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In Vitro Inhibition of Human Influenza A Virus Infection by Fruit-Juice Concentrate of Japanese Plum (Prunus mume SIEB. et ZUCC)
Abstract
Using a plaque reduction assay, treatment of human influenza A viruses with the fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC) showed strong in vitro anti-influenza activity against human influenza A viruses before viral adsorption, but not after viral adsorption, with 50% inhibitory concentration (IC50) values against A/PR/8/34 (H1N1) virus, A/Aichi/2/68 (H3N2) virus and A/Memphis/1/71 (H3N2) virus of 6.35+/-0.17, 2.84+/-1.98 and 0.53+/-0.10 microg/ml, respectively. The plum-juice concentrate exhibited hemagglutination activity toward guinea pig erythrocytes. Its hemagglutination activity was inhibited by the monosaccharide N-acetylneuraminic acid and a sialoglycoprotein (fetuin), but not by the other tested monosaccharides (mannose, galactose, glucose and N-acetylglucosamine), suggesting the presence of a lectin-like molecule(s) in the Japanese plum-juice concentrate. Our findings suggest that the fruit-juice concentrate of Japanese plum may prevent and reduce infection with human influenza A virus, possibly via inhibition of viral hemagglutinin attachment to host cell surfaces by its lectin-like activity.
... Several PDFGS interfered with IAV entry into host cells ( Table 4). PDFGS such as edible bird nest (EBN) extracts, lectinlike compounds from Japanese plum, green tea, guava tea, isorhamnetin, tannins, HS, and polysaccharides from marine algae suppressed IAV-host cellular interactions through the inhibition of viral HA activities (41,45,51,57,66,67). PDFGS such as Portulaca oleracea (P. ...
... oleracea) extracts, quercetin and EBN are able to prevent virus-host interaction by binding with strong affinity to the surface coats of IAV (25,57,70). Yingsakmongkon (Yingsakmongkon, 2008) reported that a lectin-like compound from Japanese plum which agglutinated pig erythrocytes, prevented virus-host interaction. By virtue of their structural characteristics, lectins can potentially interact with glycoprotein on the cell surface to inhibit viral entry (73). ...
... The antiviral effect of EBN extract was enhanced on digestion with pancreatin F which generated smaller 10-25 kDa sialylglycoproteins (57). Lectinlike compounds with antiviral properties have also been isolated from Japanese plums (67). Sulphated polysaccharides from Aphanothece sacrum have been shown to possess activity against influenza viruses (61). ...
Human diet comprises several classes of phytochemicals some of which are potentially active against human pathogenic viruses. This study examined available evidence that identifies existing food plants or constituents of edible foods that have been reported to inhibit viral pathogenesis of the human respiratory tract. SCOPUS and PUBMED databases were searched with keywords designed to retrieve articles that investigated the effect of plant-derived food grade substances (PDFGS) on the activities of human pathogenic viruses. Eligible studies for this review were those done on viruses that infect the human respiratory tract. Forty six (46) studies met the specified inclusion criteria from the initial 5,734 hits. The selected studies investigated the effects of different PDFGS on the infectivity, proliferation and cytotoxicity of different respiratory viruses including influenza A virus (IAV), influenza B virus (IBV), Respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), Human coronavirus NL63 (HCoV-NL63), and rhinovirus (RV) in cell lines and mouse models. This review reveals that PDFGS inhibits different stages of the pathological pathways of respiratory viruses including cell entry, replication, viral release and viral-induced dysregulation of cellular homeostasis and functions. These alterations eventually lead to the reduction of virus titer, viral-induced cellular damages and improved survival of host cells. Major food constituents active against respiratory viruses include flavonoids, phenolic acids, tannins, lectins, vitamin D, curcumin, and plant glycosides such as glycyrrhizin, acteoside, geniposide, and iridoid glycosides. Herbal teas such as guava tea, green and black tea, adlay tea, cistanche tea, kuding tea, licorice extracts, and edible bird nest extracts were also effective against respiratory viruses in vitro. The authors of this review recommend an increased consumption of foods rich in these PDFGS including legumes, fruits (e.g berries, citrus), tea, fatty fish and curcumin amongst human populations with high prevalence of respiratory viral infections in order to prevent, manage and/or reduce the severity of respiratory virus infections.
... et Zucc.) has been shown to improve human blood fluidity (Chuda et al., 1999), to inhibit angiotensin II-induced growth signals of vascular smooth muscle cells, possibly leading to reduction of cardiovascular diseases (Utsunomiya et al., 2002), and to suppress Helicobacter pylori-induced glandular stomach lesions in Mongolian gerbils (Otsuka et al., 2005). Recently, we found that it markedly inhibited the growth of influenza laboratory strains A/PR/8/34 (H1N1), A/Aichi/2/68 (H3N2) and A/Memphis/1/71 (H3N2) in vitro (Yingsakmongkon et al., 2008). In the present study, five com-pounds were isolated and identified from the fruit-juice concentrate by HPLC and NMR spectroscopy. ...
... Our previously published data (Yingsakmongkon et al., 2008) showed that the pretreatment of cells followed by inoculation of Fig. 2. (a) Separation of HMF derivatives from the fruit-juice concentrate and from fructose-citric acid reaction and fructose-malic acid reaction using a 10-ll injection on a reverse-phase Cosmosil 5C 18 -AR-II column. Arrows indicate peaks of each HMF derivative. ...
... In the absence of an influenza virus, hemagglutination activity of HMF with malic acid (MA1 and MA2: MCs of 6.3 and 1.6 mM, respectively) was comparable to that of HMF with citric acid (MF and MF': MCs of 6.3 and 12.5 mM, respectively), whereas unconjugated HMF was inactive (Fig. 3). This is in good agreement with our previous results (Yingsakmongkon et al., 2008) indicating the existence of lectin-like molecules, which probably interact with sialylsugar chains, in the fruit-juice concen-trate. In the presence of the pandemic influenza A/Narita/2009 (H1N1) virus, we found that at concentrations without hemagglutination activity, MF and MF' inhibit viral HA binding to guinea pig erythrocytes with MIC of 3.1 and 6.3 mM, respectively (Fig. 3). ...
Fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc.) has been shown to be effective against influenza A infection in MDCK cells. In this study, we isolated five components from the fruit-juice concentrate of Japanese apricot, 5-(hydroxymethyl)-2-formylfuran (HMF), 1-[5-(2-formylfuryl)methyl]dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate (mumefural, MF), 2-[5-(2-formylfuryl)methyl]dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate (MF‘), 1-[5-(2-formylfuryl)methyl]hydrogen 1-hydroxyethane-1,2-dicarboxylate (MA1) and 2-[5-(2-formylfuryl)methyl]hydrogen 1-hydroxyethane-1,2-dicarboxylate (MA2), and investigated their inhibitory activities against the novel influenza A/Narita/1/2009 (H1N1) pandemic virus hemagglutinin and neuraminidase functions, which are essential for viral attachment and budding, respectively. An hemagglutination inhibition assay indicated that MF and MF‘ were effective at minimum hemagglutination concentrations of 3.1 and 6.3 mM, respectively. An inhibition study for sialidase activity of the neuraminidase spike showed that MF was the most active anti-sialidase compound with an IC50 value of 0.21 ± 0.01 mM, followed by MA2 (IC50, 0.71 ± 0.09 mM), MA1 (IC50, 1.64 ± 0.31 mM) and MF‘(IC50, 1.62 ± 0.22 mM). Furthermore, MF was shown to inhibit the growth of the pandemic virus in a dose-dependent manner (62 ± 3% inhibition at 5 mM). The results suggest that MF, a citric acid ester linked to HMF at the 1-position of the propane backbone, might be a lead compound for the development of anti-influenza A inhibitors.Research highlights► Five compounds were isolated from fruit-juice concentrate of Japanese apricot. ► Four HMF derivatives, but not HMF, exhibited lectin-like activity. ► Mumefural and its derivative can abolish hemagglutination of influenza virus. ► Mumefural was the most active anti-sialidase compound of all five isolated compounds. ► Mumefural inhibited the growth of a novel pandemic 2009 H1N1 virus in cell culture.
... A combination of leaves (matarratón, galve, sauco, espabonilla) was crushed and left (soaked) for a complete day, then in the subsequent days, daily morning baths are given based on this water (Code: MGSES). Inhalations were made through boiling water vaopur where panela, ginger rhizome, garlic, clove, onion juice, lemon, chamomile juice were boiled and it was taken for a week continuously (Code: EJ) [55]. ...
... Commonly, in the present scenario during the ongoing pandemia the common medicinal plants which are popular in medically weak country like Colombia are: garlic, chamomile, eucalyptus, lemongrass, lemon, soon-relief, curcuma and ginger [72]. This is very well supported by the four principal medicinal plants with strong pharmacological activity in garlic, which is rich in sulfur containing phytoconstituents such as allicin, ajoenes, vinyldithiins and flavonoids such as quercetin [55,75]. Likewise, ginger has the primary agents like phenylalklketones or Vanillyl ketones [73]. ...
The main background of this study is that corona virus (COVID-19) has caused a global chaos where there was a complete lockdown of the whole planet as well as the collapse of the health system in many developed, developing and under-developed countries. This situation has caused a public health system and till date no decisive treatment is being confirmed so far. The present study from western Colombia focuses on the importance of traditional, cultural and generations history with reference to the use of importance and significance of medicinal plants, especially to find out a strategy to fight the new virus. The study was designed based on three major novel ethno-environmental strategies based on infusion, hot drinks, fresh baths and jelly types were identified. Based on the generated results, the calculated highest used species in the present pandemia indicates Zingiber officinale Roscoe (1.0), Eucalyptus globulus Labiil. (0.86), Citrus x limon (L.) Osbeck (0.80), Gliricidia sepium (Jacq.) Walp (0.56) and Matricaria recutita L. (0.52) were the species with the highest use. No significant difference was observed between men and women for the level of knowledge on these traditional medicinal plants. Moreover, many of the scientific information demonstrate their effectiveness in treating the respiratory infections caused due to the corona virus. The results infer the importance of traditional medicine, knowledge which needs more attention and research to counter attack the outbreak especially in medically weak health systems.
... Therefore, it is urgently needed to develop safe and effective new antiviral drugs to combat viral infection either for therapeutic or prophylactic purposes. As such, many research groups have been trying to find new effective antiviral drug, especially, from the natural resources [6][7][8][9]. ...
... Each value was an average from three independent experiments. Selectivity index (SI) was calculated by the ratio of TC 50 /IC 50 [6]. ...
A new lignan glycoside, (+)-pinoresinol 4-O-[6″-O-vanilloyl]-β-d-glucopyranoside (1) and two known phenolic compounds, 6'-O-vanilloyltachioside (2) and 6'-O-vanilloylisotachioside (3) were isolated from the latex of Calotropis gigantea (Asclepiadaceae). The structure of the new compound was elucidated by using spectroscopic and chemical methods. Three isolates (1-3) and one authentic compound, (+)-pinoresinol 4-O-β-d-glucopyranoside, were screened for A/PR/8/34 (H1N1) inhibitory activity by cytopathic effect (CPE) inhibition assay on MDCK cells. Compound 1 showed inhibitory activity against A/PR/8/34 (H1N1). In sharp contrast, the other three compounds (2, 3 and (+)-pinoresinol 4-O-β-d-glucopyranoside) did not show such activity. An analysis of structure-activity relationship between 1 and (+)-pinoresinol 4-O-β-d-glucopyranoside revealed that the presence of a vanilloyl group in the sugar moiety of 1 is crucial for its anti-influenza virus activity. Compound 1 was further evaluated for in vitro inhibitory activities against a panel of human and avian influenza viruses by CPE inhibition assay. It showed inhibitory effect against human influenza viruses in both subtypes A and B (IC50 values around 13.4-39.8 µM with SI values of 3.7-11.4), while had no effect on avian influenza viruses. Its antiviral activity against human influenza viruses subtype A was further confirmed by plaque reduction assay. The time course assay indicated that 1 exerts its antiviral activity at the early stage of viral replication. A mechanistic study showed that 1 efficiently inhibited influenza virus-induced activation of NF-κB pathway in a dose-dependent manner, but had no effect on virus-induced activation of Raf/MEK/ERK pathway. Further studies demonstrated that nuclear translocation of transcription factor NF-κB induced by influenza virus was significantly blocked by 1, meanwhile, nuclear export of viral ribonucleoproteins was also effectively inhibited. These findings suggest that this new lignan glycoside from Calotropis gigantea, may have therapeutic potential in influenza virus infection through inhibition of NF-κB pathway and viral ribonucleoproteins nuclear export.
