Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment

Vazhappilly, Cijo George; Amararathna, Madumani; Cyril, Asha Caroline; Linger, Rebecca S.; Matar, Rachel; Merheb, Maxime; Ramadan, Wafaa; Radhakrishnan, Rajan; Rupasinghe, H.P. Vasantha

doi:10.1016/j.jnutbio.2021.108623

Cited by 50 publications

(27 citation statements)

References 165 publications

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“…Flavonoids have been shown to induce WAT browning and activate BAT to increase energy consumption and non-shivering thermogenesis and may foster a relatively safe and effective therapeutic option to improve metabolic health [57,58]. However, factors such as a low bioavailability, a poor flavonoid stability and solubility, and ineffective targeted delivery, hinder the application of flavonoids [59]. For example, quercetin, a widely-studied natural flavonoid, has been reported to remodel white adipocytes to brownlike adipocytes [54].…”

Section: Discussionmentioning

confidence: 99%

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

et al. 2022

Pharmaceutics

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Irisin is an exercise-induced hormone that regulates lipid metabolism. The present study investigates whether the anti-obesity effect of the natural flavonoid pentamethylquercetin (PMQ) is related to irisin secretion from skeletal muscle in whole animals and cultured cells. Obese mice induced by monosodium glutamate were administered oral PMQ to determine blood irisin level and in vivo parameters of lipid metabolism, and cultured mouse C2C12 myoblasts and 3T3-L1 preadipocytes were employed to investigate the related molecular identities. PMQ increased circulating irisin and decreased bodyweight, insulin, and lipid levels accompanied with increasing brown-like adipocyte formation in obese mice. The brown adipocyte marker uncoupling protein 1 (UCP-1) and other brown-like adipocyte-specific genes and/or markers were increased in mouse white fat tissue, while PMQ treatment reversed the above changes. PMQ also dose-dependently increased the reduced levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and fibronectin type III domain-containing 5 (FNDC5) signal molecules in obese mice. Interestingly, the irisin level was increased in the culture medium of C2C12 cells treated with PMQ, and the conditioned medium stimulated the brown-like transition of 3T3-L1 preadipocytes with the increased expression of PGC-1α, FNDC5, UCP-1, and other brown-like adipocyte-specific genes. The effects of conditioned culture medium were abolished in C2C12 cells with silenced PGC-1α. On the other hand, PMQ-induced upregulation of PGC-1α and FNDC5 expression was reduced by AMPK inhibitor Compound C in C2C12 cells. Our results demonstrate the novel information that PMQ-induced irisin secretion from skeletal muscle involves the improvement of metabolic dysfunction in obese mice via activating the AMPK/PGC-1α/FNDC5 signal pathway, suggesting that PMQ modulates skeletal muscle-adipose tissue crosstalk and may be a promising drug candidate for treating obesity and obesity-related metabolic diseases.

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Section: Discussionmentioning

confidence: 99%

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

et al. 2022

Pharmaceutics

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“…The inclusion complexation was a critical step for alpinetin to devise novel dosage forms. Additionally, other encapsulation systems, such as microemulsion and phospholipid entrapment, have been designed to effectively deliver flavonoids inside the body (Vazhappilly et al, 2021). The possibility of utilizing these systems may improve the bioavailability and curative effects of alpinetin.…”

Section: Enhancement Strategiesmentioning

confidence: 99%

Alpinetin: A Review of Its Pharmacology and Pharmacokinetics

et al. 2022

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Flavonoids isolated from medicinal herbs have been utilized as valuable health-care agents due to their virous biological applications. Alpinetin is a natural flavonoid that emerges in many widely used medicinal plants, and has been frequently applied in Chinese patent drugs. Accumulated evidence has demonstrated that alpinetin possesses a broad range of pharmacological activities such as antitumor, antiinflammation, hepatoprotective, cardiovascular protective, lung protective, antibacterial, antiviral, neuroprotective, and other properties through regulating multiple signaling pathways with low systemic toxicity. However, pharmacokinetic studies have documented that alpinetin may have poor oral bioavailability correlated to its extensive glucuronidation. Currently, the reported pharmacological properties and pharmacokinetics profiles of alpinetin are rare to be scientifically reviewed. In this article, we aimed to highlight the mechanisms of action of alpinetin in various diseases to strongly support its curative potentials for prospective clinical applications. We also summarized the pharmacokinetics properties and proposed some viable strategies to convey an appreciable reference for future advances of alpinetin in drug development.

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“…One study shows that 8.98 µmol/L of quercetin may lead to the suppression of hyperplastic nodules with minimum preneolastic lesions in the parenchyma of rats with hepatic carcinoma induced by diethylnitrosamine treatment [149]. Another study demonstrated that poly (lactic-co-glycolite) nanoparticles loaded with apigenin induce the intrinsic mode of apoptotic cell death and suppress epidermal hyperplasia in Swiss albino mice [150]. Thus, it is safe to say that flavonoids may have a strong impact on tumor cell manipulation in vivo, but this topic needs further study.…”

Section: Dna Protection and Depletionmentioning

confidence: 99%

Chemical Structure, Sources and Role of Bioactive Flavonoids in Cancer Prevention: A Review

Drețcanu

Ştirbu

Leopold

et al. 2022

Plants

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There has been a major shift in the collective mindset around the world in recent decades, both in terms of food and in terms of the treatment of chronic diseases. Increasing numbers of people are choosing to prevent rather than treat, which is why many consumers are choosing plant-based diets, mainly due to their bioactive compounds. A significant case of bioactive compound is flavonoids—a wide subclass of an even wider class of phytochemicals: polyphenols. Flavonoids are a broad topic of study for researchers due to their potential in the prevention and treatment of a broad range of cancers. The aim of this review is to inform/update the reader on the diversity, accessibility and importance of flavonoids as biomolecules that are essential for optimal health, focusing on the potential of these compounds in the prevention of various types of cancer. Along with conventional sources, this review presents some of the possible methods for obtaining significant amounts of flavonoids based on a slightly different approach, genetic manipulation.

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Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment

Cited by 50 publications

References 165 publications

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

Alpinetin: A Review of Its Pharmacology and Pharmacokinetics

Chemical Structure, Sources and Role of Bioactive Flavonoids in Cancer Prevention: A Review

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