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Antiviral activity of hop constituents against a series of DNA and RNA viruses
Abstract
We investigated whether crude hop extracts and purified hop components representing every major chemical class of hop compound have antiviral activity. These hop constituents were tested for antiviral activity against bovine viral diarrhea virus (BVDV) as a surrogate model of hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza A virus (FLU-A), influenza B virus (FLU-B), rhinovirus (Rhino), respiratory syncytial virus (RSV), yellow fever virus (YFV), cytomegalovirus (CMV), hepatitis B virus (HBV), and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The extracts all failed to prevent the replication of HIV, FLU-A, FLU-B, RSV and YFV. A xanthohumol-enriched hop extract displayed a weak to moderate antiviral activity against BVDV (therapeutic index (TI)=6.0), HSV-2 (TI=>5.3), Rhino (TI=4.0) and HSV-1 (TI=>1.9) with IC(50) values in the low microg/ml range. Pure iso-alpha-acids demonstrated low to moderate antiviral activity against both BVDV (TI=9.1) and CMV (TI=4.2) with IC(50) values in the low microg/ml range. No antiviral activity was detected using beta-acids or a hop oil extract. Ultra-pure preparations (>99% pure) were used to show that xanthohumol accounted for the antiviral activity observed in the xanthohumol-enriched hop extract against BVDV, HSV-1 and HSV-2. Xanthohumol was found to be a more potent antiviral agent against these viruses than the isomer iso-xanthohumol. With Rhino, the opposite trend was observed with iso-xanthohumol showing superior antiviral activity to that observed with xanthohumol. Xanthohumol also showed antiviral activity against CMV, suggesting that it might have a generalized anti-herpesvirus antiviral activity. Again, superior antiviral activity was observed with the xanthohumol isomer against CMV. In summary, iso-alpha-acids and xanthohumol were shown to have a low-to-moderate antiviral activity against several viruses. These hop constituents might serve as interesting lead compounds from which more active anti-HCV, anti-Rhino and anti-herpesvirus antiviral agents could be synthesized.
... A pair of PSTVd highly resistant (SC-5) and sensitive (SC-96) semi-cultivar tomato genotypes were identified in the present study (Figures 2 and 3 Among the upregulated metabolites detected in positive ion mode, xanthohumol, a prenylated chalcone, was upregulated about 112-fold (Table 1). This compound exhibits antioxidant, antiproliferative (Miranda et al., 1999), and viral-resistant activities (Buckwold et al., 2004). The effects on the resistance to bovine viral diarrhea virus, hepatitis B/C virus (HBV/HCV) of xanthohumolon, were thereafter confirmed by in vitro experiments (Lou et al., 2014;Zhang et al., 2010). ...
... However, currently, we have only observed this phenomenon in terms of morphological characteristics and PSTVd titers. It is unclear how these two substances induce tomato SC-96 tolerance to PSTVd, and whether the regulatory mode is consistent with previous research on virus-induced diseases(Buckwold et al., 2004;Lou et al., 2014;Wang et al., 2013;Yu et al., 2016) deserves further exploration. In the previous study, extract of a xanthohumol enriched hop (Humulus lupulus) displayed a weak to mild BVDV (bovine viral diarrhea virus), HSV-1 (herpes simplex virus type 1), HSV-2 (herpes simplex virus type 1), and rhinovirus antiviral activity. ...
... In the previous study, extract of a xanthohumol enriched hop (Humulus lupulus) displayed a weak to mild BVDV (bovine viral diarrhea virus), HSV-1 (herpes simplex virus type 1), HSV-2 (herpes simplex virus type 1), and rhinovirus antiviral activity. Moreover, compared with purified isomer isoxanthohumol, xanthohumol was found to be a more potent antiviral agent against the above viruses(Buckwold et al., 2004). Lou et al.(2014) confirmed xanthohumol's anti-HCV (hepatitis C virus) activity at concentrations ranging from 3.53 to 14.11 μM. ...
Tomato is a popular vegetable worldwide; its production is highly threatened by infection with the potato spindle tuber viroid (PSTVd). We obtained the full‐length genome sequence of previously conserved PSTVd and inoculated it on four genotypes of semi‐cultivated tomatoes selected from a local tomato germplasm resource. SC‐5, which is a PSTVd‐resistant genotype, and SC‐96, which is a PSTVd‐sensitive genotype, were identified by detecting the fruit yield, plant growth, biomass accumulation, physiological indices, and PSTVd genome titer after PSTVd inoculation. A non‐target metabolomics study was conducted on PSTVd‐infected and control SC‐5 to identify potential anti‐PSTVd metabolites. The platform of liquid chromatography‐mass spectrometry detected 158 or 123 differential regulated metabolites in modes of positive ion or negative ion. Principal component analysis revealed a clear separation of the global metabolite profile between PSTVd‐infected leaves and control regardless of the detection mode. The potential anti‐PSTVd compounds, xanthohumol, oxalicine B, indole‐3‐carbinol, and rosmarinic acid were significantly upregulated in positive ion mode, whereas echinocystic acid, chlorogenic acid, and 5‐acetylsalicylic acid were upregulated in negative ion mode. Xanthohumol and echinocystic acid were detected as the most upregulated metabolites and were exogenously applied on PSTVd‐diseased SC‐96 seedlings. Both xanthohumol and echinocystic acid had instant and long‐term inhibition effect on PSTVd titer. The highest reduction of disease symptom was induced by 2.6 mg/L of xanthohumol and 2.0 mg/L of echinocystic acid after 10 days of leaf spraying, respectively. A superior effect was seen on echinocystic acid than on xanthohumol. Our study provides a statistical basis for breeding anti‐viroid tomato genotypes and creating plant‐originating chemical preparations to prevent viroid disease.
... In 2004, Buckwold and coworkers tested Xn against a number of DNA and RNA viruses in vitro [46]. As RNA viruses, bovine viral diarrhoea virus (BVDV), a surrogate model for hepatitis C virus, and human rhinovirus (HRV) were included. ...
... An Xnenriched extract was also tested in the same study. The Xn in the extract appeared to account for almost all of the extract's antiviral activity, as the therapeutic indices TI (TC 50 /IC 50 ) of this compound against BVDV, HSV-1, and HSV-2 were comparable to those of the Xnenriched extract [46]. Additionally, Wang and coworkers investigated the ability of Xn to inhibit various steps required for HIV-1 replication [47]. ...
Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review.
... XN purified from crude hop extracts displayed a half inhibitory concentration (IC 50 ) of 7.62 µM against the double-stranded DNA virus HSV-1, 58.41 µM against human immunodeficiency virus (HIV), which is composed of two copies of positive-sense, single-stranded RNA and 7.05 µM against the double-stranded DNA virus CMV (Wang et al. 2004). XN and iXN were also reported to inhibit the expression of the double-stranded DNA virus Epstein-Barr virus (EBV) early antigen with a half-maximal inhibitory dose (ID 50 ) of 0.35 and 0.40 µmol per grain-bearing tip while displaying low cellular toxicity (Akazawa et al. 2012;Buckwold et al. 2004). In addition, iXN showed antiviral activity against CMV (IC 50 = 12 µg/ml), HSV-2 (IC 50 = 17 µg/ml), and rhinovirus (IC 50 = 6.6 µg/ml) (Buckwold et al. 2004). ...
... XN and iXN were also reported to inhibit the expression of the double-stranded DNA virus Epstein-Barr virus (EBV) early antigen with a half-maximal inhibitory dose (ID 50 ) of 0.35 and 0.40 µmol per grain-bearing tip while displaying low cellular toxicity (Akazawa et al. 2012;Buckwold et al. 2004). In addition, iXN showed antiviral activity against CMV (IC 50 = 12 µg/ml), HSV-2 (IC 50 = 17 µg/ml), and rhinovirus (IC 50 = 6.6 µg/ml) (Buckwold et al. 2004). Other XN-derivatives have also shown anti-viral properties. ...
The COVID-19 pandemic has highlighted the importance of identifying new potent antiviral agents. Nutrients as well as plant-derived substances are promising candidates because they are usually well tolerated by the human body and readily available in nature, and consequently mostly cheap to produce. A variety of antiviral effects have recently been described for the hop chalcone xanthohumol (XN), and to a lesser extent for its derivatives, making these hop compounds particularly attractive for further investigation. Noteworthy, mounting evidence indicated that XN can suppress a wide range of viruses belonging to several virus families, all of which share a common reproductive cycle. As a result, the purpose of this review is to summarize the most recent research on the antiviral properties of XN and its derivatives, with a particular emphasis on the positive-sense RNA viruses human hepatitis C virus (HCV), porcine reproductive and respiratory syndrome virus (PRRSV), and severe acute respiratory syndrome corona virus (SARS-CoV-2).
... Hops, the seed cones of the plant Humulus lupulus from the family Cannabaceae, contain several pharmaceutically active compounds, such as humulone, lupulone, and xanthohumol (Gerhäuser, 2005;Knez Hrncic et al., 2019;Lin et al., 2019). Crude hop extracts as well as individual compounds have been described to exert anti-viral effects against several DNA and RNA viruses (Buckwold et al., 2004;Fuchimoto et al., 2013). For example, humulone, the most important bitter acid of hops, can suppress replication of the respiratory syncytial virus (RSV alias Human orthopneumovirus) in cell culture by disturbing the formation of viral filaments (Fuchimoto et al., 2013). ...
