subsequent mechanism studies, compounds 3, 17, and 18 could reduce the production of IL-1β and TNF-α by inhibiting the activation of IKBα/p65 pathway.

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Section: Rt-qpcrmentioning

confidence: 99%

Discovery of sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.)K. F. Wu and their anti-inflammatory activity by suppression of the IKBα/NF-κB p65 signaling pathway

Liu,

Wang,

Wang

et al. 2024

Preprint

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“…Recently, cordycepin was reported to induce MG-M2 polarization through the activation of cAMP-response element binding protein (CREB) activation and upregulation of NGF. This mechanism improved cognitive deficits in an APP/PS1 mouse model [ 163 ].…”

Section: Neuroprotective Potential Of Bioactive Compounds From ...mentioning

confidence: 99%

Unique Bioactives from Zombie Fungus (Cordyceps) as Promising Multitargeted Neuroprotective Agents

Sharma,

2023

Nutrients

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Cordyceps, also known as “zombie fungus”, is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the victim behave like a “zombie”. These species produce promising bioactive metabolites, like adenosine, β-glucans, cordycepin, and ergosterol. Cordyceps has been used in traditional medicine due to its immense health benefits, as it boosts stamina, appetite, immunity, longevity, libido, memory, and sleep. Neuronal loss is the typical feature of neurodegenerative diseases (NDs) (Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS)) and neurotrauma. Both these conditions share common pathophysiological features, like oxidative stress, neuroinflammation, and glutamatergic excitotoxicity. Cordyceps bioactives (adenosine, N6-(2-hydroxyethyl)-adenosine, ergosta-7, 9 (11), 22-trien-3β-ol, active peptides, and polysaccharides) exert potential antioxidant, anti-inflammatory, and anti-apoptotic activities and display beneficial effects in the management and/or treatment of neurodegenerative disorders in vitro and in vivo. Although a considerable list of compounds is available from Cordyceps, only a few have been evaluated for their neuroprotective potential and still lack information for clinical trials. In this review, the neuroprotective mechanisms and safety profile of Cordyceps extracts/bioactives have been discussed, which might be helpful in the identification of novel potential therapeutic entities in the future.

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Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targeting HKII and PDK2

Zhong,

Gong,

Meng

et al. 2024

Advanced Science

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The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG‐M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG‐M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC‐MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH‐mediated OXPHOS pathway, thereby inducing MG‐M2 polarization, promoting neuronal survival and exerting an anti‐AD role is elucidated.

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Cordycepin improved neuronal synaptic plasticity through CREB-induced NGF upregulation driven by MG-M2 polarization: a microglia-neuron symphony in AD

Cited by 7 publications

References 33 publications

Discovery of sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.)K. F. Wu and their anti-inflammatory activity by suppression of the IKBα/NF-κB p65 signaling pathway

Discovery of sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.)K. F. Wu and their anti-inflammatory activity by suppression of the IKBα/NF-κB p65 signaling pathway

Unique Bioactives from Zombie Fungus (Cordyceps) as Promising Multitargeted Neuroprotective Agents

Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targeting HKII and PDK2

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