Bufei Yishen Formula Research Articles

Three Tiaobu Feishen formulae reduces cigarette smoke-induced inflammation in human airway epithelial cells.

To investigate the therapeutic efficacy of Tiaobu Feishen formulae (TBFS) on cigarette smoke-induced inflammation in vitro using lipopolysaccharide (LPS)-induced and cigarette smoke extract (CSE)-induced NCI-H292 cells. We evaluated the inhibitory effects of Bufei Jianpi formula (BJF), Bufei Yishen formula (BYF), and Yiqi Zishen formula (YZF) on the expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-8, matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloprotease (TIMP)-1, and superoxide dismutase (SOD) in H292 cells stimulated with LPS or CSE. Their related transcription factors and signaling pathways were also analyzed. BJF, BYF, and YZF significantly inhibited the LPS- or CSE-induced expressions of TNF-α, IL-8, MMP-9, TIMP-1, and SOD in H292 cells, and suppressed the activation of transcription factors including nuclear transcription factor (NF)-κB, activator protein (AP)-1, and signal transducers and activators of transcription (STAT) 3 and their corresponding pathways, including NF-κB, mitogen-activated protein kinase (MAPK), STAT3, and peroxisome proliferator-activated receptor (PPAR). BJF, BYF, and YZF effectively suppressed inflammatory responses, protease-antiprotease imbalance, and oxidative stress induced by LPS and CSE, an effect that was closely associated with the inhibition of the NF-κB, MAPK, STAT3, and PPAR pathways.

Effective-constituent compatibility-based analysis of Bufei Yishen formula, a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease

ObjectiveCritical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF. MethodsThe active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of “Groups 1 to 4” according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD). ResultsWe identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF. ConclusionBased on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.

Effective-component compatibility of Bufei Yishen formula II inhibits mucus hypersecretion of chronic obstructive pulmonary disease rats by regulating EGFR/PI3K/mTOR signaling

Ethnopharmacological relevanceThe effective-component compatibility of Bufei Yishen formula I (ECC-BYF I), a combination of 10 compounds, including total ginsenosides, astragaloside IV, icariin, and paeonol, etc., is derived from Bufei Yishen formula (BYF). The efficacy and safety of ECC-BYF I is equal to BYF. However, the composition of ECC-BYF I needs to be further optimized. Based on the beneficial effects of BYF and ECC-BYF I on chronic obstructive pulmonary disease (COPD), this study aimed to optimize the composition of ECC-BYF I and to explore the effects and mechanisms of optimized ECC-BYF I (ECC-BYF II) on mucus hypersecretion in COPD rats. Materials and methodsECC-BYF I was initially optimized to six groups: optimized ECC-BYF I (OECC-BYF I)-A~F. Based on a COPD rat model, the effects of OECC-BYF I-A~F on COPD rats were evaluated. R-value comprehensive evaluation was used to evaluate the optimal formula, which was named ECC-BYF II. The changes in goblet cells and expression of mucins and the mRNA and proteins involved in the epidermal growth factor receptor/phosphoinositide-3-kinase/mammalian target of rapamycin (EGFR/PI3K/mTOR) pathway were evaluated to explore the effects and mechanisms of ECC-BYF II on mucus hypersecretion. ResultsECC-BYF I and its six optimized groups, OECC-BYF I-A~F, had beneficial effects on COPD rats in improving pulmonary function and lung tissue pathology, reducing inflammation and oxidative stress, and improving the protease/anti-protease imbalance and collagen deposition. R-value comprehensive evaluation found that OECC-BYF I-E (paeonol, icariin, nobiletin, total ginsenoside, astragaloside IV) was the optimal formula for improving the comprehensive effects (lung function: VT, MV, PEF, EF50, FVC, FEV 0.1, FEV 0.1/FVC; histological changes: MLI, MAN; IL-1β, IL-6, TNF-α, MMP-9, TIMP-1, T-AOC, LPO, MUC5AC, Collagen I and Collagen III). OECC-BYF I-E was named ECC-BYF II. Importantly, the effect of ECC-BYF II showed no significant difference from BYF and ECC-BYF I. ECC-BYF II inhibited mucus hypersecretion in COPD rats, which manifested as reducing the expression of MUC5AC and MUC5B and the hyperplasia rate of goblet cells. The mRNA and protein expression levels of EGFR, PI3K, Akt, and mTOR were increased in COPD rats and were obviously downregulated after ECC-BYF II administration. ConclusionECC-BYF II, which consists of paeonol, icariin, nobiletin, total ginsenoside and astragaloside IV, has beneficial effects equivalent to BYF and ECC-BYF I on COPD rats. ECC-BYF II significantly inhibited mucus hypersecretion, which may be related to the regulation of the EGFR/PI3K/mTOR pathway.

