Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies

Gandhi, Gopalsamy Rajiv; Vasconcelos, Alan Bruno Silva; Wu, Ding‐Tao; Li, Hua-Bin; Antony, Poovathumkal James; Li, Hang; Geng, Fang; Gurgel, Ricardo Queiróz; Narain, Narendra; Gan, Ren‐You

doi:10.3390/nu12102907

Cited by 153 publications

(95 citation statements)

References 132 publications

(136 reference statements)

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“…The following compounds are major PMFs in citrus fruits ( Figure 1 ): nobiletin (3′,4′,5,6,7,8-hexamethoxyflavone, C 21 H 22 O 8 ), tangeretin (4′,5,6,7,8-pentamethoxyflavone, C 20 H 20 O 7 ), and 3,3′,4′,5,6,7,8-heptamethoxyflavone (C 22 H 24 O 9 , HMF) [ 20 ]. Because of their anti-inflammatory and antioxidant effects, these citrus-derived PMFs have the potential to prevent neurodegenerative and neurological disorders [ 21 , 22 , 23 , 24 , 25 , 26 ]. In addition, these PMFs have shown beneficial effects against hyperlipidemia [ 27 , 28 ], obesity [ 29 , 30 ], diabetes [ 31 , 32 ], cardiovascular dysfunction [ 33 , 34 ], and cancer [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

Matsuzaki

Ohizumi

2021

Nutrients

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The number of patients with central nervous system disorders is increasing. Despite diligent laboratory and clinical research over the past 30 years, most pharmacologic options for the prevention and long-term treatment of central nervous system disorders and neurodegenerative disorders have been unsuccessful. Therefore, the development of drugs and/or functional foods to prevent the onset of neurodegenerative disorders is highly expected. Several reports have shown that polymethoxylated flavones (PMFs) derived from citrus fruit, such as nobiletin, tangeretin, and 3,3′,4′,5,6,7,8-heptamethoxyflavone, are promising molecules for the prevention of neurodegenerative and neurological disorders. In various animal models, PMFs have been shown to have a neuroprotective effect and improve cognitive dysfunction with regard to neurological disorders by exerting favorable effects against their pathological features, including oxidative stress, neuroinflammation, neurodegeneration, and synaptic dysfunction as well as its related mechanisms. In this review, we describe the profitable and ameliorating effects of citrus-derived PMFs on cognitive impairment and neural dysfunction in various rat and murine models or in several models of central nervous system disorders and identify their mechanisms of action.

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Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

Matsuzaki

Ohizumi

2021

Nutrients

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“…Lactobionic acid is used in the intravenous delivery of erythromycin and act as an excipient for formulations in pharmaceutical industry [ 34 , 35 ]. Neosperidin possess antidiabetic potential and used to improve and promote skin microcirculation [ 36 ]. Salvionic acid has been patented as antithrombotic agent and possesses other therapeutic value [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study

Singh

Kushwaha

Prajapati

et al. 2021

Computers in Biology and Medicine

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Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking scores and interaction profile analyses exhibited strong binding affinity of eleven FDA approved drugs and five nucleoside analogues NA 1 (−13.84), nadide (−13.65), citicholine (−13.54), NA 2 (−12.42), and NA 3 (−12.27). The lead compound NA 1 exhibited significant hydrogen bonding and hydrophobic interaction at the natural substrate binding site. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface (SASA), hydrogen bond formation, principle component analysis, and free energy landscape calculations for NA 1 bound protein displayed stable complex formation in 100 ns molecular dynamics simulation, compared to unbound macro domain and natural substrate adenosine-5-diphosphoribose bound macro domain that served as a positive control. The molecular mechanics Poisson–Boltzmann surface area analysis of NA 1 demonstrated binding free energy of −175.978 ± 0.401 kJ/mol in comparison to natural substrate which had binding free energy of −133.403 ± 14.103 kJ/mol. In silico analysis by modelling tool ADMET and prediction of biological activity of these compounds further validated them as putative therapeutic molecules against SARS-CoV-2. Taken together, this study offers NA 1 as a lead SARS-CoV-2 A1pp domain inhibitor for future testing and development as therapeutics against human coronavirus.

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“…A systematic review has highlighted the potential antidiabetic action of citrus flavonoids and their molecular mechanisms based on in vitro and in vivo studies [161]. The research identified 38 articles, mostly on experimental animals, which reported that citrus flavonoids regulate glycaemic control biomarkers, lipid profiles, kidney function, liver enzymes and antioxidant enzymes, and modulated signalling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications.…”

Section: Comorbiditiesmentioning

confidence: 99%

Reappraisal of Dietary Phytochemicals for Coronavirus Infection: Focus on Hesperidin and Quercetin

Bellavite¹

2021

Antioxidants - Benefits, Sources, Mechanisms of Action

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Food polyphenols constitute a large family of substances with beneficial properties in a large group of communicable and non-communicable diseases. These compounds support and improve the body’s defences against oxidative stress and are helpful in the prevention of pathologies related to metabolic syndrome. Furthermore, they exhibit anti-inflammatory, antiviral, and antimicrobial properties. This chapter draws attention to certain nutritional components such as hesperidin and quercetin, which are emerging as good candidates for a complementary beneficial effect in the case of diseases caused by viruses, including COVID-19. These nutraceuticals have a complex mechanism of action, which involves both cellular defence against oxidative stress and the modulation of inflammation, which although normally is a defence, repair and activation mechanism of the immune system, it can elude its controls and become a systemic and destructive pathology (cytokine storm, respiratory distress syndrome). Furthermore, recent in silico simulation tests suggest that both hesperidin and quercetin may interfere with SARS-CoV-2 by binding to cell receptors and the proteolytic enzymes involved in its replication. In addition to the inhibitory effects on the virus at cellular level, the two flavonoids can have indirect effects in respiratory infectious diseases as they prevent or improve metabolic and vascular comorbidities that can complicate the clinical course. This brief review focuses on biochemical and pharmacological mechanisms of action of polyphenols in the context of the revaluation of dietary approaches to the prevention and treatment of infectious diseases caused by viruses, with a special application to COVID-19.

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Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies

Cited by 153 publications

References 132 publications

Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study

Reappraisal of Dietary Phytochemicals for Coronavirus Infection: Focus on Hesperidin and Quercetin

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