... In addition, the unripe P. mume showed inhibitory activity against Helicobacter pylori motility [45]. Yingsakmongkon et al. studied concentrated fruit juice to prevent or reduce the virus infection in human influenza [46]. Prunate isolated from P. mume has inhibitory activity on the proliferation of cancer cells [46,47]. ...
... Yingsakmongkon et al. studied concentrated fruit juice to prevent or reduce the virus infection in human influenza [46]. Prunate isolated from P. mume has inhibitory activity on the proliferation of cancer cells [46,47]. Antioxidant activities of flowers and fresh fruits of P. mume have been examined [48,49]. ...
Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.
... Bioengineering 2023, 10, 74 ...
Prunus mume Siebold et Zuccarini is mainly consumed as processed fruits in beverages, vinegar, alcohol, or fruit syrup; studies have reported various functional effects. Many pharmacological and functional studies exist on fruit extracts or processed foods using fruits, however, efficacy studies on various parts of P. mume, including the bark, branches, flowers, and leaves, have not been sufficiently conducted. A previous study revealed that a 70% ethanol extract of P. mume branches induced vascular endothelium-dependent vasorelaxant effects in rat thoracic aortic rings. Therefore, we hypothesized that various parts (the fruits, flowers, leaves, and bark) might have vasorelaxant effects. We evaluated the effects of P. mume extracts on the vascular relaxation of isolated rat thoracic aorta and hypotensive effects in spontaneous hypertensive rats (SHR). A 70% ethanol extract of P. mume bark (PBaE) was the most effective, thus, we investigated its vasorelaxant mechanisms and hypotensive effects. PBaE lowered the blood pressure in SHR and induced the vascular endothelium-dependent relaxation of isolated rat aortic rings via the NO/sGC/cGMP and the PGI2 pathways in the vascular smooth muscle. Potassium channels, such as KCa, KATP, KV, and Kir, were partially associated with a PBaE-induced vasorelaxation. Therefore, PBaE might help prevent and treat hypertension.
... For example, Nishide et al. (2019) showed that phenolic extracts of Japanese apricot exert antiviral effects against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2); they speculated that binding of the phenolics to certain component(s) of viral particles is the likely cause of virus inactivation. Yingsakmongkon et al. (2008) also demonstrated the inhibitory effects of the fruit juice concentrate of Japanese plum on human influenza A virus infecting host MDCK cells; these effects are attributed to the activity of heat-stable lectin-like molecule(s). Taken together, P. mume extract could be valuable as a food preservative due to its potential effects against major foodborne pathogens. ...
Prunus mume Sieb. et Zucc (P. mume) is an acidic fruit native to China (named Chinese Mei or greengage plum). it is currently cultivated in several Asian countries, including Japan ("Ume"), Korea (Maesil), and vietnam (Mai or Mo). Due to its myriad nutritional and functional properties, it is accepted in different countries, and its characteristics account for its commercialization. in this review, we summarize the information on the bioactive compounds from the fruit of P. mume and their structure-activity relationships (SAR); the pulp has the highest enrichment of bioactive chemicals. The nutritional properties of P. mume and the numerous uses of its by-products make it a potential functional food. P. mume extracts exhibit antioxidant, anticancer, antimicrobial, and anti-hyperuricaemic properties, cardiovascular protective effects, and hormone regulatory properties in various in vitro and in vivo assays. SAR shows that the water solubility, molecular weight, and chemical conformation of P. mume extracts are closely related to their biological activity. However, further studies are needed to evaluate the fruit's potential nutritional and functional therapeutic mechanisms. The industrial process of large-scale production of P. mume and its extracts as functional foods or nutraceuticals needs to be further optimized.
... Lectin derived from jackfruit seeds inhibits HSV-2, VZV, and hCMV and shows mitogenic action for NK lymphocytes (CD16+/CD56+) (Wetprasit et al., 2000). (Yingsakmongkon et al., 2008). The concentrated fruit juice extract of Japanese Plum prevents and reduces the infectivity of human influenza A virus and it may be due to the presence of lectin-like compounds (with high molecular weight) which inhibits the attachment of viral hemagglutination on host cell surfaces. ...
Plant-derived bioactive molecules display potential antiviral activity against various viral targets including mode of viral entry and its replication in host cells. Considering the challenges and search for antiviral agents, this review provides substantiated data on chemical constituents of edible fruits with promising antiviral activity. The bioactive constituents like naringenin, mangiferin, α-mangostin, geraniin, punicalagin, and lectins of edible fruits exhibit antiviral effect by inhibiting viral replication against IFV, DENV, polio, CHIKV, Zika, HIV, HSV, HBV, HCV, and SARS-CoV. The significance of edible fruit phytochemicals to block the virulence of various deadly viruses through their inhibitory action against the entry and replication of viral genetic makeup and proteins are discussed. In view of the antiviral property of active constituents of edible fruits which can strengthen the immune system and reduce oxidative stress, they are suggested to be diet supplements to combat various viral diseases including COVID-19.
Practical applications
Considering the increasing threat of COVID-19, it is suggested to examine the therapeutic efficacy of existing antiviral molecules of edible fruits which may provide prophylactic and adjuvant therapy with their potential antioxidant, anti-inflammatory, and immune-modulatory effects. Several active molecules like geraniin, naringenin, (2R,4R)-1,2,4-trihydroxyheptadec-16-one, betacyanins, mangiferin, punicalagin, isomangiferin, procyanidin B2, quercetin, marmelide, jacalin lectin, banana lectin, and α-mangostin isolated from various edible fruits have showed promising antiviral properties against different pathogenic viruses. Especially flavonoid compounds extracted from edible fruits possess potential antiviral activity against a wide array of viruses like HIV-1, HSV-1 and 2, HCV, INF, dengue, yellow fever, NSV, and Zika virus infection. Hence taking such fruits or edible fruits and their constituents/compounds as dietary supplements could deliver adequate plasma levels in the body to optimize the cell and tissue levels and could lead to possible benefits for the preventive measures for this pandemic COVID-19 situation.
... In antiviral studies, a fruitjuice concentrate of P. mume inhibited human influenza A virus infection before viral adsorption in Mard in Darby canine kidney (MDCK) cells, presumably through activity of a heat-stable lectin-like molecule (Yingsakmongkon et al., 2008). Furan derivatives and phenolics extract might be the active antiviral components of P. mume relevant to the inhibition of multiplication of influenza pandemic virus and several other RNA and DNA viruses (Sriwilaijaroen et al., 2011;Ikeda et al., 2019). ...
Prunus mume is one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications of Prunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified by in vitro and in vivo studies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.
... Dietary supplements such as ginkgo biloba, resveratrol, quercetin, curcumin, catechin, and omega-3 fatty acids are known to inhibit platelet activation [6][7][8][9]. In recent decades, Prunus mume fruit extracts (PMFE) has been reported to have various health benefits [10][11][12][13], including improvements of blood flow [14] and inhibition of platelet aggregation [15]. We have previously reported that PMFE improves cognitive impairment induced by decreased blood flow through an inhibitory effect on the toll-like receptor 4(TLR4)/myeloid differentiation primary response 88/ nuclear factor (NF)-κB signaling pathways [16,17]. ...
Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague–Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.
... Antiviral activities have been reported as well. The fruit juice concentrate of P. mume was found to reduce infection with human influenza A virus (Yingsakmongkon et al., 2008) and very recently, phenolic compounds purified from a salt-extract of P. mume revealed activities against the viruses HSV-1 and HSV-2 (Nishide et al., 2019). ...
Ethnopharmacological relevance:
Extracts of the fruit of Prunus mume (Rosaceae) have been used for a long time in Eastern Asia, in many culinary and medicinal preparations. The plant originates from the south of mainland China (named méi) and was introduced later in Japan (ume), Korea (maesil) and Vietnam (mai or mo). Extracts of the fruits (Chinese plum or Japanese apricot, 'Nanko' mume cultivar of Prunus mume Sieb. et Zucc.) are used in traditional Chinese and Japanese medicine, and various Korean medical preparations, for more than 2000 years. The medicinal use of the flesh of the fruits is cited in ancient Japanese monographies (such as Shokokukodenhiho published in 1817).
Aim of the study:
To analyze the anticancer activities of P. mume extracts and their potential use to prevent or treat cancers. The use of P. mume extracts to alleviate the side effects of chemotherapy, notably drug-induced gastro-intestinal toxicities, is also reviewed.
Methods:
Extensive database retrieval, such as SciFinder and PubMed, was performed by using keywords such as "Prunus mume", "Chinese plum", "Japanese apricot", and "cancer". In addition, relevant textbooks, patents, reviews, and digital documents (in English) were consulted to collate all available scientific literature and to provide a complete science-based survey of the topic.
Results:
P. mume extracts display hepatoprotective, anti-inflammatory, antioxidative and antibacterial effects, as well as anticancer properties. A survey of the antitumor activities of MK615 and other P. mume extracts is provided here, with information about the natural products found in the extracts (such as ursolic acid and oleanic acid) and the mechanisms of action of these extracts. MK615 inhibits proliferation and induces apoptotic death of different types of cancer cells from both solid and hematological tumors.
Conclusion:
The pool of in vitro data and signs of anticancer activities in mice models and in Human, although very limited, support the use of this extract to treat cancer, notably gastro-intestinal tumors. However, more robust evidence of anticancer activity in Human are awaited. Beyond cancer treatment, the use of P. mume extracts to prevent or to treat mucositis and other gastro-intestinal damages induced by anticancer drugs is underlined. The woody plant Prunus mume, a member of the Rosaceae family, has a long plantation history in China, and has widely been planted in Asia due to its high ornamental value (colorful corollas, pleasant fragrance, weeping trait) and the culinary, nutritional and medicinal potential of the fruits from the specie Prunus mume Sieb. et Zucc (Mei). Over the past 20 years the therapeutic potential of the extract of Japanese apricot "Ume" has been regularly reported. Anti-bacterial, anti-oxidative, anti-inflammatory and anti-cancer properties have been described. A complete analysis of the published scientific literature on Ume and cancer is presented here.
... 3) In Japan, bainikuekisu is traditionally consumed for alleviating diarrhea and digestive dysfunctions. Bainikuekisu has been recently reported to strongly inhibit human influenza A virus 4) and to suppress Helicobacter pylori-induced glandular stomach lesions in Mongolian gerbils. 5) Although many studies have demonstrated antibacterial activity for P. mume-related products, no major study has yet identified the principal constituents responsible for the antibacterial activity. ...
Mume fruit, the Japanese apricot (Prunus mume SIEB. et ZUCC.), is popular in Japan and is mostly consumed in the pickled form called umeboshi. This fruit is known to have anti-microbial properties, but the principal constituents responsible for the antimicrobial properties have not yet been elucidated. We investigated the antimicrobial activities of the phenolic compounds in P. mume against enterobacteria. In this study, growth inhibitory activities were measured as an index of the antibacterial activities. The phenolic compounds were prepared from a byproduct of umeboshi called umesu or umezu (often translated as “mume vinegar”). Umesu or umezu phenolics (UP) contain approximately 20% phenolic compounds with p-coumaric acid as a standard and do not contain citric acid. We observed the inhibitory effects of UP against the growth of some enterobacteria, at a relatively high concentration (1250–5000 µg/mL). Alkali hydrolysates of UP (AHUP) exhibited similar antibacterial activities, but at much lower concentrations of 37.5–300 µg/mL. Since AHUP comprises hydroxycinnamic acids such as caffeic acid, p-coumaric acid, and ferulic acid, the antibacterial activities of each of these acids were examined. Our study shows that the phenolic compounds in P. mume other than citric acid contribute to its antimicrobial activity against enterobacteria in the digestive tract.