Effects of <i>Bufei Yishen</i> formula on klotho gene expression and inflammation-related RIG-I/NF-κB pathway in cigarette smoke extract-treated BEAS-2B cells

Purpose: To investigate the anti-inflammatory effect of Bufei yishen formula on chronic obstructive pulmonary disease (COPD) and klotho expression in cigarette smoke extract (CSE)-treated BEAS-2B cells.Methods: Cigarette smoke extract (CSE) was diluted in Dulbecco’s modified Eagle’s medium (DMEM) and used to treat a COPD cell model established using BEAS-2B cells. The CSE-treated cells were transfected with klotho overexpression plasmid, and the COPD cell model was treated with Bufei yishen formula. Dexamethasone was used as positive control. Changes in the expressions of klotho, RIG-I, and NF-ĸB were determined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, while enzyme linked immunosorbent assay (ELISA) was used to evaluate changes in the expressions of IL-6 and TNF-α.Results: Klotho expression level was reduced in COPD model. Overexpression of klotho inhibited the expressions of IL-6, TNF-α, RIG-I, NF-κB, but bufei yishen formula increased klotho expression level and decreased the expressions of RIG-I, NF-κB, IL-6 and TNF-α. However, after CSE treatment, the anti-inflammatory effect of the formula decreased significantly when klotho expression was knocked down.Conclusion: Bufei yishen formula possesses anti-inflammatory effects which are significantly decreased after klotho knockdown. This suggests that the formula probably acts by upregulating klotho expression, thereby down-regulating the expressions of IL-6 and TNF-α via RIG-I/NF-κB pathway.Keywords: Bufei yishen formula, COPD, Klotho, Inflammation, RIG-I/NF-κB

Restoring Th17/Treg balance via modulation of STAT3 and STAT5 activation contributes to the amelioration of chronic obstructive pulmonary disease by Bufei Yishen formula

Ethnopharmacology relevanceBufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), has been extensively applied in clinical treatment of chronic obstructive pulmonary disease (COPD) and provides an effective treatment strategy for the syndrome of lung-kidney qi deficiency in COPD patients. Here, we investigated its anti-COPD mechanism in COPD rats in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. MethodsRat model of cigarette smoke- and bacterial infection-induced COPD was established, and orally treated with BYF for 12 consecutive weeks. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were collected to evaluate the Th17 and Treg cells. ResultsOral treatment of BYF markedly suppressed the disease progression and alleviated the pathological changes of COPD. It also decreased the bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and Th17-related IL-17A, and induced a significant increase in Treg-related IL-10. Furthermore, BYF treatment obviously decreased the proportion of CD4+RORγt+ T (Th17) cell and increased the proportion of CD4+CD25+Foxp3+ T (Treg) cell, leading to restore the Th17/Treg balance. BYF treated groups also decreased RORγt and increased Foxp3 expression in the spleens and MLNs. BYF further inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and boosted the phosphorylation of STAT5, that were critical transcription factors for TH17 and Treg differentiation. Conclusionthese results demonstrated that BYF exerted its anti-COPD efficacy by restoring Th17/Treg balance via reciprocally modulating the activities of STAT3 and STAT5 in COPD rats, which may help to elucidate the underlying immunomodulatory mode of BYF on COPD treatment.

