Anti-influenza virus activity of synthetically polymerized phenylpropenoids

doi:10.1016/0006-291X(90)91586-H

Biochemical and Biophysical Research Communications

Volume 172, Issue 3, 15 November 1990, Pages 1267-1272

https://doi.org/10.1016/0006-291X(90)91586-H Get rights and content

Abstract

Various dehydrogenation polymers (the so-called synthetic lignins) were synthesized from four different phenylpropenoids by endwise and bulk polymerizations and investigated for their anti-influenza virus activity. All of these materials suppressed the plaque formation of influenza virus infecting MDCK cells and the RNA-dependent RNA synthesis as effectively as the high molecular weight lignin-related extract (Fr. VI) of pine cone of $Pinus$ $parviflora$ Sieb. et Zucc. The structural simplicity and higher solubility of the synthesized polymers suggest that they might be regarded as potential candidates for medicinal antiviral resources.

References (19)

T.K. Kirk et al.
Method Enzymol
(1988)
H. Suzuki et al.
Biochem. Biophys. Res. Commun
(1989)
H. Sakagami et al.
Anticancer Res
(1989)
K. Nagata et al.
Antiviral Res
(1990)
L.E. Wise et al.
Papr. Trade J
(1946)
Sakagami, H., Oh-hara, T., Kohda, K., and Kawazoe, Y....
K.V. Sarkanen et al.
Lignins
H. Sakagami et al.
Anticancer Res
(1987)
K. Kawakami et al.
J. Biochem
(1981)

There are more references available in the full text version of this article.

Cited by (17)

