bims-antpol 2023-07-02 papers

bims-antpol

Biomed News

on Antiviral properties of polyphenols

Issue of 2023–07–02
eight papers selected by
Rick Sheridan, EMSKE Phytochem

Therapeutic Potential of Polyphenols and Other Micronutrients of Marine Origin.
Fabrication of Luteolin Loaded Zein-Caseinate Nanoparticles and its Bioavailability Enhancement in Rats.
Comprehensive Metabolite Profiling of Chemlali Olive Tree Root Extracts Using LC-ESI-QTOF-MS/MS, Their Cytotoxicity, and Antiviral Assessment.
Development of Phytochemical Delivery Systems by Nano-Suspension and Nano-Emulsion Techniques.
Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies.
A systematic review and comprehensive evaluation of human intervention studies to unravel the bioavailability of hydroxycinnamic acids.
Specialized metabolites from plants as a source of new multi-target antiviral drugs: a systematic review.
Effects of Different Cooking Methods on Phenol Content and Antioxidant Activity in Sprouted Peanut.

Mar Drugs. 2023 May 26. pii: 323. [Epub ahead of print]21(6):

Therapeutic Potential of Polyphenols and Other Micronutrients of Marine Origin.

Leonel Pereira, João Cotas.

  Polyphenols are compounds found in various plants and foods, known for their antioxidant and anti-inflammatory properties. Recently, researchers have been exploring the therapeutic potential of marine polyphenols and other minor nutrients that are found in algae, fish and crustaceans. These compounds have unique chemical structures and exhibit diverse biological properties, including anti-inflammatory, antioxidant, antimicrobial and antitumor action. Due to these properties, marine polyphenols are being investigated as possible therapeutic agents for the treatment of a wide variety of conditions, such as cardiovascular disease, diabetes, neurodegenerative diseases and cancer. This review focuses on the therapeutic potential of marine polyphenols and their applications in human health, and also, in marine phenolic classes, the extraction methods, purification techniques and future applications of marine phenolic compounds.

Keywords:  anti-inflammatories; antioxidants; cancer; cardiovascular diseases; diabetes; health; marine polyphenols; neurodegenerative diseases; therapeutics

DOI:  https://doi.org/10.3390/md21060323
J Pharm Sci. 2023 Jun 24. pii: S0022-3549(23)00242-3. [Epub ahead of print]

Fabrication of Luteolin Loaded Zein-Caseinate Nanoparticles and its Bioavailability Enhancement in Rats.

Qiao-Ting Xu, Wen-Xuan Zhang, Hai-Xia Xu, Qing-Feng Zhang.

  Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD, FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm, -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.

Keywords:  Bioavailability; Luteolin; Nanoparticles; Zein

DOI:  https://doi.org/10.1016/j.xphs.2023.06.010
Molecules. 2023 Jun 17. pii: 4829. [Epub ahead of print]28(12):

Comprehensive Metabolite Profiling of Chemlali Olive Tree Root Extracts Using LC-ESI-QTOF-MS/MS, Their Cytotoxicity, and Antiviral Assessment.

Karim Toumi, Łukasz Świątek, Anastazja Boguszewska, Krystyna Skalicka-Woźniak, Mohamed Bouaziz.

  The large quantity of olive roots resulting from a large number of old and unfruitful trees encouraged us to look for ways of adding value to these roots. For this reason, the current research work is devoted to the valorization of olive roots by identifying active phytochemicals and assessing their biological activities, including the cytotoxicity and antiviral potential of different extracts from the Olea europaea Chemlali cultivar. The extract, obtained by ultrasonic extraction, was analyzed using the liquid chromatography-mass spectrometry technique (LC-MS). The cytotoxicity was evaluated through the use of the microculture tetrazolium assay (MTT) against VERO cells. Subsequently, the antiviral activity was determined for HHV-1 (Human Herpesvirus type 1) and CVB3 (Coxsackievirus B3) replication in the infected VERO cells. LC-MS analysis allowed the identification of 40 compounds, classified as secoiridoids (53%), organic acids (13%), iridoids (10%), lignans (8%), caffeoylphenylethanoid (5%), phenylethanoids (5%),sugars and derivatives (2%), phenolic acids (2%), and flavonoids (2%). It was found that extracts were not toxic to the VERO cells. Moreover, the extracts did not influence the appearance of HHV-1 or CVB3 cytopathic effects in the infected VERO cells and failed to decrease the viral infectious titer.

Keywords:  LC-MS; biological activities; olive roots; phenolic compounds; ultrasonic extraction

DOI:  https://doi.org/10.3390/molecules28124829
Int J Mol Sci. 2023 Jun 06. pii: 9824. [Epub ahead of print]24(12):

Development of Phytochemical Delivery Systems by Nano-Suspension and Nano-Emulsion Techniques.

Guendalina Zuccari, Silvana Alfei.

