Liu-Wei-Di-Huang Wan (LWDHW) has been used by traditional Chinese doctors to treat asthma patients. This study was to examine the potential effect of this decoction on the regulation of T helper (Th)1- and Th2-type cytokine gene expression in vitro. Peripheral blood mononuclear cells (PBMC) were activated with mitogen for 24 hours in the presence or absence of LWDHW extracts. Concentrations of different cytokines in the culture supernatants were determined with ELISA. RNA isolated from cultured cells was subjected to RT-PCR analysis. The results showed that the expression of all cytokines (Th2-type: IL-4, IL-5, IL-10, or IL-13 and Th1-type: IL-2 and IFN-γ) examined was inhibited at both RNA and protein levels by LWDHW. Since the cell viability was similar in all cultures, the reduction of cytokine production was not due to the toxicity of LWDHW. Moreover, the cells either retained or increased their capacity to respond to mitogen stimulation after incubation with the LWDHW decoction. Therefore, the data suggest that LWDHW functioned directly on cytokine gene expression from activated PBMC.
In traditional Chinese medicine (TCM), the imbalance of yin and yang is one of the basic pathogeneses of a disease. Preponderance of yang leads to "heat" manifestations including thirst, dryness of the throat, dark scanty urine and constipation. Treatment of asthma in TCM is based on the differentiation of "heat" Zheng according to the manifestations. Some of the patients with allergic asthma also present typical "heat" manifestations. To investigate the essence of "heat" manifestation in asthma, we measured the serum level of eosinophil cationic protein (ECP) in asthmatic patients. ECP usually represents the activation of eosinophils which are the main effectors in late allergic reactions. Our results demonstrated that asthmatic patients with "heat" manifestations had higher serum ECP levels, compared to those without "heat" manifestations (34.3 ± 4 μg/l versus 15.3 ± 3 μg/l). However, total immunoglobulin E (IgE), and the eosinophil count in peripheral blood did not show any difference between the "heat" and "non-heat" groups. Therefore, we conclude that ECP in asthmatic patients plays an important role in the development of "heat" manifestations as diagnosed by TCM.
Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-γ in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-γ and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.
The increasing incidence of asthma in developing countries emphasizes the importance of identifying more effective treatments that have low cost. Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae), a common herbal tea in China, has been used to treat lung inflammation. Since the Th2 cytokines are the major mediators in the pathogenesis of asthma, Th1-biased immune responses caused by G. pentaphyllum might have the potential to relieve asthmatic symptoms. We hypothesized that oral administration of G. pentaphyllum extracts might suppress Th2 cytokine-induced airway inflammation responses in ovalbumin (OVA)-sensitive mice. BALB/c mice were sensitized with intraperitoneal injection and challenged 3 times with OVA inhalation (IH) (the IH3 model). G. pentaphyllum was orally administered for 7 consecutive days before the end of the OVA challenge. In the IH5 model, 2 more OVA challenges were administered to mimic the encounter with an allergen after drug treatment. G. pentaphyllum extracts significantly attenuated airway hyperresponsiveness (AHR) and inhibited eosinophil infiltration in mice in both models. Serum OVA-specific antibodies were also reduced with the treatment. Decreased Th2-type cytokines and increased IFN-γ were detected in the cultures of OVA-activated splenocytes from treated mice. Our results suggest that G. pentaphyllum extracts might be beneficial for asthma airway inflammation through the suppression of Th2 activity.
The last decade has seen a wealth of information reporting the beneficial effects of Chinese herbal medicines. While a lot more studies were done using in vitro and in vivo research platforms, much fewer investigations were conducted according to evidence-based requirements in clinical settings. The Institute of Chinese Medicine at the Chinese University of Hong Kong (CUHK) has had the opportunity to collaborate with clinicians over the years to initiate and conduct dozens of clinical trials investigating and verifying the therapeutic values of Chinese herbs in selected disease conditions. Of the many disorders, we chose to focus on those that are known for their difficulties achieving perfect results with conventional treatment methods. Examples include non-healing ulcers, allergic conditions, degenerative diseases and cancer. Protective effects of the herbs in such chronic diseases as coronary artery disease and osteoporosis were also part of our focus. Even in healthy individuals and those recovering from chemotherapy, Chinese herbs could help with the immune system and were studied in our clinical trials as well. This paper aims to highlight the important findings from these clinical studies while at the same time, stressing the indispensable value of clinical trials in modernizing the use of Chinese herbs in present-day medicine.