... Hop extracts exert anti-viral effects against some virus strains, but whether these extracts are also effective against SARS-CoV-2 has not yet been experimentally verified (Buckwold et al., 2004;Zhang et al., 2010;Fuchimoto et al., 2013). ...
... Chalcones were shown to act on important viral molecular targets affecting different stages of viral replication cycle including; reverse transcriptase (RT) [31,32], IN [22,[33][34][35], protease [36][37][38], neuraminidase (NA) [39], aminotransferases [40], superoxide dismutase, glutathione peroxidase and other associated enzymes [40]. They were also found to act on important receptors such as CXCR4 chemokine receptors [41], US28 receptor of HCMV [27] and capsid pocket inside viral protein 1 (VP1) in rhinovirus [42]. Other important activities include targeting the kinase activity of epidermal growth factor receptor (EGFR) [27], inhibition of DNA hybridisation [30], mammalian target of rapamycin (mTOR) pathway [43], blocking virus-mediated cell fusion and inhibiting the late stages of viral replication [44]. ...
... 5-(Benzyloxy)-2-(5-bromo-2-methoxyphenyl)-4Hchromen-4-one, is one of these chalcones that was found to inhibit the US28 receptor of HCMV with an EC 50 of 3.5 lM [27]. In 2004, xanthohumol 1, a prenylated chalcone showed moderate antiviral activity against HCMV through its action in downregulating CXCR4 chemokine receptors [41]. Other chalcones were also found to be effective in targeting the kinase activity of EGFR and thus preventing HCMV entry into cells and limiting cellular activation [27]. ...
Some viral outbreaks have plagued the world since antiquity, including the most recent COVID-19 pandemic. The continuous spread and emergence of new viral diseases have urged the discovery of novel treatment options that can overcome the limitations of currently marketed antiviral drugs. Chalcones are natural open chain flavonoids that are found in various plants and can be synthesized in labs. Several studies have shown that these small organic molecules exert a number of pharmacological activities, including antiviral, anti-inflammatory, antimicrobial and anticancer. The purpose of this review is to provide a summary of the antiviral activities of chalcones and their derivatives on a set of human viral infections and their potential for targeting the most recent COVID-19 disease. Accordingly, we herein review chalcones activities on the following human viruses: Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, human immunodeficiency, influenza, human rhinovirus, herpes simplex, dengue, human cytomegalovirus, hepatitis B & C, rift valley fever and Venezuelan equine encephalitis. We hope that this review will pave the way for the design and development of potentially potent and broad-spectrum chalcone based antiviral drugs.
... Xanthohumol has been shown to have a wide range of antiviral effects in many in vitro and in vivo studies against both DNA and RNA viruses such as bovine viral diarrhea virus (BDDV), cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), porcine reproductive and respiratory syndrome virus (PRRSV). [3][4][5] Infection with PRRSV was first identified in the 1980s in North America and in China in 2006 resulting in a devastating epidemic in pigs. 4,5 This single-stranded RNA virus infection shares similarities with SARS-CoV -2 with high fever, significant morbidity and severe respiratory disease resulting in high mortality. ...
... µM and a high toxic concentration suggestive of potentially good therapeutic efficacy. [3][4][5] In vivo study also showed that xanthohumol was effective in reducing virus level in PRRSV infected pigs in a dose-dependent manner. 4 ...
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity and mortality and there are a lack of effective therapies. There is a need for treatment which could be available for all in the global community, as well as within hospital, which is efficacious, affordable and safe. Xanthohumol from hop extract has been shown in vitro and in vivo to have antiviral properties against RNA and DNA viruses but also importantly anti-inflammatory properties against severe respiratory syndrome via inhibition of NFκB dependent pathways. We review the evidence for xanthohumol to be considered as a treatment for SARS-CoV-2 infection. We need an economic and globally available therapy and thinking beyond the traditional is important; thus, studies are warranted to assess efficacy of xanthohumol against SARS-CoV-2.
... Previous studies have demonstrated that certain natural compounds possess the ability to inhibit the virulence factors of bacteria, thereby lessening the occurrence of pathogen infections [25,26]. Numerous studies have indicated that IXN exhibits favorable antiviral activity against bovine viral diarrhea mucosal disease (BVDV) and herpes simplex virus (HSV) [27]. Moreover, drug products based on IXN might have unique effects on the treatment of hepatitis. ...
Background
Clostridium perfringens (C. perfringens) is an important zoonotic pathogen. The diseases such as necrotic enteritis (NE), enterotoxemia, gas gangrene and food poisoning caused by its infection seriously threaten the lives of both humans and animals. However, under the severe situation of antibiotic resistance, the development of new antibacterial strategies or drugs deserves great attention.
Results
In this study, we selected the virulence factor Type IV pili (TFP) of C. perfringens as the target for drug screening. The gliding motility, biofilm formation, cell adhesion and antibacterial activity of the natural compound isoxanthohumol (IXN) against C. perfringens were determined. Transmission electron microscopy (TEM), TFP gene transcription analysis and Western blot were used to detect the expression of PilA pilin. The therapeutic effect of IXN on C. perfringens infection was demonstrated through a mouse gas gangrene model. It was confirmed that IXN inhibits the function of TFP by down-regulating TFP-encoding genes and two-component regulatory genes.
Conclusions
In conclusion, our study shows that IXN has the potential to inhibit the function of TFP in C. perfringens and for anti-infection applications.
... However, it has not been reported to decrease recombinant HIV-1 reverse transcriptase activity or HIV-1 entry [38]. Apart from HIV, XN also inhibits bovine diarrhea virus (BVDV), hepatitis C virus (HCV) replication in a cell culture system, comparable to that of IFN-α, and low-to-moderate herpes virus (HSV-1, HSV-2, CMV) [39,40]. Studies on the antiviral activity of xanthohumol against coronaviruses have shown that it is a strong pan-inhibitor of various coronaviruses, e.g., the SARS-CoV-2 betacoronavirus (IC50 value 1.53 µM) and PEDV alphacoronavirus (IC50 value 7.51 µM), targeting the major protease (Mpro), which plays a key role in viral replication and transcription. ...
Xanthohumol (XN), representing the group of chalcones, is a hydroxyl and superoxide free radical scavenger. It also has antimicrobial properties, showing antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis and Propionibacterium acnes. XN exerts an inhibitory effect on tyrosinase (it hinders the oxidation of l-tyrosine and l-DOPA). However, it also affects the transport of pigment (through a reduction in the number and length of dendrites) and its degradation (through damage to melanosomes). Additionally, it has been shown to inhibit the different activation pathways of the premeditated response in macrophages and reduce the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Xanthohumol also improves skin elasticity by reducing the activity of elastase and MMP 1, 2 and 9, and it increases the expression of type I, III and V collagen, as well as elastin and fibrillins in skin fibroblasts. It acts against the main factors contributing to the pathogenesis of acne by inhibiting pro-inflammatory mediators (e.g., COX-2, PGE2, IL-1β and TNF-α). Moreover, it shows antibacterial activity against P. acnes and S. aureus, as well as seboregulatory and antioxidant properties. It has also been recognized that XN intake could affect diabetic wound healing. XN shows antitumoral activity, e.g., in the case of skin melanoma, which is associated with the antioxidant, pro-apoptotic, anti-angiogenic and immunostimulating effects of this compound.
... This result is similar to the findings of Knez-Hrncic et al. (2019) who isolated various bio-active compounds from hops. Buckwold et al. (2014) also observed the presence of alkaloids, flavonoids, tannins, resins, glycosides from ethanol hop extract. ...
In addition to their importance in beer brewing, hops have been used in traditional herbal medicines as antimicrobial agents against pathogens. This study is aimed at investigating the phytochemical and antimicrobial profile of hop (Humulus lupulus L.) extracts on food pathogens (Escherichia coli and Salmonella species). The bacterial food pathogens were isolated and identified from soymilk by phenotypic characterization. Phytochemical screening of the extracts was carried out using standard methods. The antibacterial assay was performed using agar well diffusion method. The pathogenic isolates recovered from soymilk were Escherichia coli and Salmonella spp. The preliminary phytochemical screening revealed that flavonoid and saponin were abundantly present; alkaloid, steroids, tannin and glycosides were moderately present while terpenoids and phenol were slightly present in the hop (Humulus lupulus L.) extract. The results of antibacterial assay showed minimum inhibitory concentration (MIC) for Escherichia coli at 200mg/ml concentration with zone of inhibition 2.00mm while minimum inhibitory concentration (MIC) for Salmonella spp. at 100mg/ml concentration with zone of inhibition 1.00mm. The extract obtained from hops flowers showed little antimicrobial activity against the tested food pathogens (Escherichia coli and Salmonella spp.). The results indicated that this plant considered mainly as raw material in brewing industry has antibacterial and antioxidant potential.
... Hops also have anti-inflammatory, estrogenic, cancer chemopreventive, and anti-angiogenic properties, as well as use in obesity, type-2 diabetes and cancer treatment (Zanoli & Zavatti 2008;Chung et al. 2009). Other studies have demonstrated antimicrobial (Sefidgar et al. 2015;Cermak et al. 2017) and antiviral (Buckwold et al. 2004) activities. Because of the sedative effects, hops have been approved for treating restlessness, anxiety, and sleep disturbances by the German Commission E and the European Scientific Cooperative on Phytotherapy (Zanoli & Zavatti 2008). ...
