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Cordyceps polysaccharide ameliorates airway inflammation in an ovalbumin-induced mouse model of asthma via TGF-β1/Smad signaling pathway
Abstract
Allergic asthma is a chronic inflammatory disease characterized by airflow obstruction, airway hyperresponsiveness (AHR), airway inflammation, and mucus overproduction. Cordyceps polysaccharide (CPS) is one of the main bioactive compounds of Cordyceps militarisis, a traditional Chinese medicine. In this study, we established a mouse model of asthma using ovalbumin (OVA) challenge and evaluated the potential regulatory effect of CPS (25, 50, and 100 mg/kg) on asthmatic mice. These results showed that the asthmatic mice treated with CPS suppressed the secretion of eotaxin, IL-4, IL-5, IL-13, and IFN-γ in the blood and bronchoalveolar lavage fluid (BALF), and decreased serum IgE levels compared to the vehicle-treated mice. CPS also alleviated inflammatory cell infiltration, goblet cell hyperplasia, and the increases of inflammatory cells in the mouse model of asthma. In addition, OVA-induced AHR was inhibited by CPS treatment. Further analyses of protein expression revealed that CPS inhibited the activation of transforming growth factor β1 (TGF-β1)/Smad pathway in mice with asthma. These findings indicated that CPS might serve as a potential therapeutic agent for the management of allergic asthma.
... 4,[12][13][14][15][16][17][18] Modern pharmacological studies have demonstrated that Cordyceps sinensis and its constituents possess antioxidative, immune-regulating, and metabolic-regulating properties. 4,[19][20][21][22] Air pollution, dust, soot, trauma, and infection are important causes of lung diseases. [23][24][25][26] Inflammation, a hallmark of lung diseases, orchestrates disease progression and therapeutic outcomes by driving immune dysregulation. ...
Introduction
Cordyceps sinensis, an entomogenous fungus with unique biological properties, has demonstrated significant anti-inflammatory potential. However, its effects on inflammation regulation need to be further investigated in detail.
Methods
In this study, we aimed to analyze the Cordyceps sinensis extract (CSE) obtained via ethanol extraction and to assess its effects on inflammation regulation. The secretion of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β) and the level of MMP9, Nrf2/HO-1 and ROS were evaluated. A transwell system with THP-1 and BEAS-2B cells was used to explore the inflammatory damage. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted on the differentially expressed genes.
Results
CSE exhibited no cytotoxicity to THP-1 cells at concentrations ≤ 1.6 mg/mL. Treatment of LPS-induced THP-1 cells with CSE significantly inhibited the secretion of pro-inflammatory cytokines. CSE reduced inflammation-related protein MMP9, while upregulating the anti-inflammatory Nrf2/HO-1 signaling pathway. Fluorescence assays using DCF and JC-1 further confirmed that CSE help mitigate oxidative stress-induced inflammation. CSE treatment protected BEAS-2B cells from inflammatory damage. Moreover, the immune system process was a shared GO term between LPS-only treatment and combined LPS and CSE treatment. KEGG enrichment analysis showed that CSE is capable of regulating genes associated with inflammatory and anti-inflammatory responses.
Conclusion
These findings highlight the potential of CSE as an immune-regulating agent in functional foods and health products.
... For instance, quercetin mitigates asthma-induced airway inflammation and remodeling by reducing periostin through the TGF-β1/SMAD pathway inhibition [41]. Similarly, cordyceps polysaccharide prevents the TGF-β1/SMAD pathway activation, thereby suppressing OVA-induced airway hyperresponsiveness in asthmatic mice [42]. SMAD4, a crucial mediator in the TGF-β signaling pathway, has been associated with various cellular activities, such as inflammation and cell death [43][44][45]. ...
Background
The TGF-β/SMAD signaling pathway is crucial in the pathogenesis of asthma. However, SMAD family member 4 (SMAD4), a key mediator of TGF-β, its roles and underlying mechanisms in asthma remain unclear.
Methods
The in vivo and in vitro roles of SMAD4 in asthma were investigated through an ovalbumin (OVA)-induced mouse model and an interleukin-13 (IL-13)-induced cell model. The molecular mechanism of SMAD4 influenced asthma was examined using transcriptome sequencing, followed by feedback experiments involving recombinant human interleukin 17 A (rhIL-17 A), an IL-17 A signaling pathway activator.
Results
SMAD4 was highly expressed in the asthma models. SMAD4 silencing alleviated damage to lung tissue and decreased inflammatory infiltration. Expression levels of Caspase-3, IgG, and inflammatory factors were reduced after silencing SMAD4. Silencing SMAD4 suppressed ferroptosis. Silencing SMAD4 also enhanced IL-13-induced BEAS-2B cell proliferation and suppressed apoptosis. Furthermore. IL-17 A signaling pathway was promoted in the asthma models, as evidenced by elevated IL-17RA, IL-17 A, and Act1 protein levels. SMAD4 silencing inhibited the expression levels of these IL-17 A pathway-associated proteins. Moreover, rhIL-17 A treatment notably reversed the impacts of SMAD4 silencing on asthma in the IL-13-induced cell model and OVA-induced mouse model, indicating that silencing SMAD4 inhibited inflammation and ferroptosis in asthma by blocking the IL-17 A signaling pathway.
Conclusion
Silencing SMAD4 prevents inflammation and ferroptosis in asthma by inhibiting the IL-17 pathway, which provides a novel potential approach for asthma therapy.
... In ovalbumin-induced asthmatic mice, the Cordyceps militaris polysaccharide fraction (25-100 mg/kg) suppressed the secretion of eotaxin, IL-4, IL-5, IL-13, and IFN-γ in both blood and bronchoalveolar lavage fluid. Furthermore, it decreased serum IgE levels by inhibiting the activation of the TGF-β/Smad pathway [40,85]. These findings suggest that Cordyceps militaris polysaccharides may hold promise as potential therapeutic agents for treating allergic asthma. ...
Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis, including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps, exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris. Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation.
... Additionally, Cordyceps polysaccharide lowered IgE levels, a marker of allergic reactions, and inhibited the activation of transforming growth factor β1 (TGF-β1), which plays a significant role in asthmarelated tissue remodeling and fibrosis. These findings underline the potential of Cordyceps polysaccharide as a valuable agent for mitigating airway inflammation, reducing mucus production, and regulating immune responses in the context of asthma and related conditions [41]. ...
Asthma remains a significant global health challenge, demanding innovative approaches to treatment. Traditional medicine has a rich history of using natural products to alleviate asthmatic symptoms. However, transitioning from these traditional remedies to modern drug discovery approaches has provided fresh insights into the mechanisms and effectiveness of these natural products. This study provides our comprehensive review, which examines the current state of knowledge in the treatment of asthma. It delves into the mechanisms through which natural products ameliorate asthma symptoms, and it discusses their potential in the development of novel therapeutic interventions. Our analysis reveals that natural products, traditionally employed for asthma relief, exhibit diverse mechanisms of action. These include anti-inflammatory, bronchodilatory, immunomodulatory effects, and reducing gene expression. In the context of modern drug discovery, these natural compounds serve as valuable candidates for the development of novel asthma therapies. The transition from traditional remedies to modern drug discovery represents a promising avenue for asthma treatment. Our review highlights the substantial efficacy of natural products in managing asthma symptoms, underpinned by well-defined mechanisms of action. By bridging the gap between traditional and contemporary approaches, we contribute to the growing body of knowledge in the field, emphasizing the potential of natural products in shaping the future of asthma therapy.