This study is aimed to evaluate the effects of Psoraleae fructus (PF) on Th2 responses in a rat model of asthma in vivo and psoralen, a major constituent in PF, on Th2 responses in vitro. A rat model of asthma was established by sensitization and challenged with ovalbumin (OVA). Airway hyperresponsiveness was detected by direct airway resistance analysis. Lung tissues were examined for cell infiltration and mucus hypersecretion. Bronchoalveolar lavage fluid (BALF) was assessed for cytokine levels. In vitro study, Th2 cytokine production was evaluated in the culture supernatant of D10.G4.1 (D10 cells) followed by the determination of cell viability, meanwhile Th2 transcription factor GATA-3 expression in D10 cells was also determined. The oral administration of PF significantly reduced airway hyperresponsiveness (AHR) to aerosolized methacholine and decreased IL-4 and IL-13 levels in the BALF. Histological studies showed that PF markedly inhibited inflammatory infiltration and mucus secretion in the lung tissues. In vitro study, psoralen significantly suppressed Th2 cytokines of IL-4, IL-5 and IL-13 by ConA-stimulated D10 cells without inhibitory effect on cell viability. Furthermore, GATA-3 protein expression was also markedly reduced by psoralen. This study demonstrated that PF exhibited inhibitory effects on hyperresponsiveness and airway inflammation in a rat model of asthma, which was associated with the suppression of Th2 response. Psoralen, a major constituent of PF, has immunomodulatory properties on Th2 response in vitro, which indicated that psoralen might be a critical component of PF for its therapeutic effects.
As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease.
Asthma is a chronic respiratory symptoms with variable airflow limitation and airway hyperresponsiveness (AHR), and causes high economic burden. Traditional Chinese medicine (TCM) has a long-lasting history of using herbal medicine in the treatment of various respiratory diseases including asthma. In the last several decades, an increasing number of herbs have been shown to be effective in the treatment of asthma in clinical trials or asthmatic inflammation in animal models. Literature about the effects of TCM on the immune system were searched in electronic databases such as PubMed, Google Scholar and Scopus from 2000 to 2014. 'TCM' and 'asthma' were used as keywords for the searches. Over 400 literatures were searched and the literatures about the immune system were selected and reviewed. We only reviewed literatures published in English. Accumulating evidence suggests that TCM can directly inhibit the activation and migration of inflammatory cells, regulate the balance of Th1/Th2 responses, and suppress allergic hyperreactivity through inducing regulatory T cells or attenuating the function of dendritic cells (DCs). These studies provided useful information to facilitate the use of TCM to treat asthma. This review was conducted to classify the findings based on their possible mechanisms of action reported.
In Chinese medicine, Descurainia sophia is used to treat cough by removing the phlegm in asthma and inflammatory airway disease, but the mechanism is not clear. In this study, we evaluated whether D. sophia water extract (DSWE) can alleviate airway inflammation and airway hyperresponsiveness (AHR) in the lungs of a murine asthma model. Female BALB/c mice were divided into five groups: normal controls, ovalbumin (OVA)-sensitized asthmatic mice, and OVA-sensitized mice treated with DSWE (2, 4, 8 g/day) by intraperitoneal injection. After sacrificing the mice, serum was collected to detect OVA-specific antibodies by ELISA, as well as bronchoalveolar lavage fluid (BALF) to detect cytokine levels. We also detected gene expression and histopathologically evaluated the lungs of asthmatic mice. DSWE reduced AHR, goblet cell hyperplasia, eosinophil infiltration, and collagen aggregation in the lungs of asthmatic mice. DSWE also suppressed the gene expression of Th2-associated cytokines and chemokines in lung tissue and inhibited serum OVA-IgE and Th2-associated cytokine levels in the BALF of OVA-sensitized mice. Our findings suggest that DSWE is a powerful immunomodulator for ameliorated allergic reactions by suppressing Th2 cytokine expression in asthmatic mice.
Studies have demonstrated the effect of acupoint-based interventions in relieving the clinical symptoms of asthma. However, the effect of meridian-based interventions in asthma symptom relief is unknown. This systematic review and meta-analysis determined the effect of multiplex meridian interventions in asthma symptom relief. Eight electronic databases were searched for relevant randomized controlled trials (RCTs) that involved patients with asthma, were published before March 2018, used acupoint stimulation interventions targeting acupoints that correspond to meridians, and considered asthma symptom relief as an outcome. In 204 RCTs that were identified and used in a meta-synthesis, meridians were used 521 times, with the bladder meridian being the most frequently used. Furthermore, 23 RCTs were included in the meta-analysis. Egger’s and inconsistency tests revealed no significant differences among the studies (P>0.05). However, the interventions differed significantly in terms of asthma symptom relief effect, as demonstrated by pairwise (odds ratio [OR]=0.28, 95% confidence interval=0.21–0.37) and network (OR=0.18, 95% credibility interval=0.08–0.41) meta-analyses. Surface under the cumulative ranking (SUCRA) revealed that the bladder–conception vessel–governor vessel–stomach multiplex meridian intervention was more effective than non-meridian interventions in relieving asthma symptoms. Additionally, either bladder–conception vessel–stomach or bladder–conception vessel–governor vessel–kidney multiplex meridians may be selected in interventions. This study suggests that practitioners target multiplex meridians, especially the meridians of the bladder and conception vessel, to effectively relieve asthma symptoms.