  The awareness of the existence of plant bioactive compounds, namely, phytochemicals (PHYs), with health properties is progressively expanding. Therefore, their massive introduction in the normal diet and in food supplements and their use as natural therapeutics to treat several diseases are increasingly emphasized by several sectors. In particular, most PHYs possessing antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant properties have been isolated from plants. Additionally, their secondary modification with new functionalities to further improve their intrinsic beneficial effects has been extensively investigated. Unfortunately, although the idea of exploiting PHYs as therapeutics is amazing, its realization is far from simple, and the possibility of employing them as efficient clinically administrable drugs is almost utopic. Most PHYs are insoluble in water, and, especially when introduced orally, they hardly manage to pass through physiological barriers and scarcely reach the site of action in therapeutic concentrations. Their degradation by enzymatic and microbial digestion, as well as their rapid metabolism and excretion, strongly limits their in vivo activity. To overcome these drawbacks, several nanotechnological approaches have been used, and many nanosized PHY-loaded delivery systems have been developed. This paper, by reporting various case studies, reviews the foremost nanosuspension- and nanoemulsion-based techniques developed for formulating the most relevant PHYs into more bioavailable nanoparticles (NPs) that are suitable or promising for clinical application, mainly by oral administration. In addition, the acute and chronic toxic effects due to exposure to NPs reported so far, the possible nanotoxicity that could result from their massive employment, and ongoing actions to improve knowledge in this field are discussed. The state of the art concerning the actual clinical application of both PHYs and the nanotechnologically engineered PHYs is also reviewed.

Keywords:  acute and chronic nanotoxicity; bioactive constituents of plant; clinical applications; drug delivery systems (DDSs); nanoemulsion techniques; nanosuspension techniques; nanotechnology application; phytochemicals (PHYs); poor water solubility; toxicological risks of NPs

DOI:  https://doi.org/10.3390/ijms24129824
Molecules. 2023 Jun 08. pii: 4656. [Epub ahead of print]28(12):

Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies.

Shailesh D Dadge, Anees A Syed, Athar Husain, Guru R Valicherla, Jiaur R Gayen.

  Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, β-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 × 4.6 mm, 3 µ) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 > 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (-4 °C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ's bioanalysis and pharmacokinetic properties which is useful for future clinical trials.

Keywords:  Cissus quadrangularis; LC-MS/MS; pharmacokinetics; quercetin; trans-resveratrol; validation

DOI:  https://doi.org/10.3390/molecules28124656
Antioxid Redox Signal. 2023 Jun 29.

A systematic review and comprehensive evaluation of human intervention studies to unravel the bioavailability of hydroxycinnamic acids.

Giuseppe Di Pede, Pedro Mena, Letizia Bresciani, Mariem Achour, Rosa Mª Lamuela, Ramón Estruch, Rikard Landberg, Sabine E Kulling, David Wishart, Ana Rodriguez-Mateos, Michael N Clifford, Alan Crozier, Claudine Manach, Daniele Del Rio.

SIGNIFICANCE: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unravelling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports.
RECENT ADVANCES: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C6-C3 cinnamic acids. C6-C3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (Cmax=423 nmol/L), with Tmax values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4 and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11 %). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25 %).
CRITICAL ISSUES: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source and data from some plant based-foods were absent or inconsistent.
FUTURE DIRECTIONS: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma Cmax concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations.

DOI: https://doi.org/10.1089/ars.2023.0254
Phytochem Rev. 2023 Mar 12. 1-79

Specialized metabolites from plants as a source of new multi-target antiviral drugs: a systematic review.

Maria Ponticelli, Maria Laura Bellone, Valentina Parisi, Annamaria Iannuzzi, Alessandra Braca, Nunziatina de Tommasi, Daniela Russo, Annalisa Sileo, Paola Quaranta, Giulia Freer, Mauro Pistello, Luigi Milella.

  Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.

Keywords:  Antiviral activity; Antivirals mechanism of actions; In vivo studies; Natural compounds; Systematic review

DOI:  https://doi.org/10.1007/s11101-023-09855-2
Molecules. 2023 Jun 10. pii: 4684. [Epub ahead of print]28(12):

Effects of Different Cooking Methods on Phenol Content and Antioxidant Activity in Sprouted Peanut.

Liangchen Zhang, Haolin Qu, Mengxi Xie, Taiyuan Shi, Puxiang Shi, Miao Yu.

  Peanut sprout is a high-quality healthy food, which not only has beneficial effects, but also a higher phenol content than peanut seed. In this study, peanut sprout was treated with five cooking methods, namely boiling, steaming, microwave heating, roasting, and deep-frying, and the phenol content, monomeric phenol composition, and antioxidant activity were determined. The results showed that, compared with unripened peanut sprout, the total phenol content (TPC) and total flavonoid content (TFC) decreased significantly after the five ripening processes, and the highest retention of phenols and flavonoids was associated with microwave heating (82.05% for TPC; 85.35% for TFC). Compared with unripened peanut sprout, the monomeric phenol composition in germinated peanut was variable after heat processing. After microwave heating, except for a significant increase in the cinnamic acid content, no changes in the contents of resveratrol, ferulic acid, sinapic acid, and epicatechin were observed. Furthermore, there was a significant positive correlation of TPC and TFC with 2,2-diphenyl-1-picrylhydrazyl scavenging capacity, 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging capacity, and ferric ion reducing antioxidant power in germinated peanut, but not with hydroxyl free radical scavenging capacity, in which the main monomer phenolic compounds were resveratrol, catechin, and quercetin. The research results indicate that microwave heating can effectively retain the phenolic substances and antioxidant activity in germinated peanuts, making it a more suitable ripening and processing method for germinated peanuts.

Keywords:  antioxidant activity; cooking method; peanut sprout; phenolic compound

DOI:  https://doi.org/10.3390/molecules28124684