Neocryptotanshinone ameliorates insufficient energy production in heart failure by targeting retinoid X receptor alpha

Ma, Lin; Shao, Mingyan; Cheng, Wenkun; Jiang, Jinchi; Chen, Xu; Tan, Nannan; Ling, Guanjing; Yang, Ye; Wang, Qian; Yang, Ran; Li, Chun; Wang, Yong

doi:10.1016/j.biopha.2023.114868

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…NCTS enhanced CD36 and CPT1a expression, increasing FA uptake and FAO. Moreover, NCTS enhanced mitochondrial transcription factor A (TFAM) levels and promoted mitochondrial biogenesis [108]. Another strategy of broad current interest is to increase FAO by improving mitochondrial biogenesis and function.…”

Section: Stimulation Of Faomentioning

confidence: 99%

Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

Actis Dato,

Lange,

Cho

2024

IJMS

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This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and the implications for therapeutic strategies. The heart’s reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores the significance of metabolic flexibility, with fatty acid oxidation (FAO) being a dominant source. In HF, metabolic shifts occur with an altered FA uptake and FAO, impacting mitochondrial function and contributing to disease progression. Conditions like obesity and diabetes also lead to metabolic disturbances, resulting in cardiomyopathy marked by an over-reliance on FAO, mitochondrial dysfunction, and lipotoxicity. Therapeutic approaches targeting FA metabolism in cardiac diseases have evolved, focusing on inhibiting or stimulating FAO to optimize cardiac energetics. Strategies include using CPT1A inhibitors, using PPARα agonists, and enhancing mitochondrial biogenesis and function. However, the effectiveness varies, reflecting the complexity of metabolic remodeling in HF. Hence, treatment strategies should be individualized, considering that cardiac energy metabolism is intricate and tightly regulated. The therapeutic aim is to optimize overall metabolic function, recognizing the pivotal role of FAs and the need for further research to develop effective therapies, with promising new approaches targeting mitochondrial oxidative metabolism and FAO that improve cardiac function.

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Section: Stimulation Of Faomentioning

confidence: 99%

Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

Actis Dato,

Lange,

Cho

2024

IJMS

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“…155 In ischaemic myocardium, neocryptotanshinone promoted mitochondrial biogenesis, fatty acid oxidation and ATP production by binding directly to RXRα to upregulate both RXRα and PPARα. 156 Several ginsenosides have favourable effects in experimental chronic heart failure, primarily by signalling through SIRT1, AMPK and PGC-1α. Ginsenoside Rb3 mitigated ventricular remodelling and fibrosis and exerted antiapoptotic effects in models of pressure-overload heart failure and in osmotically stressed H9C2 cardiomyocytes, and these effects were accompanied by upregulation of PGC-1α, PPARα and RXRα and restoration of enzymes critical to fatty acid oxidation.…”

Section: Effect Of Qiliqiangxin Constituents On Sirt1-ampk-pgc-1𝛂-ppa...mentioning

confidence: 99%

“…Tanshione IIA also ameliorated diabetic cardiomyopathy and palmitic acid‐induced endoplasmic reticulum stress in neonatal rat cardiomyocytes; these effects were accompanied by upregulation of SIRT1 and were abolished by SIRT1 inhibition 155 . In ischaemic myocardium, neocryptotanshinone promoted mitochondrial biogenesis, fatty acid oxidation and ATP production by binding directly to RXRα to upregulate both RXRα and PPARα 156 …”

Section: Qiliqiangxin In Experimental Models Of Prolonged Measured Ca...mentioning

confidence: 99%

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Packer

2023

European J of Heart Fail

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The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68‐0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF‐1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF‐1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC‐1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC‐1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC‐1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC‐1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC‐1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX — astragaloside IV, ginsenosides, and tanshione IIA — share QLQX's effects on PGC‐1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+‐K+‐ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials.This article is protected by copyright. All rights reserved.

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“…Traditionally, Salvia miltiorrhiza belongs to a class of drugs that invigorate blood circulation and eliminate stasis ( Zhao et al, 2022 ). Thus, many studies have focused on its activity and mechanism in blood circulation; though recent studies have addressed the effects of Salvia miltiorrhiza in regulating energy and anti-inflammation ( Wang et al, 2022 ; Ma et al, 2023 ; Zou et al, 2023 ). Additionally, a traditional Chinese medicine formulation investigated by our research team (comprising Salvia miltiorrhiza and other herbal medicines), named Danlianhua Uterine infusion (DLH), demonstrated therapeutic efficacy across various forms of endometritis ( Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis

Tian,

Liu,

Jiang

et al. 2024

Front. Pharmacol.

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Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis.Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment.Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1β, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis.Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.

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Neocryptotanshinone ameliorates insufficient energy production in heart failure by targeting retinoid X receptor alpha

Cited by 3 publications

References 42 publications

Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis

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