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Protective effect of curcumin against herpes simplex virus and inflammation associated with this infection. HSV-2, herpes simplex virus 2; NF-κB, nuclear factor kappa B.
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Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechan...
Citations
... The Epstein-Barr Virus (EBV), a member of the herpesvirus family, is a pervasive human pathogen that infects the majority of the world's population [1,2]. It is classified as a tumor gamma-herpesvirus (human herpesvirus 4) and is transmitted through saliva, causing infectious mononucleosis, colloquially known as the "kissing disease" [3,4]. EBV establishes a lifelong latent infection in B cells (B lymphocytes), with the potential for reactivation during periods of stress or immunosuppression [5,6]. ...
The Epstein–Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors.
... It has been described that curcumin has a broad spectrum of antiviral activity against many viruses [23][24][25][26][27][28][29]. In particular, for HBV infection, using the experimental model of HepG2.215 ...
In recent decades, considerable advances have been achieved in the treatment of chronic hepatitis B. However, the currently available drugs have shortcomings. In this context, several natural compounds have been proposed as potential agents to improve either the outcome of antiviral treatment or the progression of chronic infection, with curcumin being one of the most evaluated compounds due to its pleiotropic antiviral activity. The aim of this study was to characterize the effect and mechanism of curcumin on hepatitis B virus (HBV) replication in two different experimental models. Treatment of HepG22.15 and HBV-transfected Huh7 cells with curcumin revealed that the phytochemical differentially modulated HBV replication in both cell lines. In HepG22.15 cells, the addition of curcumin had no effect on viral DNA, pregenomic RNA (pgRNA), and e antigen (HBeAg) levels, while it decreased Precore RNA and s antigen (HBsAg) levels. Conversely, in Huh-7 cells, curcumin significantly increased viral progeny more than tenfold, as well as HBV RNAs and viral antigens. Furthermore, the analysis of the cellular mechanisms associated with the modulation of viral replication revealed that in Huh-7 cells, curcumin-induced cell cycle arrest in the G2/M phase and the modulation of genes involved in proliferation, cell cycle progression, and apoptosis, whereas no changes in cell cycle progression and gene expression were observed in HepG22.15 cells. In conclusion, curcumin elicits a differential cellular response in two hepatoma cell lines, which, in the case of Huh-7 cells, would provide an optimal cellular setting that enhances HBV replication. Therefore, the antiviral effect of this phytochemical remains controversial.
... Curcumin is a natural, inexpensive, and side-effect-free compound known for its wide range of biological effects, including antioxidant, anti-inflammatory, and anticancer properties. It can also disrupt viral infections by targeting viral entry, essential viral components for replication, and other cellular or molecular processes involved in the viral life cycle [10]. Additionally, extensive research has demonstrated that curcumin, when used as a photosensitizer in combination with blue light irradiation, exhibits effective photoreactivity against cancer cells and microorganisms even at low concentrations [11]. ...
... Its antiviral activity involves inactivating viruses by targeting viral entry and essential components for viral replication and transcription. Extensive in vitro and in vivo studies have explored how curcumin combats HSV, focusing on its ability to inhibit key cellular and molecular processes crucial for viral gene expression, transcription, and pathogenicity [10]. In the quest for effective antiviral immune modulators, curcumin is a notable natural product that is inexpensive, has no side effects, and effectively stimulates key components of the immune system. ...
This study is the first to use photodynamic therapy (PDT) mediated by curcumin and blue light for the treatment of recurrent herpes labialis. According to our study, PDT effectively accelerated lesion healing and reduced its recurrence. PDT may represent a promising, safe, and cost‐effective treatment option for this challenging disease.
... 100 DovePress found to reduce immediate early gene expression in human cytomegalovirus (HCMV) infections and exhibit varying effects on Epstein-Barr virus (EBV), inhibiting its reactivation in some studies while enhancing lytic reactivation in others. 101,102 Another study also concluded that various CUR derivatives exhibit excellent absorption, distribution, metabolism, excretion, and toxicity profiles. Based on these characteristics, the study recommends these derivatives as potential antiviral agents for treating Monkeypox and Smallpox virus infections. ...
Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin’s mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin’s ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin’s comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field.
... Curcumin is mostly insoluble in water, poorly soluble in hydrocarbon solvents, but very soluble in polar solvents such as ethanol, methanol, and dimethyl sulfoxide (DMSO) [16]. Low bioavailability has been attributed to curcumin being insoluble in water at pH 7 [17]. The poor bioavailability of curcumin reduces its potential as a therapeutic agent with clinical applications [18]. ...
... Medicinal properties include antioxidant, anti-inflammatory, and [12], influenza A [13], and herpes simplex virus (HSV) 1 and 2 [14] [15]. Curcumin acts as an antiviral through multiple mechanisms [17]. The structural similarities to curcumin suggest a role of hispolon as an antiviral. ...
Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability , percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only his-polon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attach-ment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.
... The first type (HSV-1) most often causes oral herpes, while the second type (HSV-2) is responsible for genital herpes. The mechanisms of curcumin's antiviral action are related to the ability of curcumin to inhibit many cellular and molecular processes necessary for the expression, replication, and pathogenesis of viral genes [117]. The conducted research confirmed that curcumin inhibits the expression of the IE gene and hinders HSV-1 infection by using a mechanism independent of the activity of the p300/CBP histone acetyltransferase of transcription coactivator proteins [118]. ...
Curcumin is a polyphenolic molecule derived from the rhizoma of Curcuma longa L. This compound has been used for centuries due to its anti-inflammatory, antioxidant, and antimicrobial properties. These make it ideal for preventing and treating skin inflammation, premature skin ageing, psoriasis, and acne. Additionally, it exhibits antiviral, antimutagenic, and antifungal effects. Curcumin provides protection against skin damage caused by prolonged exposure to UVB radiation. It reduces wound healing times and improves collagen deposition. Moreover, it increases fibroblast and vascular density in wounds. This review summarizes the available information on the therapeutic effect of curcumin in treating skin diseases. The results suggest that curcumin may be an inexpensive, well-tolerated, and effective agent for treating skin diseases. However, larger clinical trials are needed to confirm these observations due to limitations in its in vivo use, such as low bioavailability after oral administration and metabolism.
... The proposed modes of action according to in vitro, in vivo and in silico results are the inhibitions of viral entrance, genome replication and proteins translation, as well as inhibition of virus assembly and release from cells. Immunomodulatory activities have been suggested as well (Ruchawapol et al. 2021;Šudomová and Hassan 2021). Recent studies have shown that mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs allow the enhancement of their antiviral effects (Ninfali et al. 2020). ...
Herpes viruses (HSV) are among the most common viruses that infect humans. They cause blisters and inflammation of the oral and genital mucosa as well as severe symptoms such as blindness, hearing impairment and fatal encephalitis. Although acyclovir (ACV) and its derivatives are highly effective in treating recurrent lytic infections, the emergence of resistant strains remains a concern. In this study, the in vitro anti-herpetic activity of a hydroalcoholic extract obtained from the brown seaweed Sargassum fluitans, collected from strandings in Cuba, was evaluated. The hydroalcoholic extract was not cytotoxic in Vero cells (CC50 >5000 µg mL⁻¹) and inhibited replication of HSV-1 (ACV-susceptible and -resistant) and HSV-2 (ACV-resistant) strains with EC50 of 271.66, 403.62 and 14.99 µg mL⁻¹ respectively. In addition, first studies about mechanism of action were evaluated with ACV-sensitive HSV-1 model. The extract showed strong inhibition when pre-incubated with the virus and when the extract and virus were added simultaneously on the cells. The protection of Vero cells during the post-infection assay was very effective up to 1 h. A high resolution UPLC/MS-MS analysis detected 139 compounds, of which 44 were identified. In silico analysis was performed to determine the putative interaction sites of two flavones of interest identified in the extract with the viral glycoprotein D (gD). Molecular docking analysis revealed that takakin and tectorigenin mainly interact with the gD protein active center through hydrophobic interactions (Leu44, Pro50, Thr174, Lys169, Tyr208, Gln209) while hydrogen bonding interactions are less abundant (Ser43, Asp46, Lys169, Tyr208). This research represents a contribution to the valorization of S. fluitans as a source of anti-herpetic compounds in the context of recurrent and abundant seaweed strandings.