Graphical Abstract Fullsize Image
... Its fruit has long been used as a traditional medicine and healthy food in East Asian countries [16]. It has been reported that Prunus mume fruit has antibacterial [17,18], antioxidant [19], antivirus [20], antitumor [21], immune enhancing [16] and hypouricemic [22] effects. ...
Background
Bamboo (Phyllostachys pubescens) leaves and Japanese apricot (Mume fructus) fruit are traditionally recognized to be safe herbs broadly used for food and medicinal purposes in Southeast Asia. Our group previously explored their antiplatelet effects. This study was designed to confirm inhibition effects of PM21 (a 2:1 mixture of bamboo leaf extract and Japanese apricot fruit extract) on platelet aggregation and evaluate its potency to use as an herbal remedy to prevent and/or treat the diseases caused by platelet aggregation and thrombus formation. Methods
Washed platelets were prepared and platelet aggregation was induced by adding 5 μg/mL collagen. Anti-platelet effects of PM21 (75 mg/kg, 150 mg/kg, and 300 mg/kg for ex vivo and in vivo assays, and 50, 100, 200 μg/mL for in vitro assays) were evaluated. In ex vivo assays, PM21 was orally administered to rats daily after overnight fasting for 3 days and blood was collected 1 h after the final treatment. In vivo antithrombotic effect of PM21 was observed from a carrageenan induced mouse tail thrombosis model. ResultsIn ex vivo assay, PM21 inhibited platelet aggregation significantly. PM21 showed a strong antithrombotic effect by reducing significantly the length of mouse tail thrombus. PM21 increased intracellular cAMP level and reduced the release of ATP, TXA2, and serotonin. PM21 also reduced intracellular concentration of calcium ion, fibrinogen binding to integrin αIIbβ3, and phosphorylation of ERK2, p38, PLCγ2, and PI3 K. ConclusionsPM21 showed remarkable inhibitory effects on platelet aggregation and thrombus formation. Its inhibitory function seems to influence on GPVI binding to its ligand and subsequent initiation of a signaling cascade that involves activation of effector proteins and secretion of effector molecules, such as ATP, TXA2, serotonin, and Ca2+. PM21 also appears to exert its anti-platelet effect by deactivation of ERKs activation pathway as well as inhibition of fibrinogen binding to integrin αIIbβ3.
... Influenza A virus strains, oseltamivir-sensitive A/Shizuoka/838/2009 (H1N1pdm) (838) and oseltamivir-resistant A/Shizuoka/738/2008 (H1N1) (738), were grown in MDCK cells. Hemagglutination units (HAU) of the viruses were determined as described previously [35]. HAU were expressed as the highest dilution of the virus suspension giving complete agglutination of guinea-pig erythrocytes. ...
Influenza A and B viruses possess a neuraminidase protein that shows sialidase activity. Influenza virus-specific neuraminidase inhibitors (NAIs) are commonly used for clinical treatment of influenza. However, some influenza A and B viruses that are resistant to NAIs have emerged in nature. NAI-resistant viruses have been monitored in public hygiene surveys and the mechanism underlying the resistance has been studied. Here, we describe a new assay for selective detection and isolation of an NAI-resistant virus in a speedy and easy manner by live fluorescence imaging of viral sialidase activity, which we previously developed, in order to achieve high-efficiency capture of an NAI-resistant virus. An NAI-resistant virus maintains sialidase activity even at a concentration of NAI that leads to complete deactivation of the virus. Infected cells and focuses (infected cell populations) of an oseltamivir-resistant virus were selectively visualized by live fluorescence sialidase imaging in the presence of oseltamivir, resulting in high-efficiency isolation of the resistant viruses. The use of a combination of other NAIs (zanamivir, peramivir, and laninamivir) in the imaging showed that the oseltamivir-resistant virus isolated in 2008 was sensitive to zanamivir and laninamivir but resistant to peramivir. Fluorescence imaging in the presence of zanamivir also succeeded in selective live-cell visualization of cells that expressed zanamivir-resistant NA. Fluorescence imaging of NAI-resistant sialidase activity will be a powerful method for study of the NAI resistance mechanism, for public monitoring of NAI-resistant viruses, and for development of a new NAI that shows an effect on various NAI-resistant mutations.
... PM contains phenolic compounds such as phenolic acids and flavonoids that exhibit antioxidant and free radical-scavenging activities. 14 Many studies have reported the antioxidant activities of plant extracts and other natural compounds. 15,16 Recent studies have found that oxidative stress due to excess reactive oxygen species (ROS) triggers inflammatory disease 17 and is one of the most important factors in IBD. ...
Background:
Prunus mume suppress various diseases caused by inflammation response and exhibit antioxidant and free radical scavenging activity. Therefore, this study determined the effect of an aqueous Prunus mume (PM) extract in a mouse colitis model and investigated the value of biopolymer encapsulation, facilitating targeted delivery to the colon. Colitis was induced by administration of 3% dextran sulfate sodium to male BALB/c mice for 7 days prior to treatment with vehicle, 50 mg kg(-1) PM extract or biopolymer-encapsulated PM extract, or 50 mg kg(-1) sulfasalazine.
Results:
Histological examination of the colon in BALB/c mice showed epithelial destruction and mucosal infiltration of inflammatory cells. These changes were attenuated in PM-treated mice, which had lower levels of inflammatory cytokines, cyclooxygenase 2, and immunoglobulins (IgA, IgM, and IgE), compared to the vehicle-treated colitis group. The PM extract showed concentration-dependent radical scavenging and superoxide dismutase-like anti-oxidant activities.
Conclusion:
These results indicated that the effects of the PM extract on colitis were not influenced by biopolymer encapsulation and that this PM extract could be a potential therapeutic agent for inflammatory bowel disease.
... In particular, its fruit has been eaten since ancient times in Asian countries as a traditional herbal medicine for relief of fatigue, diarrhea, fever, dyspepsia, and intestinal and skin disorders for thousands of years (Yan et al., 2014;Wen and Shi, 2012;Zhang et al., 2011;Jeong et al., 2006). The fruit of the P. mume contains abundant phenolic compounds, such as phenolic acids and flavonoids (Jeong et al., 2006;Kita et al., 2007;Mitani et al., 2013), which may be involved in the biological effects of anti-viral, anti-inflammatory, immunoenhancing, and antineoplastic activities (Zhang et al., 2011;Yingsakmongkon et al., 2008;Park et al., 2011;Enomoto et al., 2010;Tsuji et al., 2011;Jung et al., 2010;Tada et al., 2012;Lee et al., 2013;Jeong et al., 2006). Although there are several reports on the antioxidant activity and free radical scavenging activities of P. mume (Yan et al., 2014;Sang et al., 2002;Lee et al., 2013), the exact molecular mechanism(s) of actions of P. mume extract against oxidative stress involved in the Nrf2/HO-1 signaling pathway are yet to be described. ...
The fruit of the Prunus mume (Siebold) Siebold & Zucc., Rosaceae (Korean name: Maesil) has long been used as a health food or valuable medicinal material in traditional herb medicine in Southeast Asian countries. In this study, we determined the potential therapeutic efficacy of the ethanol extract of P. mume fruits (EEPM) against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in the murine skeletal muscle myoblast cell line C2C12, and sought to understand the associated molecular mechanisms. The results indicated that exposure of C2C12 cells to H2O2 caused a reduction in cell viability by increasing the generation of intracellular reactive oxygen species (ROS) and by disrupting mitochondrial membrane permeability, leading to DNA damage and apoptosis. However, pretreatment of the cells with EEPM before H2O2 exposure effectively attenuated these changes, suggesting that EEPM prevented H2O2-induced mitochondria-dependent apoptosis. Furthermore, the increased expression and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulation of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme, were detected in EEPM-treated C2C12 cells. We also found that zinc protoporphyrin IX, an HO-1 inhibitor, attenuated the protective effects of EEPM against H2O2-induced ROS accumulation and cytotoxicity. Therefore, these results indicate that the activation of the Nrf2/HO-1 pathway might be involved in the protection of EEPM against H2O2-induced cellular oxidative damage. In conclusion, these results show that EEPM contributes to the prevention of oxidative damage and could be used as a nutritional agent for oxidative stress-related diseases.
... Many chemical constituents have been isolated from Maesil extract including volatile com-pounds [27], hydroxycinnamic acid derivatives [26], citric acid derivative (mumefural) [7], and triterpenoids [16]. Maesil extract has been reported to show anticancer [1,13,30], antiviral [38], anti-microbial [29], anti-oxidant [37], and cardiovascular protective [35] effects. Maesil extract has been used pharmaceutically in folk medicine for antitussive, expectoration, antiemetic, antidiarrheal, anthelmintic, and antipyretic actions [26,37]. ...
Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced I?B-? phosphorylation and NF-?B translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-?B activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.
... These products have been known to possess various medicinal benefits and have been frequently prescribed as a traditional folk remedy. JA has been reported to possess such beneficial biological activities as improving blood fluidity [1] , antifatigue effect [2] , protection from the human influenza A virus [3] , and anti-cancer effect [4] . The biological basis of the efficacy of JA is partly attributable to anti-oxidative and free radical scavenging activities [5] , and partly to immune enhancement [6,7] . ...
To investigate the effects of Japanese apricot (JA) consumption on gastroesophageal reflux disease (GERD)-related symptoms.
Participants included individuals living in Minabe-cho, a well-known JA-growing region, who received specific medical check-ups by the local community health service in 2010. GERD-related symptoms were examined in 1303 Japanese individuals using a validated questionnaire, the Frequency Scale for Symptoms of GERD (FSSG), which consists of 7 questions associated with acid reflux symptoms and 5 questions asking about gastrointestinal dysmotility symptoms. Each question was answered using a 4-point scale, with higher scores indicating more severe GERD-related symptoms. Subjects were divided into two groups according to their intake of dried and pickled JA: daily intake (≥ 1 JA daily) (392 subjects) and none or occasional intake (< 1 JA daily) (911 subjects). FSSG scores were compared between subjects who consumed JA daily and those who did not. Next, subjects were stratified by age, gender and Helicobacter pylori (H. pylori) status for subanalyses.
Those who ate JA daily were significantly older than those who did not (60.6 ± 10.5 years vs 56.0 ± 11.0 years, P < 0.001). Total FSSG scores were significantly lower in subjects with daily JA intake than in those with none or only occasional intake (2.13 ± 3.14 vs 2.70 ± 3.82, P = 0.005). In particular, subjects who consumed JA daily showed significantly improved FSSG dysmotility scores compared with subjects who did not (1.05 ± 1.58 vs 1.46 ± 2.11, P < 0.001). In contrast, the FSSG reflux score did not differ between subjects with and without daily intake of JA (1.08 ± 1.90 vs 1.24 ± 2.11, P = 0.177). Subanalysis indicated that improvement in dysmotility by JA intake was specifically observed in non-elderly (1.24 ± 1.68 vs 1.62 ± 2.22, P = 0.005) and H. pylori-negative subjects (0.99 ± 1.58 vs 1.57 ± 2.06, P < 0.001). GERD patients (total FSSG score ≥ 8) were less frequently observed among subjects with daily intake of JA as compared to those without daily intake of JA (6.1% vs 9.7%, P = 0.040).