Hops is an economically important species due to its diverse secondary metabolites and extensive use in the brewing and medicinal industries. Although hops is widely distributed in Kosovo, the chemical composition of its essential oils and genetic variability of wild populations remain understudied. Therefore, this study aimed to evaluate the chemical and genetic variability of Kosovo's wild hop population using essential oil constituents and microsatellite (simple sequence repeat – SSR) markers.
Female hop inflorescences were collected from 21 wild populations in Kosovo. Essential oils were extracted from the dried plant material using a Clevenger apparatus. Chemical composition of the essential oils was analysed using GC‐FID‐MS. DNA was extracted from dried leaves, and 15 SSR markers were used for fragment analysis.
The main constituents of the essential oil were myrcene, α‐humulene, (E)‐β‐farnesene, α‐selinene, β‐selinene, and E‐caryophyllene. Statistical analyses based on chemical composition of essential oils and SSR markers highlighted the low variability among populations and high variability within populations.
These findings provide valuable insights for developing strategies for potential use and conservation of wild hop populations in Kosovo, laying the groundwork for future research and comparison with commercial cultivars to assess their breeding potential.
... Along with Echinacea, hop cones were also reported to possess antiviral properties [26,100,101]. Recently, Bouback et al. showed that a boiled water extract from the dried whole plant of H. lupulus possessed anticoronaviral properties against both MERS-CoV and SARS-CoV-2, blocking the viral ability to infect and replicate inside the host cells: these effects are mainly ascribed to its polyphenolic compounds [102]. ...
Respiratory viral infections continue to pose significant challenges, particularly for more susceptible and immunocompromised individuals. Nutraceutical strategies have been proposed as promising strategies to mitigate their impact and improve public health. In the present study, we developed a mixture of two hydroalcoholic extracts from the aerial parts of Echinacea purpurea (L.) Moench (ECP) and the cones of Humulus lupulus L. (HOP) that can be harnessed in the prevention and treatment of viral respiratory diseases. The ECP/HOP mixture (named ECHOPvir) was characterized for the antioxidant and cytoprotective properties in airway cells. Moreover, the immunomodulating properties of the mixture in murine macrophages against antioxidant and inflammatory stimuli and its antiviral efficacy against the PR8/H1N1 influenza virus were assayed. The modulation of the Nrf2 was also investigated as a mechanistic hypothesis. The ECP/HOP mixture showed a promising multitarget bioactivity profile, with combined cytoprotective, antioxidant, immunomodulating and antiviral activities, likely due to the peculiar phytocomplexes of both ECP and HOP, and often potentiated the effect of the single extracts. The Nrf2 activation seemed to trigger these cytoprotective properties and suggest a possible usefulness in counteracting the damage caused by different stressors, including viral infection. Further studies may strengthen the interest in this product and underpin its future nutraceutical applications.
... showed antiviral effect against HSV-1 and influenza virus strain H1N1, [6] (iii) crude extract of hop showed antiviral effect against a diverse group of viruses, suggesting the presence of broad-spectrum antiviral phytochemicals in various parts of the plants. [7] Restricted to the China, India, Japan, Pakistan, Sri Lanka, Thailand and number of African countries. A completed review has earlier explained national activities around the globe relevant to medicinal plants usage priorities. ...
Many antiviral compounds currently in clinical use have a limited spectrum of activity, narrow therapeutic adequacy and irregular toxicity. There is also an appearing problem of resistant viral tensity. This study was gear to examine the issued literature on herbs and plants with antiviral estimate, their laboratory estimates in vitro and in vivo, and confirmation of human clinical effectiveness. Medicinal plants have been generally used to treat a variety of infectious and non-infectious disease. According to one approximate, 25% of the regularly used medicines contain compounds isolated from plants. Various plants could provide a rich reserve for drug discovery of infectious diseases, especially in a stage when the latest dissociation techniques are obtainable on one hand, and the human population is dispute by a number of appearing infectious diseases on the other hand. Fixing other nutrients, viral infections, caused by connected with human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2), and newly appearing infectious viruses have disputed mankind survival. Of importance, a variety of medicinal plants have appeared assurance to treat a number of viral infections, and some of them own broad-spectrum antiviral activity. In earlier, research into the antiviral activity of several good medicinal plants was bounced due to: (a) highly infectious creation of viruses and (b) absence of proper separation techniques for the detection of antiviral components from plants. Development of vector-based plans, in which non-infectious molecular clone of a virus could be used for antiviral guarding purposes, and developing in separation technologies assurance for medicinal plants utilize in modern drug discovery. This article explains possible antiviral properties of medicinal plants in case of various group of viruses, 638 Shreyasi et al. World Journal of Pharmacy and Pharmaceutical Sciences and submit screening the probable of plants possessing broad-spectrum antiviral effects in case of emerging viral infections.
... Some of the hop constituents were tested against different kinds of viruses; nevertheless, only iso-α-acids and xanthohumol showed low to moderate inhibition. The β-acids did not have any activity assigned to any of the tested viruses; therefore, none of them was an alphavirus species [20,21]. In this work, for the first time we show that hops compounds demonstrated a promising virucidal activity against CHIKV. ...
Chikungunya virus (CHIKV) is an arthropod-borne virus that belongs to the genus Alphavirus (family Togaviridae). CHIKV causes chikungunya fever, which is mostly characterized by fever, arthralgia and, sometimes, a maculopapular rash. The bioactive constituents of hops (Humulus lupulus, Cannabaceae), mainly acylphloroglucinols, known as well as α- and β-acids, exerted distinct activity against CHIKV, without showing cytotoxicity. For fast and efficient isolation and identification of such bioactive constituents, a silica-free countercurrent separation method was applied. The antiviral activity was determined by plaque reduction test and was visually confirmed by a cell-based immunofluorescence assay. All hops compounds demonstrated a promising post-treatment viral inhibition, except the fraction of acylphloroglucinols, in mixture. β-acids fraction of 125 µg/mL expressed the strongest virucidal activity (EC50 = 15.21 µg/mL), in a drug-addition experiment on Vero cells. Hypothesis for mechanism of action were proposed for acylphloroglucinols based on their lipophilicity and chemical structure. Therefore, inhibition of some steps of the protein kinase C (PKC) transduction cascades was also discussed.
... Many studies refer to sedative [7], antispasmodic [8], estrogenic [9,10], antioxidant [4,11], antiproliferative [12,13] and anti-inflammatory properties [14,15]. In addition, hop constituents have been well-known for many years for their antimicrobial properties [5] including antibacterial [11,[16][17][18], antiviral [19,20], antiparasitic [1,18] and antifungal activities [21,22]. In human health, Gram-positive bacteria were Xanthohumol was purified from the DCM sub-extract of cones in one step by centrifugal partition chromatography (CPC) on an Armen instrument 250 mL rotor (SCPC-250-L) provided by Gilson ® (Saint-Avé, France) and connected to a Shimadzu ® pump (LC-20AP, Kyoto, Japan) [18]. ...
Botanicals represent a promising source of metabolites in the search for new biofungicides. In this context, this study aimed at evaluating the in vitro anti-oomycete activity of hop (Humulus lupulus L.) extracts and metabolites against Phytophthora infestans, an oomycete causing late blight disease in Solanaceae. Crude hydro-ethanolic extracts and dichloromethane sub-extracts of different parts (cones, leaves, stems and rhizomes) were characterized by UHPLC-UV–MS and some cone specialized metabolites were purified by CPC and preparative HPLC. A commercial hop cone essential oil was also analyzed by GC–MS. All extracts succeeded in inhibiting mycelial growth and spore germination with morphological alteration of the mycelium. Extracts of leaves showed a significant anti-oomycete activity compared to the extracts of cones, stems, and rhizomes. Moreover, no difference was noticed between the crude hydro-ethanolic extract and the dichloromethane sub-extract activity, except for leaves, with the apolar sub-extract being more active than the crude one. The extracts of cones succeeded in inhibiting more P. infestans than the essential oil, which appeared to be the less active evaluated modality. Some purified prenylated phenolic compounds also inhibited P. infestans although copper sulfate, a mineral fungicide control, was still more active. This study highlights the potential use of hop by-products as biofungicides to manage P. infestans.
... In fact, it showed an antiproliferative activity against human cell lines of breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer (DU145 and PC-3) and colon cancer (HT-29 and SW620) [30,31]. Furthermore, this compound inhibited the production of prostate membrane antigen (PSA) and exhibited an antiviral activity towards herpes virus (HSV1and HSV2) [32,33]. DXN has also been shown to possess cytotoxic activity, especially towards two colon (HCT116 and HT29) and two hepatocellular (HepG2 and Huh7) carcinoma cell lines [34]. ...
Hop (Humulus lupulus L.) is grown mainly for the production of beer. The flowers of the female plant give it the bitter taste and pungent aroma. There are a large number of hop varieties differing in their α-acid content, essential oil levels and odor profiles. Aside from their use in brewing, more recently, hops have been used for the pharmacological properties of its derivatives that are of great importance to the pharmaceutical industry. Hop is known to have a fairly complex chemistry characterized by the presence of a variety of sesquiterpenoids, diterpenoids and triterpenoids, phytoestrogens and flavonoids. Additionally, considering the countless applications in the pharmacological sector in recent years, a chemical characterization of the different cultivars is essential to better identify the source of specific secondary metabolites. For this purpose, the dried inflorescences of two hop cultivars, Chinook and Cascade, were investigated using Solid-Phase Microextraction-Gas Chromatography-Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry (SPME-GC-MS and LC-MS-MS) to describe their metabolomic and proteomic profile. Furthermore, thanks to an in-depth statistical survey, it was possible to carry out a comparative study highlighting interesting implications deriving from this investigative study.
