Anti-inflammatory and neuroprotective effects of natural cordycepin in rotenone-induced PD models through inhibiting Drp1-mediated mitochondrial fission

Zhang, Xiaoling; Huang, Wenmin; Tang, Pei-chen; Sun, Ying; Zhang, Xin; Lu, Qin; Yu, Bo-cheng; Zhang, Xiaoyan; Hong, Yuxin; He, Yun; Ge, Xiaoqun

doi:10.1016/j.neuro.2021.02.002

Cited by 37 publications

(15 citation statements)

References 42 publications

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“…Moreover, cordycepin has been reported to regulate neuronal functions [ 156 , 157 , 158 , 159 ], and further, to provide beneficial functions in several neuronal diseases, such as AD, PD, Machado–Joseph disease, and ischemia [ 160 , 161 , 162 , 163 ]. The protective mechanisms of cordycepin have been shown to regulate 5-hydroxymethylcytosine levels, TLR/NF-κB signaling, AMPK activity, acetylcholinesterase activity, etc.…”

Section: The Role Of Autophagy In the Health-promoting Effects Of Cordycepinmentioning

confidence: 99%

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

Chen

Lin

et al. 2021

Molecules

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Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin.

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Section: The Role Of Autophagy In the Health-promoting Effects Of Cordycepinmentioning

confidence: 99%

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

Chen

Lin

et al. 2021

Molecules

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“…Specifically, dynamin-related protein 1 (Drp1) governs its membrane division, mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2) govern its membrane fusion, and optic atrophy 1 (Opa1) is required for its inner membrane fusion ( Whitley et al, 2019 ). Previous studies have demonstrated that excessive mitochondrial fission is closely related to myocardial injury during ischemia–reperfusion injury in mouse models ( Serasinghe and Chipuk, 2017 ; Mui and Zhang, 2021 ) a recent study has reported that cordycepin treatment ameliorated aberrant mitochondrial dynamics in vitro ( Zhang et al, 2021 ). However, whether cordycepin regulates mitochondrial dynamics following MI/R in diabetes remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Cordycepin Decreases Ischemia/Reperfusion Injury in Diabetic Hearts via Upregulating AMPK/Mfn2-dependent Mitochondrial Fusion

Yu¹,

Hong

Liu³

et al. 2021

Front. Pharmacol.

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Diabetes mellitus is considered to be a major risk factor for cardiovascular disease, the most common cause of death in diabetes. However, therapeutic strategies for myocardial protection in patients with diabetes are still limited. Cordycepin is a traditional Tibetan medicine with a long history of widespread use, and exerts a wide range of anti-tumor, anti-inflammatory, and anti-oxidative effects. In recent years, although the therapeutic potential of cordycepin has attracted the attention of researchers, it remains unknown whether cordycepin plays a protective role in myocardial ischemia/reperfusion (MI/R) injury in diabetic patients. Here, using a diabetic mouse model, we found that cordycepin protected diabetic hearts from MI/R injury by promoting mitochondrial fusion and Mfn2 expression. Our in vitro results showed that cordycepin enhanced Mfn2-medicated mitochondrial fusion, improved mitochondrial function, and reduced cardiomyocyte apoptosis in high-glucose/high-fat cultured simulated ischemia/reperfusion cardiomyocytes. Furthermore, we found that knockout of Mfn2 significantly blocked the cardioprotective effects of cordycepin in diabetic mice. Finally, an AMPK-dependent pathway was found to upregulate Mfn2 expression upon cordycepin treatment, indicating that cordycepin protected diabetic hearts via AMPK/Mfn2-dependent mitochondrial fusion. Collectively, our study firstly demonstrated that cordycepin could be a potential cardioprotective agent for MI/R injury, and we established a novel mechanism by which upregulated AMPK/Mfn2-dependent mitochondrial fusion contributes to the cardioprotective role of cordycepin.

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“…Cordycepin, known as 3'‐deoxyadenosine, is the main active component of Cordycepin militaris . In recent years, researchers have found that cordycepin possesses anti‐inflammatory activities, anti‐tumour activities, anti‐thrombosis effects and especially, anti‐oxidative stress activities (Han et al, 2020a; Lee et al, 2015; Zhang et al, 2021; Zheng et al, 2020). At present, cordycepin has been shown to have excellent antioxidant stress ability against acute lung damage, renal ischaemia/reperfusion damage and Parkinson's disease (Cheng & Zhu, 2019; Han et al, 2020b; Lei et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

Huang

Zhou

et al. 2021

Andrologia

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Diabetes‐induced male dysfunction is considered as a worldwide challenge, and testicular damage mainly caused by oxidative stress is its most common manifestation. Cordycepin, a natural antioxidant, has been used in the treatment of diabetic complications. However, the protective action and underlying mechanism of cordycepin on hyperglycaemia‐induced testicular damage are unclear. This study aimed to investigate the protective effects and molecular mechanisms of cordycepin against diabetes‐induced testicular damage. The type 2 diabetes model was established in C57BL/6 male mice via high‐fat diet for 4 weeks and injected intraperitoneally with 50 mg/kg/day streptozotocin for five consecutive days. Then mice were treated with cordycepin (10 and 20 mg/kg, respectively) for 8 weeks. At the end of experiment, biochemical indicators, microstructure of testicular tissue, sperm morphology, TUNEL staining and protein expressions were evaluated. In the present study, cordycepin alleviated the testicular damage, restored disruption of the blood‐testis barrier, and improved spermatogenic function via the antiapoptotic and antioxidant capacity. Mechanistically, cordycepin significantly enhanced SIRT1 expression and triggered the activity of Foxo3a, further to induce the expression of its downstream antioxidant enzymes, including Mn‐SOD and CAT. These findings indicated that cordycepin could improve hyperglycaemia‐induced testicular damage by regulating downstream antioxidant enzymes activity through the SIRT1/Foxo3a signalling pathway.

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Anti-inflammatory and neuroprotective effects of natural cordycepin in rotenone-induced PD models through inhibiting Drp1-mediated mitochondrial fission

Cited by 37 publications

References 42 publications

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

Cordycepin Decreases Ischemia/Reperfusion Injury in Diabetic Hearts via Upregulating AMPK/Mfn2-dependent Mitochondrial Fusion

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

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