The CXCL12-CXCR4-NLRP3 axis promotes Schwann cell pyroptosis and sciatic nerve demyelination in rats.

Studies have shown that the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is detrimental to the functional recovery of the sciatic nerve, but the regulatory mechanisms of the NLRP3 inflammasome in peripheral nerves are unclear. C-X-C motif chemokine 12 (CXCL12) can bind to C-X-C chemokine receptor type 4 (CXCR4) and participate in a wide range of nerve inflammation by regulating the NLRP3 inflammasome. Based on these, we explore whether CXCL12-CXCR4 axis regulates the NLRP3 inflammasome in the peripheral nerve. We found that CXCR4/CXCL12, NLRP3 inflammasome-related components, pyroptosis-related proteins and inflammatory factors in the sciatic nerve injured rats were markedly increased compared with the sham-operated group. AMD3100, a CXCR4 antagonist, reverses the activation of NLRP3 inflammasome, Schwann cell pyroptosis and sciatic nerve demyelination. We further treated rat Schwann cells with LPS (lipopolysaccharide) and adenosine triphosphate (ATP) to mimic the cellular inflammation model of sciatic nerve injury, and the results were consistent with those in vivo. In addition, both in vivo and in vitro experiments demonstrated that AMD3100 treatment reduced the phosphorylation of nuclear factor κB (NF-κB) and the expression of thioredoxin interacting protein (TXNIP), which contributes to activating NLRP3 inflammasome. Therefore, our findings suggest that, after sciatic nerve injury, CXCL12-CXCR4 axis may promote Schwann cell pyroptosis and sciatic nerve demyelination through activating NLRP3 inflammasome and slow the recovery process of the sciatic nerve.

Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-ß1/smad2 signaling in rats with chronic obstructive pulmonary disease.

BACKGROUND: The three Tiao-Bu Fei-Shen (Bufei Jianpi, Bufei Yishen, Yiqi Zishen) granules have been confirmed for their beneficial clinical efficacy in chronic obstructive pulmonary disease (COPD) patients on reducing frequency and duration of acute exacerbation, improving syndromes, pulmonary function and exercise capacity. But the short- or long-term mechanism of them is not fully clear. Nuclear factor (NF)-κB/transforming growth factor (TGF)-ß1/smad2 signaling pathway is involved in the progress of inflammation and remodeling in chronic obstructive pulmonary disease COPD. This study aimed to explore the long-term effects mechanism of Tiao-Bu Fei-Shen granules by regulating NF-κB/TGF-ß/Smads signaling in rats with COPD. METHODS: Sprague Dawley rats were randomized into control, model, Bufei Jianpi, Bufei Yishen, Yiqi Zishen and aminophylline groups. COPD rats, induced by cigarette smoke and bacterial infections exposures, were administrated intragastricly by normal saline, Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or aminophylline from week 9 through 20, respectively. At week 20 and 32, lung tissues were harvested. Immunohistochemistry was used to detect interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, quantitative real-time polymerase chain reaction (qRT-PCR) was used for TGF-ß1 and Smad2 mRNA analysis, western blotting was used to determine the phosphorylation of NF-κB (p-NF-κB) and IκBα (p-IκBα). RESULTS: COPD rats had marked airway injury, such as chronic airway inflammation and remodeling, emphysema, which were improved in the three traditional Chinese medicines (TCM)-treated animals. The levels of IL-1ß, TNF-α, p-NF-κB, p-IκBα, TGF-ß1 and Smad2 were significantly higher in COPD rats than in controls, while they were dramatically reduced in the three TCM- and aminophylline-treated groups. At the meantime, all these endpoints were significantly lower in three TCM-treated groups than in aminophylline group, especially in Bufei Jianpi and Bufei Yishen groups. Compared to week 20, all endpoints decreased significantly in three TCM groups at week 32. CONCLUSION: The three Tiao-Bu Fei-Shen therapies can reduce pulmonary inflammation and remodeling in COPD and have significant long-term effects. NF-κB/TGF-ß1/smad2 signaling might be involved in the mechanism.