Daily JA intake may improve digestive dysmotility symptoms, resulting in relief of GERD symptoms. The effect is more obvious in non-elderly and H. pylori-negative subjects.
... A beneficial effect of PM-mediated antimicrobial activity against pathogens such as H. pylori (Nakajima et al., 2006;Enomoto et al., 2010) and human influenza A virus (Yingsakmongkon et al., 2008) could affect immunity, although there is still a lack of evidence that dietary PM affects the health of birds. A recent study reported that fermented PM diet with probiotics increased immune activity in mice, especially against Bordetella bronchiseptica, via the potent stimulation of immune responses (Jung et al., 2010a). ...
The present study was designed to evaluate whether plum (Prunus mume Siebold and Zucc., PM) products affect growth performance, digestive enzymes, enteric microflora and inflammatory cytokines in growing broiler chicks. A total of one hundred twenty eight, 3-d-old broiler chicks were assigned to a basal diet (CON) and a basal diet supplemented with antibiotics (ANT), freeze-dried Prunus mume powder (PMP, 0.25%) and Prunus mume extract (PME, 0.125%) until 35 days of age. Throughout the entire feeding period (3-35 days), there were no differences in body weight, feed intake, total gain and feed to gain ratio among the birds fed the basal diet and those fed the diet supplemented with antibiotics, either PM powder or extract. The specific activities of pancreatic alpha-amylase and trypsin significantly increased (P<0.05) in birds fed the PME diet compared with those fed the CON and ANT diets. However, the specific activities of intestinal hydrolases such as maltase, sucrase and leucine aminopeptidase were not affected by the dietary groups. The colony forming units (CFU) of E. coli in the digesta of ileo-cecum in the PMP and PME groups were similar to those in the ANT group. The CPU of lactobacilli in the PMP and PME groups was significantly greater (P<0.05) than that in the ANT group, although there was no difference between the PMP and PME groups. The mRNA expression of splenic IL-1 beta and IL-6, pro-inflammatory cytokines, was significantly higher (P<0.05) in the PME group than in the CON group without affecting thymic cytokines. In summary, the dietary PM extract showed beneficial effects on pancreatic digestive enzymes, enteric microflora population and inflammatory cytokine mRNA expression, suggesting that PM extract might be a potential candidate as an alternative to antibiotics in birds.
... (Japanese Plum, Rosaceae) which showed strong in vitro anti-influenza activity against human influenza A viruses before viral adsorption, but not after viral adsorption, with 50% inhibitory concentration (IC50) values against A/PR/8/34 (H1N1), A/Aichi/2/68 (H3N2) and A/Memphis/1/71 (H3N2) viruses. These compounds may prevent and reduce infection with human influenza A virus, possibly via inhibition of viral hemagglutinin attachment to host cell surfaces by its lectin-like activity [61]. ...
This review highlights a wide range of research on antiviral natural products in Asia in the period from 2000 to 2008. It focuses on the most important findings in this field specifically on the plants' components with potential antiviral activity against wide range of pathogenic DNA and RNA viruses. In addition, the difference between Asians and other populations regarding their habits of using natural products containing antiviral activity instead of allopathic medicine has been reviewed briefly. In conclusion, Asian continent serves as the most important source for providing the candidate natural products for the future antiviral drugs which could save the lives of millions in the world.
... If you have prunes that are extremely dry, soaking them in hot water for a few minutes will help to refresh them. If you are planning on cooking the prunes, soaking them in water or juice beforehand will reduce the cooking time 5 . ...
Prunes are fruits that are dried plums. They are very much liked by many people. It is eaten for its health benefits. The number of health benefits related to prunes is increasing each day. As a fruit, it has many benefits as scientists are telling the people to eat fruits and vegetables more than any other kind of foods. This is because fruits contain many essential foods that help to get the body's defense mechanism to be ready to fight against all kinds of diseases. In the present review we have focused on selection and storage, tips for preparing prunes, nutritional values of prunes, content of prunes, the various health benefits of prunes and side effects of prunes.
... 장미과(Rosaceae)에 속하며 한국, 일본 및 중국 등지에 분포 하는 매화(Prunus mume)의 열매인 매실은 구연산, 사과산, 화 박산 등과 같은 유기산과 함께 풍부한 비타민 및 무기질이 많이 함유되어 있어 피로회복, 간기능 향상, 소화불량, 위장장 애, 만성 변비, 피부미용 등에 효과가 좋아서 예로부터 민간처 방 약재로 사용되었을 뿐만 아니라 매실주, 매실장아찌, 매실 정과, 매실잼 및 매실차 등과 같은 건강식품으로 사용되어져 왔다. 또한 최근 연구에 따르면 free radical scavenger, influenza A virus 억제, Helicobacter pylori의 운동성 억제, 혈액 유 동성 개선 및 항염증 작용 등과 같은 많은 약리학 및 생물학적 활성을 가지는 것으로 알려져 있어 많은 관심을 받고 있다[5,6,23,34,51]. 또한 매실은 많은 인체 암세포에 있어서 항암활 성을 가지는 것으로 보고되어지고 있으나[35,36,38], 항암 효능 에 따른 분자생물학적 기작에 대해서는 명확히 밝혀져 있지 않다. ...
In the present study, the pro-apoptotic effects of methanol extract of Prunus mume fruits (MEPM) in human leukemia U937 cells were investigated. It was found that exposure to MEPM resulted in growth inhibition in a concentration-dependent manner by inducing apoptosis. The induction of apoptotic cell death in U937 cells by MEPM was correlated with a down-regulation of inhibitor of apoptosis protein (IAP) family, such as X-linked inhibitor of apoptosis protein (XIAP) and survivin, anti-apoptotic Bcl-2, up-regulation of FasL and cleavage of Bid. MEPM treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP) and -catenin. In addition, apoptotic cell death induced by MEPM was significantly inhibited by z-DEVD-fmk, a caspase-3 specific inhibitor, which demonstrates the important role of caspase-3 in the apoptotic process by MEPM in U937 cells. Taken together, these findings suggest that P. mume extracts may be a potential chemotherapeutic agent for the control of human leukemia cells and further studies will be needed to identify the active compounds.
... Influenza A virus strains, oseltamivir-sensitive A/Shizuoka/838/2009 (H1N1pdm) (838) and oseltamivir-resistant A/Shizu- oka/738/2008 (H1N1) (738), were grown in MDCK cells. Hemagglutination units (HAU) of the viruses were determined as described previously [35]. HAU were expressed as the highest dilution of the virus suspension giving complete agglutination of guinea-pig erythrocytes. ...
Influenza virus is rich in variation and mutations. It would be very convenient for virus detection and isolation to histochemically detect viral infection regardless of variation and mutations. Here, we established a histochemical imaging assay for influenza virus sialidase activity in living cells by using a new fluorescent sialidase substrate, 2-(benzothiazol-2-yl)-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac). The BTP3-Neu5Ac assay histochemically visualized influenza virus-infected cells regardless of viral hosts and subtypes. Influenza virus neuraminidase-expressed cells, viral focus formation, and virus-infected locations in mice lung tissues were easily, rapidly, and sensitively detected by the BTP3-Neu5Ac assay. Histochemical visualization with the BTP3-Neu5Ac assay is extremely useful for detection of influenza viruses without the need for fixation or a specific antibody. This novel assay should greatly improve the efficiency of detection, titration, and isolation of influenza viruses and might contribute to research on viral sialidase.
... Furthermore, RDC has been shown to possess anti-cancer properties (Chang et al., 2010) and anti-viral applications (Lee et al., 2008; Min et al., 2001). On the other hand, FM juice has also been shown to inhibit human influenza-A virus infection by inhibiting viral hemagglutinin attachment to host cell surfaces (Yingsakmongkon et al., 2008; Zhao et al., 2007). In recent reports, the combination of FM, Schizandrae Fructus or Coptidis Rhizoma has shown an effective antimicrobial activity against enterohemorrhagic Escherichia coli infection (Lee and Stein, 2011). ...
Currently, Infectious Bursal Disease (IBD) is a highly contagious disease leading to huge economic losses in poultry industry. Our objective was to investigate potential therapeutic effects of the combined extracts of Rhizoma Dryopteridis crassirhizomatis and Fructus mume (RDCFM) against IBDV infection. Seventy-two 4-week-old SPF chickens were randomly divided into six groups and inoculated intranasally with 0.2 ml of 10 2.5 EID 50 of IBDV strain CJ801. Twenty-four hours post infection, the birds were orally administered with 400, 200 and 100 mg/kg BW of RDCFM, respectively, 125 mg/kg Astragalus polysaccharide (ASP) and saline water, respectively for 5 days and then monitored daily for 10 days. Finally, the remaining birds were euthanized to collect the sera for detecting antibodies and immune organs for determining the immune organs index as well as virus loads. The herbal extracts improved survival rate and relative body gain rate. Virus loads in bursa of Fabricius in herbal treated groups decreased significantly while higher antibody levels were detected in the three RDCFM groups as compared to those of ASP and infection group. These results implied that chickens administered with 100-200 mg/kg of RDCFM for 5 days could improve protection against IBDV infection and RDCFM may be a promising alternative to ASP and egg yolk antibody. He, 2013. Therapeutic efficacy of the combined extract of herbal medicine against infectious bursal disease in chickens. Pak Vet J, xx(x): xxx.
... MDCK cells (0.8-1.0x10 5 ) were seeded into each well of 12-well plastic plates and cultured at 37˚C for 24-48 h. For the antiinfluenza activity assay and identification of the affected viral life cycle, cells were treated with clemastanin B using three different protocols (19)(20)(21) (Fig. 2). First, before viral adsorption, the cells were pre-incubated with clemastanin B for 2 h at 37˚C. ...
Clemastanin B, 7S,8R,8'R-(-)-lariciresinol-4,4'-bis-O-β-D-glucopyranoside, is one of the major lignans extracted from Isatis indigotica root (IIR). In this study, the anti-influenza activities of clemastanin B were evaluated in vitro. Clemastanin B was found to inhibit different subtypes of human (H1N1, including swine-origin H1N1; H3N2 and influenza B) and avian influenza viruses (H6N2, H7N3, H9N2) at different magnitudes of activity (IC50 0.087-0.72 mg/ml) while this compound was inactive against respiratory syncytial virus (RSV), adenovirus 3 (ADV3), parainfluenza virus 3 (PIV3), enterovirus 71 (EV71) and human rhinovirus (HRV). An apparent virus titer reduction was detected when MDCK cells were treated with clemastanin B after viral infection, particularly at the early stage, and the ribonucleoprotein (RNP) of the influenza virus was retained in the nucleus after treatment with clemastanin B. These results demonstrated that clemastanin B targets viral endocytosis, uncoating or RNP export from the nucleus. Furthermore, treatment with clemastanin B did not easily result in the emergence of viral drug resistance. The effects of clemastanin B demonstrated in this study may promote the antiviral study of IIR, but additional studies are required to define the anti-influenza mechanism(s).
... MDCK cells (0.8-1.0x10 5 ) were seeded into each well of 12-well plastic plates and cultured at 37˚C for 24-48 h. For the anti-influenza activity assay and identification of the virus life cycle that was affected, cells were treated with G2 using three different protocols (18)(19)(20) (Fig. 2). First, prior to viral adsorption, the cells were pre-incubated with G2 for 2 h at 34˚C. ...