... Isobavachalcone showed antifungal effects against Candida albicans and Cryptococcus neoformans [8]. Moreover, xanthohumol demonstrated antiviral properties against bovine viral diarrhoea virus, HSV-1 (herpes simplex virus) and HSV-2, CMV (cytomegalovirus) [9], and coronaviruses [10] and showed anti-HIV-1 activity [11]. Xanthohumol caused a dose-dependent decrease in the growth of human breast cancer (MCF7) [12,13], colon cancer (HT-29) [14,15], ovarian cancer (A-2780) [16] and prostate cancer cells in vitro [17]. ...
An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1H-pyrazol-3-ols bearing a formyl or acetyl group on the C4 position of pyrazole ring, employing a base-catalysed Claisen–Schmidt condensation reaction, is described. Isomeric chalcones were further reacted with N-hydroxy-4-toluenesulfonamide and regioselective formation of 3,5-disubstituted 1,2-oxazoles was established. The novel pyrazole-chalcones and 1,2-oxazoles were characterized by an in-depth analysis of NMR spectral data, which were obtained through a combination of standard and advanced NMR spectroscopy techniques.
... (i) an extract of the Trifollium species Secomet-V showed broad spectrum antiviral effect against a human papillomavirus, influenza, Marburg, HIV, HBV and HCV (Kotwal et al., 2005), (ii) Pandanin, a lectin isolated from the leaf extract of Pandanus amaryllifolius Roxb. showed antiviral effect against HSV-1 and influenza virus strain H1N1 (Ooi et al., 2004), (iii) crude extract of hop displayed antiviral effect against a diverse group of viruses, suggesting the presence of broad-spectrum antiviral phytochemicals in various parts of the plants (Buckwold et al., 2004). ...
Plants are a fascinating group of plants that have been
dominating the earth for 400 million years. During evolution, they
have undergone series of evolutionary changes to suit themselves
with the surrounding environment. These evolutionary changes
not only included morphological changes to suit varied climatic
conditions but also armed with intricate physiological changes to
synchronize with the former and fortify better adaptability. These
physiological changes of the plant later proved to be of immense help
to the humans who evolved much later somewhere between 6 million
to 2 million years ago. The physiological and biochemical evolution
of the plants with the synchronous origin of various taxa resulted
in the formation of numerous biochemical pathways producing a
large number of secondary metabolites whose one primary aim is to
protect the plants from herbivores and insect which in the due course
of evolution became an integral part of the food chain. However, the
secondary metabolites also proved to be of immense use to humans
since antiquity who unknowingly since prehistoric times used
plants for their food and medicine. It is only in the past hundred
years or so, people became aware of the chemical constituent of the
plants and started exploring their various beneficial properties. The
agricultural activities also coevolved with human civilization and
with the increase in population, higher yield along with protection
of crops from pathogen attack became a necessity. This lead to the
formulation of fertilizers which consequently paved the way for
biofertilizers with a fewer side effects on humans and animals but
with a more green approach towards fertility enhancement. With
the advent of industrialization the menace of pollution cropped up
and presently this pollution is encroaching soil water and air. This
is having a deleterious effect on the ecosystem concerning human
and animal health and also agricultural productivity. Thus keeping
this in mind the scientific community was determined to remediate
the polluted sites with the help of biological agents in which the
plants and microbes played an important role. This provided major
protection to agriculture from contamination thereby sustaining
productivity. Thus, an attempt is made to highlight the progress
and advances in the field of agriculture and plant science. Thus A
handbook of Agricultural and Plant Sciences is an attempt to compile
information related to the field of agriculture and plant science.
The main purpose of the book is to provide relevant information
to the readers on aspects largely cantered on plants. The book is
divided into three sections namely agriculture and sustainable
development, plants and microbes as nutraceutical agents, and
medicinal potential of plants. Selected chapters in relevance to
the sections have been accommodated to provide an overview. The
first section deals with various aspects through which crops can
be fortified through bio fertilization and also decontamination of
polluted lands. The world population is presently stressing upon
consumption of foods from natural sources as consumption of fast
food with artificial agents is leading to the onset of several diseases.
This has led to a group of foods that confers nutrition as well as
a medicinal benefit at the same time. They are presently termed
and considered nutraceuticals. The second section of the book deals
with the nutraceutical potential of plants and microbes which
are symbiotically associated with plants. The third section is also
related to the second one concerning the medicinal importance. This
section encompasses the medicinal importance of plants. Plants as
antiviral agents have been accommodated because of the current
pandemic situation. The section also contains a chapter on the ant
diabetic potential of plants and also the medicinal importance of
gymnosperms and bioactive potentials of bryophytes which adds
up to the variation in chapters focusing on the medicinal aspect.
The book is also accompanied by several tables within each chapter
which gives a clear and systematic description of the theme that is
discussed upon. The book is an academic venture and would benefit
the scientific community and readers who are interested in the field
of plant sciences.
... 19 With regard to the antiinflammatory activity, some reports indicate that derivatives of chalcone and those of 2'-hydroxychalcone are able to inhibit COX-2 as well as this enzyme catalyzed PGE 2 production. [20][21][22] Moreover, flavonoids, including chalcones, have interesting anti-viral properties against herpesviruses including CMV. [23][24][25] As part of our efforts directed toward the development of novel flavonoid derivatives as potent HCMV growth inhibitors, we report here the synthesis of new 2'hydroxychalcone compounds. Considering the relationship between PGE 2 production and HCMV infection, the chalcone derivatives were designed to present PGE 2 synthesis inhibitory properties. ...
Background
Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity.
Purpose
As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxychalcone compounds to inhibit human cytomegalovirus.
Study design
We first selected the most efficient new synthetic chalcones for their effect against COX-2-catalyzed PGE2.
Study sample
Among the selected compounds, we assessed the antiviral efficacy against different HCMV strains, such as the laboratory strain AD169 and clinical strains (naïve or multi-resistant to conventional drugs) and toxicity on human cells.
Results
The most efficient and less toxic compound (chalcone 7) was tested against HCMV in combination with other antiviral molecules: artesunate (ART), baicalein (BAI), maribavir (MBV), ganciclovir (GCV), and quercetin (QUER) using Compusyn software. Association of chalcone 7 with MBV and BAI is synergistic, antagonistic with QUER, and additive with GCV and ART.
Conclusion
These results provide a promising search path for potential bitherapies against HCMV.
... Buckwold et al. [53] documented that lectin, an isolate from leaves of Pandanus specie using saline medium showed antiviral potential against influenza virus, HSV-1. Also, the crude extract of Pandanus displayed antiviral effectiveness against different groups of viruses which showed the presence of different antiviral agents in various parts of the plant. ...
Influenza A virus has been identified as a major factor responsible for most critical respiratory disease of the Influenza viruses around the globe. Moreover, it has been validated that several medicinal plants could be applied in the management of Influenza when compared to several synthetic drugs which has been acclaimed with several adverse effect A virus. This might be linked to several factors such as their low toxicity, ease of access, low cost, and cultural acceptance. Hence, this chapter intends to provide a detailed information on the application of medicinal plant on the treatment of Influenza A virus. Detailed information was also provided on the mechanism of action utilized by these medicinal plants against Influenza A virus.
... It was reported that xanthohumol, a prenylchalcone flavonoid isolated from the ethanolic extract of the hop cones of Humulus lupulus L. was effective against HIV-1 and might serve as an interesting lead compound as a novel chemotherapeutic agent for HIV-1 infection (18,19). ...
Plants have been used as medicine by mankind to treat health-threatening diseases and still popular to develop new drug candidates. Plants have a combination of phytochemicals also known as secondary metabolites that are naturally occurred gives different therapeutic benefits. Natural products have been recognized as an important role in the drug discovery process moreover the other sources. Presently, over 100 natural product-derived pharmaceuticals are being used in modern medicine. Some of them play as important tools in the immune system exhibiting antiviral potentials. This review presents a survey of natural products and herbal extracts that have indicated broad antiviral activity. © 2020 by Gazi University Medical Faculty - Available on-line at web site http://medicaljournal.gazi.edu.tr/
... Pioneering studies also show that specific hop bitter acids have antivirus effects. For example, iso-α-acids in hops showed antibiotic effects towards bovine viral diarrhea virus and cytomegalovirus (Buckwold et al. 2004;Shimura et al. 2005). Xanthohumol from Humulus lupulus inhibited HIV-1 induced viral reverse transcription in C8166 lymphocytes (Wang et al. 2004). ...
Diversified members of hop bitter acids (α- and β-acids) have been found in hop (Humulus lupulus). Mixtures of hop bitter acids have been traditionally applied in brewing and food industries as bitterness flavors or food additives. Recent studies have discovered novel applications of hop bitter acids and their derivatives in medicinal and pharmaceutical fields. The increasing demands of purified hop bitter acid promoted biosynthesis efforts for the heterologous biosynthesis of objective hop bitter acids by engineered microbial factories. In this study, the updated information of hop bitter acids and their representative application in brewing, food, and medicine fields are reviewed. We also speculate future trends on the development of robust microbial cell factories and biotechnologies for the biosynthesis of hop bitter acids.
