Nootkatone Ameliorates Doxorubicin Induced Myocardial Injury through Modulation of NF-κB Signals and Oxidative Stress

Al‐Salam, Suhail; Karthishwaran, Kandhan; Sudhadevi, Manjusha; Tariq, Saeed

doi:10.33594/000000559

Cited by 7 publications

(2 citation statements)

References 43 publications

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“…On the contrary, nootkatone administration (10 mg kg –1 ) significantly restored the altered biochemical and molecular parameters in ISO-induced rats, showing the cardioprotective effect. Similar results were also reported by other papers, in which oral treatment of nootkatone was found to attenuate lipid peroxidation and oxidative stress, decrease inflammatory markers in hearts, reduce myocardial damage, and modulate the NF-κB signals in the mouse model of MI. , …”

Section: Biological Propertiessupporting

confidence: 91%

“…Similar results were also reported by other papers, in which oral treatment of nootkatone was found to attenuate lipid peroxidation and oxidative stress, decrease inflammatory markers in hearts, reduce myocardial damage, and modulate the NF-κB signals in the mouse model of MI. 150,151 Consequently, inhibition of oxidative stress and lipid peroxidation, suppression of the NF-κB inflammatory pathway, and activation of HO-1and Nrf2 are the possible mechanisms for their cardioprotective effect.…”

Section: Cardioprotective Effectmentioning

confidence: 99%

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Production, Function, and Applications of the Sesquiterpenes Valencene and Nootkatone: a Comprehensive Review

Zhang

Chen

et al. 2022

J. Agric. Food Chem.

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Valencene and nootkatone, two sesquiterpenes, extracted from natural sources, have great market potential with diverse applications. This paper aims to comprehensively review the recent advances in valencene and nootkatone, including source, production, physicochemical and biological properties, safety and pharmacokinetics evaluation, potential uses, and their industrial applications as well as future research directions. Microbial biosynthesis offers a promising alternative approach for sustainable production of valencene and nootkatone. Both compounds exert various beneficial activities, including antimicrobial, insecticidal, antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, hepatoprotective, and nephroprotective and other activities. However, most of the studies are performed in animals and in vitro, making it difficult to give a conclusive description about their health benefits and extend their application. Hence, more attention should be paid to in vivo and long-term clinical studies in the future. Moreover, valencene and nootkatone are considered safe for consumption and show great promise in the applications of food, cosmetic, pharmaceutical, chemical, and agricultural industries.

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Section: Biological Propertiessupporting

confidence: 91%

Section: Cardioprotective Effectmentioning

confidence: 99%

Production, Function, and Applications of the Sesquiterpenes Valencene and Nootkatone: a Comprehensive Review

Zhang

Chen

et al. 2022

J. Agric. Food Chem.

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Rational Engineering of a Mitochondrial‐Mimetic Therapy for Targeted Treatment of Dilated Cardiomyopathy by Precisely Regulating Mitochondrial Homeostasis

Chen

et al. 2023

Adv Funct Materials

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Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most common indication for heart transplantation. Currently, there is still an unmet clinical need in effective therapies for DCM. Herein a mitochondrial‐mimetic therapy capable of efficiently targeting the heart, cardiomyocytes, and myocardial mitochondria as well as effectively regulating mitochondrial homeostasis for targeted treatment of DCM is reported. A bioactive conjugate TPT is first synthesized by integrating three functional moieties onto a scaffold, which can assemble into small‐size nanomicelles (i.e., TPTN). Intravenously delivered TPTN efficiently accumulates in the heart and mainly localizes in cardiomyocytes and myocardial mitochondria of DCM mice, thereby alleviating DCM. Mechanistically, TPTN inhibits intracellular oxidative stress, alleviates mitochondrial injury, improves mitochondrial dynamics, regulates mitochondrial oxidative phosphorylation, and reduces calpain‐1 and NLRP3 inflammasome activation, thus restoring mitochondrial homeostasis and inhibiting adverse cardiac remodeling. By packaging TPTN into outer mitochondrial membrane‐derived vesicles, a mitochondrial‐mimetic therapy is engineered, which displays significantly enhanced three‐level targeting capability to the heart, cardiac cells, and myocardial mitochondria, thereby affording notably potentiated therapeutic effects in DCM mice. Accordingly, the three‐level targeting mimetics is promising for targeted treatment of DCM. The findings provide new insight into rational design of precision therapies for mitochondrial dysfunction‐associated diseases.

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(+)-Nootkatone, the flavor of grapefruit

Ramachanderan,

Schaefer

2024

ChemTexts

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Nootkatone is one of the most valuable citrus flavors. Originally isolated from the heartwood of the Nootka cypress (Callitropsis nootkatensis), it was probably the identification of nootkatone as a minor component of grapefruit oil that catapulted this sesquiterpene into the focus of flavor research and made it a highly sought-after citrus aroma in recent decades. The odors of ( +)-nootkatone and (−)-nootkatone are perceptible in the air at threshold concentrations of 30 ppm and 66,000 ppm of saturated vapor, respectively. While ( +)-nootkatone embodies a strong grapefruit scent and has a bitter taste, (−)-nootkatone has a faint woody vetiver note and is virtually tasteless. In 2020, nootkatone was registered by the US Environmental Protection Agency as an insect repellent and natural insecticide that may repel and kill mosquitoes, fleas, ticks, mites, lice, and termites. Moreover, numerous pharmacological activities of nootkatone have been thoroughly investigated. As expected, a wealth of synthetic approaches, which are essentially based on the oxidation of valencene and on total syntheses, have been published in the last 60 years since its discovery. However, in addition to extraction from natural sources (e.g., grapefruit peel), the enzymatic oxidation of valencene and fermentative processes are the preferred production technologies today. The market is expected to grow considerably over the next 10 years, not least owing to the wide range of potential applications in the pharmaceutical, personal, and home care sector.How the reader may benefit: learn more about the total synthesis of natural products, allylic oxidation, and Robinson annulation, gain deeper insights into the biosynthesis of sesquiterpenes and finally discover how enantiopure compounds, such as ( +)-nootkatone, are produced at an industrial scale. Graphical Abstract

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Nootkatone Ameliorates Doxorubicin Induced Myocardial Injury through Modulation of NF-κB Signals and Oxidative Stress

Cited by 7 publications

References 43 publications

Production, Function, and Applications of the Sesquiterpenes Valencene and Nootkatone: a Comprehensive Review

Production, Function, and Applications of the Sesquiterpenes Valencene and Nootkatone: a Comprehensive Review

Rational Engineering of a Mitochondrial‐Mimetic Therapy for Targeted Treatment of Dilated Cardiomyopathy by Precisely Regulating Mitochondrial Homeostasis

(+)-Nootkatone, the flavor of grapefruit

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