... Management of allergic asthma inhibited the expression of eotaxin, il-4, il-5, il-13, and iFn-γ in the blood and bronchoalveolar lavage fluid (BalF), lowered serum ige levels in mice. [157]. ...
The Clavicipitaceae family’s largest and most diverse genus is Cordyceps. They are most abundant and diverse in humid temperate and tropical forests and have a wide distribution in: Europe, North America, and East and Southeast Asian countries, particularly: Bhutan, China, Japan, Nepal, Korea, Thailand, Vietnam, Tibet, and the Himalayan region of India, and Sikkim. It is a well-known parasitic fungus that feeds on insects and other arthropods belonging to 10 different orders. Over 200 bioactive metabolites, that include: nucleotides and nucleosides, polysaccharides, proteins, polypeptides, amino acids, sterols, and fatty acids, among others have been extracted from Cordyceps spp. demonstrating the phytochemical richness of this genus. These components have been associated with a variety of pharmacological effects, including: anti-microbial, anti-apoptotic, anti-cancer, anti-inflammatory, antioxidant, and immunomodulatory activities. In this paper, the bioactivity of various classes of metabolites produced by Cordyceps spp., and their therapeutic properties have been reviewed in an attempt to update the existing literature. Furthermore, one of its nucleoside and a key bioactive compound, cordycepin has been critically elaborated with regard to its biosynthesis pathway and the recently proposed protector-protégé mechanism as well as various biological and pharmacological effects, such as: suppression of purine and nucleic acid biosynthesis, induction of apoptosis, and cell cycle regulation with their mechanism of action. This review provides current knowledge on the bioactive potential of Cordyceps spp.
... Here, we review the anti-inflammatory activity of these polysaccharides based on an analysis of the literature. Some polysaccharides of C. militaris are found to suppress secretion of eotaxin, IL-4, IL-5, IL-13, and IFN-γ, and reduce serum IgE level, inflammatory cell infiltration, and goblet cell hyperplasia by inhibiting transforming growth factor β1 (TGF-β1) and the phosphorylation of Smad2/3 proteins in ovalbumin challenged asthmatic mice (92). A recent study demonstrated that cordyceps polysaccharide can reduce acute liver injury by promoting hepatocyte proliferation, liver vascular regeneration, and liver tissue repair in line with the upregulation of vascular endothelial growth factor (VEGF), stromal cellderived factor-1α, proliferating cell nuclear antigen, and signal regulatory protein α1, and the reduction of IL-18 and caspase-1 (93). ...
Cordyceps militaris is a parasitic edible fungus and has been used as tonics for centuries. Polysaccharides are a major water-soluble component of C. militaris. Recently, C. militaris-derived polysaccharides have been given much attention due to their various actions including antioxidant, anti-inflammatory, anti-tumor, anti-hyperlipidemic, anti-diabetic, anti-atherosclerotic, and immunomodulatory effects. These bioactivities are determined by the various structural characteristics of polysaccharides including monosaccharide composition, molecular weight, and glycosidic linkage. The widespread use of advanced analytical analysis tools has greatly improved the elucidation of the structural characteristics of C. militaris-derived polysaccharides. However, the methods for polysaccharide structural characterization and the latest findings related to C. militaris-derived polysaccharides, especially the potential structure-activity relationship, have not been well-summarized in recent reviews of the literature. This review will discuss the methods used in the elucidation of the structure of polysaccharides and structural characteristics as well as the signaling pathways modulated by C. militaris-derived polysaccharides. This article provides information useful for the development of C. militaris-derived polysaccharides as well as for investigating other medicinal polysaccharides.
... Anti-allergic remedies made from herbal constituents or extracts derived from ancient medicinal plants or fungi are gaining popularity because of their lower toxic effects. C. militaris, also known as Dong-Choong-Ha-Cho in Korea, is a medicinal fungus that has long been used to treat cancer [1], hyperlipidemia [27], hepatic cirrhosis [28], bronchitis [29], and asthma [30] in East Asia. ...
Cordyceps militaris (C. militaris) has various biomedical applications in traditional oriental medicine for different diseases including inflammatory and immune-dysregulated diseases. It is a reservoir of nutritional components such as cordycepin, polysaccharides, and antioxidants. To improve its bioactivity, we fermented C. militaris with a Pediococcus pentosaceus strain isolated from a salted small octopus (SC11). The current study aimed to evaluate whether P. pentosaceus (SC11) fermentation could enhance the anti-allergic potential of C. militaris cultured on germinated Rhynchosia nulubilis (GRC) against a type I hypersensitive reaction in in vitro and in vivo studies. Total antioxidant capacity and cordycepin content were significantly increased in GRC after SC11 fermentation. GRC-SC11 showed significantly enhanced anti-allergic responses by inhibiting immunoglobulin E (IgE)/antigen-induced degranulation in RBL-2H3 cells, compared to GRC. The results demonstrated the significant inhibition of phosphorylated spleen tyrosine kinase (Syk)/ p38/GRB2-associated binding protein 2 (Gab2)/c-jun in IgE/Ag-triggered RBL-2H3 cells. Furthermore, suppressed mRNA levels of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in IgE/Ag-activated RBL-2H3 cells were observed. GRC-SC11 significantly ameliorated IgE-induced allergic reactions by suppressing the ear swelling, vascular permeability, and inflammatory cell infiltration in passive cutaneous anaphylaxis (PCA) BALB/c mice. In conclusion, GRC fermented with P.pentosaceus exerted enhanced anti-allergic effects, and increased the cordycepin content and antioxidants potential compared to GRC. It can be used as bio-functional food in the prevention and management of type I allergic diseases.
... The polysaccharide, designated as CPS, reduced IgE levels in a mouse model of asthma, inhibited cell proliferation and infiltration and alleviated inflammation and airway hyperresponsiveness. CPS also inhibited the secretion of IL-4, IL-5, IL-13 and IFN-γ and reduced the expression of TGF-β1 [129]. ...
Cordyceps spp. mushrooms have a long tradition of use as a natural raw material in Asian
ethnomedicine because of their adaptogenic, tonic effects and their ability to reduce fatigue and
stimulate the immune system in humans. This review aims to present the chemical composition
and medicinal properties of Cordyceps militaris fruiting bodies and mycelium, as well as mycelium
from in vitro cultures. The analytical results of the composition of C. militaris grown in culture media
show the bioactive components such as cordycepin, polysaccharides,
-aminobutyric acid (GABA),
ergothioneine and others described in the review. To summarize, based on the presence of several
bioactive compounds that contribute to biological activity, C. militaris mushrooms definitely deserve
to be considered as functional foods and also have great potential for medicinal use. Recent scientific
reports indicate the potential of cordycepin in antiviral activity, particularly against COVID-19.
... Besides, the Cordyceps militaris mycelium extract was found to modulate airway inflammation induced by OVA sensitization in mice [30]. In particular, a Cordyceps polysaccharide was shown to reduce the extent of airway inflammation in an OVA-induced mouse model of asthma [31]. An ultra-performance liquid chromatography coupled with ultraviolet detection (UPLC-UV) quantitative analysis indicated that Cs-4 contains adenine, adenosine, and cordycepin as the major constituents. ...
Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma.
... Furthermore, TGF-β1 secretion is related to increased ECM protein production, leading to enhanced proliferation [27]. Previous studies have demonstrated that allergic airway inflammation can be prevented or ameliorated by suppressing the TGF-β1/Smad signalling pathway [28][29][30][31]. Moreover, TGF-β1 has been confirmed to modulate the expression of various growth factors, such as VEGF [32]. ...
Introduction:
The association between age-related macular degeneration (AMD) and asthma is controversial. Transforming growth factor beta (TGF-β), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-β and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-β inhibitor on CNV development in asthma mouse models.
Methods:
Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into five groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography (FFA) and histology of CNV lesions stained with haematoxylin-eosin (HE) were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-β1, TGF-β2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissue from each group.
Results:
In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-β1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissue were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-β inhibitor, a distinct decline in VEGF, TGF-β1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased.
Conclusion:
We provide new evidence that asthma could be a risk factor for CNV development via the TGF-β1/Smad signalling pathway. A TGF-β inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.
Cordyceps is a genus of fungus usually found at high altitudes on the Tibetan Plateau and its surrounding areas. It has a rich history in traditional Chinese medicine, with traditional books recording its use as remedies for diseases such as those affecting the kidney and lungs. Recent scientific research has further validated the extensive range of biological properties possessed by various Cordyceps species (antioxidant, anticancer, and hepatoprotective activities) and elucidated the underlying bioactive constituents contributing to their potent pharmacological effects. In modern medicine, the scientifically evident health-benefiting properties of Cordyceps have propagated significant developments in the scientific field to ultimately increase their suitability for industrial applications. These include the utilization of methods such as illumination, optimization of medium components, and generation of mutant strains to enhance compound content and production, along with making modifications to isolated bioactive compounds into more advantageous derivatives. As a result of their robust health-promoting effects, a wide range of products consisting of Cordyceps as the main ingredient have been developed and approved for commercial use, further highlighting the medicinal value of Cordyceps in both traditional medicine and pharmaceutical industries.
Cordyceps spp. (CS), a well-known medicinal mushroom that belongs to Tibetan medicine and is predominantly found in the high altitudes in the Himalayas. CS is a rich reservoir of various bioactive substances including nucleosides, sterols flavonoids, peptides, and phenolic compounds. The bioactive compounds and CS extract have antibacterial, antioxidant, immunomodulatory, and inflammatory properties in addition to organ protection properties across a range of disease states. The study aimed to review the potential of CS, a medicinal mushroom, as a treatment for sepsis. While current sepsis drugs have side effects, CS shows promise due to its anti-inflammatory, antioxidant, and antibacterial properties. We have performed an extensive literature search based on published original and review articles in Scopus and PubMed. The keywords used were Cordyceps, sepsis, and inflammation. Studies indicate that CS extract and bioactive compounds target free radicals including oxidative as well as nitrosative stress, lower inflammation, and modulate the immune system, all of which are critical components in sepsis. The brain, liver, kidneys, lungs, and heart are among the organs that CS extracts may be able to shield against harm during sepsis. Traditional remedies with anti-inflammatory and protective qualities, such as Cordyceps mushrooms, are promising in sepsis. However, more research including clinical trials is required to validate the usefulness of CS metabolites in terms of organ protection and fight infections in sepsis.
The pharmacological use of plant-derived active compounds, such as their antitumor, antiallergic, antiviral, and antioxidative properties, has garnered significant attention. The allergy epidemic poses a serious threat to public health and safety worldwide. Plant-based active ingredients exhibit strong antiallergic properties, which makes them a valuable resource for the creation of antiallergic drugs. This chapter introduced the latest developments in plant-derived actives’ antiallergic efficacy. It also contains information on cellular and animal models used to study plant-derived antiallergic active ingredients. To give a theoretical foundation for the research and application of these active ingredients as antiallergic products, the present problems and potential future prospects in this sector are also covered. This chapter primarily addresses plant-derived substances with antiallergic activity categorized according to three aspects, polyphenols, polysaccharides, and others, and will serve as a reference for readers engaged in the screening of active substances and drug development.
Cordyceps militaris (L.) (Clavicipitaceae) is a favorite member of the genus Cordyceps and has been used for various purposes in traditional medicine applications as a functional food, an energetic, an aphrodisiac, and a remedy for a variety of ailments, such as chronic bronchitis, asthma, inflammation, hemoptysis, allergy, epilepsy, anemia, arrhythmia, and cancer. As evidenced by scientific literature, C. militaris or its containing molecules have demonstrated various pharmacological properties ranging from renal to neurological diseases. Within the context of the present chapter, we focused on C. militaris in terms of ethnobotanical and pharmacological perspectives. We initially pointed out its traditional uses and then mentioned relevant medicinal aspects proved by scientific research worldwide. In this regard, we aimed to emphasize the therapeutic potential of mushrooms with a special interest in C. militaris.Keywords
Cordyceps militaris
EthnobotanyPharmacologyFungusTraditional medicine
Polysaccharides, as one of the main types of bioactive components of Cordyceps militaris, have anti-allergic asthma effects. Herein, an ovalbumin-induced allergic asthma mouse model was established to assess the potential mechanisms of the separated and purified Cordyceps militaris polysaccharide (CMP). CMP is an α-pyranose with a molecular weight of 15.94 kDa that consists of Glc, Man, Gal, Xyl, Ara and GlcA in a molar ratio of 81.25:21.96:13.88:3.92:3.58:1.00. CMP improved inflammatory cytokine levels, alleviated the histopathological changes in the lung and intestinal tissues, regulated the expression of mRNA and proteins related to oxidative stress and inflammatory pathways, reversed gut dysbiosis at the phylum and family levels and improved microbiota function in allergic asthma mice. Moreover, it was found that the levels of inflammatory cytokines in lung tissue of mice were significantly correlated with some intestinal microbial communities. Overall, CMP improved oxidative stress and the inflammatory response in allergic asthma mice by regulating the Nrf2/HO-1 and NF-κB signaling pathways, which may be closely correlation with maintaining the stability of the gut microbiota.
Asthma as an individual disease has blighted human health for thousands of years and is still a vital global health challenge at present. Though getting much progress in the utilization of antibiotics, mucolytics, and especially the combination of inhaled corticosteroids (ICS) and long-acting β-agonists (LABA), we are confused about the management of asthmatic airway inflammation and remodeling, which directly threatens the quality of life for chronic patients. The blind addition of ICS will not benefit the remission of cough, wheeze, or sputum, but to increase the risk of side effects. Thus, it is necessary to explore an effective therapy to modulate asthmatic inflammation and airway remodeling. Traditional Chinese Medicine (TCM) has justified its anti-asthma effect in clinical practice but its underlying mechanism and specific role in asthma are still unknown. Some animal studies demonstrated that the classic formula, direct exacts, and natural compounds isolated from TCM could significantly alleviate airway structural alterations and exhibit the anti-inflammatory effects. By investigating these findings and data, we will discuss the possible pathomechanism underlined airway inflammation and remodeling in asthma and the unique role of TCM in the treatment of asthma through regulating different signaling pathways.