Isatis indigotica root (IIR) has been widely used as a Chinese medicinal herb to treat regular seasonal influenza over the long history of traditional Chinese medicinal practice. However, its inhibitory activities against influenza virus infections along with the associated mechanisms have not been investigated comprehensively. In this study, the chemical nature, mode of action and in vitro anti-influenza activities of a crude extract (G2) of IIR were characterized. The extract was found to inhibit different subtypes of human or avian influenza viruses at various magnitudes of activity (IC50 0.39‑4.3 mg/ml) in vitro, including A/PR/8/34 (H1N1), A/FM/1/47 (H1N1), A/Aichi/2/68 (H3N2), seasonal influenza (A/Guangzhou/GIRD/02/09 H1N1, B/Guangzhou/GIRD/08/09), novel swine-originating influenza (A/Guangzhou/GIRD/07/09, H1N1), A/Duck/Guangdong/09 (H6N2), A/Duck/Guangdong/94 (H7N3) and A/Chicken/Guangdong/96 (H9N2), while G2 was inactive against respiratory syncytial virus (RSV), adenovirus 3 (ADV3), parainfluenza virus 3 (PIV3) and enterovirus 71 (EV71). An apparent virus titer reduction was detected when the influenza viruses were pretreated with G2, and it was also shown that G2 exhibited inhibitory effects on influenza virus hemagglutination. In addition, G2 played a role in the early stages of infection, which did not easily result in the emergence of virus drug resistance. Thus, G2 may affect the attachment of influenza virus by interfering with the viral particles, thereby preventing the binding of influenza virus to the host cell surface.
... Serum amyloid P component (SAP), which is a pentraxin protein, can inhibit hemagglutinin cleavage of influenza virus (16). Furthermore, the extract of Japanese plum contains lectin-like molecules capable of inhibiting viral infection by reducing hemagglutination activity of influenza virus (55). In the present study, we used the whole virion, rather than viral glycoproteins used FIG. ...
Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactose-containing oligosaccharides. Since the envelope proteins of influenza virus are highly glycosylated, we studied the role of galectin-1 in influenza virus infection in vitro and in mice. We found that galectin-1 was upregulated in the lungs of mice during influenza virus infection. There was a positive correlation between galectin-1 levels and viral loads during the acute phase of viral infection. Cells treated with recombinant human galectin-1 generated lower viral yields after influenza virus infection. Galectin-1 could directly bind to the envelope glycoproteins of influenza A/WSN/33 virus and inhibit its hemagglutination activity and infectivity. It also bound to different subtypes of influenza A virus with micromolar dissociation constant (K(d)) values and protected cells against influenza virus-induced cell death. We used nanoparticle, surface plasmon resonance analysis and transmission electron microscopy to further demonstrate the direct binding of galectin-1 to influenza virus. More importantly, we show for the first time that intranasal treatment of galectin-1 could enhance survival of mice against lethal challenge with influenza virus by reducing viral load, inflammation, and apoptosis in the lung. Furthermore, galectin-1 knockout mice were more susceptible to influenza virus infection than wild-type mice. Collectively, our results indicate that galectin-1 has anti-influenza virus activity by binding to viral surface and inhibiting its infectivity. Thus, galectin-1 may be further explored as a novel therapeutic agent for influenza.
... Prunus mume, a member of the Rosaceae family, is widely distributed in Korea, Japan, and China, and has long been used as a traditional drug and health food. Previous reports have suggested that P. mume exerts a wide array of pharmacological and biological activities, such as potential sources of free radical scavengers, inhibition of influenza A virus, inhibition of the motility of Helicobacter pylori, improvement of blood fluidity, and inhibition of pro-inflammatory mediators (20)(21)(22)(23)(24)(25). In addition, P. mume has been known to exert anticancer activities in several types of human cancer cells (26)(27)(28). ...
Prunus mume (P. mume), a traditional drug and health food in Korea, Japan and China, possesses various pharmacological activities that include a potential source of free radical scavenging, anti-viral, anti-microbial, anti-inflammatory and anti-cancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. mume in human cancer cells are poorly understood. In the present study, we conducted an investigation of the pro-apoptotic effects of an ethanol extract of P. mume (EEPM) in U937 human leukemia cells. Exposure to EEPM was found to result in a concentration-dependent growth inhibition by induction of apoptosis. Induction of apoptotic cell death of U937 cells by EEPM showed a correlation with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family, including X-linked inhibitor of apoptosis protein (XIAP) and survivin, and anti-apoptotic Bcl-2, up-regulation of FasL, and cleavage of Bic. EEPM treatment induced proteolytic activation of caspase-3, -8 and -9, and degradation of caspase-3 substrate proteins, including poly(ADP-ribose) polymerase (PARP) and β-catenin. In addition, apoptotic cell death induced by EEPM was significantly inhibited by z-DEVD-fmk, a caspase-3-specific inhibitor, which demonstrated the important role played by caspase-3 in the process. Taken together, these findings suggest that EEPM may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells and that further studies are needed for the identification of the active compounds.
Viral respiratory infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of virus species and subtypes have been associated with these conditions, with influenza viruses (IFV), respiratory syncytial virus (RSV) and the rhinoviruses (RV) being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission or even just the symptoms. Strategies targeting all these aspects are concurrently developing and several novel and promising approaches are emerging. In this perspective, we overview the entire range of options and highlight some of the most promising approaches, including new antivirals, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, as well as vaccines and public health policies towards prevention. Wide scale prevention through immunisation appears to be within reach for RSV and promising for IFV, while additional effort is needed in regard to RV, as well as other respiratory viruses.
Naringin, which is one of the flavonoids contained in citrus fruits, is well known to possess various healthy functions to humans. It has been reported that naringin suppresses cancer cell growth in vitro and in vivo, although the underlying mechanisms are not fully understood. Recently, the roles of glycoconjugates, such as gangliosides, in cancer cells have been focused because of their regulatory effects of malignant phenotypes. Here, to clarify the roles of naringin in the negative-regulation of cancer cell growth, the alteration of glycoconjugates induced by naringin exposure and its significance on cell signaling were investigated. Human cancer cells, HeLa and A549, were exposed to various concentrations of naringin. Naringin treatment induced the suppression of cell growth toward HeLa and A549 cells accompanied with an increase of apoptotic cells. In naringin-exposed cells, GM3 ganglioside was drastically increased compared to the GM3 content prior to the treatment. Furthermore, naringin inhibited NEU3 sialidase, a GM3 degrading glycosidase. Similarly, NEU3 inhibition activities were also detected by other flavanone, such as hesperidin and neohesperidin dihydrocalcone, but their aglycones showed less inhibitions. Naringin-treated cancer cells showed suppressed EGFR and ERK phosphorylation levels. These results suggest a novel mechanism of naringin in the suppression of cancer cell growth through the alteration of glycolipids. NEU3 inhibitory effect of naringin induced GM3 accumulation in HeLa and A549 cells, leading the attenuation of EGFR/ERK signaling accompanied with a decrease in cell growth.
originated in the south of mainland China around the Yangtze River and was later introduced to Japan, Korea, Taiwan and Vietnam. It can be found in sparse forests, stream sides, forested slopes along trails and mountains, sometimes at altitudes up to 1700–3100 m, and regions of cultivation (Uematsu et al in Jpn J Genet 66(1):59–69, 1991).
In this study, the anti-influenza virus effects of the polysaccharides of Radix isatidis and its possible target were explored. The hot water reflux extraction and stepwise ethanol precipitation were performed to extract and separate the polysaccharides from R. isatidis, the isolated constituents' activities against the influenza virus were subsequently evaluated through in vitro experiments. The ELISA assay was performed to verify the binding ability of 80% alcohol-precipitated crude polysaccharides against the hemagglutinin (HA) of influenza A virus (A/PR/8/34, H1N1). The 70, 80 and 90% alcohol-precipitated crude polysaccharides extracted from R. isatidis exhibited the anti-influenza virus activities,with the selection indexes (SI) as 2.69,7.52 and 5.75, respectively. Furthermore, the ELISA results showed that this constituent existed the specific binding capacity with the influenza virus HA with a dose-dependent manner. The 80% alcohol-precipitated crude polysaccharides was one of the active components of this medicinal plant and the influenza virus HA protein might be its active target.
抄録
ウメ‘南高’果実の着果位置の違いが果実の成熟や化学成分含量に及ぼす影響について，4年間調査した．いずれの年も，収穫指標とした毛じの抜け具合が30％以上となった時期が内層の果実では遅く，収穫の開始が外層の果実よりも4～10日遅かった．果実重，果皮色L*値およびb*値は，果実発育が進むにつれて増大し，硬度は減少する傾向があったが，樹冠の内層と外層の青果収穫開始期に採取した果実間で比較すると，両者に差はなかった．果肉のクエン酸，ソルビトールおよびβ-カロテン含量は，果実発育が進むにつれて増加する傾向であったが，樹冠の内層と外層の青果収穫開始期に採取した果実間で比較すると，両者に差はなかった．一方，ポリフェノール含量および抗酸化能は，果実発育が進むにつれて減少する傾向があり，樹冠の内層と外層の青果収穫開始期に採取した果実間で比較すると，内層の果実で少なかった．これらの結果は，内層の果実は収穫を遅らせることにより，果実重やいくつかの機能性成分を外層の果実と同等にできるが，ポリフェノール含量や抗酸化能は同等にできないことを示している．
The effects of freezing rate on the efficiency of the subsequent osmotic extraction and the quality of the osmotically extracted juice from Prunus mume fruits were evaluated. Fresh fruits of P. mume were frozen at -20 or -50 degrees C, thawed, and mixed with sucrose. The juices after osmotic treatment were then prepared from these mixtures. Nonfrozen fruits were used as control. Nominal freezing times were 74 and 28 min for -20 and -50 degrees C, respectively. Drip loss was higher in fruits frozen at -20 degrees C than at -50 degrees C. Clarity and browning index of the juice from frozen fruits were higher and lower, respectively, than those of the nonfrozen fruits. Contents of glucose, fructose, citric acid, tartaric acid, malic acid, and chlorogenic acid in juices ranked in descending order as follows: juice from fruits frozen at -20 degrees C > juice from fruits frozen at -50 degrees C > juice from nonfrozen fruits. These results suggest that freezing pretreatment affected the quality of osmotically extracted juice and that slow freezing could be a more useful method in osmotically extracting fruit juice.
The effects of pretreatment by freezing on juice expression and drying characteristics of Prunus mume fruit were investigated. Fresh fruit slices were frozen at , thawed, and then either pressed (to yield juice) or dried. Fresh fruit slices were used as controls. Both juice yield and drying rate were higher when pre-frozen fruit was tested, compared to fresh fruit. The L and b color values were lower in the juice and dried powder of pre-frozen compared to fresh fruit. The a color value was higher in juice and powder prepared from pre-frozen fruit compared to fresh fruit. There was no significant difference in free sugar or organic acid content between juices and powders from pre-frozen and fresh fruit. None of soluble solid content, titratable acidity, or juice pH was affected by freezing pretreatment. The results suggest that such pretreatment may be useful to increase juice yield and drying rate. However, browning of juice and powder may be elevated.
Influenza is a serious respiratory illness which can be debilitating and cause complications that lead to hospitalization and death. Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. Given temporal and geographic changes and the shifts in antiviral drug resistance among influenza viruses, it is time to consider natural antiviral agents against influenza virus. Jatropha curcas is known for various medicinal uses. Its antimicrobial, anti-cancer and anti-HIV activity has been well recognized. Because of its broad-spectrum activity, we investigated aqueous and methanol leaf extracts for cytotoxicity and its potential to inhibit hemagglutinin protein of influenza virus. The bioactive compounds from leaf extracts were characterized by high-performance thinlayer chromatography which revealed the presence of major phytochemicals including flavonoids, saponins and tannins. The cytotoxic concentration 50 for aqueous and methanol extracts were determined using trypan blue dye exclusion assay. Inhibition of hemagglutinin protein was assessed using minimal cytotoxic concentrations of the extracts and 10(2.5) TCID50 (64 HA titre) of the Influenza A (H1N1) virus with different exposure studies using hemagglutination assay. Aqueous and methanol extracts were found to be non toxic to Madin darby canine kidney cells below concentration of 15.57 and 33.62 mg/mL for respectively. Inhibition of hemagglutinin was studied using reducing hemagglutination titre which confirmed that the J. curcas extracts have direct effect on the process of virus adsorption leading to its inhibition. Our results provide the information which shows the potential of Jatropha extracts in the treatment of influenza A (H1N1) virus infection. With an established reduced toxicity and prevention of infection by inhibiting hemagglutinin protein, these extracts and its derivatives may be further developed as broad spectrum anti-influenza drugs for prevention and treatment of infections by different types of influenza viruses with further mechanistic studies on anti-influenza.