Key points
• Structures and applications of hop bitter acids are summarized in this study.
• Biosynthesis of hop bitter acids remains challenging.
• We discuss potential strategies in the microbial production of hop bitter acids.
... Xanthohumol commonly found in hops, serves as a potent inhibitor of enzyme reverse transcriptase thereby inhibiting the process of viral replication [216] The replication of HIV-1 is also inhibited in the peripheral blood mononuclear cells. Buckwold and his coworkers examined antiviral action of a xanthohumol enriched extracts of hops against herpes simplex virus type 2 (HSV-2), bovine viral diarrhea virus (BVDV) and rhinovirus (rhino) [217]. It was found that chalcone 74 from the genus Desmos exhibited potent antiviral activity against HIV. ...
To date, the leading causes of mortality and morbidity worldwide include viral infections , such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review fo-cuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioa-vailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these Citation: Behl, T.; Rocchetti, G.; Chadha, S.; Zengin, G.; Bungau, S.; Kumar, A.; Mehta, V.; Uddin, M.S.; Khullar, G.; Setia, D.; et al. Phyto-chemicals from Plant Foods as Po
... Перечень пищевых продуктов и напитков с антивирусным действием включает зеленый чай [82][83][84][85], морские водоросли [86,87], некоторые лекарственные растения [89][90], яблоки [91], черную смородину [92], чеснок [93], прополис [94], гранат [95], ежевикообразную малину [96] и хмель [97]. ...
... Chalcones ( Fig. 1) represent an important class of natural compounds with a variety of biological activities such as anticancer [2][3][4][5], antimalarial [6,7], antimicrobial [8][9][10], anti-inflammatory [11,12], anti-HIV [13], antiviral [14,15], anti-hyperglycemic [16], tyrosinekinase inhibitory [17] properties. 2-Hydroxy chalcones are natural compounds which have been used as key intermediates for the synthesis of various flavonoids [18][19][20][21][22]. Furthermore, they are considered as important precursors for various biologically active heterocyles [23][24][25][26][27]. ...
An extremely simple, expeditious and greener synthetic method for a variety of chalcone derivatives (3) under mild and solvent free reaction conditions has been developed. The present protocol discloses the use of p-toluenesulfonic acid (p-TSA) as a solid phase organocatalyst which accelerates the Claisen–Schmidt condensation reaction dramatically under mild conditions. Various aryl aldehydes (1) were treated with differently substituted aryl ketones (2) in the presence of p-TSA at 50–60 °C to yield the desired products in a very short period of reaction time. Mild reaction conditions, clean reaction media, expulsion of hazardous solvents, simple work-up, exclusive formation of products in high yields without side products, and easy purification are advantages of the present methodology.
... It was reported that xanthohumol, a prenylchalcone flavonoid isolated from the ethanolic extract of the hop cones of Humulus lupulus L. was effective against HIV-1 and might serve as an interesting lead compound as a novel chemotherapeutic agent for HIV-1 infection (18,19). ...
Plants have been used as medicine by mankind to treat health-threatening diseases and still popular to develop new drug candidates. Plants have a combination of phytochemicals also known as secondary metabolites that are naturally occurred gives different therapeutic benefits. Natural products have been recognized as an important role in the drug discovery process moreover the other sources. Presently, over 100 natural product-derived pharmaceuticals are being used in modern medicine. Some of them play as important tools in the immune system exhibiting antiviral potentials. This review presents a survey of natural products and herbal extracts that have indicated broad antiviral activity.
... Xn has been reported to convey anti-inflammatory effects against lipopolysaccharide (LPS)-induced acute lung injury and ischemia reperfusion-induced liver injury in mice (Ge et al., 2017;Lv et al., 2017), as well as anti-proliferative activities towards breast, colon, and ovarian cancer cell lines (Miranda et al., 1999). Xn also reportedly conveys antiviral activities against human immunodeficiency virus, bovine viral diarrhea virus, and herpes simplex viruses 1 and 2 (Buckwold et al., 2004;Cos et al., 2008). In our previous study, Xn was screened from 386 natural products to inhibit PRRSV proliferation and alleviate oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis in Marc-145 cells . ...
... It was observed that proanthocyanidins C1 nonspecifically bind proteins, but selectively inhibit nuclear factor kappa B (NFkB)-dependent gene expression, that modulate apoptosis [Cos et al., 2004]. A Xanthohumol-enriched Humulus lupulus (hop) extract showed moderate antiviral activity against HSV-1, HSV-2 and CMV in plaque reduction assay [Buckwold et al., 2004]. An interesting SAR is noted with dimeric procyanidins and related polyphenols, where epicatechin-containing dimers showed pronounced anti-HSV activities, as the ortho-trihydroxyl groups in the B-ring with the double interflavan linkages lead to a significant increase of anti-HSV activity. ...
This Reference e-Book contain 11 Chapters with an attempt to summarize the current knowledge of promising ethnomedicines and their phytophores, to compounds tested against diverse diseases. The therapeutic properties and structure activity relationship (SAR) of some important and potentially useful ethnomedicines is addressed with a focus on how these ethnic knowledge can led to the development of useful therapeutic lead for preclinical or clinical evaluation.
In general it is a snapshot of different areas of research on the role of
phytochemicals in health, comprehensively presented and is useful of tidbits
of knowledge or ideas for research, covering the ethnomedicines uses in the
management of several diseases, particularly, infectious diseases (like viral,
bacterial and fungal) and lifestyle related disorders mostly validated by
modern scientific methods. In depth information prepared by experts all over
the globe traces the evolution of herbal drugs with civilization and their
use as antiviral, antibacterial, antifungal, antiparasitic, antioxidants,
anticancerous, chemopreventors, memory enhancers, neuroprotective,
immunomodulator, laxatives, analgesic and anti-inflammatory disorders,
along with safety issues and toxic effects.
... The proanthocyanidin A1 had remarkable anti-herpes activity that block HSV-2 attachment and penetration 6 , while procyanidin C1 inhibit HIV-1 7 . The anti-HSV activity of epicatechin dimers is due to ortho-trihydroxyl groups and the double interflavan linkages 5 , while xanthohumol of Humulus lupulus might serve as a lead for anti-HSV agent 7 . The bis-catechol l-chicoric acid, a dicaffeoyltartaric acid (DCTA), is the most active inhibitor of HIV integrase and envelope gp120 8 . ...
Ethnomedicinal plants have been used as source of drugs for almost all diseases, but none are used against viruses probably because there are a very few specific viral targets for natural molecules to interact. Most of the available antiviral drugs often lead to side effects, viral resistance, recurrence and latency. A wide range of ethnomedicinal plants showed strong antiviral activities either by inhibiting replication, or genome synthesis of many viruses. Hence, development of new antivirals from natural source is an alternate approach. This review will discuss some of the promising antivirals of ethnomedicinal plants with proven in vitro and some documented in vivo activities. People of all continents have long used poultices and infusions of indigenous plants like cedar wood and cypress oil, juice of licorice, myrrh and poppy for the treatment of coughs and colds to parasitic infections and inflammation 1. The clinical virologists are looking into the antiviral plant extracts as (i) the effective life span of antiviral drug is limited; (ii) many viral diseases are intractable to most of the orthodox antivirals, (iii) development of viral resistance, latency and recurrence, and (iv) rapid spread of emerging and reemerging viral diseases like HIV/AIDS, SARS etc. All these spurred intensive investigation into the ethnomedicines, especially for people unable to afford expensive antivirals, and the impressive array of knowledge and wisdom of indigenous people about their generation old medicaments for the development of new or complementary antivirals.
... [9][10][11] According to literary sources, phloroglucinol derivatives (flavaspidic acids, xanthohumol, and euglobals) are responsible for antimicrobial activity; moreover, these compounds have some other important activities, such as anthelmintic, antiviral, antitumor, anti-inflammatory, and antioxidant. [12][13][14][15][16][17] Thus, plants that contain this group of biologically active substances are very promising for further study and development or improvement of phytodrugs technology, especially those having antibacterial activity. Plants of Eucalyptus genus are widely used in medicine all over the world. ...
The article presents the results related to the study of distribution of biologically active substances from the plant raw material between solid and liquid phases. The aim of this study is to develop theoretical bases of the extraction process in the equilibrium state by the example of study and modeling of the distribution process of biologically active substances from Eucalyptus viminalis leaves. In these studies, we used ground plant raw material of E. viminalis leaves with particle fraction of 0.1–0.5 mm; and ethanol with concentration 80% ±1% v/v was used as an extractant. Qualitative and quantitative analyses were carried out by reversed phase high-performance liquid chromatography with rutin, chlorogenic acid, and euglobal standards equivalent to spissum extract of chlorophyllipt of the State Pharmacopoeia of Ukraine. A hypothesis has been suggested that Henry's adsorption law and the law of conservation of matter play a fundamental role in this process. The experimental data are described well by the suggested equation with high value of determination coefficient R² =0.99. At the same time, F-test and the significance of coefficients in equations satisfy the statistic condition, which means that the current hypothesis about the adsorption mechanism of distribution of biologically active substances in the extraction system is not refuted. The results of these studies demonstrate good agreement of experimental data and theoretical model based on Henry's adsorption law and mass balance. The numerical values of constants in the model suggested have been calculated.
