bims-antpol Biomed News
on Antiviral properties of polyphenols
Issue of 2023–08–27
six papers selected by
Rick Sheridan, EMSKE Phytochem



  1. Front Nutr. 2023 ;10 1241016
       Objectives: Devastating consequences of COVID-19 disease enhanced the role of promoting prevention-focused practices. Among targeted efforts, diet is regarded as one of the potential factors which can affect immune function and optimal nutrition is postulated as the method of augmentation of people's viral resistance. As epidemiological evidence is scarce, the present study aimed to explore the association between dietary intake of total polyphenols, lignans and plant sterols and the abundance of immunomodulatory gut microbiota such as Enterococcus spp. and Escherichia coli and the risk of developing COVID-19 disease.
    Methods: Demographic data, dietary habits, physical activity as well as the composition of body and gut microbiota were analyzed in a sample of 95 young healthy individuals. Dietary polyphenol, lignan and plant sterol intakes have been retrieved based on the amount of food consumed by the participants, the phytochemical content was assessed in laboratory analysis and using available databases.
    Results: For all investigated polyphenols and phytosterols, except campesterol, every unit increase in the tertile of intake category was associated with a decrease in the odds of contracting COVID-19. The risk reduction ranged from several dozen percent to 70 %, depending on the individual plant-based chemical, and after controlling for basic covariates it was statistically significant for secoisolariciresinol (OR = 0.28, 95% CI: 0.11-0.61), total phytosterols (OR = 0.47, 95% CI: 0.22-0.95) and for stigmasterols (OR = 0.34, 95% CI: 0.14-0.72). We found an inverse association between increased β-sitosterol intake and phytosterols in total and the occurrence of Escherichia coli in stool samples outside reference values, with 72% (OR = 0.28, 95% CI: 0.08-0.86) and 66% (OR = 0.34, 95% CI: 0.10-1.08) reduced odds of abnormal level of bacteria for the highest compared with the lowest tertile of phytochemical consumption. Additionally, there was a trend of more frequent presence of Enterococcus spp. at relevant level in people with a higher intake of lariciresinol.
    Conclusion: The beneficial effects of polyphenols and phytosterols should be emphasized and these plant-based compounds should be regarded in the context of their utility as antiviral agents preventing influenza-type infections.
    Keywords:  SARS-CoV-2; gut microbiota; lignans; nutrition; phytochemicals; plant-sterols; polyphenols
    DOI:  https://doi.org/10.3389/fnut.2023.1241016
  2. Molecules. 2023 Aug 10. pii: 6001. [Epub ahead of print]28(16):
      According to traditional Chinese medicine, Scutellaria baicalensis Georgi possesses the therapeutic properties of heat-clearing, dampness-drying, diarrhea alleviation, and detoxification, making it a clinically used remedy for respiratory infections. The objective of this study was to investigate the changes in constituent content, pharmacodynamic effects, and material basis of Scutellaria baicalensis Georgi in the plasma of mice infected with respiratory syncytial virus (RSV). The results showed that a sensitive and efficient high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was established in this study. Multiple quantitative analyses of Baicalein, Apigenin-7-glucuronide, Baicalin, Oroxylin A 7-O-beta-d-glucuronide, Wogonoside, Norwogonin, Wogonin, Chrysin, and Oroxylin A in mouse plasma revealed a bimodal absorption phenomenon within the time frame of 0.167 h to 6 h post-administration, with the exception of chrysin. Following 6 h of administration, the concentrations of 9 components continued to decrease until they became undetectable. In comparison to the model group, all administered groups exhibited significant reductions in lung index and viral load, with their lung index repair rate and viral suppression rate aligning with the blood concentration-time curve. Finally, through the application of the gray correlation analysis method, we identified Baicalein, Baicalin, Oroxylin A 7-O-beta-d-glucuronide, Wogonoside, Norwogonin, and Wogonin as potential pharmacodynamic material bases of Scutellaria baicalensis Georgi against RSV infection.
    Keywords:  HPLC-MS/MS; RSV; Scutellaria baicalensis Georgi; pharmacodynamic effect; pharmacodynamic material basis
    DOI:  https://doi.org/10.3390/molecules28166001
  3. Eur J Pharmacol. 2023 Aug 21. pii: S0014-2999(23)00518-6. [Epub ahead of print]957 176006
      Macrophages are the mature form of monocytes that have high plasticity and can shift from one phenotype to another by the process of macrophage polarization. Macrophage has several vital pharmacological tasks like eliminating microorganism invasion, clearing dead cells, causing inflammation, repairing damaged tissues, etc. The function of macrophages is based on their phenotype. M1 macrophages are mostly responsible for the body's immune responses and M2 macrophages have healing properties. Inappropriate activation of any one of the phenotypes often leads to ROS-induced tissue damage and affects wound healing and angiogenesis. Therefore, maintaining tissue macrophage homeostasis is necessary. Studies are being done to find techniques for macrophage polarization. But, the process of macrophage polarization is very complex as it involves multiple signalling pathways involving innate immunity. Thus, identifying the right pathways for macrophage polarization is essential to apply the polarizing technique for the treatment of various inflammatory diseases where macrophage physiology influences the disease pathology. In this review, we highlighted the various techniques so far used to change macrophage plasticity. We believe that soon macrophage targeting therapeutics will hit the market for the management of inflammatory disease. Hence this review will help macrophage researchers choose suitable methods and materials/agents to polarize macrophages artificially in various disease models.
