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| Epigoitrin improved MAVS antiviral signaling after influenza infection in stressed mice. (A) Effects of epigoitrin on MFN2, MAVS, IFN-β, and IFITM3 protein expressions in the lung tissues. (B) Effects of epigoitrin on corticosterone level in the plasma. (C) Effects of epigoitrin on MFN2, NP protein expressions in the lung tissues. Actin was used as an internal control and the relative densities of the measured protein were quantified by image J software. * * * P < 0.001 vs. H1N1 group; ns, no significance (P ≥ 0.05) vs. Stress+H1N1 group.
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Stress has been proven to modulate an individual’s immune system through the release of pituitary and adrenal hormones such as the catecholamines, growth hormone, and glucocorticoids. These signal molecules can significantly alter the host immune system and make it susceptible to viral infection. In this study, we investigate whether epigoitrin, a...
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Context 1
... to the "H1N1" group, restraint stress obviously reduced these protein expressions with a higher MFN2 level. However, this process was improved by epigoitrin treatment (Figure 3A). Stressors could activate the hypothalamic-pituitary-adrenal axis and thereby trigger increases in stress hormone levels, which lead to dysregulation of immune function. ...
Context 2
... effects of epigoitrin on corticosterone level in the plasma of stressed mice were investigated. As show in Figures 3B,C, restraint stress significantly elevated the plasma corticosterone levels and the expression of MFN2 and virus nucleoprotein (NP) in lungs of mice. Interestingly, Epigoitrin-H and Epigoitrin- L had no significant effects on the plasma corticosterone level, but decreased the protein level of MFN2 and NP in stressed mice. ...
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Influenza A virus matrix protein M1 is involved in multiple stages of the viral infectious cycle. Despite its functional importance, our present understanding of this essential viral protein is limited. The roles of a small subset of specific amino acids have been reported, but a more comprehensive understanding of the relationship between M1 seque...
Citations
... Epigoitrin is extracted from the root of R. isatidis and exhibits antiviral activity, inhibiting viral attachment and proliferation [15]. It was reported that 88 mg/kg of epigoitrin significantly decreased the susceptibility of restraint mice to influenza virus, as evidenced by a lowered mortality, attenuated inflammation and decreased viral replications in lungs [16]. Given its multifaceted nature, R. isatidis is acknowledged for its substantial potential in the domain of laying hen production. ...
... One possibility is that RIHR may introduce or enhance the growth of other beneficial microorganisms in the gut, thereby compensating for the decline in Lactobacillus and maintaining or even improving the gut's ecological balance. Furthermore, RIHR itself may contain phytochemicals with anti-inflammatory properties that could mitigate the effects of reduced Lactobacillus levels, serving as immunomodulators that suppress the immune response to potential gut pathogens [16,40]. Alternatively, the reduction in Lactobacillus could be part of a broader microbial community shift that favors anti-inflammatory species or strains, thereby indirectly reducing intestinal inflammation. ...
China produces more than 30 million tons of drug residues every year. Therefore, innovative solutions are needed to mitigate environmental damage. Certain plant compounds boost hens’ health and performance. Radix isatidis is promising for layer production. This study elucidates the multidimensional impact of Radix isatidis residual material (RIHR) on laying hens, focusing on the egg quality, intestinal health and the microbial landscape. A total of 288 55-week-old Peking powder laying hens with similar laying rates and body weights were randomly divided into four groups, with eight replicates per group and nine hens per replicate. The groups were divided into a control group, an RIHR low-dose group, a medium-dose group and a high-dose group according to a single-factor, completely randomized design. For the three RIHR treatment groups, the added amounts were 5 kg/t, 10 kg/t and 15 kg/t, respectively. Liquid chromatography- mass spectrometry (LC-MS), molecular docking, fluorescence quantitative PCR and other methods were used. The results showed that three main anti-inflammatory and antiviral compounds were identified in RIHR-indirubin (0.21 μg/g), deoxyvasicinone (0.18 μg/g) and epigoitrin (0.39 μg/g). RIHR significantly increased the eggshell thickness, Haugh unit and protein height (p < 0.05). It also had significant antioxidant and anti-inflammatory effects on ilea and ceca (p < 0.05). The microbial analysis demonstrated that RIHR supplementation led to a significant reduction in foregut Lactobacillus levels (p < 0.05). In the hindgut, a significant increase in pathogenic bacteria was observed (p < 0.05). The study concludes that RIHR’s anti-inflammatory compounds may directly act on the intestinal tract to modulate inflammation, highlighting its potential for targeted interventions in poultry health and nutrition.