The prevalence of food allergies has increased in Asian countries. The aim of this study was to determine the potential value of sea cucumber peptide (SCP) for anti-allergic therapeutics in terms of their effect on immune response and gut microbiota composition. Results exhibited that SCP could significantly improve the allergy symptoms caused by ovalbumin and could reduce the risk of IgE mediated allergic disorders, as well as repair the morphological damage in the colon. Flow cytometry analysis indicated that SCP could improve the ratio of CD4+/CD8+ T lymphocytes. 16S rRNA results indicated that SCP could differently impact the composition of microbiota. The relative abundances of Bacteroidetes and Firmicutes and the Bacteroidetes/Firmicutes ratio were altered in normal mice. When compared with the OVA treated group, the SCP treated groups showed an increase in the relative abundance of Lachnospiraceae, Muribaculaceae and Ruminococcaceae, and a decrease in Bacteroidaceae, Prevotellaceae, and Lactobacillaceae. These results demonstrate that SCP exhibits potential antiallergic activities in a mouse model of ovalbumin allergy by regulating intestinal microbiota diversity and upregulating the immune response of T lymphocyte subpopulations, which might provide important evidence that SCP can be developed into a novel functional food for inhibiting ovalbumin allergy.
Background
Cordyceps militaris is a fungus that parasitizes insects. Compounds from C. militaris are valuable in medicine and functional food. There are many kinds of bacteria in the natural sclerotia of C. militaris . However, the community structure of microorganisms in samples from different places may be different, and their corresponding ecological functions require experimental verification.
Methods
We used high-throughput sequencing technology to analyze bacterial 16S rRNA gene sequences in sclerotia of three samples of C. militaris from Liaoning Province, China. We isolated, identified and verified the function of culturable bacterial strains from the sclerotia.
Results
Pseudomonas , Pedobacter , Sphingobacterium , and Serratia were the dominant bacterial genera in the sclerotia. And function prediction showed that Pseudomonas and Pedobacter could be heterotrophic, Sphingobacterium could decompose urea, and Serratia could reduce nitrate. Two strains of bacteria isolated from the sclerotia of C. militaris , N-2 and N-26, were identified as Stenotrophomonas maltophilia and Pseudomonas baetica , respectively, based on culture and biochemical characteristics. When these isolated strains were co-cultured with C. militaris , the mycelium biomass and mycelium pellet diameter decreased, and the content of extracellular polysaccharide increased. Strain N-26 decreased the cordycepin content in C. militaris .
Conclusions
Bacteria in sclerotia have an important effect on the growth of C. militaris and the production of its metabolites.
Photoaging is a complex and multistage process triggered mainly by ultraviolet (UV) radiation due to exposure to sunlight. Photoaging induces DNA damage and oxidative stress that initiate an inflammatory response and an increase of matrix metalloproteinases (MMPs) expression, which results in cumulative changes in skin appearance, structure, and functions, and eventually causes skin carcinogenesis. Dietary polysaccharides from bio-resources have been utilized as functional ingredients in healthy food, cosmetics, and drug due to their good bioactivities. However, a systematic introduction to their effects and underlying mechanisms in anti-photoaging is limited. This review discusses the damage and pathogenesis of UV-induced photoaging and summarizes the up-to-date advances in research on the anti-photoaging activity of non-starch polysaccharides from natural edible resources considering the influence of oxidative stress, DNA damage, MMPs regulation, inflammation, and melanogenesis, primarily focusing on the cellular and molecular mechanisms. This paper will help to understand the anti-photoaging functions of dietary non-starch polysaccharides from natural resources and further application in drug and functional food.
Ethnopharmacological relevance
Asthma is a costly global health problem that negatively influences the quality of life of patients. The Chinese Materia Medica (CMM) contains remedies that have been used for the treatment of asthma for millennia. This article strives to systematically summarize the current research progress so that more comprehensive examinations of various databases related to CMM anti-asthma drugs, can be performed, so as to sequentially provide effective basic data for development and application of anti-asthma drugs based on the CMM.
Materials and methods
The research data published over the past 20 years for asthma treatment based on traditional CMM remedies were retrieved and collected from libraries and online databases (PubMed, ScienceDirect, Elsevier, Spring Link, Web of Science, PubChem Compound, Wan Fang, CNKI, Baidu, and Google Scholar). Information was also added from classic CMM, literature, conference papers on classic herbal formulae, and dissertations (PhD or Masters) based on traditional Chinese medicine.
Results
This review systematically summarizes the experimental studies on the treatment of asthma with CMM, covering the effective chemical components, typical asthma models, important mechanisms and traditional anti-asthma CMM formulae. The therapy value of the CMM for anti-asthma is clarified, and the original data and theoretical research foundation are provided for the development of new anti-asthmatic data and research for the CMM.
Conclusions
Substantial progress against asthma has been made through relevant experimental research based on the CMM. These advances improved the theoretical basis of anti-asthma drugs for CMM and provided a theoretical basis for the application of a asthma treatment that is unique. By compiling these data, it is expected that the CMM will now contain a clearer mechanism of action and a greater amount of practical data that can be used for future anti-asthma drug research.
The aim of this study was to determine the effects of wheat germ polysaccharides (WGPs), which are indigestible carbohydrate fibers, on mice in early life, and the changes leading to long-lasting consequences. We determined the influences of early life ceftriaxone and WGP treatment on intestinal microbiota and immunity both in newborn and adulthood mice. The results showed that ceftriaxone significantly altered the intestinal microbiota, short-chain fatty acids' (SCFAs) metabolism, organ index, and serum OVA-specific IgE levels in newborn mice. Comparing adulthood mice to ceftriaxone-treated mice, the diversity and composition of intestinal microbiota were significantly improved after WGP treatment. In addition, the levels of OVA-specific IgE in the WGP-treated mice were significantly decreased, and the expression of cytokines (IL-2, IL-4, IL-6, IFN-γ, and TNF-α) were obviously increased. Therefore, we speculate that the mechanism of action of the indigestible carbohydrate fibers of WGPs is through maintaining immune homeostasis in newborns, which may partly last into adulthood. More importantly, this may be closely related to alterations in the intestinal microbiota.
Dibutyl phthalate (DBP), an important plastic contaminant in the environment, is known to cause organ toxicity. Although current research has shown that DBP-induced organ toxicity is associated with oxidative stress, the toxic effect of DBP on the lungs have not been fully elucidated. Therefore, we investigated the potential mechanism by which DBP induces pulmonary toxicity using a model of DBP-induced allergic airway inflammation in rats. The results showed that chronic exposure to DBP induced histopathological damage, inflammation, oxidative stress, apoptosis, and increased the protein levels of thymic stromal lymphopoietin (TSLP) and its downstream protein Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Moreover, DBP exposure inhibited nuclear factor-erythroid-2-related factor 2 (Nrf2) and levels of its target genes NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Additionally, using in vitro experiments, we found that DBP induced oxidative stress, reduced cell viability, and inhibited the Nrf2/HO-1/NQO1 pathway in mouse alveolar type II epithelial cell line. Overall, these data demonstrate that DBP induces allergic airway inflammation in rats via inhibition of the Nrf2/TSLP/JAK1 pathway.