... Isoxanthohumol (1) has received most attention as a proestrogen [2] and an antiviral agent [3]. It has also the ability to inhibit growth of breast cancer (MCF-7), ovarian cancer (A-2780), and colon cancer (HT-29) [4]. ...
Microbial transformations of isoxanthohumol ( 1 ), a beer prenylated flavonoid, by 51 fungi were investigated. Many of the tested fungi cultures were capable of effective transformation of 1 . Mucor hiemalis and Fusarium oxysporum converted isoxanthohumol ( 1 ) into isoxanthohumol 7- O -β- d -glucopyranoside ( 3 ) and (2 R )-2″-(2″′-hydroxyisopropyl)-dihydrofurano[2″,3″:7,8]-4″,5-hydroxy-5-methoxyflavanone ( 4 ), respectively. No product was obtained in the transformation of 1 by Absidia glauca conducted in a phosphate buffer. In the same medium, Beauveria bassiana converted isoxanthohumol ( 1 ) to isoxanthohumol 7- O -β- d -4″′- O -methylglucopyranoside ( 2 ).
The genus Humulus currently includes 7 listed species that have common but also differentiating chemical characteristics. Due in particular to their richness in original specialized metabolites, the female infructescences of hop are widely used as a bittering, aromatic and stabilizing ingredient in beer. Wild hops are chemically more diverse than cultivars that come from a common gene pool. Initially oriented towards the study of disease resistance and productivity potential, research on wild hops has exploded in recent decades and in various countries to focus on the search for organoleptic qualities. Wild hops have been hybridized with cultivars, intentionally or spontaneously, giving rise to new original varieties thanks to the heritability of their chemical characteristics transmitted to their descendants. This research has proven itself with the development of cultivars with interesting organoleptic qualities for hopping beer. Depending on the hopping technique used, which has diversified considerably in recent decades, hop compounds undergo numerous chemical reactions during the brewing process, offering the brewer a wide organoleptic spectrum in terms of bitterness and aromas. The volatile compounds of hops, from the more classic terpenes to polyfunctional thiols, have been particularly studied in recent years due to the search for new varieties rich in original aromas.
Chalcones and their derivatives have been widely studied due to their versatile pharmacological and biological activities, such as anti-inflammatory, antibacterial, antiviral, and antitumor effects. These compounds have shown suitable antiviral effects through the selective targeting of a variety of viral enzymes, including lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, protein tyrosine phosphatase, topoisomerase-II, protein kinases, integrase/protease, and lactate/isocitrate dehydrogenase, among others. Chalcones and their derivatives have displayed excellent potential for combating pathogenic bacteria and fungi (especially, multidrug-resistant bacteria). However, relevant mechanisms should be further explored, focusing on inhibitory effects against DNA gyrase B, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), and efflux pumps (e.g., NorA), among others. In addition, the antifungal and antiparasitic activities of these compounds (e.g., antitrypanosomal and antileishmanial properties) have prompted additional explorations. Nonetheless, systematic analysis of the relevant mechanisms, biosafety issues, and pharmacological properties, as well as clinical translation studies, are vital for practical applications. Herein, recent advancements pertaining to the antibacterial, antiviral, antiparasitic, and antifungal activities of chalcones and their derivatives are deliberated, focusing on the relevant mechanisms of action, crucial challenges, and future prospects. Furthermore, due to the great importance of greener and more sustainable synthesis of these valuable compounds, especially on an industrial scale, the progress made in this field has been briefly discussed. Hopefully, this review can serve as a catalyst for researchers to delve deeper into the exploration and designing of novel chalcone compounds with medicinal properties, especially against pathogenic viruses and multidrug-resistant bacteria as major causes of concern for human health.
The female flowers of the Humulus lupulus plant or Hops have been used extensively within the brewing industry for their aroma and bitterness properties. It was also found that beer that contained hops was less likely to spoil, thus revealing the antimicrobial potential of these plants. One species of bacteria, Mycobacterium spp., is of particular interest as it is the causative agent of both human and animal forms of tuberculosis (TB). In this study an aqueous extraction process was employed to analyse the antibacterial properties of 50 hop extracts (45 individual variants); against M. bovis BCG. Using an agar well diffusion assay we found that all hops exhibited a level of inhibitory activity which ranged from 1.2 mm (+/− 0.08 mm) in the case of hop variant; Target, to 15.7 mm (+/− 0.45 mm) in the case of hop variant Citra. The Citra variant had a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 16% v/v. This is the first study to analyse a wide range of hops for their antimicrobial potential against M. bovis BCG and recommends that further research focuses on other Mycobacteria spp., the potential for antimicrobial synergy and the antibacterial effect of individual components.
The COVID-19 pandemic has provided an opportunity for repurposing of drugs, including complex, natural drugs, to meet the global need for safe and effective antiviral medicines which do not promote multidrug resistance nor inflate medical costs. The author herein describes his own repurposing of herbal tinctures, previously prepared for oncology, into a possibly synergistic, anti-COVID 41 “herb” formula of extracts derived from 36 different plants and medicinal mushrooms. A method of multi-sample in vitro testing in green monkey kidney vero cells is proposed for testing the Hypothesis that even in such a large combination, antiviral potency may be preserved, along with therapeutic synergy, smoothness, and complexity. The possibility that the formula’s potency may improve with age is considered, along with a suitable method for testing it. Collaborative research inquiries are welcome.
Dihydrochalcones are a class of secondary metabolites, possessing several biological properties such as antitumor, antioxidant, antibacterial, antidiabetic, estrogenic, anti-inflammatory, antithrombotic, antiviral, neuroprotective and immunomodulator properties; therefore, they are currently considered promising candidates in the drug discovery process. This review intend to debate their pharmacological actions with a particular attention to their antitumor activity against a panel of cancer cell-lines and to the description of the inhibition mechanisms of cell proliferation such as the regulation of angiogenesis, apoptosis, etc etc.
Hops (Humulus lupulus L.), a major constituent of beer, is composed of resins, polyphenols, hop essential oils, various proteins, cellulose, and water. Hops and hop components are well-known for their antimicrobial effects on bacterial growth. Hop components contribute to human health, and numerous studies have shown hops as potent antimicrobial, anti-inflammatory, and anticancer agents. Most health benefits are derived from three main hop components: polyphenols, bitter acids, and essential oil. The effect of hop components on oral health cannot be ignored, considering their role in systemic health. Hop components may have potential uses in treating oral diseases, such as dental caries, periodontal diseases, oral lichen planus, oral candidiasis, and others. However, few studies have focused on the effects of hops on oral health. This review discusses the beneficial effects of hop components on systemic health and potential applications in oral diseases.
The female inflorescence of hops is traditionally used in the brewing industry to impart bitterness, aroma, flavour and longer shelf life to beer, where the bittering acids are the main compounds that enhance the quality of the beer. In recent years, a wide variety of bioactive compounds have been reported to be present in female flowers. Due to the growing consumer interests in natural ingredients, a great deal of research has been carried out in the last few years to find new sources of functional biomolecules. This paper reviews the recent applications of hops in the food, pharmaceutical and cosmetic industries and provides an overview of the bioactive potential of hops. In addition, the analytical techniques of hops compound are reviewed. The biological activities of hops compound such as antibacterial, antifungal, cardioprotective, antioxidant, anti‐inflammatory and anticancer are reviewed and the recent effects of hop bittering derivatives on beer‐related microbial activity are also presented. It is thus clear that hops have a high potential as bioactive components for use as preservatives in fresh foods to extend shelf life and as cosmetic formulations for skin care products as well as nutraceutical and health implications. The female inflorescence of hops is recognised in the brewing industry as a bittering agent and is traditionally used in the brewing industry to impart bitterness, aroma, flavour and longer shelf life to beer, where the bittering acid is the main compound that en‐hances the quality of the beer. The biological activities of hops extracts such as antibacterial, antifungal, cardioprotective, antioxidant, anti‐inflammatory and anticancer are reviewed and the recent effects of hops and their derivatives on beer‐related microbial activity are presented.
Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ubiquitous in edible and medicinal plants, and they are bioprecursors of plant flavonoids. Chalcones and their natural derivatives are important intermediates of the flavonoid biosynthetic pathway. Plants containing chalcones have been used in traditional medicines since antiquity. Chalcones are basically α,β-unsaturated ketones that exert great diversity in pharmacological activities such as antioxidant, anticancer, antimicrobial, antiviral, antitubercular, antiplasmodial, antileishmanial, immunosuppressive, anti-inflammatory, and so on. This review provides an insight into the chemistry, biosynthesis, and occurrence of chalcones from natural sources, particularly dietary and medicinal plants. Furthermore, the pharmacological, pharmacokinetics, and toxicological aspects of naturally occurring chalcone derivatives are also discussed herein. In view of having tremendous pharmacological potential, chalcone scaffolds/chalcone derivatives and bioflavonoids after subtle chemical modification could serve as a reliable platform for natural products-based drug discovery toward promising drug lead molecules/drug candidates.
Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (Mpro) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, we report that Xanthohumol, a small molecule in clinical trials from hops (Humulus lupulus), was a potent pan-inhibitor for various coronaviruses by targeting Mpro, for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 μM), and alphacoronavirus PEDV (IC50 value of 7.51 μM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.