... This suggests that MFN2 functions as a negative regulator of RLR signaling. Also, recent study has revealed that inhibiting MFN2 expression with epigoitrin leads to upregulation of influenza virus-induced MAVS and IFN-β activation (Luo et al. 2019). ...
Unlabelled:
In mammals, mitofusin 2 (MFN2) is involved in mitochondrial fusion, and suppresses the virus-induced RIG-I-like receptor (RLR) signaling pathway. However, little is known about the function of MFN2 in non-mammalian species. In the present study, we cloned an MFN2 ortholog (LcMFN2) in large yellow croaker (Larimichthys crocea). Phylogenetic analysis showed that MFN2 emerged after the divergence of amphioxus and vertebrates. The protein sequences of MFN2 were well conserved from fish to mammals. LcMFN2 was expressed in all the tissues/organs examined at different levels, and its expression was upregulated in response to poly(I:C) stimulation. Overexpression of LcMFN2 inhibited MAVS-induced type I interferon (IFN) promoter activation and antiviral gene expression. In contrast, knockdown of endogenous LcMFN2 enhanced poly(I:C) induced production of type I IFNs. Additionally, LcMFN2 enhanced K48-linked polyubiquitination of MAVS, promoting its degradation. Also, overexpression of LcMFN2 impaired the cellular antiviral response, as evidenced by the increased expression of viral genes and more severe cytopathic effects (CPE) in cells infected with spring viremia of carp virus (SVCV). These results indicated that LcMFN2 inhibited type I IFN response by degrading MAVS, suggesting its negative regulatory role in cellular antiviral response. Therefore, our study sheds a new light on the regulatory mechanisms of the cellular antiviral response in teleosts.
Supplementary information:
The online version contains supplementary material available at 10.1007/s42995-023-00189-8.
... Moreover, its granules have been occupying a huge share of the international market in recent decades. Previous studies only paid attention to the antiviral and virus-induced inflammatory inhibition activity of goitrin [25,26]. Our recent research has shown that the aqueous extract of Radix Isatidis significantly reduced LPS-induced lung damage and inflammation by inhibiting the IFN-β pathway [27]. ...
Septic shock is defined as a subset of sepsis, which is associated with a considerably high mortality risk. The caspase-11 non-canonical inflammasome is sensed and activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis, it plays a critical role in septic shock. However, there are few known drugs that can control caspase-11 non-canonical inflammasome activation. We report here that goitrin, an alkaloid from Radix Isatidis, shows protective effects in LPS-induced septic shock and significant inhibitory effect in caspase-11 non-canonical inflammasome pathway. Male C57BL/6J were injected intraperitoneally with LPS (20 mg/kg) to induce experimental septic shock. The results demonstrated that the survival rates of mice pretreated with goitrin or Toll-like receptor 4 (TLR4) inhibitor TKA-242 increased, and LPS-induced hypothermia and lung damage improved by inhibiting inflammatory response. Elucidating the detailed mechanism, we surprisingly found goitrin is really different from TAK-242, it independent of the TLR4 signal activation, but significantly inhibited the activation of caspase-11 non-canonical inflammasome, including cleaved caspase-11 and N-terminal fragment of gasdermin D (GSDMD-NT). Furthermore, with a nonlethal dose of the TLR3 agonist poly(I:C)-primed and subsequently challenged with LPS to induce caspase-11-mediated lethal septic shock, the efficacy of goitrin had been verified. Those results revealed the effect of goitrin in protective against LPS-induced septic shock via inhibiting caspase-11 non-canonical inflammasome, which provided a new therapeutic strategy for clinical treatment of septic shock.
... Differently from the natural active molecules seen so far, epigoitrin reduced IV-susceptibility via mitochondrial antiviral signaling since it might reduce mitofusin-2 (MFN2) expression determining an increase in the mitochondria antiviral signaling expression and then an enhancement of IFN-b and interferon-inducible transmembrane 3 (IFITM3) production. Therefore, epigoitrin acted by maintaining the antiviral signaling of mitochondria antiviral signaling, generally suppressed under restraint stress by MFN2, ensuring INF-b release and so reducing viral replication (Luo et al. 2019). Moreover, it was seen that epigoitrin existed as a stereometric mixture of an equal amount of epigoitrin of (R)-goitrin, and goitrin or (S)-goitrin, where the S enantiomer claimed a greater activity than the R-enantiomer (Nie et al. 2020). ...
Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.
... Both IIR scraps and IIR's decoction residues contain a large amount of available starch components. These starches can be hydrolyzed into fermentable sugars for fermentation, but it is still necessary to consider whether there are residual bioactive components, such as epigoitrin [57]. ...