High value valorization of lignin as environmental benign antimicrobial
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Citation Excerpt :
Also, the anti-HIV activity of synthetic lignin could be noticeably altered by the synthetic methods, reaction parameter, and post treatments [197]. Similarly, Sakagami et al. [198] reported impact of synthetic methods on the anti-influenza activity of DHP, while Harada et al. [202] reported that the anti-influenza activity of both pine cone extract and commercial alkaline lignin was reduced by treatment with sodium chlorite, but not with sulfuric acid nor trifluoroacetic acid. Li et al. [183] reported that antiviral effects of the lignin carbohydrate complex extracted from beech wood by microwave acidolysis were significantly decreased by treatment with hemicellulose hydrolysis.
Lignin is a natural aromatic polymer of p-hydroxyphenylpropanoids with various biological activities. Noticeably, plants have made use of lignin as biocides to defend themselves from pathogen microbial invasions. Thus, the use of isolated lignin as environmentally benign antimicrobial is believed to be a promising high value approach for lignin valorization. On the other hand, as green and sustainable product of plant photosynthesis, lignin should be beneficial to reduce the carbon footprint of antimicrobial industry. There have been many reports that make use of lignin to prepare antimicrobials for different applications. However, lignin is highly heterogeneous polymers different in their monomers, linkages, molecular weight, and functional groups. The structure and property relationship, and the mechanism of action of lignin as antimicrobial remains ambiguous. To show light on these issues, we reviewed the publications on lignin chemistry, antimicrobial activity of lignin models and isolated lignin and associated mechanism of actions, approaches in synthesis of lignin with improved antimicrobial activity, and the applications of lignin as antimicrobial in different fields. Hopefully, this review will help and inspire researchers in the preparation of lignin antimicrobial for their applications.
Therapeutic potential of solubilized nanolignin against oral diseases
2017, Nanostructures for Oral Medicine
Lignocellulosic biomass is a complex biopolymer that is primarily composed of cellulose, hemicellulose, and lignin. Lignin, the main natural aromatic polymer, has a very complex and complicated structure that depends on the separation method and plant species. Their molecular weights fluctuate largely from monolignols to nanofibers, depending on pH, extraction conditions (pH, temperature, Fe²⁺/³⁺) and shearing process. Limited digestion of LCC demonstrated the importance of lignin moiety, but not carbohydrate moiety for antihuman-immunodeficiency virus (HIV) activity induction. Dehydrogenation polymers of p-coumaric acid, felluric acid, or caffeic acid showed much higher anti-HIV activity than their respective monomers, suggesting the importance of highly polymerized structures. [¹²⁵I]-labeled LCC rapidly bound to the virus and reduced its infectivity. Bioavailability of orally administered [¹²⁵I]-LCC was very low, validating its application through oral mucosa. Alkaline extraction was superior to hot water extraction in recovering anti-HIV activity from green tea, black tea, and oolong tea-leaves and licorice root. Oral intake of alkaline extract of Sasa senanensis Rehder leaf (SE) (OTC drug) and LCC/vitamin C tablet significantly improved the symptoms of lichenoid dysplasia and herpes simplex virus (HSV)-patients, respectively. Use of SE-enriched tooth-paste significantly reduced halitosis. These data suggest the applicability of solubilized nanolignin against various oral diseases.
Species difference in reactivity to lignin-like enzymatically polymerized polyphenols on interferon-γ synthesis and involvement of interleukin-2 production in mice
2016, International Immunopharmacology
Citation Excerpt :
To date, several research groups have focused on lignin function. Initially, the anti-viral activities of lignin were well studied [25–27], and more recently, the unique function of lignin-carbohydrate in promoting the expression of immune receptors such as TLR2 and dectin-2 has been reported [28]. There have also been reports to suggest that modulation of the innate immune function by lignin-carbohydrate is mainly mediated by the carbohydrate moiety [29,30].
Recent studies have revealed that lignin-like polymerized polyphenols can activate innate immune systems. In this study, we aimed to evaluate whether these polymerized polyphenols could activate leukocytes from different murine strains. Splenocytes from 12 mouse strains were investigated. Our results revealed species differences in reactivity to phenolic polymers on interferon-γ (IFN-γ) release. Mice that possessed the H2^a or H2^k haplotype antigens were the highly responsive strains. To clarify these different points in soluble factors, multiplex cytokine profiling analysis was carried out and we identified interleukin (IL)-2 as a key molecule for IFN-γ induction by polymerized polyphenols. Furthermore, inhibition of IL-2 and IL-2Rα by neutralizing antibodies significantly decreased cytokine production in the highly responsive mice strains. Our results indicate that species difference in reactivity to phenolic polymers is mediated by adequate release of IL-2 and its receptor, IL-2Rα.
Biological activities and possible dental application of three major groups of polyphenols
2014, Journal of Pharmacological Sciences
The present article reviewed the biological activities and possible dental application of three major polyphenols, i.e., lignin-carbohydrate complexes, tannins, and flavonoids, citing mostly our in vitro studies together with those from other groups. All these polyphenols showed much lower tumor-selective cytotoxicity against oral squamous cell carcinoma cells vs. normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), in comparison to popular chemotherapeutic antitumor drugs. Several compounds showing higher tumor-selectivity did not induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in oral carcinoma cell lines. Lignin-carbohydrate complex protected the cells from the cytopathic effects of HIV infection and UV irradiation more efficiently than other polyphenols. Limited digestion of lignin-carbohydrate complex suggests that the lignin moiety is involved in the prominent anti-HIV activity, whereas the carbohydrate moiety may function in immunopotentiating activity through a cell surface receptor. Alkaline extract of plant leaf, which contains higher amounts of lignin-carbohydrate complex, showed potent anti-inflammatory action against IL-1β-stimulated human gingival fibroblasts. Local application of lignin-carbohydrate complex through oral mucosa is recommended, considering its poor intestinal absorption.
Distribution of lignin-carbohydrate complex in plant kingdom and its functionality as alternative medicine
2010, Pharmacology and Therapeutics
Lignin–carbohydrate complexes (LCCs) are major cell wall components formed by the dehydrogenation of three monolignols, p-coumaryl, coniferyl and sinapyl alcohols. Diverse pharmacological activities of LCCs distributed into various plants were summarized. LCCs showed one order higher anti-HIV activity than tannins and flavonoids. Mechanism of anti-HIV activity induction includes the inhibition of HIV adsorption to and penetration into the cells, and inhibition of reverse transcriptase and protease. Limited digestion experiments demonstrated that a phenylpropenoid polymer, but not a sugar moiety, is important for anti-HIV activity. Dehydrogenation polymers of phenylpropenoids without carbohydrate showed higher anti-HIV activity, whereas phenylpropenoid monomers were inactive, suggesting the importance of highly polymerized structure. LCCs inhibited the plaque formation and RNA polymerase activity of influenza virus, and reduced the lethality of virus infection in mice. LCCs inhibited the plaque formation of HSV-1, and oral intake of LCC-vitamin C tablet reduced the symptoms in HSV-1-infected patients. LCCs stimulated the iodination of myeloperoxidase-positive human monocytes, neutrophiles and promyelocytic leukemia that may be involved in the bacterial killing mechanism. LCCs stimulated splenocyte proliferation, and showed both pro- and anti-inflammatory activity in activated macrophage. Preliminary DNA array analysis demonstrated the activation of the signal pathway of chemokine expression via TLR2. The molecular weight, solubility, sterilization method and association with other components during extraction step may produce diverse biological activity of LCCs. Broad and potent anti-viral activity and synergism with vitamin C suggest functionality of LCC as alternative medicine.
Molecular requirements of lignin-carbohydrate complexes for expression of unique biological activities
2005, Phytochemistry
Lignins are major cell wall components formed by the dehydrogenative polymerization of three monolignols, p-coumaryl, coniferyl and sinapyl alcohols. We prepared lignin–carbohydrate complexes (Fr. VI and Fr. VII) from pine cones by acid and ethanol precipitation, and investigated which part of these molecules is essential for expression of biological activities. They showed potent antiviral activity upon direct interaction with the virus. The antiviral activity of Frs. VI and VII required the higher-order structure of polyphenols without polysaccharides. Pretreatment of mice with Fr. VI or VII induced higher antiparasite activity than those of natural and chemically modified antitumor polysaccharides. Fr. VI or VII at higher concentrations enhanced the radical intensity and cytotoxic activity of vitamin C, whereas tannins counteracted the effect of vitamin C. Fr. VI at lower concentrations enhanced the $O_{2}^{-}$ -scavenging activity of vitamin C. Frs. VI and VII stimulated mouse macrophage-like cells Raw 264.7 to produce nitric oxide (NO), citrulline (CIT) and asparagine (ASN), via the enhanced expression of iNOS and ASN synthetase, whereas phenylpropenoid monomers and polymers inhibited NO/CIT/ASN production. These data suggest that the polymerized structure of phenylpropenoids in lignin–carbohydrate complexes is required for the induction of antiviral activity, and that the higher-order structure of phenylpropenoid polymers and polysaccharides is required for immunopotentiation, including macrophage activation.

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Anti-influenza virus activity of synthetically polymerized phenylpropenoids

Abstract

Method Enzymol

Biochem. Biophys. Res. Commun

Anticancer Res

Antiviral Res

Papr. Trade J

Lignins

Anticancer Res

J. Biochem