... Regulation of the intensity and type of the immune response depends on many factors, including readiness of the immune system to quickly and accurately recognize and respond to a pathogen. Active search is underway for compounds that prevent the development of inflammatory processes, including those from natural raw materials [4][5][6][7][8][9]. Commensal microorganisms help to keep the immune system in constant readiness for an adequate response. ...
Relevance. Inflammation is a defense response of an organism to a pathogen. It appears in order to maintain homeostasis and is regulated by the immune, nervous, and endocrine systems. The hormones epinephrine and norepinephrine are produced in the adrenal medulla and in the brain, and are universal messengers that trigger the transmission of nerve impulses at synapses, and also have a receptor-mediated effect on immunocompetent cells. The aim of this study was to investigate adrenergic pathway regulation of inflammation on the neutrophil granulocytes in the presence of activators of innate immunity receptors. Materials and Methods. Neutrophil granulocytes were obtained from peripheral blood of healthy volunteers in a density gradient of Histopaque 1077 and Histopaque 1119 (Sigma Aldrich, Steinheim, Germany), and cultured in the presence of LPS, GMDP, epinephrine and norepinephrine. The amount of human neutrophil peptides 1-3 (HNP1-3) was examined using an enzyme-linked immunosorbent assay; the gene expression of TLR4, NOD2, ATF3 and A20 was determined using RT-PCR. Results and Discussion. Norepinephrine (noradrenaline) was found to decrease the synthesis of human neutrophils peptides 1-3 (HNP 1-3 defensins, alone and in the combination with agonists of TLR4 and NOD2 receptors - LPS and GMDP respectively. It was found out that there was no a statistically significant effect of epinephrine (adrenaline) on the production of HNP 1-3, including when combined with LPS and GMDP. As a result of the study, an increase in the levels of expression of the genes TLR4, NOD2 and regulator of inflammatory reactions A20 both in LPS- and GMDP- induced neutrophil culture were uncovered, while ATF3 was increased only in LPS-induced neutrophil culture. Epinephrine demonstrated the absence of a statistically significant effect on the expression of the studied genes. While norepinephrine significantly increased the expression of A20 genes. Conclusion. The data obtained shows that norepinephrine can reduce the synthesis of HNP 1-3, including the one induced by LPS and GMDP. Moreover, the ability of norepinephrine to induce the expression of A20 may play a significant role in modulation of inflammation.
... With the ability to establish lifelong relationships with their hosts and trigger recurrent outbreaks, herpesviruses have emerged as formidable players in the realm of infectious diseases [1][2][3]. Human herpesviruses, including herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and others, continue to exert a substantial impact on global public health [4,5]. Likewise, the animal kingdom encounters viral obstacles, as equine, bovine herpesviruses, feline, and canine herpesvirus, pseudorabies virus, and other related viruses cause considerable risks to agriculture and veterinary fields [6][7][8][9]. ...
Herpesviruses, a family of enveloped DNA viruses, pose significant threats to both humans and animals [...]
... In recent years, scientific inquiry into the antiviral potential of flavonoids has expanded, shedding light on their synergistic effects when combined with conventional antiviral drugs. These combination therapies hold significant promise for enhancing efficacy and addressing some of the challenges associated with treating HSV infections, including drug resistance [48,90]. Wu and colleagues [70] investigated the combined impact of EGCG at 25 µg/mL and acyclovir at 50 µg/mL on HSV-1 infection in oral epithelial cells. ...
The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.