Intravenous dezocine pretreatment reduces the incidence and intensity of myoclonus induced by etomidate.

To evaluate the suppressive effect of intravenous dezocine on the incidence and severity of myoclonic movements induced by etomidate, a total of 80 patients, American Society of Anesthesiologists physical status I-II, were randomized into two equally sized groups (n = 40). These two groups were assigned to give either intravenous dezocine 0.1 mg/kg or a matching placebo (equal volume of 0.9% saline) 30 s before administration of etomidate. For anesthesia induction, 0.3 mg/kg etomidate was injected over a period of 1 min. One minute after etomidate administration, the severity of myoclonus was assessed. Pretreatment with dezocine significantly reduced both the incidence and intensity of myoclonus. These results demonstrate that intravenous dezocine 0.1 mg/kg 30 s prior to induction was effective in suppressing myoclonic movements in our patients.

CXCL1-CXCR2 axis mediates inflammatory response after sciatic nerve injury by regulating macrophage infiltration.

Macrophages play a crucial role in the inflammatory response following sciatic nerve injury. Studies have demonstrated that C-X-C motif chemokine (CXCL) 1 recruit macrophages by binding to C-X-C chemokine receptor (CXCR) 2 and participates in the inflammatory response of various diseases. Based on these findings, we aimed to explore the role of the CXCL1-CXCR2 axis in the repair process after peripheral nerve injury. Initially, we simulated sciatic nerve injury and observed an increased expression of CXCL1 and CXCR2 in the nerves of the injury group. Both in vivo and in vitro experiments confirmed that the heightened CXCL1 expression occurs in Schwann cells and is secreted, while the elevated CXCR2 is expressed by recruited macrophages. In addition, in vitro experiments demonstrated that the binding of CXCL1 to CXCR2 can activate the NLRP3 inflammasome and promote the production of interleukin-1 beta (IL-1ß) in macrophages. However, after mice were subjected to sciatic nerve injury, the number of macrophages and the expression of inflammatory factors in the sciatic nerve were reduced following treatment with the CXCR2 inhibitor SB225002. Simultaneously, we evaluated the sciatic nerve function index, the expression of p75 neurotrophic factor receptor (p75NTR), and myelin proteins, and all of these results were improved with the use of SB225002. Thus, our results suggest that after sciatic nerve injury, the CXCL1-CXCR2 axis mediates the inflammatory response by promoting the recruitment and activation of macrophages, which is detrimental to the repair of the injured nerves. In contrast, treatment with SB225002 promotes the repair of injured sciatic nerves.

The protective effect of erythropoietin and its novel derived peptides in peripheral nerve injury.

Peripheral nerve injury seriously endangers human life and health, but there is no clinical drug for the treatment of peripheral nerve injury, so it is imperative to develop drugs to promote the repair of peripheral nerve injury. Erythropoietin (EPO) not only has the traditional role of promoting erythropoiesis, but also has a tissue-protective effect. Over the past few decades, researchers have confirmed that EPO has neuroprotective effects. However, side effects caused by long-term use of EPO limited its clinical application. Therefore, EPO derivatives with low side effects have been explored. Among them, ARA290 has shown significant protective effects on the nervous system, but the biggest disadvantage of ARA290, its short half-life, limits its application. To address the short half-life issue, the researchers modified ARA290 with thioether cyclization to generate a thioether cyclized helical B peptide (CHBP). ARA290 and CHBP have promising applications as peptide drugs. The neuroprotective effects they exhibit have attracted continuous exploration of their mechanisms of action. This article will review the research on the role of EPO, ARA290 and CHBP in the nervous system around this developmental process, and provide a certain reference for the subsequent research.

Pathogenic Th17 cell-mediated liver fibrosis contributes to resistance to PD-L1 antibody immunotherapy in hepatocellular carcinoma.