O Brasil chama atenção pela alta biodiversidade e disponibilidade da biomassa fl orestal. O conhecimento de polifenóis, principalmente, biofl avonóides de espécies fl orestais, com grande potencial como agente antiviral (fi tofármacos) é estratégico no tratamento terapêutico contra o SARS-CoV-2, novo coronavírus. Particularmente, nos extratos de espécies fl orestais tropicais, esses biofl avonóides podem ser encontrados em uma gama de compostos químicos, que têm diversos efeitos bioquímicos, e alguns apresentam atividade antiviral comprovada, tais como: kaempferol, herbacetina, quercetina, roifolina, pectolinarina, rutina e quercetina-polioses. Vários trabalhos apontam a protease SARS-CoV 3CLpro como o principal desafi o dos SARS-CoVs, já que a mesma é responsável pela replicação do vírus. Por consequência, é o alvo ideal para identifi cação e desenvolvimento de agentes inibidores da atividade antiviral. Seguindo a mesma linha de raciocínio, outro trabalho demonstrou o potencial inibidor de vários biofl avonóides por estudo de ancoramento molecular da principal protease 3CLpro/Mpro @ PDB ID: 6LU7 do SARS-CoV-2. Foi demonstrado na literatura especializada que os biofl avonóides apresentam baixa toxicidade na dieta humana. Portanto, o principal objetivo desta revisão de literatura é contribuir com uma alternativa a ser considerada para o enfrentamento da COVID-19 com fi tofármacos de baixo custo. É importante salientar que o conhecimento da atividade antiviral destes biofl avonóides de biomassa fl orestal é estratégico no combate a longo prazo ao vírus SARS-CoV-2, bem como de novas pandemias decorrentes do mesmo, ou de outros vírus da família SARS CoV
A well-validated in-silico approach can provide promising drug candidates for the treatment of the ongoing CoVID19 pandemic. In this study, we have screened 32 phytochemical constituents (PCCs) with Mpro binding site (PDB:6W63) based on which we identified three possible candidates that are likely to be effective against CoVID19—viz., licoleafol (binding energy: −8.1 kcal/mol), epicatechin gallate (–8.5 kcal/mol) and silibinin (–8.4 kcal/mol) that result in higher binding affinity than the known inhibitor, X77 (–7.7 kcal/mol). Molecular dynamics (MD) simulations of PCCs-Mpro complex confirmed molecular docking results with high structural and dynamical stability. The selected compounds were found to exhibit low mean squared displacements (licoleafol: 2.25 ± 0.43 Å, epicatechin gallate: 1.93 ± 0.35 Å, and silibinin: 1.39 ± 0.19 Å) and overall low fluctuations of the binding complexes (root mean squared fluctuations below 2 Å). Visualization of the MD trajectories and structural analyses revealed that they remain confined to the initial binding region, with mean fluctuations lower than 3 Å. To access the collective motion of the atoms, we performed principal component analysis demonstrating that the first 10 principal components are the major contributors (approximate contribution of 80%) and are responsible for the overall PCCs motion. Considering that the three selected PCCs share the same flavan backbone and exhibit antiviral activity against hepatitis C, we opine that licoleafol, epi-catechin gallate, and silibinin can be promising anti-CoVID19 drug candidates.
Communicated by Ramaswamy H. Sarma
Idiopathic pulmonary fibrosis (IPF) is a group of lung disease that mainly affects the interstitium and ultimately results in the inflammation and damaging to the lung tissues [1]. The tissues present around the air sacs are called interstitium. Because of the thickening and scarring, lung tissues become damaged, and make it difficult to work. The scarring gets worse by the time which makes it difficult to breathe and keep the optimum levels of oxygen in the bloodstream. This affects the functioning of the vital organs as they are slowly depriving off oxygen. This disease is characterised by destruction of alveoli along with abnormal accumulation of fibroblasts giving the lungs a “honeycomb” like structure. Generally, this disease is more common in men over 50 years of age and two-thirds are diagnosed after 60 years of age [2]. Approximately 50,000 new cases of IPF are diagnosed each year and the symptoms came first into notice between the age of 50 and 70 years. Earlier the symptoms begin with the shortening of breathe but by the time this condition gets worse by eating or talking. At present, in the USA more than 80,000 adults are suffering from this disease and more than 30,000 cases are diagnosed every year [3]. Here the term “idiopathic” is used because the exact cause of scarring of tissues cannot be figured out (Fig. 15.1).
Tuberculosis is a highly contagious infectious disease triggered by Mycobacterium tuberculosis, which is widely spread by aerosol. The major site of infection is usually the lungs however the disease can attack any extra-pulmonary site as well, which is further diagnosis by necrotizing granulomatous inflammation. World Health Organization reported almost 8.9–10 million people are suffering from tuberculosis in 2019, including 56% men and 32% women, and 12% children. Multidrug-resistant tuberculosis (MDR-TB) is a medical condition in which Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin. In-vitro studies suggest that several bioactive compounds and their synthetic derivatives obtained from plants, fungi, and marine organism possesses antimycobacterial affinity. Phenolic compounds such as dihydrocubebin, hinokinin, ethoxycubebin possess the antimycobacterial activity. Mycobacterial cell envelope antagonists have been shown to obstruct the synthesis of mycolic acids, arabinogalactan, and peptidoglycan, essential components of the mycobacterial cell wall. The paramount antituberculous drugs hamper the development of mycolic acids or the aid mechanism which links them to the cell membrane. Medicines targeting RNA synthesis encompass those that restrict the assembly of bacterial DNA-dependent RNA polymerases, that are indispensable enzymes for RNA synthesis. Various molecular pathways for the target to cure tuberculosis entail the targets of M. tuberculosis cell wall synthesis, energy metabolism, folate metabolism, DNA replication, and RNA synthesis. Interestingly, in preserving the health of patients diagnosed with tuberculosis, medicinal plants have tremendous advantages with limited side effects as compare to the standard drugs.
Objective: To explore natural compounds as potential inhibitors against main protease (Mpro) of SARS-CoV-2.
Methods: In the current study, systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro. Selected natural compounds were further validated using a combination of molecular dynamic (MD) simulations and molecular mechanic Poisson-Boltzmann surface area (MM/PBSA) free energy calculations.
Results: Out of twenty natural compounds, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis. During MD simulations, all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein.
Conclusions: Guggulsterone is a potential inhibitor of COVID- 19 main protease Mpro. Further in vitro and pre-clinical studies are needed.
During the time of the novel coronavirus disease 2019 (COVID-19) pandemic, it has been crucial to search for novel antiviral drugs from plants and well as other natural sources as alternatives for prophylaxis. This work reviews the antiviral potential of plant extracts, and the results of previous research for the treatment and prophylaxis of coronavirus disease and previous kinds of representative coronaviruses group. Detailed descriptions of medicinal herbs and crops based on their origin native area, plant parts used, and their antiviral potentials have been conducted. The possible role of plant-derived natural antiviral compounds for the development of plant-based drugs against coronavirus has been described. To identify useful scientific trends, VOSviewer visualization of presented scientific data analysis was used.
Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families–Herpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Poxviridae, Nimaviridae, Coronaviridae, Reoviridae, and Rhabdoviridae–that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.
Flavonoids by to their natural properties and diverse applications are a group of compounds whose study of their origin, characteristics and applications has been dedicated to extensive research. For the organic synthesis of chalcones, due to their interest as precursor molecules of different compounds, several pathways have been developed that have been reported in numerous works. Given the importance of flavonols, as compounds of pharmacological interest mainly, new synthesis routes are proposed, in addition to those already existing. In this work, the main pathways for the synthesis of chalcones are presented and new pathways for the synthesis of flavonols such as (-) melacacidin are proposed.
The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.
The female flowers of the hop plant are used as a preservative and as a flavoring agent in beer. However, a recurring suggestion has been that hops have a powerful estrogenic activity and that beer may also be estrogenic. In this study, sensitive and specific in vitro bioassays for estrogens were used for an activity-guided fractionation of hops via selective solvent extraction and appropriate HPLC separation. We have identified a potent phytoestrogen in hops, 8-prenylnaringenin, which has an activity greater than other established plant estrogens. The estrogenic activity of this compound was reflected in its relative binding affinity to estrogen receptors from rat uteri. The presence of 8-prenylnaringenin in hops may provide an explanation for the accounts of menstrual disturbances in female hop workers. This phytoestrogen can also be detected in beer, but the levels are low and should not pose any cause for concern.
