Polyphenols and respiratory health -
Nowadays, no effective therapeutic approaches have been licensed, despite the rising interest of the scientific research in this specific field, and the daily growing number of publications, while the need to find novel strategies is urgent. Evidence in the literature reported the antiviral activity of polyphenols, the largest class of bioactive compounds in nature.
Interestingly, a limited number of studies investigated the efficacy of polyphenols from different raw materials, directly against coronaviruses. The present manuscript aimed to report this evidence and provide a viewpoint on the possibility to use it as a start point for the development of novel natural approaches against this viral infection, eventually designing further appropriate researches.
The coronavirus SARS-CoV2 pandemic, reported for the first time in Wuhan China , in December 1 , is rapidly growing with marked morbidity and mortality, resulting in a dramatic socio-economic impact. The diagnosis of SARS-CoV2 infection is based on qualitative Real-time reverse transcriptase-polymerase chain reaction rRT-PCR analysis on a nasopharyngeal swab.
However, the presence of this virus has been also demonstrated in further tissues, including sputum, feces, bronchoalveolar fluids, and blood, with different viral kinetics 1 — 3.
In several countries, subjects tested positive are receiving off-label and compassionate therapies, including chloroquine, hydroxychloroquine, azithromycin, lopinavir-ritonavir, favipiravir, remdesivir, ribavirin, interferon, convalescent plasma, steroids, and anti—IL-6 inhibitors 4 — 8.
The need to find a strategy that is both effective and safe to face this emergency is urgent. Polyphenols are the largest class of bioactive compounds present in plants, where are produced as secondary metabolites with protective functions against ultraviolet radiations, pathogen aggression, and oxidative stress protection.
Structurally, the term polyphenol refers to the presence of one or more phenolic rings with hydroxyl groups. On that bases, polyphenols can be classified into flavonoid including anthocyanins, flavones, flavanones, flavonols, isoflavones, and flavanols , phenolic acids, polyphenolic amides, and other polyphenol compounds including stilbenes or lignans 9.
Besides the well-known antioxidant and anti-inflammatory activities of polyphenols, evidence highlighted the antiviral potential exerted by this class of bioactive compounds. In particular, a large number of studies demonstrated the efficacy of polyphenols against several pathogens, including Epstein-Barr virus 10 , 11 , enterovirus 71 12 , herpes simplex virus HSV 13 , 14 , influenza virus 15 , and other virus causing respiratory tract-related infections 16 — In this context, a great interest has been focused on resveratrol RSV , whose antiviral mechanisms of actions are mainly attributable to its ability to inhibit the viral replication via i inhibition of immediate-early virus protein expression i.
The present mini-review aimed to report the few promising evidence regarding the potential anti-coronavirus activity of polyphenols, which may serve to drive the research toward the development of novel strategies to counteract the SARS-CoV2 pandemic.
Besides the general mechanisms of action described against various viruses, a limited number of studies investigated the effects of polyphenols directly against coronaviruses. These are in vitro studies conducted on different experimental models of infection, using microorganisms belonging to the coronavirus family Table 1.
Table 1. In vitro studies investigating the effects of polyphenols against coronavirus. In , Lin et al. The antiviral activity of RSV was evaluated on Vero E6 cells infected with Middle East Respiratory Syndrome coronavirus MERS-CoV and treated with RSV at concentrations ranging from to 7.
It was demonstrated that RSV i reduced the cell death caused by MERS-CoV at concentrations ranging from to μM, ii inhibited the viral RNA replication at concentrations ranging from to Thus, this study evidenced the ability of RSV to counteract MERS-CoV infection acting on the main putative mechanisms of action.
In addition to MERS-CoV, further studies investigated the antiviral potential of polyphenols against infectious bronchitis virus IBV , another microorganism belonging to the coronavirus family. In particular, the anti-IBV activity of Forsythoside A FTA Figure 2 , a phenylethanoid glycoside with chemical formula C 29 H 36 O 15 isolated from Forsythia suspense , was evaluated on chicken embryo kidney CEK cells.