Integration of transcriptomics, proteomics, metabolomics and systems pharmacology data to reveal the therapeutic mechanism underlying Chinese herbal Bufei Yishen formula for the treatment of chronic obstructive pulmonary disease.

Bufei Yishen formula (BYF) is a traditional Chinese medicine formula, which has long been used as a therapeutic agent for the treatment of chronic obstructive pulmonary disease (COPD). Systems pharmacology has previously been used to identify the potential targets of BYF, and an experimental study has demonstrated that BYF is able to prevent COPD. In addition, the transcriptomic and metabolomic profiles of lung tissues from rats with COPD and BYF-treated rats have been characterized. The present study aimed to determine the therapeutic mechanisms underlying the effects of BYF on COPD treatment by integrating transcriptomics, proteomics and metabolomics, together with systems pharmacology datasets. Initially, the proteomic profiles of rats with COPD and BYF-treated rats were analyzed. Subsequently, pathway and network analyses were conducted to integrate three-omics data; the results demonstrated that the genes, proteins and metabolites were predominantly associated with oxidoreductase activity, antioxidant activity, focal adhesion and lipid metabolism. Finally, a comprehensive analysis of systems pharmacology, transcriptomic, proteomic and metabolomic datasets was performed, and numerous genes, proteins and metabolites were found to be regulated in BYF-treated rats; the potential target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhesion. In conclusion, BYF exerted beneficial effects against COPD, potentially by modulating lipid metabolism, the inflammatory response, oxidative stress and cell junction pathways at the system level.

System biology analysis of long-term effect and mechanism of Bufei Yishen on COPD revealed by system pharmacology and 3-omics profiling.

System pharmacology identified 195 potential targets of Bufei Yishen formula (BYF), and BYF was proven to have a short-term therapeutic effect on chronic obstructive pulmonary disease (COPD) rats previously. However, the long-term effect and mechanism of BYF on COPD is still unclear. Herein, we explored its long-term effect and underlying mechanism at system level. We administered BYF to COPD rats from week 9 to 20, and found that BYF could prevent COPD by inhibiting the inflammatory cytokines expression, protease-antiprotease imbalance and collagen deposition on week 32. Then, using transcriptomics, proteomics and metabolomics analysis, we identified significant regulated genes, proteins and metabolites in lung tissues of COPD and BYF-treated rats, which could be mainly attributed to oxidoreductase-antioxidant activity, focal adhesion, tight junction or lipid metabolism. Finally, based on the comprehensive analysis of system pharmacology target, transcript, protein and metabolite data sets, we found a number of genes, proteins, metabolites regulated in BYF-treated rats and the target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhension. In conclusion, BYF exerts long-term therapeutic action on COPD probably through modulating the lipid metabolism, oxidative stress, cell junction and inflammatory response pathways at system level.

Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease.

The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo. Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF.

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 (IL1β, 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.

