Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway

Wang, Hui‐Bo; Duan, Mingxia; Xu, Man; Huang, Shuqi; Yang, Jun; Yang, Jian; Liu, Libo; Huang, R. Stephanie; Chen, Wan; Ma, Zhengliang; Wu, Qin; Tang, Qi‐Zhu

doi:10.1111/jcmm.14485

Cited by 22 publications

(11 citation statements)

References 39 publications

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“…Five of these met the eligibility criteria (see the Methods section). The outcomes were activation of AMPK indicated by increasing phosphorylation at Thr 172 (three articles) and also inhibiting mTOR indicated by reduced the phosphorylation at Ser 2448 (two articles), confirming the effects observed in tissue culture [35,142,164,183,184]. For details see Table 2.…”

Section: Signal Transduction Effects In Animal Modelssupporting

confidence: 56%

“…We noted 45 papers claiming that the cytotoxic effect of cordycepin at bioactive concentrations was low. We noted the highest concentration which promoted cell survival or did not cause statistically significant cell death in these papers and determined the median and the range [ 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 69 , 70 , 80 , 95 , 98 , 102 , 105 , 106 , 117 , 142 , 145 , 164 , 184 , 240 , 270 , 301 , 315 , 317 , 326 , 327 , 328 , 329 , 330 , 331 , 332 , 333 , 334 , 335 , 336 ].…”

Section: Methodsmentioning

confidence: 99%

“…For example, in papers studying the effect of cordycepin on osteoarthritic animal models where pain was also measured, the study was categorised under bone disorders. The range of cordycepin dose administered to the animal was examined in 131 papers, in which the cordycepin dose could be calculated as mg/kg [ 11 , 18 , 23 , 24 , 28 , 37 , 38 , 42 , 64 , 66 , 76 , 79 , 80 , 97 , 107 , 108 , 119 , 120 , 121 , 122 , 126 , 130 , 134 , 142 , 143 , 145 , 150 , 164 , 183 , 184 , 185 , 186 , 187 , 188 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 202 , 204 , 205 , 206 , 207 ...…”

Section: Methodsmentioning

confidence: 99%

“…Concerning the cardiovascular system, 15 articles were found for a variety of animal models. Cordycepin was reported to have beneficial effects for cardiac hypertrophy [184], ischemia [122,183,[204][205][206], dyslipidaemia [37,164,207,208] and other heart disease models [76,120,[209][210][211]. Categories which had only one entry were excluded, as described in the Methods section.…”

Section: Cordycepin Activity In Animal Modelsmentioning

confidence: 99%

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A Systematic Review of the Biological Effects of Cordycepin

Radhi

Ashraf²,

Lawrence

et al. 2021

Molecules

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We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.

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Section: Signal Transduction Effects In Animal Modelssupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Cordycepin Activity In Animal Modelsmentioning

confidence: 99%

See 2 more Smart Citations

A Systematic Review of the Biological Effects of Cordycepin

Radhi

Ashraf²,

Lawrence

et al. 2021

Molecules

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“…Numerous studies have found that AMPK activation appears to have a protective effect on cardiomyocytes under MI/R by decreasing apoptosis, improving post-ischemic recovery, and reducing myocardial infarction (MI) ( Wu and Zou, 2020 ). Interestingly, cordycepin has been reported as a pro-drug that activates AMPK by being converted into the AMP analog cordycepin monophosphate ( Wu et al, 2014 ; Wang et al, 2019 ; Hawley et al, 2020 ). Moreover, recent studies have demonstrated that AMPK regulates mitochondrial fusion and mitophagy to sustain mitochondrial homeostasis under stress conditions ( Toyama et al, 2016 ; Zhang et al, 2019 ), indicating the key role of AMPK in mitochondrial dynamics.…”

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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Edible mushrooms as potential functional foods in amelioration of hypertension

Rauf

Joshi

Ahmad

et al. 2023

Phytotherapy Research

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Edible mushrooms are popular functional foods attributed to their rich nutritional bioactive constituent profile influencing cardiovascular function. Edible mushrooms are omnipresent in various prescribed Dietary Approaches to Stop Hypertension, Mediterranean diet, and fortified meal plans as they are rich in amino acids, dietary fiber, proteins, sterols, vitamins, and minerals. However, without an understanding of the influence of mushroom bioactive constituents, mechanism of action on heart and allergenicity, it is difficult to fully comprehend the role of mushrooms as dietary interventions in alleviating hypertension and other cardiovascular malfunctions. To accomplish this endeavor, we chose to review edible mushrooms and their bioactive constituents in ameliorating hypertension. Hypertension and cardiovascular diseases are interrelated and if the former is managed by dietary changes, it is postulated that overall heart health could also be improved. With a concise note on different edible varieties of mushrooms, a particular focus is presented on the antihypertensive potential of mushroom bioactive constituents, mode of action, absorption kinetics and bioavailability. Ergosterol, lovastatin, cordycepin, tocopherols, chitosan, ergothioneine, γ-aminobutyric acid, quercetin, and eritadenine are described as essential bioactives with hypotensive effects. Finally, safety concerns on allergens and limitations of consuming edible mushrooms with special reference to chemical toxins and their postulated metabolites are highlighted. It is opined that the present review will redirect toxicologists to further investigate mushroom bioactives and allergens, thereby influencing dietary interventions for heart health.

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Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway

Cited by 22 publications

References 39 publications

A Systematic Review of the Biological Effects of Cordycepin

A Systematic Review of the Biological Effects of Cordycepin

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

Edible mushrooms as potential functional foods in amelioration of hypertension

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