Icariin inhibits isoproterenol-induced cardiomyocyte hypertropic injury through activating autophagy via the AMPK/mTOR signaling pathway

Hu, Lin; Wang, Ziyuan; Li, Huan; Wei, Jiarui; Tang, Fengyue; Wang, Qing; Wang, Jing; Zhang, Xiaoqiao; Zhang, Qiufang

doi:10.1016/j.bbrc.2022.01.029

Cited by 18 publications

(10 citation statements)

References 32 publications

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“…Xanthohumol inhibits abnormal ryanodine receptor Ca 2+ release, possesses antiarrhythmic properties, attenuates isoproterenol-induced cardiac hypertrophy and fibrosis and protects rat myocardia from ischemia/reperfusion injury-induced ferroptosis (59)(60)(61). Icariin inhibits isoproterenol-induced cardiomyocyte hypertrophic injury and severe heart failure, protects cardiomyocytes from ischemia/reperfusion injury and attenuates Ang II-induced H9c2 cardiomyocyte hypertrophy and apoptosis (62)(63)(64)(65). In Fructus Psoraleae, only bakuchiol, a terpene phenol, was reported to block aortic banding-induced cardiac hypertrophy by blocking the NF-κB signaling pathway and to attenuate pressure overload-induced fibrosis and inflammation (66).…”

Section: Discussionmentioning

confidence: 99%

4'‑O‑methylbavachalcone inhibits succinate induced cardiomyocyte hypertrophy via the NFATc4 pathway

et al. 2023

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Pathological cardiac hypertrophy is an independent risk factor for complications such as arrhythmia, myocardial infarction, sudden mortality and heart failure. Succinate, an intermediate product of the Krebs cycle, is released into the bloodstream by cells; its levels increase with exacerbations of hypertension, myocardial and other tissue damage and metabolic disease. Succinate may also be involved in several metabolic pathways and mediates numerous pathological effects through its receptor, succinate receptor 1 (SUCNR1; previously known as GPR91). Succinate-induced activation of SUCNR1 has been reported to be related to cardiac hypertrophy, making SUCNR1 a potential target for treating cardiac hypertrophy. Traditional Chinese medicine (TCM) and its active ingredients have served important roles in improving cardiac functions and treating heart failure. The present study investigated whether 4'-O-methylbavachadone (MeBavaC), an active ingredient of the herbal remedy Fructus Psoraleae, which is often used in TCM and has protective effect on myocardial injury and hypertrophy induced by adriamycin, ischemia-reperfusion and sepsis, could ameliorate succinate-induced cardiomyocyte hypertrophy by inhibiting the NFATc4 pathway. Using immunofluorescence staining, reverse transcription-quantitative PCR, western blotting and molecular docking analysis, it was determined that succinate activated the calcineurin/NFATc4 and ERK1/2 pathways to promote cardiomyocyte hypertrophy. MeBavaC inhibited cardiomyocyte hypertrophy, nuclear translocation of NFATc4 and ERK1/2 signaling activation in succinate-induced cardiomyocytes. Molecular docking analysis revealed that MeBavaC interacts with SUCNR1 to form a relatively stable binding and inhibits the succinate-SUCNR1 interaction. The results demonstrated that MeBavaC suppressed cardiomyocyte hypertrophy by blocking SUCNR1 receptor activity and inhibiting NFATc4 and ERK1/2 signaling, which will contribute to the preclinical development of this compound.

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Section: Discussionmentioning

confidence: 99%

4'‑O‑methylbavachalcone inhibits succinate induced cardiomyocyte hypertrophy via the NFATc4 pathway

et al. 2023

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“…mTORC1 is directly involved in the regulation of some major cellular autophagy proteins, and its upstream regulatory factor is PI3K/AKT, which can integrate signal pathways from the cellular environment and eventually regulate autophagy [32]. Studies have shown that phosphorylation of AMPK directly activates ATG1 in glucose deficiency, thereby promoting autophagy [33]. When nutrients are sufficient, the expression of AMPK is reduced, and its inhibitory effect on the phosphorylation of mTORC1 is weakened [34].…”

Section: Discussionmentioning

confidence: 99%

Comparative Genomic and Transcriptomic Profiling Revealed the Molecular Basis of Starch Promoting the Growth and Proliferation of Balantioides coli

Zhao

Jiang

et al. 2023

Animals

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Carbohydrates are the main source of nutrition for B. coli, supplying energy for cell growth and development. The research aimed at investigating the mechanism of starch on the growth and replication of B. coli. Single-cell separation was used to isolate single trophozoites of B. coli under a stereomicroscope, transcriptomic profiling was conducted based on the SMART-seq2 single-cell RNA-seq method. Comparative genomic analysis was performed on B. coli and eight other ciliates to obtain specific and expanded gene families of B. coli. GO and KEGG enrichment analysis were used to analyze the key genes of B. coli under the action of starch in the present study. The results of single-cell RNA-seq depicts starch affected the growth and replication of B. coli in two ways: (1) the cell cycle was positively promoted by the activation of the cAMP/PKA signaling pathway via glycolysis; (2) the cell autophagy was suppressed through the PI3K/AKT/mTOR pathway. Genes involved in endocytosis, carbohydrate utilization, and the cAMP/PKA signaling pathway were highly enriched in both specific and expanded gene families of B. coli. Starch can be ingested and hydrolyzed into glucose, in turn affecting various biological processes of B. coli. The molecular mechanism of the effect of starch on the growth and proliferation of B. coli by promoting cell cycle and inhibiting the autophagy of trophozoites has been elucidated in our study.

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“…Icariin, a flavonoid isolated from several species of plants in the genus Epimedium , has several pharmacological properties, such as immunomodulatory, anti-inflammatory, anti-oxidative and lipid-lowering effects [ 62 , 63 ]. Adipogenesis and autophagy were considered two important mechanisms in TAO [ 18 , 24 , 40 ].…”

Section: Potential Therapeutic Effects Of Tcm Active Ingredients In Taomentioning

confidence: 99%

“…Icariin attenuated cardiomyocyte hypertrophy induced by isoproterenol in mice, by suppressing apoptosis and promoting autophagic flux. Isoproterenol promoted phosphorylation of AMPK (p-AMPK) and inhibited phosphorylation of mTOR (p-mTOR), while icariin reversed these effects, suggesting that the cardioprotective effect was mediated through AMPK/mTOR signaling pathway [ 62 ].…”

Section: Potential Therapeutic Effects Of Tcm Active Ingredients In Taomentioning

confidence: 99%

Traditional Chinese medicine in thyroid-associated orbitopathy

Hai

Lee

Chen

et al. 2023

J Endocrinol Invest

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Purpose Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. Methods The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. Results Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. Conclusions Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

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Icariin inhibits isoproterenol-induced cardiomyocyte hypertropic injury through activating autophagy via the AMPK/mTOR signaling pathway

Cited by 18 publications

References 32 publications

4'‑O‑methylbavachalcone inhibits succinate induced cardiomyocyte hypertrophy via the NFATc4 pathway

4'‑O‑methylbavachalcone inhibits succinate induced cardiomyocyte hypertrophy via the NFATc4 pathway

Comparative Genomic and Transcriptomic Profiling Revealed the Molecular Basis of Starch Promoting the Growth and Proliferation of Balantioides coli

Traditional Chinese medicine in thyroid-associated orbitopathy

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