Influenza poses a particular risk of severe outcomes in the elderly, the very young and those with underlying diseases. Tea polyphenols are the natural phenolic compounds in teas, and principally consist of catechins, proanthocyanidins, flavonols, and theaflavins, which antiviral activities have been reported recently. This study is to gain a further insight into potential of various tea polyphenols for inhibiting influenza virus infection. Five tea polyphenols exhibited inhibitory activity against influenza A virus in the trend of theaflavin>procyanidin B-2>procyanidin B-2 digallate>(-)-epigallocatechin(EGC)>(-)-epigallocatechingallate(EGCG) with IC50 values in the range of 16.2-56.5μg/ml. Six of the tested compounds showed anti-influenza B virus activity in the order of kaempferol>EGCG>procyanidin B-2>(-)-EGC~methylated EGC>theaflavin with IC50 values in the range of 9.0-49.7μg/ml. Based on these results, the structure-activity relationship (SAR) was explained as follows. First, the dimeric molecules, such as theaflavin and procyanidin B-2, generally displayed more potent antiviral activity against both influenza A and B viruses than the catechin monomers. Second, the kaempferol for inhibition of influenza B virus indicated that the more planar flavonol structure with only one C-4' phenolic hydroxyl group in the B ring is necessary for the anti-influenza B virus activity. A similar SAR can be drawn from the assays of another enveloped RNA virus, such as respiratory syncytial virus. These results are expected to provide guides for rational design of antiviral drugs based on polyphenols.
We have evaluated the antioxidant and radical scavenging activity of the water extract of Mume Fructus by applying various in vitro assays. We have determined total phenolic and flavonoid contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), hydroxyl radical (OH•), superoxide radical (O2-•) and nitrite scavenging activities, inhibition of linoleic acid oxidation and reducing power activity. The extract exhibited high scavenging activities on DPPH, ABTS, hydroxyl and superoxide radicals with the IC50 of 0.40, 0.36, 1.75 and 1.60 mg/mL, respectively. The extract also showed nitrite scavenging and reducing power activity in a dose-dependent manner. It inhibited 69.42% of linoleic acid oxidation at the concentration of 0.4 mg/mL. Owing to have high antioxidant activity, the water extract of Mume Fructus may serve as a new dietary supplement.
Mume Fructus has been used as a medicine in China, Korea and Japan. It has been reported that the water extract of Mume Fructus is able to inhibit pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages. The fruit has been used for stomachic, alexipharmic expectorant and eye pain and skin disease since before. People also used fruits as folk medicine for fever, cough and intestinal disorder, etc. Dried fruits have been used for thirst, refrigerant, laxative. In addition, previous reporters showed the inhibitory activities of fruit juice against Helicobacter pylori motility, human influenza disease as well as proliferation of cancer cells. In this context, we studied antioxidant and free radical-scavenging activities of Mume Fructus in vitro. The results of this study suggest that it may have potential as new source of natural antioxidant and dietary supplement.
Background:
Berries are known to have many kinds of biological activities. We focused on their antiviral effect, which has not yet been well evaluated.
Results:
We compared the anti-influenza viral effects of berries belonging to the genus Vaccinium - 35 species of blueberry (Vaccinium cyanococcus), the Natsuhaze (Vaccinium oldhamii), bilberry (Vaccinium myrtillus) and cranberry (Vaccinium oxycoccos)- with those belonging to the genus Ribes, i.e. blackcurrant (Ribes nigrum). Only Elliott and Legacy among Northern Highbush varieties but many Rabbiteye varieties such as Austin, Baldwin, Brightblue, Festival, T-100 and Tifblue showed anti-influenza viral activity. Natsuhaze, bilberry, cranberry and blackcurrant had high antiviral effects. A relationship was observed between the antiviral effect and total polyphenol content.
Conclusions:
Antiviral effects were found to differ markedly between berry species. Rabbiteye varieties tended to have higher antiviral effects than Northern, Southern and Half Highbush blueberry varieties. We also found that Natsuhaze, which has recently been harvested in Japan as a potential functional food, had an antiviral effect comparable to that of bilberry, cranberry and blackcurrant. There was a positive relationship between antiviral activity and polyphenol content, indicating the possibility that polyphenol is one of the key factors in the antiviral effects of berries.
Maesil (the fruit of Prunus mume Siebold & Zucc.) has long been used as an alternative medicine and functional food in Korea and Japan for preventive and therapeutic purposes. We examined the laxative effect of unripe Maesil (UM) and ripe Maesil (RM) in a rat model on constipation induced by a low-fibre diet and the possible mechanisms of Maesil in the rat colon. In vivo studies were conducted on the low-fibre diet-induced constipation rat model, and isolated rat colon was used in in vitro experiments to measure the changes in spontaneous colon contraction generated by Maesil and organic acids as standard and effectual ingredients, respectively. The aqueous extract of both UM and RM applied orally (100 and 300 mg/kg) produced significant increase of faeces frequency (p < 0.05) and moisture (p < 0.001). Moreover, the number faecal pellets number was reduced (p < 0.05) in the distal colons of the Maesil-treated rats. Gastrointestinal (GI) motility, measured by charcoal meal, was activated more fully by UM than in the low-fibre diet group. Both UM and RM and its organic acids produced a dose-dependent stimulation of the spontaneous contractile amplitude (p < 0.001) and frequency (p < 0.01) of the isolated rat colon. Although both UM and RM were an effective laxative, the RM was significantly more effective than the UM in the in vivo and in vitro constipation experiments because of the changes in the composition of organic acids during the ripening of the fruit. Our results demonstrated that Maesil was effective in promoting the frequency of defaecation and contraction of the rat colon, which provided scientific basis to support the use of Maesil as potential therapeutics in treating constipation.
In the elderly, immunosenescence and malnourishment can contribute to increased risk and severity of upper respiratory tract infections (URTI). Gold kiwifruit (Actinidia chinensis 'Hort16A') contains nutrients important for immune function and mitigation of symptoms of infection, including vitamins C and E, folate, polyphenols and carotenoids. The objective of the present study was to evaluate whether regular consumption of gold kiwifruit reduces symptoms of URTI in older people, and determine the effect it has on plasma antioxidants, and markers of oxidative stress, inflammation and immune function. A total of thirty-two community-dwelling people ( ≥ 65 years) participated in a randomised crossover study, consuming the equivalent of four kiwifruit or two bananas daily for 4 weeks, with treatments separated by a 4-week washout period. Participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily, and blood samples were collected at baseline and at the end of each treatment and washout period. Gold kiwifruit did not significantly reduce the overall incidence of URTI compared with banana, but significantly reduced the severity and duration of head congestion, and the duration of sore throat. Gold kiwifruit significantly increased plasma vitamin C, α-tocopherol and lutein/zeaxanthin concentrations, and erythrocyte folate concentrations, and significantly reduced plasma lipid peroxidation. No changes to innate immune function (natural killer cell activity, phagocytosis) or inflammation markers (high-sensitivity C-reactive protein, homocysteine) were detected. Consumption of gold kiwifruit enhanced the concentrations of several dietary plasma analytes, which may contribute to reduced duration and severity of selected URTI symptoms, offering a novel tool for reducing the burden of URTI in older individuals.
The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to be one of the most promising targets for combating influenza. Despite the substantial medical potential of NA inhibitors (NAIs), only three of these drugs are currently on the market (zanamivir, oseltamivir, and peramivir). Moreover, sudden changes in NAI susceptibility revealed the urgent need in the discovery/identification of novel inhibitors. Nature offers an abundance of biosynthesized compounds comprising chemical scaffolds of high diversity, which present an infinite pool of chemical entities for target-oriented drug discovery in the battle against this highly contagious pathogen. This review illuminates the increasing research efforts of the past decade (2000-2011), focusing on the structure, function and druggability of influenza NA, as well as its inhibition by natural products. Following a critical discussion of publications describing some 150 secondary plant metabolites tested for their inhibitory potential against influenza NA, the impact of three different strategies to identify and develop novel NAIs is presented: (i) bioactivity screening of herbal extracts, (ii) exploitation of empirical knowledge, and (iii) computational approaches. This work addresses the latest developments in theoretical and experimental research on properties of NA that are and will be driving anti-influenza drug development now and in the near future.
The effect of a plum ethanol extract (PEE) on immunity was analyzed. An oral administration of PEE increased the interleukin (IL)-12p40 concentration in the serum and T-cell ratio in the spleen. In vitro studies revealed that PEE stimulated IL-12p70 production in peritoneal macrophages and natural killer activity. These findings suggest that PEE enhanced the immune function by stimulating innate immune cells.
Osteoporosis is a serious disease caused by decreased bone mass. There is constant matrix remodeling in bones, by which bone formation is performed by osteoblastic cells, whereas bone resorption is accomplished by osteoclast cells. We investigated the effect of a Japanese apricot (Prunus mume SIBE. et ZUCC.) extract on the proliferation and osteoblastic differentiation in pre-osteoblastic MC3T3-E1 cells. An alkaline phosphatase (ALP) activity assay, cell proliferation assay, alizarin red staining and expression analysis of osteoblastic genes were carried out to assess the proliferation and osteoblastic differentiation. The water-soluble fraction of Prunus mume (PWF) increased the ALP activity, cell proliferation and mineralization. The gene expression of osteopontin and bone morphogenetic protein-2, which are markers in the early period of osteoblastic differentiation, were significantly enhanced by the PWF treatment. PWF therefore stimulated the proliferation and osteoblastic differentiation of cells and may have potential to prevent osteoporosis.
Influenza A viruses are spherical particles that attach to cells through bonds between hemagglutinin and specific cellular receptors. Numerous studies performed have recently revealed that Sialic acid (SA) is a crucial component of influenza A virus receptors. This brief review summarizes recent advances in our understanding of influenza A virus receptors. The introduction describes the classification of influenza A virus receptors and the review continues with a survey of the distribution of SA in different tissue and host. This is followed by research applications of influenza A virus receptors, and explanation of why receptor studies are so important on a world-wide scale.
The emergence of novel H1N1 has posed a situation that warrants urgent global attention. Though antiviral drugs are available in mainstream medicine for treating symptoms of swine flu, currently there is no preventive medicine available. Even when available, they would be in short supply and ineffective in a pandemic situation, for treating the masses worldwide. Besides the development of drug resistance, emergence of mutant strains of the virus, emergence of a more virulent strain, prohibitive costs of available drugs, time lag between vaccine developments, and mass casualties would pose difficult problems. In view of this, complementary and alternative medicine (CAM) offers a plethora of interesting preventive possibilities in patients. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing pandemic flu. Potentially active herbs can serve as effective anti influenza agents. The role of CAM for managing novel H1N1 flu and the mode of action of these botanicals is presented here in an evidence-based approach that can be followed to establish their potential use in the management of influenza pandemics. The complementary and alternative medicine approach deliberated in the paper should also be useful in treating the patients with serious influenza in non pandemic situations.
the aim of this study was to evaluate the antimicrobial efficacy of Traditional Chinese Medicine Fructus mume on a monospecies-biofilm model established on orthodontic brackets in vitro.
the antimicrobial effect of Fructus mume aqueous extract on the planktonic Streptococcus mutans (S. mutans) was tested by microdilution method (MIC). The cell viability of S. mutans biofilm on Damon3 MX bracket (Ormco, USA) after exposed to Fructus mume extract was quantified by XTT reduction assay. Visualization of the samples was performed by fluorescence microscope and confocal laser scanning microscopy (CLSM).