We have previously reported that 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and its 2-bromo analog (2-bromo-5,6-dichloro-1-(beta-D-ribofuranosy)benzimidazole [BDCRB]) are potent and selective inhibitors of human cytomegalovirus (HCMV) replication that block viral DNA maturation via HCMV gene products UL89 and UL56. To determine if phosphorylation is required for antiviral activity, the in vitro metabolism of BDCRB was examined and the antiviral activities of nonphosphorylatable 5'-deoxy analogs were determined. Reverse-phase high-performance liquid chromatography (HPLC) analysis of extracts from uninfected and HCMV-infected cells incubated with [(3)H]BDCRB revealed two major metabolites. Both were less polar than naturally occurring nucleoside monophosphates, but one peak coeluted with a BDCRB-5'-monophosphate (BDCRB-5'-MP) standard. Further analysis revealed, however, that neither metabolite partitioned with BDCRB-5'-MP on anion-exchange HPLC. Their retention patterns were not affected by incubation with alkaline phosphatase, thereby establishing that the compounds were not nucleoside 5'-monophosphates. Both compounds were detected in uninfected and HCMV-infected cells and in mouse live extracts, but neither has been identified. Like TCRB and BDCRB, the nonphosphorylatable 5'-deoxy analogs were potent and selective inhibitors of HCMV replication. The 5'-deoxy analogs maintained inhibition of HCMV replication upon removal of BDCRB, whereas an inhibitor of DNA synthesis did not. Similar to TCRB, its 5'-deoxy analog (5'-dTCRB) did not affect viral DNA synthesis, but 5'-dTCRB did inhibit viral DNA maturation to genome-length units. Additionally, virus isolates resistant to TCRB were also resistant to 5'-dTCRB and the 5'-deoxy analog of BDCRB. Taken together, these results confirm that TCRB, BDCRB, and their 5'-deoxy analogs have common mechanisms of action and establish that these benzimidazole ribonucleosides, unlike other antiviral nucleosides, do not require phosphorylation at the 5' position for antiviral activity.
Characterization and use of effective cancer chemopreventive agents have become important issues in public health-related research. Aiming to identify novel potential chemopreventive agents, we have established an interrelated series of bioassay systems targeting molecular mechanisms relevant for the prevention of tumor development. We report anticarcinogenic properties of Xanthohumol (XN), a prenylated chalcone from hop (Humulus Iupulus L.) with an exceptional broad spectrum of inhibitory mechanisms at the initiation, promotion, and progression stage of carcinogenesis. Consistent with anti-initiating potential, XN potently modulates the activity of enzymes involved in carcinogen metabolism and detoxification. Moreover, XN is able to scavenge reactive oxygen species, including hydroxyl- and peroxyl radicals, and to inhibit superoxide anion radical and nitric oxide production. As potential antitumor-promoting mechanisms, it demonstrates anti-inflammatory properties by inhibition of cyclooxygenase-1 and cyclooxygenase-2 activity and is antiestrogenic without possessing intrinsic estrogenic potential. Antiproliferative mechanisms of XN to prevent carcinogenesis in the progression phase include inhibition of DNA synthesis and induction of cell cycle arrest in S phase, apoptosis, and cell differentiation. Importantly, XN at nanomolar concentrations prevents carcinogen-induced preneoplastic lesions in mouse mammary gland organ culture. Because XN is easily cyclized to the flavanone isoxanthohumol, activities of both compounds were compared throughout the study. Together, our data provide evidence for the potential application of XN as a novel, readily available chemopreventive agent, and clinical investigations are warranted once efficacy and safety in animal models have been established.
Monotherapy of hepatitis C virus infection with either alpha interferon or ribavirin alone is rather ineffective, while the
use of the two antivirals together is much more efficacious. In vitro drug-drug combination analysis utilizing related members
of the family Flaviviridae, bovine viral diarrhea virus and yellow fever virus, revealed significant direct synergistic interactions between these drugs'
antiviral activities that might explain this clinical observation.
The flavonoids of hops include flavonol glycosides, condensed tannins, and prenylflavonoids. The first two flavonoid classes are located intracellularly, while the prenylflavonoids are secreted along with bitter acids and essential oils by the lupulin glands of the inflorescences. The chemistry and biological activities of prenylflavonoids isolated from the lupulin fraction are reviewed. An LC-MS method was developed for quantitation of these phenolics in hops, hop-derived products, and beer. The fate of xanthohumol and related prenylflavonoids during the brewing process was investigated by LC-MS. The partial carryover of the prenylflavonoids from hops into beer was attributed mainly to incomplete extraction and adsorption to insoluble proteins and yeast. Moreover, the prenylchalcone-type flavonoids were largely converted into isomeric prenylflavanones during wort boiling. The biological activities of some of the prenylflavonoids isolated were examined using in vitro techniques. Some of the prenylflavonoids inhibited the growth of breast cancer (MCF-7) cells in a dose-dependent manner. Xanthohumol and related prenylflavonoids also inhibited the cytochrome P450-mediated activation of procarcinogens and induced the activity of the carcinogen-detoxifying enzyme, quinone reductase. The prenylflavonoids were not toxic to normal cells (rat hepatocytes) at the same concentrations. Recent literature reports of biological activities are briefly discussed: inhibition of bone resorption, inhibition of diacylglycerol acyltransferase, and antimicrobial activities.
The subject of beer flavor is presented and a description of the aroma and taste properties is given. Importance of studying the taste character of beer is stressed and a brief review is presented of the chemistry and taste properties of some nonvolatile resin constituents of hops. Some results are presented on the application of ion-exchange Chromatographic and high-pressure liquid Chromatographie analysis for the separation of hop resin compounds present in beer as well as in some samples representing different parts of the brewing process. The ion-exchange Chromatographic procedure, while capable of resolving some beer bitter compounds, suffers from being a slow procedure with the possibilities of producing artifacts when working with the rather unstable group of hop compounds. The high-pressure liquid Chromatographic procedure appears to have great potential in the analysis of hop bitter compounds. The method is rapid and produces a good resolution of hop compounds.
We have developed an effective and optimally safe microculture method for rapid and convenient assay of the in vitro cytopathic effects of human immunodeficiency virus (HIV-1) on human lymphoblastoid or other suitable host cells. The assay procedure is applicable to the evaluation of drug effects on in vitro infections induced directly in cultured host cells by cell-free HIV-1 or by coculture with H9 cells chronically infected with HIV-1. The assay uses a newly developed tetrazolium reagent that is metabolically reduced by viable cells to yield a soluble, colored formazan product measurable by conventional colorimetric techniques. This simple microassay minimizes the number of plate manipulations typically required with other assay methods and, coupled with computerized data collection and analysis, facilitates large-scale screening of agents for potential antiviral activity. To support and enhance the discovery of new anti-HIV-1 agents, the National Cancer Institute is offering investigators worldwide the opportunity to submit new candidate agents for anti-HIV-1 screening with this method.
Hop bitter acids, humulones (1) and lupulones (2), were shown to have potent DPPH radical scavenging activity (RSA) and lipid peroxidation inhibitory activity (LIA). Furthermore, 5-acetyl lupulones (3) and 4-methyl lupulones (4) had more potent LIA than native lupulones but no RSA. This result indicates that the beta, beta'-triketone moiety of the lupulones has LIA.
The active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of myelomonocytic leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. VD3 mobilizes calcium stores from bone by inducing the dissolution of bone mineral and matrix. We have recently found that humulone, a bitter in the hop extract for beer brewing, effectively inhibits bone resorption. In this study we examined the effect of humulone on the differentiation of human myelogenous leukemia cells. Humulone alone inhibited the growth of monoblastic leukemia U937 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Humulone effectively enhanced the differentiation-inducing action of VD3. Other myelomonocytic leukemia cells were induced to differentiate by VD3 and this was also enhanced by humulone. Since humulone is a less-toxic inhibitor of bone resorption, the combination of humulone and VD3 may be useful in differentiation therapy of myelomonocytic leukemia.
A method for quantitation of six prenylflavonoids (xanthohumol, isoxanthohumol, desmethylxanthohumol, 6- and 8-prenylnaringenins and 6-geranylnaringenin) in hops and beer by HPLC-tandem mass spectrometry has been developed. The method allows direct analysis of beer and crude methanolic extracts of hops. After HPLC separation, prenylflavonoids were detected by positive ion multiple-reaction monitoring using a triple-quadrupole mass spectrometer equipped with a heated nebulizer--atmospheric pressure chemical ionization interface. The accuracy and precision were evaluated by replicate analyses of (spiked) samples. Thirteen commercial beers were analysed with the method. Isoxanthohumol, formed by isomerization of xanthohumol during the brewing process, was the most abundant flavonoid in hopped beers, ranging from 0.04 to 3.44 mg/l.
The fate of three prenylated flavonoids of the chalcone type, xanthohumol, desmethylxanthohumol, and 3'-geranylchalconaringenin, was monitored with LC/MS-MS from hops (Humulus lupulus L.) to beer in two brewing trials. The three prenylchalcones were largely converted into their isomeric flavanones, isoxanthohumol, prenylnaringenins, and geranylnaringenins, respectively, in the boiling wort. Losses of prenylflavonoids were due to incomplete extraction from the hops into the wort (13-25%), adsorption to insoluble malt proteins (18-26%), and adsorption to yeast cells (11-32%) during fermentation. The overall yield of xanthohumol, after lagering of the beer and largely in the form of isoxanthohumol, amounted to 22-30% of the hops' xanthohumol. About 10% of the hops' desmethylxanthohumol, completely converted into prenylnaringenins, remained in the beers. 3'-Geranylchalconaringenin behaved similarly to desmethylxanthohumol. Solubility experiments indicated that (1) malt carbohydrates form soluble complexes with xanthohumol and isoxanthohumol and (2) solubility does not dictate the isoxanthohumol levels of finished beers.
The Cultivated Hop. In Hops
- R A Neve
Neve, R.A., 1991. The Cultivated Hop. In Hops. Chapman & Hall, London (Chapter 2).
Composition and Analysis of Hops and Derived Products
- H Pfenninger
- F Schur
- P Anderegg
Pfenninger, H., Schur, F., Anderegg, P., 1979. In: Pollock, J.R.A. (Ed.), Composition and Analysis of Hops and Derived Products. Part D. Brewing Science, Academic Press, London.