Cells both prior to and after virus infection were treated with FTA 0. It was observed that FTA i induced a dose-dependent decrease in viral load, ii reduced the gene expression of IBV nucleocapsid proteins, and iii dose-dependently inhibited the IBV infection, but had no effect on infected cells 19 , suggesting the potential of this bioactive compound as an antiviral agent against IBV.
Similarly, the same virus was used to infect Vero cells and the anti-IBV activity of the polyphenols of Sambucus nigra was tested. In particular, a crude polyphenolic extract 0. The pre-treatment with the S.
nigra polyphenolic extract resulted in the i inhibition of the viral replication, ii dose-dependent reduction of the virus titers by four to six orders of magnitude at 1. Although the results regarding the anti-IBV potential of S. nigra polyphenols are promising, the authors did not characterize the crude extract, thus, the main actors responsible for the antiviral activity cannot be identified.
However, previous studies described the phytochemicals contained in S. Interestingly, it was also reported that some of these S. nigra -derived polyphenols exhibited antivirus activities 27 , In this sense, it can be speculated that the antiviral activity is exerted by the phytocomplex including a large number of polyphenolic compounds that, in turn, are eventually responsible for a synergistic effect.
Figure 1. Resveratrol C 14 H 12 O 3. A Trans -resveratrol; B cis- resveratrol. Besides the investigations on the aforementioned cell lines, two mechanistic studies have been performed to elucidate the specific targets of polyphenols in their anti-coronavirus activity.
Particularly, it was tested the anti-MERS- and SARS-CoV activity of ten different polyphenols isolated from Brussonetia papyrifera , whose chemical structures are reported in Figure 3. On the other hand, a large number of polyphenolic compounds were tested in a quantum dots-conjugated oligonucleotide system for the inhibitor screening of SARS-CoV nucleocapsid proteins.
More specifically, the following compounds were studied: quercetin, acacetin, apigenin, baicalein, hesperidin, morin, rutin, naringin, naringenin, — -catechin, — -catechin gallate, — -gallocatechin gallate, diosmin, daidzein, genistein, glycitein, kaempferol, luteolin, myricetin, silibinin, silymarin, orientin, oroxylin A.
Among these, — -catechin gallate and — -gallocatechin gallate Figure 4 exhibited a marked anti-SARS-CoV nucleocapsid protein activity. Moreover, they allow to limit the large variety of polyphenolic compounds, leading to identification of such polyphenols for the development of novel natural approaches against coronavirus infection.
Figure 3. Polyphenols isolated from Brussonetia papyrifera. A Broussochalcone B C 20 H 20 O 4 ; B broussochalcone A C 20 H 20 O 5 ; C kazinol A C 25 H 30 O 4 ; D 3'- 3-methylbutenyl -3',4,7-trihydroxyflavone C 20 H 22 O 4 ; E papyriflavonol A C 25 H 26 O 7 ; F 4-hydroxyisolonchocarpin C 20 H 20 O 4 ; G kazinol B C 25 H 28 O 4 ; H broussoflavan A C 25 H 30 O 6 ; I kazinol F C 25 H 32 O 4 ; J kazinol J C 26 H 34 O 4.
Figure 4. A - -catechin gallate C 22 H 18 O 10 ; B - -gallocatechin C 22 H 18 O Although these studies are appealing and well-conducted, and provide promising results, their careful analysis leads to individuate the following limitations. Firstly, evidence from the anti-coronavirus activity of polyphenols is only provided by in vitro studies, although animal-based studies reported the efficacy of polyphenols on other kinds of viruses.
No clinical evidence, nor, at least, animal-based studies, are available. However, this lack might be due to the difficulty of designing appropriate studies on animals infected with this kind of virus, due to its dangerousness.
Similarly, the need to eventually test natural compounds in humans have not emerged until now, since no many cases were registered. Another limitation is due to the fact that polyphenols are a very large class of bioactive compounds, in which further subclasses can be identified.
Although promising, these studies do not provide evidence to establish which subclass of polyphenols deserves to be further investigated.
Moreover, taking into account the in vitro nature of these studies, no information is provided by authors concerning a possible dose in humans, necessary to design clinical trials.
Overall, this evidence suggests that polyphenols may exert a marked and well-demonstrated activity against coronaviruses, at least in vitro , in addition to the previously demonstrated antiviral activity in vivo.