HPLC analysis revealed that the main compounds of Fructus mume are organic acids. The MIC of Fructus mume extract on the planktonic S. mutans was 50mg/mL. The optical density (OD) values, measured by XTT reduction assay from S. mutans biofilms after 1-min exposure to different test agents, demonstrated that the cell viability of S. mutans biofilms exposed to 250mg/mL Fructus mume extract<BHI (-) (p<0.01). Microscope image showed that Fructus mume extract obviously increased the amount of dead bacteria on the surface of bracket.
Fructus mume extract showed antimicrobial effect on S. mutans biofilm on orthodontic bracket in vitro which may indicate its potential use as an oral antimicrobial agent for orthodontic patients.
Human influenza A virus isolates bearing antigenically different H1 (A/PR/8/34), H2 (A/Japan/305/57), and H3 (A/Aichi/2/68, A/X-31) hemagglutinin serotypes caused extensive hemagglutination, low pH fusion, and hemolysis of asialoerythrocytes reconstituted with gangliosides. Sialylparaglobosides (IV3NeuAc-nLc4Cer, IV6NeuAc-nLc4Cer), I-active and i-active (VI3NeuAc-nLc6Cer) gangliosides, and GM3-NeuAc commonly exhibited significant specific receptor activity toward the viruses. A/PR/8/34 recognized IV3NeuAc-nLc4Cer containing the NeuAc alpha 2-3Gal sequence preferentially over IV6NeuAc-nLc4Cer containing NeuAc alpha 2-6Gal, whereas the other two recognized the NeuAc alpha 2-6Gal sequence preferentially over NeuAc alpha 2-3Gal. Responsiveness of erythrocytes labeled with gangliosides containing NeuGc to the viruses used was considerably lower than that of erythrocytes labeled with gangliosides containing NeuAc. The activities of GM1a, GM2, and GD1b bearing NeuAc on inner galactose of the ganglio series core were also very low. These results indicate that sialyloligosaccharides of IV3NeuAc-nLc4Cer, IV6NeuAc-nLc4Cer, I-active ganglioside, and VI3NeuAc-nLc6Cer in addition to GM3-NeuAc and GM1b-NeuAc (Suzuki, Y., Matsunaga, M., and Matsumoto, M. (1985), J. Biol. Chem. 260, 1362-1365; Suzuki, Y., Matsunaga, M., Nagao, Y., Taki, T., Hirabayashi, Y., and Matsumoto, M. (1985) Vaccine 3, 201-203) are functional receptor determinants toward hemagglutinin of human influenza A viruses, and the viruses differentiate microdomains of the gangliosides, such as the sialic acid species (NeuAc, NeuGc) and the sequence of sialic acid linkages (NeuAc alpha 2-3Gal, NeuAc alpha 2-6Gal).
Agglutinates of native chicken erythrocytes caused by influenza virus A/Aichi/2/68 (H3N2) at 4 degrees C were potently fused and lysed at low pH (optimum pH 5.3) at 37 degrees C. Exogenous gangliosides GM3 (Sia alpha 2-3Gal beta 1-4Glc beta 1-ceramide) and GM2 (GalNAc beta 1-4(Sia alpha 2-3)-Gal beta 1-4Glc beta 1-ceramide) were integrated into the membranes of chicken asialoerythrocytes within 5-min incubation at 37 degrees C. We found that the incorporation of ganglioside GM3 containing N-acetylneuraminic acid into asialoerythrocytes restored the biological responsiveness to the virus as established by agglutination at 4 degrees C and fusion and hemolysis at 37 degrees C at pH 5.3. Biological responsiveness of GM3-NeuAc-erythrocytes to the virus was considerably higher than that of GM3-NeuGc-erythrocytes under the same experimental conditions. Treatment of the GM3-NeuAc-erythrocytes with neuraminidase again resulted in the complete abolishment of the response to the virus. Erythrocytes containing GM2-NeuAc showed no detectable biological responses toward the virus. The above results indicate that the hemagglutinin of influenza virus A/Aichi/2/68 (H3N2) recognizes the sialyloligosaccharide chain of ganglioside GM3 as its receptor which mediates the adsorption and fusion process on the virus entry into the host cells and has more preferential specificity for binding to N-acetylneuraminic acid-containing GM3 than that to N-glycolyl type in the target cell membranes.
The persistence of H5N1 avian influenza viruses in many Asian countries and their ability to cause fatal infections in humans have raised serious concerns about a global flu pandemic. Here we report the isolation of an H5N1 virus from a Vietnamese girl that is resistant to the drug oseltamivir, which is an inhibitor of the viral enzyme neuraminidase and is currently used for protection against and treatment of influenza. Further investigation is necessary to determine the prevalence of oseltamivir-resistant H5N1 viruses among patients treated with this drug.
A methanol extract from unripe Japanese apricot showed inhibitory activity of Helicobacter pylori motility. Inhibitory compound 1 was isolated and identified as (+)-syringaresinol (1) by spectoroscopic means. (+)-Syringaresinol (1) inhibited >90% of the H. pylori motility at a concentration of 500 microg/ml and the IC50 value was 50 microg/ml.
Since 2003, highly pathogenic A(H5N1) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N1) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the N1 neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L26I and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5N1) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5N1) virus infections.
This report describes the preparation of a sodium (4-methylumbelliferyl-α-d-N-acetylneuraminate) substrate and its use in a sensitive fluorometric assay of neuraminidase (EC 3.2.1.18) from Vibrio cholerae, cultured fibroblasts, and human leucocytes. V. cholerae neuraminidase showed maximum activity at pH 4.6 and an apparent Km of 1.5 mm and was activated by CaCl2 and inhibited by ethylenediaminetetraacetate, NaCl, and N-acetylneuraminic acid. The inhibition by N-acetylneuraminic acid was competitive (Ki = 6.1 mm). Cultured fibroblast and leucocyte neuraminidases showed maximum activity between pH 4.2 and 4.4 and apparent Km values of 0.13 and 0.22 mm, respectively. Neuraminidase activity was considerably reduced in cultured fibroblasts of patients with mucolipidosis types I, II, and III.
Amantadine- and rimantadine-resistant viruses have been recovered from approximately 30% of patients treated for acute H3N2 subtype influenza and less often from their close contacts receiving drug prophylaxis. The limited data suggest that resistant viruses can emerge rapidly during drug therapy, as early as 2-3 days into treatment. These viruses retain their resistance phenotype during multiple passages in the laboratory and appear to be genetically stable in this regard. Studies in families and in nursing homes indicate that resistant isolates appear to be transmissible from treated patients and cause typical influenza in contacts receiving drug prophylaxis. It is unknown whether resistant human viruses are capable of competing with wild-type ones during multiple cycles of infection in the absence of the drug. These viruses appear to be pathogenic, and no evidence indicates that they differ from wild-type strains. Thus, these viruses clearly possess the biologic properties that are associated with clinically important drug resistance. However, limited information is available to assess their actual impact. It is unknown what degree of selective drug pressure would be required to cause substantial transmission of resistant viruses during community outbreaks. Natural selection of antigenic variants and disappearance of previous variants may prevent the emergence of viruses that have been altered in the genes coding both for the surface glycoproteins and for the M2 protein. However, the emergence of drug-resistant influenza viruses appears to pose potential clinical problems in certain epidemiologic situations involving close contact with treated patients.
We found, by using a virus overlay assay, that influenza A virus isolates bind to sulphatide (HSO3-Gal beta 1-->1'Cer), which has no sialic acid residue, and that the infection of Madin-Darby canine kidney cells with the human influenza virus A/Memphis/1/71 (H3N2) is inhibited by sulphatide. A/Memphis/1/71 (H3N2) causes obvious haemagglutination and low-pH haemolysis of asialoerythrocytes reconstituted with sulphatide. All influenza A virus isolates from the species of animals so far tested bound to sulphatide. The sulphatide-binding specificity of the isolates was different from the viral sialyl-linkage specificity. Influenza A virus isolates also bound to galactosyl ceramide (GalCer; Gal beta 1-->1'Cer), as well as sulphatide, in the virus overlay assays. In contrast, the influenza virus did not bind to N-deacyl, a derivative of sulphatide, glucosyl ceramide or the other neutral glycolipids tested. These results indicate that the linkage of galactose, or sulphated galactose, to ceramide is important for viral binding.
The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.
Mannan-binding lectin (MBL) is a C-type serum lectin that is believed to play an important role in innate immunity. It is one of the collectin family, which is characterized by having a collagen-like sequence and a carbohydrate recognition domain. MBL can bind to sugar determinants of several micro-organisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. Bovine conglutinin and mouse MBL inhibit the infective and haemagglutinating activities of influenza A viruses. To identify the direct antiviral activity of human MBL against influenza A viruses that does not depend on complement activation or opsonization, we isolated native MBL from human serum and produced a recombinant MBL in Chinese hamster ovary (CHO) cells using a pNOW/CMV-A expression vector system. Native and recombinant human MBL exhibited neutralization activity against A/Ibaraki/1/90 (H3N2), with the plaque focus reduction assay at the viral attachment phase. Their activities were inhibited by EDTA, mannose and anti-human MBL antibody. Furthermore, at the viral expansion phase both MBL in culture medium prevented viral spreading from primary infected cells to neighbour cells. A virus recovery study using EDTA indicated that interaction between MBL and virus was reversible and non-damaging to the virus. Lectin blot and immunohistochemistry assays showed that these antiviral activities involved binding between MBL and two viral envelope proteins, haemagglutinin and neuraminidase. These findings suggest that human MBL can play an important role in innate immunity by direct viral neutralization and inhibition of viral spread, as well as an indirect role through opsonization and complement activation.
The effects of food components on blood fluidity were studied by in vitro assay using a dedicated microchannel instrument for model capillaries. We found that the fruit-juice concentrate of the Japanese apricot (Prunus mume Sieb. et Zucc), a traditional Japanese food, markedly improved the fluidity of human blood. Using HPLC, we isolated the active compounds and characterized them using UV, MS, IR, and NMR. They included a novel compound, 1-[5-(2-formylfuryl)methyl] dihydrogen 2-hydroxypropane-1,2, 3-tricarboxylate (mumefural), and a related compound, 5-hydroxymethyl-2-furfural (HMF). Mumefural markedly improved blood fluidity in all subjects, while HMF worked differently in different individuals. The flow rate of blood spiked with mumefural or HMF was compared to that of the two predominant organic acids in the fruit. Citric acid, malic acid, and furfuryl alcohol also improved fluidity in all subjects. The activity of P. mume is derived from not only artifacts produced during thermal processing, such as mumefural, but also from endogenous organic acids.
The effects of a mixture of tea-seed saponins obtained from the seeds of Camellia sinensis var. sinesis on human influenza viruses types A and B were investigated. At the concentrations of 60, 80, and 100 micrograms/ml, respectively, the mixture inactivated viruses A/Memphis/1/71 (H3N2), B/Lee/40, and A/PR/8/34 (H1N1) almost completely. The mixture also inactivated type A virus A/PR/8/34 after inoculation at concentrations of 1-30 micrograms/ml dose-dependently.
Amantadine and rimantadine are effective in the treatment and prophylaxis of influenza A. Neither drug, however, has achieved widespread acceptance because of the rapid development of viral resistance, their lack of activity against influenza B and, in the case of amantadine, adverse events. Complete cross-resistance occurs with these compounds and is associated with a single nucleotide change in the M2 protein. Resistant variants are transmissible and fully pathogenic. Zanamivir is the first widely approved neuraminidase inhibitor for the treatment of influenza. It is delivered directly to the primary site of viral replication, the respiratory tract, and is well tolerated and effective in the treatment of both influenza A and B. Data in prophylaxis are also encouraging. During the extensive clinical programme no evidence for the emergence of drug-resistant strains with acute therapy was found. Zanamivir represents a significant advance over older agents in the management of influenza A and B.