Understanding the mechanisms of resistance of hepatocellular carcinoma (HCC) to targeted therapies and immune checkpoint blockade is critical for the development of new combination therapies and improving patient survival. Here, we found that in HCC, anti-programmed cell death 1 ligand 1 (PD-L1) therapy reduces liver cancer growth, but the tumors eventually become resistant to continued therapy. Experimental analyses shows that the infiltration of pathogenic T helper 17 (pTh17) cells increases in drug-resistant HCC, and pTh17 cells secrete interleukin-17A (IL-17A), which promotes the expression of PD-L1 on the surface of HCC cells and produces resistance to anti-PD-L1 therapy. Anti-IL-17A combined with PD-L1 blockade significantly increased the infiltration of cytotoxic CD8+ T cells expressing high levels of interferon-γ and reduced treatment resistance in HCC. These results support the combination of anti-PD-L1 and anti-IL-17A as a novel strategy to induce effective T cell-mediated anti-tumor immune responses.

[Influence and long-term effects of three methods for regulating and invigorating fei-shen on T lymphocyte subsets and CD4+ CD25+ in COPD rats].

OBJECTIVE: To evaluate the therapeutic and long-term effects of three methods for regulating and invigorating Fei-Shen [reinforcing Fei and invigorating Pi (RFIP), reinforcing Fei and invigorating Shen (RFIS), benefiting qi and nourishing Shen (BQNS)] on T lymphocyte subsets and CD4+ CD25+ in rats with chronic obstructive pulmonary disease (COPD). METHODS: Totally 120 rats were randomly divided into the control group, the model group, the RFIP group, the RFIS group, the BQNS group, and the aminophylline group, 20 in each group. Except those in the control group, the rest rats were exposed to cigarette smoking and bacterial infection to prepare the COPD rat model. Rats in the RFIP group, the RFIS group, the BQNS group, and the aminophylline group were administrated with Bufei Jianpi Recipe, Bufei Yishen Recipe, Yiqi Zishen Recipe, and aminophylline from week 9 to 20. After rats were sacrificed at week 20 and 32, lung pathological impairments and the levels of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+ / CD8+) and CD4+ CD25+ in the peripheral blood and the bronchoalveolar lavage fluid (BALF) were detected. RESULTS: At week 20 and 32, the impairments in the lungs were obvious in rats of the model group, while the levels of CD3+, CD4+, CD8+, and CD4+ CD25+ were significantly lower in the peripheral blood and the BALF in the model group than in the controls group (P < 0.05, P < 0.01), and they were higher in the four groups than in the model group (P < 0.05, P < 0.01). However, the levels of CD3+ and CD4+ in the peripheral blood and the BALF were higher in the three TCM-treated groups than in the aminophylline group (P < 0.05, P < 0.01). CD4+ in the peripheral blood in the RFIP group was higher than in the RFIS group and the BQNS group (P < 0.01). At week 20, the ratio of CD4+ /CD8+ was higher in the RFIP group than in the aminophylline group (P < 0.01). CD4+ was higher in the three TCM-treated groups than in the aminophylline group (P < 0.05, P < 0.01). At week 32, the ratio of CD4+ / CD+ in the three TCM- and aminophylline-treated groups was higher than that of the model group (P < 0.05). CD4+ in the RFIP group and the RFIS group was higher than that of the aminophylline group (P < 0.05, P < 0.01). Compared with that at week 20, the ratio of CD4+/CD8+ in the BALF group was significantly higher in the RFIP at week 32 (P < 0.05). The CD4+ CD25+ levels in the peripheral blood and BALF of the BQNS group was significantly lower (P < 0.05). CONCLUSIONS: The efficacy and long-term effects of three methods for regulating and invigorating Fei-Shen might be possibly associated with regulating T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+ / CD8+) and CD4+ CD25+ levels. Of them, RFIP showed significant effects in regulating CD4+ and CD4+ / CD8+ in the peripheral blood and BALF.