Efficacy of Herbal Drugs in Human Diseases and Disorders

According to a ballpark figure by World Health Organization, more than three-quarters of population of the developing nations exploit herbal medicine for their primary health care. Herbal drugs and their constituents have advantageous effects on long-term fitness and can be used to efficiently treat human diseases or disorders. In veracity, herbs frequently include various active ingredients that imaginably have drug allying commotion in the body. Bringing into play, herbs are often more affordable than procuring expensive contemporary pharmaceuticals to take care of ailments. A large number of herbs have proved their usefulness in managing various illnesses. Latest advances in biology and medicine have introduced new technologies to study the biological significance of herbal drugs in various human diseases and disorders. Hence it is important to understand the mechanism(s) of herbal drug action for the knowledge and development of successful therapies. The current special issue brings together several exciting papers defining the efficacy of herbal drugs in an assortment of human diseases and disorders. J. Li et al. have tested the effects and mechanism of Bufei Yishen formula (BYF) in a rat chronic obstructive pulmonary disease (COPD) model and provided the basis for mechanisms of BYF on COPD and new therapeutic drug targets. X. Yu et al. have reported the treatment of Si-Jun-Zi decoction, a famous Chinese medicine that promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis. Tong xinluo (TXL), a Chinese herbal compound, has been used in China with traditional therapeutic efficacy in patients with diabetic nephropathy (DN). N. Zhang et al. demonstrated that TXL successfully inhibits TGF-β1-induced epithelial-to-mesenchymal transition in DN, which may account for the therapeutic efficacy in TXL-mediated renal protection. W. Zhang et al. explored the effects of Jian-Pi-Zhi-Dong decoction (JPZDD) on Tourette syndrome (TS) by investigating the expression of gamma-aminobutyric acid (GABA) and its type A receptor (GABAAR) in the striatum of a TS mice model induced by 3,3′-iminodipropionitrile (IDPN) treatment. It was revealed that JPZDD alleviates TS symptoms which may be associated with GABAAR expression downregulation in striatum thereby controlling GABA metabolism. TZQ-F has been traditionally used as a traditional Chinese medicine formula for the treatment of diabetes. H. Yuhong et al. compared the pharmacologic effects and gastrointestinal adverse events between TZQ-F and acarbose in Chinese healthy volunteers. T. Numata et al. reported the treatment of posttraumatic stress disorder (PTSD) using the traditional Japanese herbal medicine Saikokeishikankyoto in survivors of the great east Japan earthquake and tsunami. The traditional medicine may be a valid choice for the treatment of psychological and physical symptoms in PTSD patients. Y. Ewnetu et al. evaluated the synergetic antimicrobial effect of Ethiopian honey and ginger powder extract mixtures on standard and resistant clinical isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. The combination has the potential to serve as cheap source of antibacterial agents especially for the drug resistant strains. Herbs are now gaining much attention as the main source of effective drugs for lowering serum lipids and lipid peroxidation. M. Rafieian-kopaei et al. assessed the impact of Ferulago angulata on serum lipid profiles and on levels of lipid peroxidation in male Wistar rats. Administration of a hydroalcoholic extract reduces the serum levels of total cholesterol, triglycerides, and LDL comparable to atorvastatin (a standard lipid lowering drug). A-J. Lee et al. investigated the absolute counts and percentages of peripheral blood (PB) lymphocyte subtypes in end-stage cancer patients before and after localized radiotherapy (RT) and after oral administration of Bojungikki-tang water extract (BJITE) and to evaluate the changes mediated by RT and BJITE. It was observed that immune deterioration occurs after RT and administration of BJITE was found effective in its restoration. T. Shimizu provides a good overview of efficacy of Kampo medicine (KM) in treating atopic dermatitis (AD). KM is a traditional herbal medicine in Japan and has a long history and plays an important role in the prevention and treatment of various diseases including AD. Y. Ma et al. explored the efficacy of herb-partitioned moxibustion in patients with diarrhoea-predominant irritable bowel syndrome (DPIBS) and suggest it as a promising, efficacious, and well-tolerated treatment for patients. Melinjo (Gnetum gnemon L.) seed extract containing transresveratrol (3,5,4′-trihydroxy-trans-stilbene) and other derivatives exerts diverse beneficial effects. H. Konno et al. reported melinjo seed extract decreases serum uric acid levels in nonobese Japanese males regardless of insulin resistance and may improve lipid metabolism by increasing HDL cholesterol. We anticipate that readers and scientific fraternity working in the area of herbal drugs will find not only the updated review on the subject but also a compilation of precise data on the efficacy of herbal drugs in some lifestyle diseases and disorders with their suggested mechanism of action. Suaib Luqman Syed Ibrahim Rizvi Andre-Michael Beer Sunil Kumar Khare Pinar Atukeren