Isatis indigotica Fort. root (Ban-lan-gen, IIR), a traditional Chinese medicine (TCM), has an ancient and well-documented history for its medicinal properties. Aside from epigoitrin, indole alkaloids, and their corresponding derivatives as medicinal ingredients, it also contains lots of biomass such as starch. Herein, a new starch was isolated from IIR and the physicochemical properties such as amylose content, moisture content, ash content, morphology, thermal properties, and crystallography were characterized systematically. The amylose content of IIR starch was 19.84 ± 0.85%, and the size and shape of starch granules is ellipsoidal shape with sizes from 2 to 10 μm. IIR starch exhibited a C-type pattern and had 25.92% crystallinity (higher than that of corn starch). The gelatinization temperature of IIR starch was 58.68–75.41 °C, and its gelatinization enthalpy was ΔHgel = 4.33 J/g. After decocting, the IIR’s residues can be used to prepare anhydro-sugars in a polar aprotic solvent. The total carbon yield of levoglucosan (LG), levoglucosenone (LGO), 5-hydroxymethylfurfural (HMF), and furfural (FF) could reach 69.81% from IIR’s decoction residues in 1,4-dioxane with 15 mM H2SO4 as the catalyst. Further, the residues after dehydration were prepared into biochar by thermochemical conversion and the BET surface area of biochar was 1749.46 m²/g which has good application prospect in soil improvement and alleviates obstacles of IIR continuous cropping.
... Moreover,extensive researches of LHQW related to antiviral and pneumonia effects displayed a serial coincident results with GO and KEGG ( Figure 4A,B,C, Table 1,2). Speci cally,BLG,an important ingredient of LHQW,widely used as a traditional Chinese medicine with antiviral activities including in uenza virus,hepatitis B/C virus,respiratory syncytial virus,herpes simplex virus,mumps virus and coxsackie virus by heat-clearing, detoxicating and in ammation-diminishing 18, 19 .Gandan oral extracts from BLG was widely used in the treatment of exudative pneumonia Clinically 20 .Forsythiaside from LQ can reduce lung in ammation by provocate Nrf2-HO-1 and down regulate the expression of nuclear factor kappa-B (NF-κB) 21 .Dryocrassin ABBA stem from GZ acted both anti H5N1 avian in uenza virus and anti pneumonia effects 22 .Sodium Houttuyfonate, the active compound of YXC,is mainly used for treating respiratory tract infections including pneumonia and chronic bronchitis 23 .The extracts inhibits lipopolysaccharide-induced rapid pulmonary brosis by upregulating Interferon γ(IFN-γ) and inhibiting the transforming growth factor-β(TGF-β1)/Smad pathway 24 .Otherwise,different solvent extracts of YXC and their active biomolecules have been shown to be effective against in ammation via the interaction with tumor necrosis factor-α(TNF-α),interleukin(IL),inducible nitric oxide synthase (iNOS),inhibitor of NF-κBα (IκBα) which su ciently provided evidence of the anti-in ammatory role of YXC extracts against both bacterial and ionic toxins 25 .GHX is of broad-spectrum antivirus effects including inhibits in uenza virus and porcine epidemic diarrhea virus 26, 27 .Emodin from DH blocks the SARS-CoV spike protein and show a high antiviral effect 28 .Chlorogenic acid is a key component from JYH acts as a neuraminidase blocker to inhibit infectious bursal disease virus,in uenza A virus.GC is applied widely as an enabler in the formulation of traditional Chinese medicineas.Glabrone of GC is one of the main ingredients playing a role on broad-spectrum antiviral activity with signi cant peroxisome proliferator-activated receptor γ (PPAR-γ) ligand binding activity.The other components like lsoliquiritigenin,licorice,glycoside C2 and glabranine also cover antiviral activity of in uenza virus,cowpox virus and dengue fever virus.Gancaonin N proven to be a natural anti-in ammatory agent of curing acute pneumonia in vitro via inactivating the MAPK and NF-κB signaling pathways 29 . ...
Background
Porcine respiratory and reproductive syndrome(PRRS) is still the most undermine viral disease in hog(Sus scrofa domestica,Sus) farming without effective drug of treatment. This study is aimed to discover its molecular mechanism and provide potential drug targets of LHQW(Lanhua Qingwen) against PRRS.
Methods
An LHQW target gene set was established from Traditional Chinese Medicine Systems Pharmacology database(TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP),PRRSV(Porcine respiratory and reproductive syndrome virus)-associated pneumonia–related gene set was obtained from 5 disease-gene databases.,Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-protein interaction (PPI) network were performed to discover the potential proteins.Molecular docking was performed to identify the patterns of interactions between the effective molecules and targeted proteins.
