Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview

Zhao, Jing; Yang, Jun; Xie, Yan

doi:10.1016/j.ijpharm.2019.118642

Cited by 263 publications

(164 citation statements)

References 177 publications

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“…However, like other flavonoids, AP has poor solubility in water and fat, therefore having low bioavailability. PVP, a hydrophilic excipient, could convert drugs to an amorphous form, and immensity enhances the solubility and dissolution of drugs [44,45]. In this study, we prepared AP-SD with PVP K30; the results showed that the formation of solid dispersion increased the solubility and dispersion of AP, so the oral bioavailability of AP-SD was better than that of AP in rats.…”

Section: Discussionmentioning

confidence: 85%

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.

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Section: Discussionmentioning

confidence: 85%

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In addition, active constituents such as amarogentin, ἀ-amyrin, β-sitosterol, kutkin, glycyrrhetic acid and belladonnine may have less oral bioavailability. However, various methods are available to improve oral drug absorption, including preparation of prodrugs and drug conjugates, improving the drug solubility and dissolution rate, use of permeation enhancers and co-administration with delivery agents (Zhao et al, 2019 ). Besides these methods, various nanotechnology based approaches like liposomes, solid lipid nanoparticles, polymeric nanoparticles, magnetic nanoparticles, and nanoemulsion are available that increases the oral absorbtion, BBB permeability, and facilitates the targeted delivery of natural products with reduced toxicity (Vaiserman et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Antiviral activity of traditional medicinal plants from Ayurveda against SARS-CoV-2 infection

Maurya

Kumar

Bhatt

et al. 2020

Journal of Biomolecular Structure and Dynamics

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SARS-CoV-2 is the etiological agent of COVID-19 and responsible for more than 6 million cases globally, for which no vaccine or antiviral is available. Therefore, this study was planned to investigate the antiviral role of the active constituents against spike glycoprotein of SARS-CoV-2 as well as its host ACE2 receptor. Structure-based drug design approach has been used to elucidate the antiviral activity of active constituents present in traditional medicinal plants from Ayurveda. Further, parameters like drug-likeness, pharmacokinetics, and toxicity were determined to ensure the safety and efficacy of active constituents. Gene network analysis was performed to investigate the pathways altered during COVID-19. The prediction of drug–target interactions was performed to discover novel targets for active constituents. The results suggested that amarogentin, eufoliatorin, α-amyrin, caesalpinins, kutkin, β-sitosterol, and belladonnine are the top-ranked molecules have the highest affinity towards both the spike glycoprotein and ACE2. Most active constituents have passed the criteria of drug-likeness and demonstrated good pharmacokinetic profile with minimum predicted toxicity level. Gene network analysis confirmed that G-protein coupled receptor, protein kinase B signaling, protein secretion, peptidyl-serine phosphorylation, nuclear transport, apoptotic pathway, tumor necrosis factor, regulation of angiotensin level, positive regulation of ion transport, and membrane protein proteolysis were altered during COVID-19. The target prediction analysis revealed that most active constituents target the same pathways which are found to be altered during COVID-19. Collectively, our data encourages the use of active constituents as a potential therapy for COVID-19. However, further studies are ongoing to confirm its efficacy against disease.

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“…The poor water solubility, low lipophilicity, and instability, as well as extensive first pass (intestine-liver) metabolism contribute to the low bioavailability of orally ingested flavonols [198]. Recently, research on developing novel delivery systems to improve their bioavailability, target-specificity and efficacy has gained much attention.…”

Section: Bioavailability Of Allium-derived Flavonolsmentioning

confidence: 99%

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

2020

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Allium species are revered worldwide as vegetables, condiments, and spices as well as the therapeutic agents in traditional medicine. The bioactive compounds in alliums mainly include organosulfur compounds, polyphenols, dietary fibers, and saponins. Flavonoids, particularly flavonols from alliums, have been demonstrated to have the antioxidant, anticancer, hypolipidemic, anti-diabetic, cardioprotective, neuroprotective, and antimicrobial activities. However, flavonols are mostly characterized from onions and have not been comprehensively reviewed across different species. This article therefore focuses on flavonol profiles from different Allium species, their health effects, underlying molecular mechanisms, and bioavailability. Intriguingly, the functional health effects of flavonols were mainly ascribed to their antioxidant and anti-inflammatory activities involving a cascade of multiple signaling pathways. Although the Allium-derived flavonols offer tremendous potential in preventing chronic disease risks, in-depth studies are needed to translate their clinical application.

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Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview

Cited by 263 publications

References 177 publications

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Antiviral activity of traditional medicinal plants from Ayurveda against SARS-CoV-2 infection

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

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