[Impact and long-term effect of three prescriptions regulating and tonifying lung and kidney on JAK/STAT signaling in rats].

OBJECTIVE: To evaluate the impact and long-term effect of three prescriptions regulating and tonifying lung and kidney (prescription tonifying lung and spleen, prescription tonifying lung and kidney, and prescription tonifying Qi and kidney) on JAK/STAT signaling of COPD rats. METHOD: Rats were randomly divided into the control group, the model group, the Bufeijianpi group, the Bufeiyishen group, the Yiqizishen group and the aminophyline group. The COPD rat model was established by smoke inhalations and bacterial infections. In the 9th week, the control group and the model group were administered with normal saline, while the remaining groups are orally given corresponding medicines. In the 20th and 32nd week, the rats were sacrificed in batches to observe the pathology in their lung tissues, protein expressions of JAK2, STAT1, STAT3, STAT5, and expressions of JAK2 and SOCS3 mRNA. RESULT: In the 20th and 32nd week, protein expressions of JAK2 mRNA and phosphorylation-JAK2, STAT1, STAT3 and STAT5 in the model group were higher than the control group (P < 0.01), whereas the three traditional Chinese medicine (TCM) (Bufeijianpi, Bufeiyishen and Yiqizishen) groups and the aminophyline group were significantly lower (P < 0.05, P < 0.01). The expression of SOCS3 mRNA in the model group was higher than the control group (P < 0.01), whereas the level was notably higher in the three TCM groups and the aminophylline group (P < 0.01). The three TCM groups were remarkably higher than the aminophylline group (P < 0.05, P < 0.01). Compared with the figures in the 20th week, JAK2 mRNA and phosphorylation-JAK2, STAT3 and STAT5 were significantly lower in the Bufeijianpi group in the 32nd week (P < 0.05, P < 0.01), and so did phosphorylation-STAT3 in Bufeiyishen group (P < 0.01) and phosphorylation-STAT3 and STAT5 in the Yiqizishen group (P < 0.05, P < 0.01). However, the aminophylline group showed no significant difference in above indicators. CONCLUSION: The three medicines regulating and tonifying lung and kidney can effectively relieve injury of lung tissues, and have long-term effect, which may be related to the regulation of JAK/ STAT signaling. Specifically, prescription tonifying lung and spleen shows good effect in reducing JAK2, STAT3 and STAT5, prescription tonifying lung and kidney shows good effect in reducing p-STAT3, and prescription tonifying Qi and kidney shows good effect in reducing p-STAT3 and p-STAT5.

The role of the sex hormone-gut microbiome axis in tumor immunotherapy.

Accumulating evidence suggested that both gut microbiome and sex play a critical role in the efficacy of immune checkpoint blockade therapy. Considering the reciprocal relationship between sex hormones and gut microbiome, the sex hormone-gut microbiome axis may participate in the regulation of the response to immune checkpoint inhibitors (ICIs). In this review, it was attempted to summarize the current knowledge about the influences of both sex and gut microbiome on the antitumor efficacy of ICIs and describe the interaction between sex hormones and gut microbiome. Accordingly, this review discussed the potential of enhancing the antitumor efficacy of ICIs through regulating the levels of sex hormones through manipulation of gut microbiome. Collectively, this review provided reliable evidence concerning the role of the sex hormone-gut microbiome axis in tumor immunotherapy.

IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment.