Despite major advances in the treatment of asthma and the development of several asthma guidelines, people still die of asthma currently. According to WHO estimates, approximately 250,000 people die prematurely each year from asthma. Trends of asthma mortality rates vary very widely across countries, age and ethnic groups. Several risk factors have been associated with asthma mortality, including a history of near-fatal asthma requiring intubation and mechanical ventilation, hospitalization or emergency care visit for asthma in the past year, currently using or having recently stopped using oral corticosteroids (a marker of event severity), not currently using inhaled corticosteroids, a history of psychiatric disease or psychosocial problems, poor adherence with asthma medications and/or poor adherence with (or lack of) a written asthma action plan, food allergy in a patient with asthma. Preventable factors have been identified in the majority of asthma deaths. Inadequate education of patients on recognising risk and the appropriate action needed when asthma control is poor, deficiencies in the accuracy and timing of asthma diagnosis, inadequate classification of severity and treatment, seem to play a part in the majority of asthma deaths. Improvements in management, epitomized by the use of guided self-management systems of care may be the key goals in reducing asthma mortality worldwide
Background/aims:
Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice.
Methods:
A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor β (TGF-β), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, α-SMA, TGF-β1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis.
Results:
Lower expression of miR-485 and higher expression levels of TGF-β1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, α-SMA, TGF-β1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor.
Conclusion:
Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma.
Background:
During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking.
Objective:
The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016.
Methods:
Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma.
Results:
The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.
Conclusions and clinical relevance:
The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.
Purpose
Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma.
Methods
Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells.
Results
OVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment.
Conclusions
Resveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.
Moderate-to-severe asthma has a substantial impact on the health-related quality of life (HR-QOL) of the patients. Cordyceps sinensis is a traditional Chinese medicine that is evaluated clinically for the treatment of many diseases, such as chronic allograft nephropathy, diabetic kidney disease, and lung fibrosis. In order to investigate the effects of Cordyceps sinensis on patients with moderate-to-severe persistent asthma, 120 subjects were randomized to receive Corbin capsule containing Cordyceps sinensis for 3 months (treatment group, n=60 ), whereas the control group ( n=60 ) did not receive treatment with Corbin capsule. Inhaled corticosteroid and as-needed β -agonists were used in the treatment of both groups. HR-QOL was measured with the Juniper’s Asthma Quality of Life Questionnaire (AQLQ). The incidence of asthma exacerbation, pulmonary function testing, and serum measurements of inflammatory mediators were also evaluated. The results showed that the treatment group indicated a significant increase in AQLQ scores and lung function compared with the control group. The expression levels of the inflammation markers IgE, ICAM-1, IL-4, and MMP-9 in the serum were decreased and IgG increased in the treatment group compared with the control group. Therefore, the conclusion was reached that a formulation of Cordyceps sinensis improved the HR-QOL, asthma symptoms, lung function, and inflammatory profile of the patients with moderate-to-severe asthma. This trial is registered with ChiCTR-IPC-16008730 .
This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ (Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria.
Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the nineteenth century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms. Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of asthma.
Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway.
Allergic asthma is a chronic airway inflammatory disease in which exposure to allergens causes intermittent attacks of breathlessness,
airway hyper-reactivity, wheezing, and coughing. Allergic asthma has been called a “syndrome” resulting from a complex interplay
between genetic and environmental factors. Worldwide, >300 million individuals are affected by this disease, and in the United
States alone, it is estimated that >35 million people, mostly children, suffer from asthma. Although animal models, linkage
analyses, and genome-wide association studies have identified numerous candidate genes, a solid definition of allergic asthma
has not yet emerged; however, such studies have contributed to our understanding of the multiple pathways to this syndrome.
In contrast with animal models, in which T-helper 2 (TH2) cell response is the dominant feature, in human asthma, an initial exposure to allergen results in TH2 cell-dependent stimulation of the immune response that mediates the production of IgE and cytokines. Re-exposure to allergen
then activates mast cells, which release mediators such as histamines and leukotrienes that recruit other cells, including
TH2 cells, which mediate the inflammatory response in the lungs. In this minireview, we discuss the current understanding of
how associated genetic and environmental factors increase the complexity of allergic asthma and the challenges allergic asthma
poses for the development of novel approaches to effective treatment and prevention.
The cardinal features of asthma include pulmonary inflammation and airway hyperresponsiveness (AHR). Classically, asthma, specifically allergic asthma, has been attributed to a hyperactive Th2 cell immune response. However, the Th2 cell-mediated inflammation model has failed to adequately explain many of the clinical and molecular aspects of asthma. In addition, the outcomes of Th2-targeted therapeutic trials have been disappointing. Thus, asthma is now believed to be a complex and heterogeneous disorder, with several molecular mechanisms underlying the airway inflammation and AHR that is associated with asthma. The original classification of Th1 and Th2 pathways has recently been expanded to include additional effector Th cell subsets. These include Th17, Th9 and Treg cells. Emerging data highlight the involvement of these new Th cell subsets in the initiation and augmentation of airway inflammation and asthmatic responses. We now review the roles of these recently classified effector Th cell subsets in asthmatic inflammation and the insights they may provide in addition to the traditional Th2 paradigm. The hope is that a clearer understanding of the inflammatory pathways involved and the mediators of inflammation will yield better targeted therapeutics.
Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFbeta1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1beta.
BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFbeta1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1beta. Results were analyzed using non-parametric statistical tests.
Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFbeta1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFbeta1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and alpha-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFbeta1 induced transition but IL-1beta enhanced the transition.
Our results indicate, that TGFbeta1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFbeta1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.
Cordyceps militaris is a well-known fungus with immunomodulatory activity. It is generally used in traditional Chinese medicine to treat hemoptysis, bronchial or lung inflammation, and urogenital disorders. The purpose of our study was to evaluate the effect of cultivated C. militaris on airway inflammation in a mouse asthma model.
BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and were then given intranasal OVA on Day 14 and Days 25-27. Randomized treatment groups of sensitized mice were administered C. militaris, prednisolone, montelukast, or placebo by gavage from Days 15-27. Airway hyperreactivity to aerosolized methacholine was determined. Bronchoalveolar lavage fluid and serum were analyzed to assess airway inflammation.
OVA-sensitized mice developed a significant airway inflammatory response that was inhibited by prednisolone and montelukast, whilst C. militaris reduced airway inflammation less effectively. Airway hyperresponsiveness to methacholine was observed in OVA-sensitized mice and was reversed by both prednisolone and montelukast. C. militaris initially reversed airway hyperreactivity, but this effect disappeared at higher methacholine doses.
C. militaris can modulate airway inflammation in asthma, but it is less effective than prednisolone or montelukast. These results demonstrate that C. militaris is unable to adequately block the potent mediators of asthmatic airway inflammation.
Allergic asthma is a complex disease that has been modeled extensively in small rodents. Airway eosinophilia and changes in lung function have been documented using a variety of protocols. However, recent efforts have improved these models by trying to replicate the structural remodeling that occurs in the lung as a consequence of chronic allergen-driven inflammation. This review documents the recent developments in protocols and systems designed to examine pathways leading to allergen-induced airway remodeling.
Persistent activation of nuclear factor-kappaB has been associated with the development of asthma. Glycogen synthase kinase-3beta is known to regulate the activity of nuclear factor-kappaB.
We hypothesized that inhibition of glycogen synthase kinase-3beta may have anti-inflammatory effects in allergic asthma.
BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and for cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and for the expression of inflammatory biomarkers. Serum immunoglobulin E levels were determined by enzyme-linked immunosorbant assay. Airway hyperresponsiveness was monitored by direct airway resistance analysis.