    Keywords:  Drug delivery; Inflammation; Macrophage; Plasticity; Polarization
    DOI:  https://doi.org/10.1016/j.ejphar.2023.176006
  4. Pharmaceuticals (Basel). 2023 Aug 12. pii: 1147. [Epub ahead of print]16(8):
      Currently, there is no cure for human immunodeficiency virus type 1 (HIV-1) infection. However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles, and are released from cells as a form of intercellular communication. This study investigates the impact of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308, on the EVs released from HIV-1-infected myeloid cells as well as HIV-1-infected 3D neurospheres. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1β and TNF-α mRNA. This decrease in viral RNA occurs in in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, and infected neurospheres. Furthermore, a 3D neurosphere model shows an overall decrease in proinflammatory mRNA with HU308. Finally, using a humanized mouse model of HIV-1 infection, plasma viral RNA was shown to significantly decrease with HU308 alone and was most effective in combination with cART, even when compared to the typical cART treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART.
    Keywords:  CBD; EVs; HAND; HIV-1; HU-308; HU308; cannabidiol; extracellular vesicles; human immunodeficiency virus type 1
    DOI:  https://doi.org/10.3390/ph16081147
  5. Antioxidants (Basel). 2023 Jul 28. pii: 1509. [Epub ahead of print]12(8):
      Olive tree by-products have been deeply studied as an invaluable source of bioactive compounds. Several in vitro and in vivo studies showed that olive leaf extract (OLE) has anti-inflammatory and antioxidant properties. Here, we wanted to assess the valuable benefits of two less-studied OLE components-3,4-DHPEA-EDA (Oleacin, OC) and 3,4-DHPEA-EA (Oleuropein-Aglycone, OA)-directly purified from OLE using a cost-effective and environmentally sustainable method, in line with the principles of circular economy. OLE, OC and OA were then tested in human cellular models involved in acute and chronic inflammation and in the pathogenesis of viral infections, i.e., lipopolysaccharide (LPS)-treated monocyte/macrophages (THP-1) and endothelial cells (HUVECs), senescent HUVECs and Poly(I:C)-treated small airway epithelial cells (hSAECs). Results showed that OC and OA are efficient in ameliorating almost all of the pro-inflammatory readouts (IL-1β, TNF-α, IL-8, ICAM, VCAM) and reducing the release of IL-6 in all the cellular models. In hSAECs, they also modulate the expression of SOD2, NF-kB and also ACE2 and TMPRSS2, whose expression is required for SARS-CoV-2 virus entry. Overall, these data suggest the usefulness of OLE, OC and OA in controlling or preventing inflammatory responses, in particular those associated with viral respiratory infections and aging.
    Keywords:  anti-inflammatory; antioxidant; oleacin; oleuropein-aglycone; olive leaf extract; respiratory infections; senescence
    DOI:  https://doi.org/10.3390/antiox12081509
  6. Gels. 2023 Aug 18. pii: 671. [Epub ahead of print]9(8):
      Flavonoids are hydroxylated phenolic substances in vegetables, fruits, flowers, seeds, wine, tea, nuts, propolis, and honey. They belong to a versatile category of natural polyphenolic compounds. Their biological function depends on various factors such as their chemical structure, degree of hydroxylation, degree of polymerization conjugation, and substitutions. Flavonoids have gained considerable attention among researchers, as they show a wide range of pharmacological activities, including coronary heart disease prevention, antioxidative, hepatoprotective, anti-inflammatory, free-radical scavenging, anticancer, and anti-atherosclerotic activities. Plants synthesize flavonoid compounds in response to pathogen attacks, and these compounds exhibit potent antimicrobial (antibacterial, antifungal, and antiviral) activity against a wide range of pathogenic microorganisms. However, certain antibacterial flavonoids have the ability to selectively target the cell wall of bacteria and inhibit virulence factors, including biofilm formation. Moreover, some flavonoids are known to reverse antibiotic resistance and enhance the efficacy of existing antibiotic drugs. However, due to their poor solubility in water, flavonoids have limited oral bioavailability. They are quickly metabolized in the gastrointestinal region, which limits their ability to prevent and treat various disorders. The integration of flavonoids into nanomedicine constitutes a viable strategy for achieving efficient cutaneous delivery owing to their favorable encapsulation capacity and diminished toxicity. The utilization of nanoparticles or nanoformulations facilitates drug delivery by targeting the drug to the specific site of action and exhibits excellent physicochemical stability.
    Keywords:  drug delivery systems; encapsulation; flavonoids; hydrogels; nanogel; nanomedicine; topical infection
    DOI:  https://doi.org/10.3390/gels9080671