In fruits with therapeutic properties for antidiarrheal and laxative uses, the presence of lectins may be the bioactive properties that interfere with bacterial adhesion, thought to be competition for glycoside signal sites in the attachment.
This study identifies lectins in crude extracts from fruits such as Tamarindus indica (tamarind), Spontia vulgaris (plum), Psidium guava (guava), Mangifera indica (mango), Cydonia vulgaris (quince), and Crataegus mexicanus (tejocote). To verify the procedures, extracts from Ricinus communis (castor bean), Glycine max (soybean), Phaseolus vulgaris (beans), Vicia fava (fava bean), and Solanum tuberosum (potato) were used as controls for lectin activity. Both sources of lectins were analyzed to determine their participation in the host-parasite interaction, using as a model the hemagglutinating properties of Escherichia coli O157:H7 (EHA).
All extracts showed hemagglutination to group O erythrocytes test (HA) with the exception of mango. Two new galactose-specific lectins were identified from tamarind and guava. When analyzed for participation in EHA, only guava lectins inhibited this, while soybean lectin induced hemolysis; as both lectins bind to galactose, it is probable that their recognition occurs in different domains. Sugars involved in the attachment between Escherichia coli O157:H7 and red cells were identified and again, galactose in addition to mannose was found to be related in EHA. On the other hand, guava lectins also agglutinated E. coli O157:H7, perhaps due to the same galactose-specific lectin or to another type of lectin.
In summary, guava has a galactose-specific lectin that prevents adhesion of E. coli O157:H7 to red cells; this lectin is mediated by galactose. Prevention could also be due to their capacity of agglutinating E. coli by guava lectins. Soybean lectin induced hemolysis only when bacteria was present, but not with floating secretions. This finding showed that guava is a source of lectin that can be explored to prevent adhesion of E. coli to epithelial intestinal cells; contrariwise, soya must be studied to see its participation in the uremia caused during E. coli O157:H7 pathogenesis.
Helicobacter pylori (H.p.) bacteria are the major causes of gastro-duodenal disease, and some association with stomach cancer has been suggested. Recently, H.p. eradicating treatment has been practiced using antibiotics and proton-pump inhibitors. However, at the same time, some reports have been made on the sideeffects of this treatment ; allergic reactions and uneffective resistant bacteria. Under these circumstances, there is a strong need for medicines, which are less harmful to the body, can be administered repeatedly, are less expensive, and yet as effective as antibiotics in inhibiting the bacteria, and in fact, some studies have been undertaken in this regard.
We placed our focus on Bainiku-ekisu (Concentrate of Japanese apricot juice) which, as a Japanese folk remedy, has been used for the treatment of gastritis and enteritis since ancient times, and studied its bacteriosterile affects. The major ingredients of Bainiku-ekisu are citric acid (32%) and malic acid (11%), while its pH represents strong acid.
We measured the bacteriosterile effects of Bainiku-ekisu by culturing ten H.p. strains originatig from gastro mucous membrane respectively in a Bainiku-ekisu concentration of 0.156%, 0.313%, 0.625% and 0.9%, and measured the level of MIC (minimum inhibiting concentration of development). As a result, out of ten H.p. strains four of them presented strong bacteriosterile effects in a concentration of less than 0.156%, and six of them, in a concentration of less than 0.313%. Furthermore, in order to measure the bacteriosterile effects against H.p. in the stomach we measured the quantity of bacteria in 0 minutes, five minutes, and ten minutes after mixing ten H.p. strasins suspended in physiological salt solution with a Bainiku-ekisu solution of 0.3% and 0.9% dissolved in aseptic physiological salt solution.
As a result, within five minutes after mixing, every one of the ten H.p. strains was observed to present strong bacteriosterile effects. These results suggest that Bainiku-ekisu can be considered as a fool likely to prevent the development of H.p. as well as the future possibility of making clinical applications to H.p. infection.
The Ugi four-component reaction (U-4CR) was utilized to prepare divalent and trivalent cluster mannosides with different scaffolds. The glycoclusters obtained were tested for their relative inhibitory potency against the binding of yeast mannan to concanavalin A by solid-phase enzyme-linked lectin assays (ELLA) using methyl alpha-D-mannopyranoside as a standard. Among them, a divalent mannoside containing aromatic groups showed the strongest binding affinity to concanavalin A.
Disodium cromoglycate (DSCG) is one of the safest drugs for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infection is still controversial. Here we investigated DSCG inhibition of influenza virus infection in vivo and in vitro. In vivo effects of DSCG on viral infection were assessed using a murine model of respiratory tract infection. Intranasal administration of DSCG protected mice from death induced by infection with influenza virus A/PR/8/34. We analyzed DSCG anti-viral effects in vitro by either (i) treating cells prior to viral adsorption, (ii) treating cells concurrently with viral adsorption, or (iii) treating cells after viral adsorption. DSCG treatment of cells during or after, but not before, viral adsorption significantly inhibited influenza viral infection, indicating DSCG acts on events late in viral infection. DSCG exerts anti-influenza effect both in vitro and in vivo at the doses compatible with treatment for asthma. DSCG marginally inhibited influenza viral neuraminidase and membrane fusion functions, suggesting that DSCG inhibition of viral neuraminidase and fusion activities may partially mediate this anti-influenza effect. Our results indicate that treatment of patients including children with DSCG may take advantages for prevention from influenza virus infection.
A widely held view of influenza virus infection is that the viral receptor consists of cell surface carbohydrate sialic acid, which can be present as glycoprotein or glycolipid. Here, we examined influenza virus entry and infection in Lec1 cells, a mutant CHO cell line deficient in terminal N-linked glycosylation caused by a mutation in the N-acetylglucosaminyltransferase I (GnT1) gene. We show that influenza virus cannot infect Lec1 cells, despite having full capacity to undergo virus binding and fusion. Lec1 cells also show no virus replication defect, and infection was restored in Lec1 cells expressing wild-type GnT1. Viruses were apparently arrested at the level of internalization from the plasma membrane and were not endocytosed. Lec1 cells were refractory to infection by several strains of influenza virus, including H1 and H3 strains of influenza A, as well as influenza B virus. Finally, cleavage of N-glycans from wild-type CHO cells markedly reduced infection by influenza virus. We suggest that influenza virus specifically requires N-linked glycoprotein for entry into cells, and that sialic acid, although acting as an efficient attachment factor, is not sufficient as an influenza virus receptor in vivo.
The gene pool of influenza A viruses in aquatic birds provides all of the genetic diversity required for human and lower animals. Host range selection of the receptor binding specificity of the influenza virus hemagglutinin occurs during maintenance of the virus in different host cells that express different receptor sialo-sugar chains. In this paper, functional roles of the hemagglutinin and neuraminidase spikes of influenza viruses are described in the relation to 1) host range of influenza viruses, 2) receptor binding specificity of human and other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host range variation of influenza viruses, 5) role of the neuraminidase spike for the host range of influenza viruses, and 6) Development of anti-influenza drugs.
An active compound that inhibits cancer cells was isolated from the fruit of Prunus mume, and its structure and in vitro activities were characterized. The n-hexane fraction obtained from methanol extracts exhibited the strongest inhibitory effect on the growth of cancer cells. From the n-hexane fraction, a new compound named B-1 was purified through preparative thin-layer chromatography, ODS column chromatography, and reverse phase high-performance liquid chromatography and its structure was analyzed by fast atom bombardment mass spectrometry and 1H and 13C NMR. The molecular formula of B-1 was C19H22O6 {2-hydroxy-1-[(7-hydroxy-2-oxo-2H-chromen-6-yl)methyl]-2-methylpropyl-(2Z)-3-methyl-but-e-enoate:prunate}, and the IC50 value was in the range of 39-58 microg/mL in descending order of the cancer cell lines Hep-2, SW-156, HEC-1-B, and SK-OV-3. B-1 exhibited 81-96% inhibition at a concentration level of 100 microg/mL against all cells, based on an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. However, B-1 showed little effect against normal cells with only 23% or less growth inhibition at 100 microg/mL. Thus, B-1 has a highly specific inhibitory effect against cancer cells but little effect against normal cells. When the cancer cell lines Hep-2 and SK-OV-3 were incubated with B-1 for 72 h, most of the tested cells suffered strong growth inhibition. The compound has the potential to be developed as a nutraceutical.
Edible bird's nest (EBN) is the nest of the swift that is made from its saliva. Although EBN has been widely used for enhancing immunocompetence, its antiviral efficacy has not been studied in detail. We found that EBN extract could strongly inhibit infection with influenza viruses in a host range-independent manner when it was hydrolyzed with Pancreatin F. Western blotting assay showed that the EBN extract bound to influenza virus. Furthermore, EBN extract could neutralize the infection of MDCK cells with influenza viruses and inhibit hemagglutination of influenza viruses to erythrocytes, but it could not inhibit the activity of influenza virus sialidase. Fluorometric HPLC indicated that the major molecular species of sialic acid in EBN is N-acetylneuraminic acid. The results suggest that EBN is a safe and valid natural source for the prevention of influenza viruses.
To investigate involvement of cellular glycosphingolipids in the propagation of influenza viruses in host cells, MDCK cells were treated with inhibitors for sphingolipid biosynthesis, fumonisin B1 and d,l-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. Continuous treatment of the cells with either inhibitor during pre- and post viral inoculation, but not the pretreatment alone, significantly reduced viral infection, but not viral attachment to the cells. Immunocytochemical analysis demonstrated that cellular distribution of hemagglutinin, a viral glycoprotein, was drastically altered when the cells were continuously treated with the inhibitors during pre- and post viral inoculation, but not the pretreatment alone. Our findings strongly suggest that cellular sphingolipids play important roles in the events after viral adsorption to the host cells.
Influenza A viruses resistant to adamantanes(amantadine and rimantadine) have drastically increased in the last few years. Moreover, these adamantane-resistant viruses have acquired resistance without compromising viral pathogenicity and transmissibility. Viruses resistant to the other anti-influenza drugs, neuraminidase (NA) inhibitors, have also been shown to emerge at a rate higher than previously thought. In addition, several recent observations suggest that human-to-human transmission of variants resistant to NA inhibitors may have occurred, contrary to earlier predictions that such variants were much less likely to be transmitted. Although the prevalence of NA inhibitor resistants remains low, surveillance of drug-resistant influenza viruses in communities is essential. Here, we review antiviral resistance in influenza viruses and the molecular mechanisms of the acquisition of resistance to these drugs.
Substantial increase in amantadine-resistant influenza A (H3N2) was reported in Asia and North America in 2005. In this study the frequency and genetic characteristics of amantadine-resistant influenza A, circulated in Japan in 2005-2006 season, were investigated. Isolates were tested by amantadine susceptibility test (TCID(50)/0.2 ml method), and sequencing of the M2 gene to identify mutations that confer resistance. Additionally, the hemagglutinin (HA) and neuraminidase (NA) genes of the viruses were examined. In total, 415 influenza A isolates from six prefectures were screened, and 231 (65.3%) of 354 influenza A (H3N2) were amantadine-resistant, with a serine to asparagine (S31N) change in the M2 gene. However, none of 61 A (H1N1) isolates were resistant. In addition, genetic analyses of the HA gene showed all amantadine-resistant viruses clustered in one (named clade N), possessing specific double mutations at 193, serine to phenylalanine (S193F), and at 225, asparatic acid to asparagine (D225N), and sensitive viruses belonged to another group (clade S). The clinical presentations at the clinical visit did not differ between patients shedding clade N virus and those shedding clade S virus. None of the patients had received previous treatment with amantadine. The results indicate an unusually high prevalence and wide circulation of the amantadine-resistance influenza A (H3N2) in Japan in the 2005-2006 season. These strains had the characteristic double mutations in the HA, in addition to the M2 mutation responsive for resistance. Antiviral resistance monitoring should be intensified and maintained for rapid feedback into treatment strategies, and selection of alternative therapeutic agents.