Intravenous administration of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a selective glycogen synthase kinase-3beta inhibitor, significantly inhibited ovalbumin-induced increases in total cell counts, eosinophil counts, and IL-5, IL-13, and eotaxin levels recovered in bronchoalveolar lavage fluid in a dose-dependent manner. TDZD-8 substantially reduced the serum levels of ovalbumin-specific IgE. Histologic studies showed that TDZD-8 dramatically inhibited ovalbumin-induced lung tissue eosinophilia and airway mucus production. TDZD-8 also markedly suppressed ovalbumin-induced mRNA expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, Muc5ac, and three members of the chitinase family (acidic mammalian chitinase, Ym1, and Ym2). In addition, TDZD-8 significantly reduced ovalbumin-induced airway hyperresponsiveness to inhaled methacholine. Western blot analysis of whole lung lysates revealed that TDZD-8 markedly attenuated the phosphorylation of the nuclear factor-kappaB subunit p65 from ovalbumin-challenged mice.
Our findings suggest that inhibition of glycogen synthase kinase-3beta may provide a novel means for the treatment of allergic airway inflammation.
Allergic diseases have reached epidemic proportions worldwide. An understanding of the cellular and soluble mediators that are involved in allergic inflammatory responses not only helps in understanding the mechanisms of current treatments, but is also important for the identification of new targets that are amenable to both small-molecule and biological interventions. There is now considerable optimism with regards to tackling the allergy epidemic in light of improvements in systemic and mucosal allergen-specific immunotherapy, the identification of key cytokines and their receptors that drive T-helper-2-cell polarization, a clearer understanding of the pathways of leukocyte recruitment and the signalling pathways that are involved in cell activation and mediator secretion, and new approaches to vaccine development.
Cordycepin (Cor), which is a naturally occurring nucleoside derivative isolated from Cordyceps militaris, has been shown to exert excellent antiinflammatory activity in a murine model of acute lung injury. Thus, this study aimed to evaluate the antiasthmatic activity of Cor (10, 20, and 40mg/kg) and to investigate the possible underlying molecular mechanisms. We found that Cor attenuated airway hyperresponsiveness, mucus hypersecretion, and ovalbumin (Ova)-specific immunoglobulin (Ig) E, and alleviated lung inflammation with decreased eosinophils and macrophages in the bronchoalveolar lavage (BAL) fluid. Notably, Cor reduced the upregulation of eotaxin, intercellular cell adhesion molecule-1 (ICAM-1), IL-4, IL-5, and IL-13 in the BAL fluid. Furthermore, Cor markedly blocked p38-MAPK and nuclear factor-kappaB (NF-κB) signalling pathway activation in the Ova-driven asthmatic mice. In conclusion, this study demonstrated that some of the antiasthmatic benefits of Cor attributable to diets and/or tonics may result from reductions in inflammatory processes and that these antiasthmatic properties involve the inhibition of Th2-type responses through the suppression of the p38-MAPK and NF-κB signalling pathways.
Copyright © 2015. Published by Elsevier B.V.
We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism.
Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-β1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis.
Triptolide significantly inhibited TGF-β1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-β1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment.
Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway.
Copyright © 2014 Elsevier Inc. All rights reserved.
Abstract Cordyceps militaris is a potential harborer of biometabolites for herbal drugs. For a long time, C. militaris has gained considerable significance in several clinical and biotechnological applications. Much knowledge has been gathered with regard to the C. militaris's importance in the genetic resources, nutritional and environmental requirements, mating behavior and biochemical pharmacological properties. The complete genome of C. militaris has recently been sequenced. This fungus has been the subject of many reviews, but few have focused on its biotechnological production of bioactive constituents. This mini-review focuses on the recent advances in the biotechnological production of bioactive compositions of C. militaris and the latest advances on novel applications from this laboratory and many others.
CPS-2, a Cordyceps sinensis polysaccharide, has been demonstrated to have significant therapeutic activity against chronic renal failure. However, little is known about the underlying molecular mechanism. In this study, we found that CPS-2 could inhibit PDGF-BB-induced human mesangial cells (HMCs) proliferation in a dose-dependent manner. In addition, CPS-2 notably suppressed the expression of α-SMA, PDGF receptor-beta (PDGFRβ), TGF-β1, and Smad 3 in PDGF-BB-treated HMCs. Furthermore, PDGF-BB-stimulated ERK activation was significantly inhibited by CPS-2, and this inhibitory effect was synergistically potentiated by U0126. CPS-2 could prevent the PDGFRβ promoter activity induced by PDGF-BB, and return expression of PDGFRβ, TGF-β1, and TGFβRI to normal levels while cells were under PDGFRβ and ERK silencing conditions and transfected with DN-ERK. Taken together, these findings demonstrated that CPS-2 reduces PDGF-BB-induced cell proliferation through the PDGF/ERK and TGF-β1/Smad pathways, and it may have bi-directional regulatory effects on the PDGF/ERK cellular signaling pathway.
The role of interferon-γ (IFN-γ) in asthma is controversial. However, this cytokine has been proposed to play a role both acute severe asthma and chronic stable asthma. We have shown that in a chronic low-level challenge model of allergic asthma in mice, which replicates characteristic features of airway inflammation and remodelling, the mechanisms of airway hyperreactivity (AHR) are markedly different to those in short-term high-level challenge models. Notably, AHR is independent of various Th2 cytokines and their signalling pathways. However, administration of a neutnalising antibody to IFN-γ suppresses AHR. More recently, we have found that following chronic allergen challenge, but not acute challenge, IFN-γ-producing CD4+ T cells are demonstrable in peribronchial lymph nodes, both in wild-type mice and in STAT6 -/- mice. Treatment with anti-IFN-γ decreases the number of IFN-γ-producing CD4+ T cells in both wild-type and gene-targeted mice, providing a possible explanation for the ability of anti-IFN-γ to inhibit AHR in the setting of chronic challenge. These data further strengthen the notion that the pathogenesis of the lesions of asthma, and especially of AHR, involves a co-operative interaction between Th2 and Th1 cytokines. This may be particularly relevant to acute exacerbations of asthma, in which setting there may be justification for therapeutic inhibition of IFN-γ.
Aiming the extract of Cordyceps sinensis significantly inhibits airway inflammation, airway hyperresponsiveness, and the infiltration of eosinophils in the airway of rats and may be related to the modulation of T helper (Th)1 and Th2 cells functions. The mechanisms of C. sinensis involved in modulation of suppression inflammation are not yet determined. In this study, the mechanism involved in the extract of C. sinensis-C.S.3-modulated suppression of inflammation was investigated in vivo and in vitro systems. The results showed that C.S.3 reduced airway inflammation in ovalbumin-induced allergic mice. Furthermore, we found C.S.3 could decrease extracellular signal-regulated kinase 1/2 signaling pathway to suppress activity of nuclear factor-κB in lung cells and cultured airway smooth muscle cells. Conclusion C.S.3 may provide clinical applications for asthma in the future.