Asthma is a common allergic airway inflammatory disease, characterized by abnormal breathing due to bronchial inflammation. Asthma aggravates the patient’s quality of life and needs continuous pharmacological treatment. Therefore, discovery of drugs for the treatment of asthma is an important area of human health. The aim of the present study was to evaluate whether Cynanchum atratum extract (CAE) modulates the asthma-like allergic airway inflammation and to study its possible mechanism of action using ovalbumin (OVA)-induced airway inflammation and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, as well as a mast cell-based in vitro model. The histological analysis showed that CAE reduced the airway constriction and immune cell infiltration. CAE also inhibited release of β-hexosaminidase and expression of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-5 in bronchoalveolar lavage fluid and lung tissues. In addition, CAE reduced the OVA-specific immunoglobulin (Ig) E, total IgE, IgG1, and IgG2a levels in the serum. In the LPS-induced ALI model, CAE suppressed the LPS-induced lung barrier dysfunction and the release of proinflammatory cytokines. Because allergic airway inflammatory responses are associated with the activation of mast cells, RBL-2H3 cells were used to evaluate the underlying mechanism of CAE effects. In RBL-2H3 cells, CAE down-regulated release of β-hexosaminidase and histamine by reducing the intracellular calcium influx. In addition, CAE suppressed the expression of proinflammatory cytokines by inhibiting nuclear translocation of nuclear factor-κB. Taken together, our findings suggest that CAE may help in the prevention or treatment of airway inflammatory diseases.
In this paper, some nonlinear mathematical models are proposed and analyzed to study the spread of asthma due to inhaled pollutants from Industry. The following two types of demographics are considered here; (i) population with constant immigration, (ii) population with logistic growth. In each type of demography, the following three cases have been considered regarding the release of pollutant into the environment; (i) when emission of the pollutant into the environment is constant, (ii) when emission of the pollutant is population dependent, and (iii) when emission of the pollutant is periodic. Using stability theory of differential equations and computer simulation, it is shown that due to an increase in the air pollutant, the asthmatic (diseased) population increases in the region under consideration.
In previous models, heart-lung-blood interactions and their physicochemical properties have not been considered in comprehensive simulators and an integrated mathematical model has not been presented. The aim of the present study is to combine different phenomena involved in the cardiopulmonary function, which are often considered separately. In this study, the variables that constitute a comprehensive model; which includes physicochemical reactions of O2 and CO2 in the blood and fluid compartments, V/Q, pH, body temperature and diffusion limitation in the adult human and its ability to provide realistic response under different physiological and pathophysiological conditions; have been evaluated. The new biological system model consists of two subsystems: physicochemical properties of blood and physiological subsystem models. Based on the mentioned parameters, comprehensive simulator model has been suggested as following:
Purpose: Skeletal muscle affection already in the eosinophilic stage of Churg–Strauss syndrome (CSS) is unusual.
Case report: In a 36-year-old woman with a history of recurrent bronchial infections since childhood, recurrent poly-sinusitis and nasal polyps, and bronchial asthma, easy fatigability, weakness of the lower arms and lower legs, generalized myalgias with predominance of the lower arms, recurrent vertigo and falls developed. There was recurrently elevated creatine-kinase, glutamate-oxalate-transaminase, aldolase, lactate-dehydrogenase, eosinophilic granulocyte-count, thrombocyte-count, cholesterol, and blood sedimentation rate. Histologically polyps showed diffuse infiltrations of eosinophils exclusively. Muscle biopsy revealed grouped atrophic fibers, necrotic fibers, rarely regenerating fibers, epitheloid cells and rarely perimysial eosinophilic granulozytes. According to established criteria, CSS was diagnosed.
Conclusions: This case shows that affection of the skeletal muscle in CSS, may manifest as easy fatigability, myalgias, and recurrently elevated CK, and that skeletal muscle involvement may be a dominant feature not only of the vasculitic but also of the eosinophilic stage of CSS.
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