Interleukin 17A (IL-17A) is a major member of the IL-17 cytokine family and is produced mainly by T helper 17 (Th17) cells. Other cells such as CD8+ T cells, γδ T cells, natural killer T cells and innate lymphoid-like cells can also produce IL-17A. In healthy individuals, IL-17A has a host-protective capacity, but excessive elevation of IL-17A is associated with the development of autoimmune diseases and cancer. Monoclonal antibodies (mAbs) targeting IL-17A (e.g., ixekizumab and secukinumab) or IL-17A receptor (IL-17RA) (e.g., brodalumab) would be investigated as potential treatments for these diseases. Currently, the application of IL-17A-targeted drugs in autoimmune diseases will provide new ideas for the treatment of tumors, and its combined application with immune checkpoint inhibitors has become a research hotspot. This article reviews the mechanism of action of IL-17A and the application of anti-IL-17A antibodies, focusing on the research progress on the mechanism of action and therapeutic blockade of IL-17A in various tumors such as colorectal cancer (CRC), lung cancer, gastric cancer and breast cancer. Moreover, we also include the results of therapeutic blockade in the field of cancer as well as recent advances in the regulation of IL-17A signaling.

The role of CXCL1/CXCR2 axis in neurological diseases.

The C-X-C chemokine ligand (CXCL) 1 and its receptor C-X-C chemokine receptor (CXCR) 2 are widely expressed in the peripheral nervous systems (PNS) and central nervous systems (CNS) and are involved in the development of inflammation and pain after various nerve injuries. Once a nerve is damaged, it affects not only the neuron itself but also lesions elsewhere in its dominant site. After the CXCL1/CXCR2 axis is activated, multiple downstream pathways can be activated, such as c-Raf/MAPK/AP-1, p-PKC-µ/p-ILK/NLRP3, JAK2/STAT3, TAK1/NF-κB, etc. These pathways in turn mediate cellular motility state or cell migration. CXCR2 is expressed on the surface of neutrophils and monocytes/macrophages. These cells can be recruited to the lesion through the CXCL1/CXCR2 axis to participate in the inflammatory response. The expression of CXCR2 in neurons can activate some pathways in neurons through the CXCL1/CXCR2 axis, thereby causing damage to neurons. CXCR2 is also expressed in astrocytes, and when CXCR2 activated, it increases the number of astrocytes but impairs their function. Since inflammation can occur at almost any site of injury, elucidating the mechanism of CXCL1/CXCR2 axis' influence on inflammation may provide a favorable target for clinical treatment. Therefore, this article reviews the research progress of the CXCL1/CXCR2 axis in neurological diseases, aiming to provide a more meaningful theoretical basis for the treatment of neurological diseases.

A rat model for stable chronic obstructive pulmonary disease induced by cigarette smoke inhalation and repetitive bacterial infection.

To develop a stable chronic obstructive pulmonary disease (COPD) model in rats. Sprague-Dawley rats were treated with cigarette-smoke inhalation (CSI) for 12 weeks, repetitive bacterial infection (RBI) for 8 weeks, or the combination of the two (CCR) for 12 weeks and followed up for the additional 20 weeks. Tidal volume (V(T)), peak expiratory flow (PEF) and 50% V(T) expiratory flow (EF(50)), histological changes in the lungs, and levels of the cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-10 in serum and bronchial alveolar lavage fluid (BALF) were examined at intervals during the 32 week study period. The right ventricular hypertrophy index (RVHI) was also determined at the same times. V(T), PEF, and EF(50) were decreased in rats with COPD compared to the control. The expression of TNF-α, IL-8 and IL-10 increased in both serum and BALF with a similar trend. Bronchiole and arteriole wall thickness and the degree of bronchiole stenosis and alveolar size increased in COPD rats. RVHI was reduced gradually following the treatment. All of these changes were more pronounced in the CCR-treatment group than in the other groups. Our results have shown that CSI or RBI alone can induce COPD in rats, but that the combination of CSI with RBI induces a stable COPD that has more similarity to complications seen in patients with COPD. This combination may therefore provide a more appropriate model for study of human COPD.

Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the influence and long-term effects on systemic and local inflammation responses in rat with stable chronic obstructive pulmonary disease (COPD) treated with traditional Chinese medicine (TCM) for regulating and invigorating the lung and kidney, including invigorating the lung and spleen (Bufei Jianpi) therapy, supplementing the lung and kidney (Bufei Yishen) therapy, and nourishing qi and kidney (Yiqi Zishen) therapy. METHODS: Rats were randomly divided into six groups: control, model, aminophyline, Bufei Jianpi, Bufei Yishen and Yiqi Zishen groups. The stable COPD model of rat was duplicated by cigarette smoke inhalations and bacterial infection. From the ninth week, the rats with stable COPD were treated with Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or aminophyline respectively until the 20th week. Half of the animals were sacrificed at the 20th or 32nd week respectively. The leukocyte count and neutrophil percentage in peripheral blood and bronchoalveolar lavage fluid (BALF) were measured; levels of interleukin (IL)-8, IL-10 and tumor necrosis factor-α (TNF-α) in BALF, and levels of IL-1ß, IL-6, IL-8, IL-10 and TNF-α and soluble tumor necrosis factor receptor II (sTNFR2) in serum and lungs were detected by enzyme-linked immunosorbent assay or immunohistochemical method. RESULTS: There were no statistical differences in leukocyte count and neutrophil percentage in peripheral blood among six groups (P>0.05). At the 20th week, leukocyte count in BALF was higher in the model group than in the control group (P<0.01), and was lower in the three TCM groups and the aminophyline group than in the model group (P<0.05, P<0.01), and that of the Bufei Jianpi group was lower than the aminophyline group (P<0.01); while at the 32nd week, leukocyte count in BALF of the three TCM groups decreased and was lower than that of the aminophyline group (P<0.05, P<0.01). At the 20th and 32nd weeks, levels of IL-1ß, IL-6, IL-8, IL-10, TNF-α and sTNFR2 in serum and lungs, and IL-8, IL-10 and TNF-α in BALF of the model group increased, which were higher than those in the control group (P<0.05, P<0.01); the mentioned cytokines were decreased in the three TCM groups compared with the model group (P<0.05, P<0.01), and were also lower in serum and BALF of the three TCM groups than those of the aminophyline group (P<0.05, P<0.01). Expressions of cytokines in lung tissues were depressed in the three TCM groups as compared to those in the aminophyline group. There was no statistical difference on expressions of the mentioned cytokines either in serum and BALF or in the lungs between week 32 and week 20. CONCLUSION: The Bufei Jianpi, Bufei Yishen and Yiqi Zishen therapies can significantly reduce the systemic and local inflammation responses in rats with stable COPD, and have evident long-term effects.

Research progress of targeting NLRP3 inflammasome in peripheral nerve injury and pain.

Nerve injury and nerve pain are common diseases caused by neuroinflammation. Numerous studies have shown that the activation of NLRP3 (nod-like receptor family, pyrin domain-containing 3) inflammasome is involved in a various inflammatory response, such as Alzheimer's disease, diabetes, nerve damage and other diseases. The NLRP3 inflammasome is a complex containing NLRP3 protein, ASC (apoptosis-associated speckle-like protein), and pro-caspase-1, which is highly expressed and activated to promote the secretion of IL-1ß and IL-18 in response to the stimulation of danger-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) in immune cells such as macrophages and dendritic cells. The activation of NLRP3 inflammasome can cause cell death through caspase-1-mediated cell pyroptosis and plays an important role in the development of nervous system injury and inflammation-related diseases. This discussion aims to summarize the mechanisms of nerve damage and pain caused by excessive activation of the NLRP3 inflammasome.

Metabolomics study on model rats of chronic obstructive pulmonary disease treated with Bu­Fei Jian­Pi.