Airway remodeling, or structural changes of the airway wall arising from injury and repair, plays an important role in the pathophysiology of asthma. Remodeling is characterized as structural changes involving the composition, content, and organization of many of the cellular and molecular constituents of the bronchial wall. These structural changes can include epithelial injury, subepithelial thickening/fibrosis, airway smooth muscle hyperplasia, goblet cell hypertrophy and hyperplasia, and angiogenesis. Historically, these changes are considered a consequence of long-standing airway inflammation. Recent infant and child studies, however, suggest that remodeling occurs in parallel with inflammation in asthmatic subjects. Despite advancements in the recognition of key cellular and molecular mechanisms involved in remodeling, there remains a paucity of information about which treatments or interactions are most likely to regulate these processes. Furthermore, it is unclear as to when is the best time to initiate treatments to modify remodeling, which components to target, and how best to monitor interventions on remodeling. Indeed, inhaled corticosteroids, which are generally considered to have limited influence on remodeling, have been shown to be beneficial in studies in which the dose and duration of treatment were increased and prolonged, respectively. Moreover, several studies have identified the need to identify novel asthma indices and phenotypes that correlate with remodeling and, as a consequence, might specifically respond to new therapies, such as anti-IgE, anti-IL-5, and anti-TNF-α mAbs. Our review will evaluate the development of remodeling in asthmatic subjects and the effects of treatment on these processes.
Airway remodelling contributes to increased morbidity and mortality in asthma. We have reported that triptolide, the major component responsible for the immunosuppressive and anti-inflammatory effects of Tripterygium wilfordii Hook F, inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether triptolide inhibits airway remodelling in a mouse asthma model and observed the effects of triptolide on the transforming growth factor-β₁ (TGF-β₁)/Smad pathway in ovalbumin (OVA)-sensitized mice. BALB/c mice were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 8 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2 mg/kg). The area of bronchial airway (WAt/basement membrane perimeter) and smooth muscle (WAm/basement membrane perimeter), mucus index and collagen area were assessed 24 hr after the final OVA challenge. Levels of TGF-β(1) were assessed by immunohistology and ELISA, levels of TGF-β(1) mRNA were measured by RT-PCR, and levels of pSmad2/3 and Smad7 were assessed by Western blot. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway and smooth muscle, mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β(1) , TGF-β(1) mRNA and pSmad2/3 were significantly reduced in mice treated with triptolide and dexamethasone, and this was associated with a significant increase in levels of Smad7. Triptolide may function as an inhibitor of asthma airway remodelling. It may be a potential drug for the treatment of patients with a severe asthma airway.
We try to find out the influence of traditional Chinese Medicine Astragali-Cordyceps Mixtura (ACM) on TGF-beta/Smad signal pathway in the lung of asthma airway remodeling.
Mice were sensitized and challenged by OVA to establish a model of asthma. To assess the effects of ACM on the mice, animals of the ACM groups were treated with ACM. Data were achieved by using techniques as follow: counting cell number of BALF, assaying the amount of collagen deposition by Masson's staining, performing RT-PCR and immunohistochemistry for mRNA and protein expression of TGF-beta1, Smad3 and Smad7.
The depositions of collagen in airway wall greatly increased at the model group compared with that of the normal group. In contrast, these decreased at the ACM groups. As compared with the control group, TGF-beta1 expression also decreased at both mRNA and protein level at the ACM-M group versus increased both at the model group. Whereas, Smad7 significantly decreased only at the model group and partly restored at the ACM-M group.
ACM greatly improves the symptoms of asthma airway remodeling by inhibiting the expression of TGF-beta1 and upregulating the amount of Smad7.
Airway remodeling refers to the structural changes that occur in both the large and the small airways of miscellaneous diseases, including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, enlargement of glands, neovascularization, and epithelial alterations. Although controversial, airway remodeling is commonly attributed to the underlying chronic inflammatory process. These remodeling changes contribute to thickening of airway walls and consequently lead to airway narrowing, bronchial hyperresponsiveness, airway edema, and mucous hypersecretion. Airway remodeling is associated with poorer clinical outcome among patients with asthma. Early diagnosis and prevention of airway remodeling has the potential to decrease disease severity, to improve control, and to prevent disease expression. In this article, we briefly provide an update on the characteristic features of airway remodeling observed in asthma and their clinical consequences.
Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiological and immunological processes are not fully understood. Animal models have been used to elucidate asthma pathophysiology, and to identify and evaluate novel therapeutic targets. Several recent review articles (Epstein, 2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed the potential value of these models. Allergen challenge models reproduce many features of clinical asthma and have been widely used by investigators; however, the majority involve acute allergen challenge procedures. It is recognised that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation, and there has been a recent focus on developing chronic allergen exposure models, predominantly in mice. Here, we review the acute and chronic exposure mouse models, and consider their potential role and impact in the field of asthma research.
To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta 2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.
Cordyceps sinensis (C. sinensis) is one of the well known fungi used in traditional Chinese medicine for treatment asthma and bronchial and lung inflammation. In this study, effects of C. sinensis methanolic extracts on bronchoalveolar lavage fluids (BALF) cells proliferation, inflammatory cytokines production, and genes expression were evaluated. The proliferative response of BALF cells to lipopolysaccharide (LPS) was determined by the tritiated thymidine uptake method. The cell-free supernatants were harvested then tested for interlukin-1beta (IL-1beta), interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), and interferon-gamma (IFN-gamma) by the enzyme immunoassay. The results indicated that the CS-19-22 fraction dose dependently suppressed BALF cells proliferation activated by LPS. The CS-19-22 fraction also reduced IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha production in LPS activated BALF cell cultures. Furthermore, the IL-12 and IFN-gamma production in activated BALF cells were enhanced by CS-19-22 treatment. The CS-19-22 fraction did not affect IL-1beta, IL-6, TNF-alpha, and IL-8 mRNAs expression in BALF cells detected by reverse transcription-polymerase chain reaction (RT-PCR). By contrast, the CS-19-22 fraction increased IL-12 and IFN-gamma mRNAs expression and decreased IL-10 mRNA expression in the BALF cells activated with LPS. These results indicated the CS-19-22 fraction suppressed IL-1beta, IL-6, TNF-alpha, and IL-8 cytokines production in BALF cells through other than inhibition of mRNAs expression pathway. These results also demonstrate that the therapeutic activity of C. sinensis in Chinese medicine may be related to modulation of TH1 and TH2 cells functions in bronchial airway.
Cordyceps, one of the well-known traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of the caterpillar. It is commonly used for the replenishment of body health. One of the known pharmacological effects is its anti-oxidation activity. However, there is a great variation of the quality in different sources of Cordyceps. Here, the water extracts of various sources of natural C. sinensis and cultured Cordyceps mycelia were analyzed for their anti-oxidation activity by using three different assay methods such as the xanthine oxidase assay, the induction of hemolysis assay and the lipid peroxidation assay. The results showed that Cordyceps, in general, possesses a strong anti-oxidation activity in all assays tested. However, both natural and cultured Cordyceps showed the lowest inhibition in the lipid peroxidation when compared with the other two assay methods. The cultured Cordyceps mycelia had equally strong anti-oxidation activity as compared to the natural Cordyceps. Besides, the anti-oxidation activities were increased to 10-30 folds in the partially purified polysaccharide fractions from the cultured Cordyceps mycelia, which suggested that the activity could be derived partly from Cordyceps polysaccharides.