Results
A total of 509 bioactive ingredients and 255 targets of LHQW as well as 2738 PRRSV-associated pneumonia genes were obtained.The GO and KEGG indicated that LHQW can act by regulating stress response,virus infection and immune response.PPI networks and subnetworks identified 9 core genes.The molecular docking was conducted on the most significant gene MAP kinase-activated protein kinase 3(MAPK3) and other genes of RAC-alpha serine/threonine-protein kinase(AKT1),estrogen receptor 1(ESR1),MAP kinase-activated protein kinase 1(MAPK1),transcription factor p65(RELA) and Heat shock protein HSP 90-alpha(HSP90AA1),which are involved in virus infection,inflammation and oxidative stress pathways.Naringenin can target simultaneously the active pockets of these 6 proteins which exerting potential therapeutic effects in PRRS.
Conclusions
The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LHQW.Naringenin is a promising molecule for target of MAPK3,AKT1,ESR1,MAPK1,RELA and HSP90AA1 involving in oxidative stress,metabolic regulation,anti-inflammatory and immune defence pathways to treat PRRSV-associated pneumonia.
... Based on previous discussion, epigoitrin was a marker compound in PLG according to the 2020 edition of the Chinese pharmacopoeia [68]. In addition, it has been known to be effective against viral infections caused by changes in the immune system in both in vitro and in vivo experiments [69]. Adenosine is widely known as a primary nucleoside in PLG, producing a variety of important biological effects. ...
Background
Isatis tinctoria L (PLG) is a medicinal herb from the roots of Isatis indigotica Fort (Family Cruciferae). Previous studies have shown that PLG has anti-inflammatory and therapeutic effects against conditions such as acute and chronic hepatitis, various respiratory inflammations, and cancer. The purpose of this study was to define the pharmacological effects of PLG on inflammatory reactions and skin hyperkeratosis, which are the main symptoms of atopic dermatitis (AD), in vivo and in vitro.
Methods
For the AD in vivo experiment, 2,4-dinitrochlorobenzene (DNCB) induction and oral administration of PLG were performed on male BALB/c mice for four weeks. For in vitro experiments, keratinocytes were activated using TNF-α/IFN-γ in cultured human keratinocyte (HaCaT) cells. PLG inhibited inflammatory chemokine production and blocked the nuclear translocation of NF-κB p65 in activated keratinocytes.
Results
As a result of oral administration of PLG, dermis and epidermis thickening, as well as eosinophil and mast cell infiltration, were attenuated in AD skin lesions. In addition, the levels of immunoglobulin E (IgE), pro-inflammatory cytokines, and the MAPK/NF-κB signaling pathway were decreased in serum and dorsal skin tissues. Furthermore, PLG inhibited inflammatory chemokine production and blocked the nuclear translocation of NF-κB p65 in activated keratinocytes. In addition, epigoitrin and adenosine, the standard compounds of PLG, were identified as candidate AD compounds.
Conclusions
These results indicate that PLG is a potent therapeutic agent for attenuating symptoms of AD.
... Epigoitrin (EP) is one of the sulfur-containing alkaloids isolated from the extract of Isatidis Radix, which is the main bioactive constituent of Isatidis Radix. 1 It has obvious antiviral activities and significant potential for the prevention and treatment of obesity. [2][3][4] What's more, Isatidis Radix is widely used in the treatment and prevention of influenza and other viral respiratory infections for hundreds of years in China, and it has been demonstrated that Isatidis Radix has pharmacological effects on COVID-19 in certain studies. [5][6][7] In addition, it is used as the principal substance in the production of prevention and treatment drugs for some diseases. ...
Identification and quantification of epigoitrin (EP) in some herbs and traditional Chinese medicine (TCM) preparations are critical to pharmacokinetic study and pharmaceutical quality control due to their distinct antiviral pharmacological activity. Developing an efficient, sensitive, rapid method for determination of EP is therefore essential for clinical treatment and drug development. Here, a novel molecularly imprinted electrochemical sensor for determination of EP was constructed using double-layered membranes consisting of polyaniline functionalized graphene oxide with excellent electrochemical performance and molecularly imprinted polymers on surface of electrode. The follow-up constructed polyacrylamide (PAM) films afford several specific binding cavities, endowing the exclusive recognition ability. Moreover, the PAM chain is anchored to the PANI chain by covalent bonds, and the sensitivity is further improved. Under optimized conditions, the sensor demonstrated good linearity over a wide range of 4.6×10-7 mol/L ~ 4.6×10-5 mol/L with a low detection limit of 8.21×10-8 mol/L (S/N = 3). Additionally, the sensor showed good repeatability, stability and selectivity, and can be used for the detection of EP in the extraction from Isatidis Radix with a recovery of 97.8% above. This work also provided a novel strategy for on-site, real-time and rapid detection of indicator components from TCM.