The therapeutic effect of Traditional Chinese Medicine (TCM) on chronic obstructive pulmonary disease (COPD) has been know for numerous years; however, the mechanism of action of the beneficial effects of TCM remains to be elucidated. The present study aimed to investigate the molecular mechanisms of COPD through metabolomic analysis as well as explore the targets and intervention mechanisms of TCM therapy using the common TCM granules Bu­Fei Jian­Pi. COPD rat models were established using smoke inhalations and recurrent bacterial infections. Rats were then divided into three groups as follows: A1, control healthy rats; B1, COPD model; and D1, Bu­Fei Jian­Pi­treated COPD rats. Following administration of the medicine, the metabolomic profile of the lung tissue of rats in each group was assessed using high­performance liquid chromatography/quadrupole­time­of­flight mass spectrometry. The results demonstrated that there was a significanlty different spectrum of metabolites in the lung tissue of the model group compared to that of the control group as well as the Bu­Fei Jian­Pi­treated COPD group; in addition, following treatment with Bu­Fei Jian­Pi, the metabolites of COPD rats were comparable with those of the control. Notable changes were observed in 31 metabolites between the Bu­Fei Jian­Pi­treated group and the model group; however, there were 13 comparable metabolites between the Bu­Fei Jian­Pi and control groups as well as the model and control groups. Eleven metabolites showed a negative fold change in the Bu­Fei Jian­Pi­treated groups compared to concentrations in the model group; however, minimal changes were observed in phenylpyruvic acid and α­D­fucose expression. In conclusion, the results of the present study demonstrated that Bu­Fei Jian­Pi granules had beneficial effects on measured outcomes in a rat model of stable COPD, indicated by a significantly different spectrum of metabolites. This therefore indicated that the metabolites which had significantly altered expression in the model group compared with that of the control and Bu­Fei Jian­Pi­treated groups may be potential biomarkers of COPD.

Identification of Metabolites and Metabolic Pathways Related to Treatment with Bufei Yishen Formula in a Rat COPD Model Using HPLC Q-TOF/MS.

As a traditional Chinese medicine, Bufei Yishen Formula (BYF) is widely used in China as an effective treatment for chronic obstructive pulmonary disease (COPD). Because of the component complexity and multiple activities of Chinese herbs, the mechanism whereby BYF affects COPD is not yet fully understood. Herein, pulmonary function experiments and histomorphological assessments were used to evaluate the curative effect of BYF, which showed that BYF had an effect on COPD. Additionally, a high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC QTOF/MS) metabonomics method was used to analyze the mechanism of the actions of BYF on rats with COPD induced by a combination of bacteria and smoking. Partial least squares discriminate analysis (PLS-DA) was used to screen biomarkers related to BYF treatment. Candidate biomarkers were selected and pathways analysis of these metabolites showed that three types of metabolic pathways (unsaturated fatty acid metabolism-related pathways, phenylalanine metabolism-related pathways, and phospholipid metabolism-related pathways) were associated with BYF treatment. Importantly, arachidonic acid and related metabolic pathways might be useful targets for novel COPD therapies.

Effects and mechanism of bufei yishen formula in a rat chronic obstructive pulmonary disease model.

Bufei Yishen Formula (BYF) has been used for centuries in Asia to effectively treat patients with chronic obstructive pulmonary disease (COPD). This study established a COPD animal model in rats, wherein three groups (control, COPD, and BYF) were used to evaluate the mechanism(s) and curative effect of BYF. Pulmonary function and histomorphology demonstrated that BYF had an evident effect on COPD. Gene microarray was then exploited to analyze the effects of BYF on COPD. ClueGO analysis of differentially expressed genes indicated that BYF improved COPD by regulating expression of interleukins, myosin filament assembly components, and mitochondrial electron transport-related molecules. Moreover, ELISA revealed that expression of several interleukins (IL1 ß , IL6, IL8, and IL10) was reduced in peripheral blood and bronchoalveolar lavage fluid by BYF treatment. It was concluded that BYF has therapeutic effects on COPD in rats through its effects on interleukin expression and/or secretion. Furthermore, pharmacological or targeted expression of two differentially expressed genes, F2R and Sprik1, might be useful in novel COPD therapies. This study provides the basis for mechanisms of BYF on COPD and new therapeutic drug targets.