Eotaxin is a small protein that is produced in the lungs of asthmatic patients and is a potent chemoattractant for eosinophils. Eotaxin, a CC chemokine, stimulates the migration of eosinophils from the small blood vessels in the lungs by acting on the CC chemokine receptor CCR3, which is located on the leukocyte cell surface. In the past year, three low molecular weight compounds have been developed that can block this receptor. Such compounds may be developed into orally available drugs aimed at preventing eosinophil recruitment and, hence, the pathogenesis associated with the activation of these cells within the lung tissue.
Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyperreactivity, and airway remodeling. The etiology of asthma is complex and multifactorial. Recent advances have demonstrated the importance of genetics in the development of asthma, particularly atopic asthma. Environmental stimuli, particularly early childhood infections, have also been associated with the development of asthma. Most current data seem to suggest that these factors drive the development of a Th-2 lymphocyte-predominant immune response, which has been associated with atopy and IgE-mediated inflammation. The concept of reversible airflow obstruction has also recently been challenged. It is now clear that chronic airway changes occur, which may contribute to progressive airflow obstruction. We discuss the important influence of genetic and environmental factors on the emergence of the asthmatic phenotype. The significance of Th-1 and Th-2 lymphocyte-mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.
We examined the effect of airway inflammation on airway remodeling and bronchial responsiveness in a mouse model of allergic asthma.
BALB/c mice were sensitized to ovalbumin (OA), and exposed to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen challenge, bronchial responsiveness was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out.
Repeated antigen exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes, collagen deposition in the lungs, subepithelial fibrosis associated with increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of eosinophils in BALF was significantly correlated with TGF-beta1 production in BALF and the amount of hydroxyproline. Furthermore, significant correlations were found between these fibrogenic parameters and the bronchial responsiveness.
These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.
Recent clinical studies have brought asthma's complex inflammatory processes into clearer focus, and understanding them can help to delineate therapeutic implications. Asthma is a chronic airway inflammatory disease characterized by the infiltration of airway T cells, CD(+) (T helper) cells, mast cells, basophils, macrophages, and eosinophils. The cysteinyl leukotrienes also are important mediators in asthma and modulators of cytokine function, and they have been implicated in the pathophysiology of asthma through multiple mechanisms. Although the role of eosinophils in asthma and their contribution to bronchial hyperresponsiveness are still debated, it is widely accepted that their numbers and activation status are increased. Eosinophils may be targets for various pharmacologic activities of leukotriene receptor antagonists through their ability to downregulate a number of events that may be key to the effector function of these cells.
Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumour, anti-oxidation and stimulating the immune system; however, the identity of active component(s) is not determined. By using anti-oxidation activity-guided fractionation, a polysaccharide of molecular weight approximately 210 kDa was isolated from cultured Cordyceps mycelia by ion-exchange and sizing chromatography. The isolated polysaccharide, having strong anti-oxidation activity, contains glucose, mannose and galactose in a ratio of 1 : 0.6 : 0.75. The pre-treatment of isolated polysaccharide on the cultured rat pheochromocytoma PC12 cells shows strong protective effect against hydrogen peroxide (H(2)O(2))-induced insult. Treatment of the cells with the isolated polysaccharide at 100 microg/ml prior to H(2)O(2) exposure significantly elevated the survival of PC12 cells in culture by over 60%. In parallel, the H(2)O(2)-induced production of malondialdehyde in cultured cells was markedly reduced by the polysaccharide treatment. Moreover, the pre-treatment of the isolated polysaccharide significantly attenuated the changes of glutathione peroxidase and superoxide dismutase activities in H(2)O(2)-treated cells in a dose-dependent manner. This is the first report in identifying a polysaccharide from Cordyceps, which protects against the free radical-induced neuronal cell toxicity.
Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of allergic asthma and other airway diseases. Signals from the activated TGF-beta receptor complex are transduced to the nucleus of airway cells by Smad proteins, which represent a family of transcription factors that have recently been implicated to play a major role as intracellular mediators of inflammation. The Smad family consists of the receptor-regulated Smads, a common pathway Smad, and inhibitory Smads. Receptor-regulated Smads (R-Smads) are phosphorylated by the TGF-beta type Ireceptor. They include Smad2 and Smad3, which are recognized by TGF-beta and activin receptors, and Smads 1, 5, 8, and 9, which are recognized by bone morphogenetic protein (BMP) receptors. Smad4 is a common pathway Smad, which is also defined as cooperating Smad (co-Smad) and is not phosphorylated by the TGF-beta type I receptor. Inhibitory Smads(anti-Smads) include Smad6 and Smad7, which down-regulate TGF-beta signaling. To date, the Smads are the only TGF-beta receptor substrates with a demonstrated ability to propagate signals and with regard to the growing number of investigations of Smad-mediated effects in the airways, Smads may prove to be an important target for future development of new therapeutic strategies for asthma and chronic obstructive pulmonary disease.
Asthma is increasing in prevalence in the developing world, affecting 10% of the world’s population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.
Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-ß is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.
This review highlights the role of transforming growth factor-ß in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-ß and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.
A fuller comprehension of the actions of transforming growth factor-ß, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.
Cordyceps sinensis, a well-known and valued traditional Chinese medicine, is also called DongChongXiaCao (winter worm summer grass) in Chinese. It is commonly used to replenish the kidney and soothe the lung for the treatment of fatigue, night sweating, hyposexualities, hyperglycemia, hyperlipidemia, asthemia after severe illness, respiratory disease, renal dysfunction and renal failure, arrhythmias and other heart disease, and liver disease. As the rarity and upstanding curative effects of natural Cordyceps, several mycelial strains have been isolated from natural Cordyceps and manufactured in large quantities by fermentation technology, and they are commonly sold as health food products in Asia. In addition, some substitutes such as Cordyceps militaris also have been used and adulterants also confused the market. Therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Herein, markers and analytical methods for quality control of Cordyceps were reviewed and discussed.
The Chinese herb DongChong-XiaCao originating from Cordyceps sinensis is widely used as a traditional medicine in China for treatment of a wide variety of diseases. The extracts of Cordyceps sinensis (CSE) and Cordyceps militaris (CME) are well-known for their biological effects. In the present study, the antioxidant efficiency of CME and CSE in protecting lipid, protein, and low-density lipoprotein (LDL) against oxidative damage was investigated. CME and CSE showed weakly inhibitory effect on liposome oxidation, that of CME being superior to that of CSE. As for the protein oxidation model system, the inhibitory effect of CME on protein oxidation was inferior to that of CSE. CME and CSE at 1.0 mg/mL showed 50.5 and 67.1% inhibition of LDL oxidation, respectively. The contents of bioactive ingredients cordycepin and adenosine in CME are higher than those of CSE; however, both cordycepin and adenosine showed no significant antioxidant activity as determined by the Trolox equivalent antioxidant capacity method. Polyphenolic and flavonoid contents are 60.2 and 0.598 microg/mL in CME and 31.8 and 0.616 microg/mL in CSE, respectively, which may in part be responsible for their antioxidant activities. In addition, a polysaccharide present in CME and CSE displayed antioxidant activity, which suggested that the activity might be derived partly from polysaccharides of CME and CSE. The tendency to scavenge the ABTS(*)(+) free radical and the reducing ability of CME and CSE display concentration-dependent manners, suggesting that CME and CSE may be potent hydrogen donators. On the basis of the results obtained, the protective effects of CME and CSE against oxidative damage of biomolecules are a result of their free radical scavenging abilities.
Performing bronchoalveolar lavage in the mouse
- Daubeuf