... Novel anti-influenza therapeutic techniques are a prerequisite for its control in the present era, and these developments can be achieved through the search for new ways to modulate the viral mechanism and immune system (Figure 4) (105-107). Numerous herbal species with potential inhibitory effects on the replication of influenza viruses were frequently described using in vitro cell culture methods and embryonated eggs or in vivo mouse models (108,109). Many phytochemicals of relatively low molecular weight, such as polyphenols, flavonoids, terpenes, glucosides, and alkaloids extracted from different plants have been shown to be endowed with an antiviral activity against AIV (110,111). ...
The growth of poultry farming has enabled higher spread of infectious diseases and their pathogens among different kinds of birds, such as avian infectious bronchitis virus (IBV) and avian influenza virus (AIV). IBV and AIV are a potential source of poultry mortality and economic losses. Furthermore, some pathogens have the ability to cause zoonotic diseases and impart human health problems. Antiviral treatments that are used often lead to virus resistance along with the problems of side effects, recurrence, and latency of viruses. Though target hosts are being vaccinated, the constant emergence and re-emergence of strains of these viruses cause disease outbreaks. The pharmaceutical industry is gradually focusing on plant extracts to develop novel herbal drugs to have proper antiviral capabilities. Natural therapeutic agents developed from herbs, essential oils (EO), and distillation processes deliver a rich source of amalgams to discover and produce new antiviral drugs. The mechanisms involved have elaborated how these natural therapeutics agents play a major role during virus entry and replication in the host and cause inhibition of viral pathogenesis. Nanotechnology is one of the advanced techniques that can be very useful in diagnosing and controlling infectious diseases in poultry. In general, this review covers the issue of the poultry industry situation, current infectious diseases, mainly IB and AI control measures and, in addition, the setup of novel therapeutics using plant extracts and the use of nanotechnology information that may help to control these diseases.
... Brassicaceae vegetables rich in GSLs were proven to be helpful in protecting the liver and other organs [12]. Epigoitrin is the hydrolysate of epiprogoitrin (EPI), a dominant GSL in I. indigotica, and can be used as an antiviral compound [4,13] and allelochemical [14]. Currently, an increasing number of researchers focus on GSLs and their functions. ...
... A pair of chiral isomers, goitrin and epigoitrin, showed differences in their activities [4,13,84]. Goitrin and epigoitrin are derived from progoitrin and epiprogoitrin, respectively [85]. Goitrin results in a goitrogenic reaction, but epigoitrin does not [86]. ...
Background
Glucosinolates (GSLs) play important roles in defending against exogenous damage and regulating physiological activities in plants. However, GSL accumulation patterns and molecular regulation mechanisms are largely unknown in Isatis indigotica Fort.
Results
Ten GSLs were identified in I. indigotica , and the dominant GSLs were epiprogoitrin (EPI) and indole-3-methyl GSL (I3M), followed by progoitrin (PRO) and gluconapin (GNA). The total GSL content was highest (over 20 μmol/g) in reproductive organs, lowest (less than 1.0 μmol/g) in mature organs, and medium in fresh leaves (2.6 μmol/g) and stems (1.5 μmol/g). In the seed germination process, the total GSL content decreased from 27.2 μmol/g (of seeds) to 2.7 μmol/g (on the 120th day) and then increased to 4.0 μmol/g (180th day). However, the content of indole GSL increased rapidly in the first week after germination and fluctuated between 1.13 μmol/g (28th day) and 2.82 μmol/g (150th day). Under the different elicitor treatments, the total GSL content increased significantly, ranging from 2.9-fold (mechanical damage, 3 h) to 10.7-fold (MeJA, 6 h). Moreover, 132 genes were involved in GSL metabolic pathways. Among them, no homologs of AtCYP79F2 and AtMAM3 were identified, leading to a distinctive GSL profile in I. indigotica . Furthermore, most genes involved in the GSL metabolic pathway were derived from tandem duplication, followed by dispersed duplication and segmental duplication. Purifying selection was observed, although some genes underwent relaxed selection. In addition, three tandem-arrayed GSL-OH genes showed different expression patterns, suggesting possible subfunctionalization during evolution.
Conclusions
Ten different GSLs with their accumulation patterns and 132 genes involved in the GSL metabolic pathway were explored, which laid a foundation for the study of GSL metabolism and regulatory mechanisms in I. indigotica .