Studies available in the literature agree in establishing that the reduction of virus titer and the inhibition of nucleocapsid protein expression are their main general mechanisms of action at the base of this promising effect of polyphenols.
These elucidated mechanisms are of great interest, since nowadays no effective treatments have been licensed, and the development of novel synthetic drugs against specific coronavirus molecular targets are still far from being achieved. Despite the aforementioned limitations, these studies should be taken into consideration to design clinical trials.
In this sense, the main strength concerning the use of polyphenols in this global emergency is related to the well-established absence of both side effects and drug interactions of such polyphenols with concomitant pharmacological treatments.
Indeed, it is well-known that coronavirus-infected subjects are highly prone to develop such respiratory diseases, sometimes complicated by the co-existence of previous cardio-metabolic or chronic diseases.
This articulated pathological scenario drastically limits the use of such therapeutic schemes. As an example, the French non-randomized clinical trial showed encouraging results on the efficacy of the combination hydroxychloroquine and azithromycin against COVID19 6 , although both drugs are potentially associated with QT-prolongation 29 , Another relevant point that should be taken into account, is the proper formulation of polyphenol-based nutraceuticals that may be efficient for this scope.
Undoubtedly, according to the available studies, potential anti-COVID nutraceutical approaches should contain polyphenols whose effects against coronaviruses have been demonstrated. However, the evaluation of potential synergistic effects between different polyphenols is intriguing.
Despite the different structure, indeed, polyphenols share the same chemical features, including the presence of phenolic rings with hydroxyl groups 9. Thus, it could be hypothesized that, although not directly investigated, different classes of polyphenols might exert, at least in part, similar antiviral activities, but eventually with different mechanisms of action.
In this sense, according to the studies of Rho 20 and Lin et al. With this rationale, it should be stressed the importance to investigate the effect of natural polyphenolic extract, rather than the single purified molecules.
Interestingly, various plant- or food-derived extracts have been found to be polyphenol-rich matrices for formulation of nutraceutical supplements.
Among these, grape pomace extract GPE has been reported as an excellent source of bioactive compounds, mainly polyphenols, including RSV, cathechins, and proanthocyanidins 31 — Notably, evidence indicated the antiviral activity of GPE against various microorganisms, including human immunodeficiency virus type 1 34 , human enteric virus, human norovirus surrogates [feline calicivirus FCV F9 and murine norovirus MNV ] 35 , hepatitis A virus 36 , and hepatitis C virus HCV Different mechanisms of actions have been demonstrated, including down-regulation of the HIV-1 entry co-receptor expression for the activity against HIV 34 , suppression of virus replication via reduction of COX2 expression and regulation of NFκB and MAPK signaling pathways and reduction of virus-induced inflammation for the anti-HCV activity Interestingly, two in vitro studies investigated the effects of GPE against respiratory syncytial virus, using an airway epithelial A cell model 38 , In particular, it was demonstrated that GPE interfered with nucleoprotein and fusion protein expression, reducing virus replication.
In this sense, the anti-inflammatory potential of polyphenols, mainly exerted via reduction of the interleukin levels, appears noteworthy, and investigating this effect in the context of a virus-induced inflammatory status is intriguing.
Overall, this evidence may support the use of polyphenolic extracts, including GPE, for the formulation of potential nutraceutical supplements aimed to counteract the COVID infection.
This potential activity might be considered in addition to the well-established antioxidant and anti-inflammatory effects of polyphenols, which may contribute to the general management of respiratory complications of coronavirus infection.
Considering this background, the ideal way to test the antiviral polyphenol effect in humans would be a controlled randomized clinical trial with measurable, reproducible, and clinically relevant outcomes. Most of the current trials are set on the compassionate use of the studied treatment or based on single-arm intervention.
Thus, definitive conclusion related to efficacy or safety is hardly deducible. On balance, controlled randomized clinical trials with meaningful clinical outcomes are mandatory to best assess the therapeutic effects and the clinical impact of polyphenol treatment on COVID All the authors contributed to conceptualization, evaluation of the literature and draft-writing.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Xu Y, Li X, Zhu B, Liang H, Fang C, Gong Y, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. doi: PubMed Abstract CrossRef Full Text Google Scholar.
Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid Gov Adaptive COVID Treatment Trial. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID results of an open-label non-randomized clinical trial.
Int J Antimicrob Agents. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically Ill patients with COVID with convalescent plasma.
CrossRef Full Text Google Scholar. The naturally-derived compound belongs to the family of polyphenols, which are found abundantly in natural plant food sources.
Polyphenols are known to have antioxidant properties, consequently preventing cell damage. Additionally, because polyphenols are found in food, isorhapontigenin can be easily absorbed when taken orally, adding to its profile for becoming a potential candidate for the treatment of COPD.
Lin Haishu, from the Department of Pharmacy at NUS in Singapore, said in a press release. Haishu and his PhD student Yeo Chao Ming Samuel used a broad range of techniques to investigate the medicinal properties of isorhapontigenin and other natural compounds.
One polyphenol that has shown anti-inflammatory activity is resveratrol , a molecule often found in red wine and grapes. Researchers at Georgia State University studied the effects of resveratrol against inflammation caused by nontypeable Haemophilus influenzae NTHi , a common pathogen colonizing the respiratory tract of COPD and asthma patients.
The team found that resveratrol significantly decreased NTHi-induced inflammation in both airway epithelial cells and in the lungs of mice by increasing the activity of MyD88 short, a key factor halting inflammation.
Isorhapontigenin, on the other hand, was identified as a promising candidate with the characteristics necessary to be a successful therapeutic agent for COPD treatment.
Moving ahead, the team plans to further evaluate the therapeutic potential of isorhapontigenin in animal studies. News Researchers Identify Grape Polyphenol that May Suppress COPD Lung Inflammation Researchers Identify Grape Polyphenol that May Suppress COPD Lung Inflammation by Patrícia Silva, PhD October 17, Share this article: Share article via email Copy article link.
This narrative Antioxidant supplements for healthy aging review summarizes current knowledge Heqlth the Polyphenols and respiratory health of polyphenols in respidatory outcomes—and respiraatory diseases specifically—and discusses the implications of this evidence Polyphenols and respiratory health public Hypertension and relaxation exercises, and for future directions for public health practice, Polyphrnols, and reespiratory. The publications respirtory originate mainly from animal models and feeding experiments, Polypheno,s well as human cohort and case-control studies. Hypothesized protective effects of polyphenols in acute and chronic diseases, including obesity, neurodegenerative diseases, type 2 diabetes, and cardiovascular diseases, are evaluated. Potential harmful effects of some polyphenols are also considered, counterbalanced with the limited evidence of harm in the research literature. Recent international governmental regulations are discussed, as the safety and health claims of only a few specific polyphenolic compounds have been officially sanctioned. The implications of food processing on the bioavailability of polyphenols are also assessed, in addition to the health claims and marketing of polyphenols as a functional food. Polyphenols are a large family of more Polyphenols and respiratory health 10, Hypertension and relaxation exercises occurring compounds, which exert countless pharmacological, Hypertension and relaxation exercises and physiological benefits Nutritional Nut Facts Hypertension and relaxation exercises health including several chronic diseases respjratory as Caffeine energy boost pills, Polyphenols and respiratory health, cardiovascular, respiratlry neurological diseases. Their role in traditional medicine, such as the use Polyphemols a wide range of remedial herbs thyme, PPolyphenols, rosemary, sage, Polyohenols, basil African mango extract and digestive health, has been well ane Polyphenols and respiratory health known for treating respirtory respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID through the enhancement of host immune response against viral infections by different biological mechanisms. Since the first unveiling of the novel coronavirus COVID in the city of Wuhan, Hubei province, China in late Decemberexceptional and unprecedented dares presented by the rapidly rising of COVID pandemic health crisis are confronting people worldwide. COVID, a single-stranded RNA virus is actually complicated by severe acute respiratory syndrome coronavirus 2 SARS-CoV-2a newly identified virus alike SARS-CoV and MERS-CoV-2 that cause the severe acute respiratory syndrome and Middle East respiratory syndrome respectively [ 1 ].
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