Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters

Kaci, Hana; Bodnárová, Slávka; Fliszár-Nyúl, Eszter; Lemli, Beáta; Valentová, Kateřina; Bakos, Éva; Özvegy‐Laczka, Csilla; Poór, Miklós

doi:10.1016/j.biopha.2022.114078

Cited by 13 publications

(6 citation statements)

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“…Studies carried out in rats have shown that luteolin has moderate bioavailability (26 ± 6%), undergoes enterohepatic recycling, and has an extensive metabolism by conjugation [ 61 ]. Limited in vitro investigations have studied the interaction of luteolin with CYP enzymes, showing moderate inhibitory action on CYP2C8 and CYP1A2 [ 62 ], CYP2C9, and CYP3A [ 63 , 64 , 65 ]. In general, the data suggest interest in the development of luteolin in therapy, and several drug delivery studies are ongoing [ 66 ].…”

Section: Resultsmentioning

confidence: 99%

Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters

Djeujo,

Stablum,

Pangrazzi

et al. 2023

Pharmaceutics

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The aqueous decoctions of Vernonia amygdalina (VA) leaves and roots are widely used in traditional African medicine as an antidiabetic remedy. The amount of luteolin and vernodalol in leaf and root extracts was detected, and their role was studied regarding α-glucosidase activity, bovine serum albumin glycation (BSA), reactive oxygen species (ROS) formation, and cell viability, together with in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Vernodalol did not affect α-glucosidase activity, whereas luteolin did. Furthermore, luteolin inhibited the formation of advanced glycation end products (AGEs) in a concentration-dependent manner, whereas vernodalol did not reduce it. Additionally, luteolin exhibited high antiradical activity, while vernodalol demonstrated a lower scavenger effect, although similar to that of ascorbic acid. Both luteolin and vernodalol inhibited HT-29 cell viability, showing a half-maximum inhibitory concentration (IC50) of 22.2 µM (−Log IC50 = 4.65 ± 0.05) and 5.7 µM (−Log IC50 = 5.24 ± 0.16), respectively. Finally, an in silico ADMET study showed that both compounds are suitable candidates as drugs, with appropriate pharmacokinetics. This research underlines for the first time the greater presence of vernodalol in VA roots compared to leaves, while luteolin is prevalent in the latter, suggesting that the former could be used as a natural source of vernodalol. Consequently, root extracts could be proposed for vernodalol-dependent antiproliferative activity, while leaf extracts could be suggested for luteolin-dependent effects, such as antioxidant and antidiabetic effects.

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Section: Resultsmentioning

confidence: 99%

Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters

Djeujo,

Stablum,

Pangrazzi

et al. 2023

Pharmaceutics

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“…Cytochrome P450 (CYP) enzymes are involved in the oxidative biotransformation of most drug (Meunier et al, 2004). CYP3A4 takes part in the biotransformation of more than 50% of the orally administered medications, and some other CYP isoforms (Kaci et al, 2023). Organic anion transporting polypeptides (OATPs) are solute carrier-type membrane transporters, which are commonly involved in the tissue uptake of nutrients, drugs, and toxins (Mandery et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism

Wang,

Li,

Liu

et al. 2023

Front. Pharmacol.

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Background:Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear.Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics.Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites.Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.

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“…In another study conducted in 2023, Yang et al [46] aimed to investigate the pH-dependent binding mechanisms between cyandin-3-O-glucoside (C3G) and BSA, exploring the interactions of natural pigments, anthocyanins, with proteins under varying pH conditions. Fluorescence quenching experiments and microscale thermophoresis (MST) analyses revealed a pH-dependent binding affinity, with the order pH 7 > pH 5 > pH 3, and dissociation constants (K d ) of 43.1 μmol/L (fluorescence quenching) and 33.0 μmol/L (MST) at pH 7.…”

Section: Potential Findings and Latest Applications Of Serum Protein ...mentioning

confidence: 99%

“…In contrast, uncharged forms of C3G at all pH values bound to the BSA surface through hydrophobic interactions and hydrogen bonds, possibly in a weak and nonspecific manner. Anionic quinoidal bases, prevalent C3G forms at pH 7, predominantly bound to positively charged pockets on BSA, establishing several hydrogen bonds with surrounding amino acids, resulting in enhanced binding affinity [46]. Luteolin and naringenin are flavonoids found extensively in various foods and beverages, and they are also constituents of specific dietary supplements.…”

Section: Potential Findings and Latest Applications Of Serum Protein ...mentioning

confidence: 99%

Current analytical methods and applications used in the insight of serum proteins interactions with various food additives, pesticides, and contaminants

Erkmen,

Kabir

2024

Explor Foods Foodomics

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In recent years, many societies have expressed increasing apprehension regarding the potential negative impacts of food additives, pesticides, and environmental contaminants on human health. Environmental or occupational exposure to these compounds can cause significant adverse effects on human health by causing temporary or permanent changes in the immune system. There is supporting evidence linking pesticides/food ingredients/contaminants-induced immune alterations to the prevalence of diseases associated with changes in immune responses. Hence, it is essential to comprehensively understand the key mechanisms contributing to immune dysregulation induced by these substances, including direct immunotoxicity, endocrine disruption, and antigenicity. The impact of pesticides/food ingredients and contaminants on the human body ranges from mild to severe, depending on their affinity for blood components. These compounds form complexes with blood serum proteins, influencing their metabolism, transport, absorption, and overall toxicity. Numerous studies in the literature have explored the interactions between serum proteins and various molecules, including pesticides, drugs, and food dyes. These investigations employed a range of techniques, including spectroscopy, electrochemical and chromatographic methods as well as molecular modeling and molecular dynamics simulations analyses. This recent review, spanning from 2020 to the present, has been employed to investigate the binding characteristics, mechanisms, and attributes of different food additives, pesticides, and contaminants with serum proteins by using various techniques such as steady-state fluorescence, circular dichroism and ultra-violet spectroscopies, and computational docking methods. The review provides insights into these compounds’ positions and affinities to proteins and possible effects on human health through detailed research studies.

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Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters

Cited by 13 publications

References 76 publications

Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters

Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters

Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism

Current analytical methods and applications used in the insight of serum proteins interactions with various food additives, pesticides, and contaminants

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