Mucosal immunomodulatory evaluation and chemical profile elucidation of a classical traditional Chinese formula, Bu-Zhong-Yi-Qi-Tang

Liu, Li‐Yin; Hu, Linlin; Yao, Zhihong; Qin, Z. H.; Idehara, Mayu; Dai, Yi; Kiyohara, Hiroaki; Yamada, Hideaki; Yao, Xin‐Sheng

doi:10.1016/j.jep.2018.08.003

Cited by 20 publications

(12 citation statements)

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“…Additionally, evidence also suggests that poor oral bioavailable components may play therapeutic benefits by influencing the intestinal system (Xu et al, 2021). Therefore, based on our previous research about the chemical and in vivo metabolic profiles of BZYQT, and its xenobiotics analysis in the small intestinal contents (Supplemetary Table S3, Supplementary Figure S3), 46 compounds including flavonoids, triterpenoids, lactone, alkaloid, etc., that derived from a set of 10 composed medicinal herbs were screened out as the potential bioactive components of BZYQT (Hu et al, 2019;Liu et al, 2019) (Table 1). It should be noted that although lobetyolin was not detected in bio-samples following oral administration of BZYQT under current conditions, it was also considered as a potential bioactive component due to its immunomodulatory activity (Gao et al, 2019), and senkyunolide H was screened out because its metabolites could be detected in the urine (Hu et al, 2019).…”

Section: Potential Bioactive Components In Bzyqtmentioning

confidence: 99%

“…Bu-Zhong-Yi-Qi-Tang (BZYQT), a well-known traditional Chinese medicine (TCM) formula recorded in the “Treatise on Spleen and Stomach (Pi-Wei-Lun, 1249 A.D.)” for invigorating spleen and replenishing qi (a TCM term, which is thought to provide the vital energy of the body by TCM), has been extensively used in clinical practice of China to improve respiratory and gastrointestinal disorders ( Zheng et al, 2014 ; Kim et al, 2017 ; Liu et al, 2019 ). It is composed of ten herbal medicines, including Astragali Radix praeparata cum melle, wheat-fried Atractylodis Macrocephalae Rhizoma , Codonopsis Radix , Glycyrrhizae Radix et Rhizoma praeparata cum melle, Citri Reticulatae Pericarpium , Angelicae Sinensis Radix , Cimicifugae Rhizoma , Bupleuri Radix , Jujubae Fructus , Zingiberis Rhizoma Recens .…”

Section: Introductionmentioning

confidence: 99%

“…In addition to having a profound influence in China, BZYQT is also prevalent in Japan (named hochuekkito) and South Korea (called Bojungikki-tang) due to its extensive pharmacological activities like immunomodulation, anti-inflammation, anti-fatigue, anti-bacterial, etc. ( Yamaoka et al, 2000 ; Yang and Yu, 2008 ; Chen et al, 2009 ; Yang et al, 2015 ; Liu et al, 2019 ). Currently, BZYQT has been reported with multiple effects on respiratory diseases, for example, reducing systemic inflammation, improving the exercise capacity, lung function, and quality of life for COPD patients ( Shinozuka et al, 2007 ; Chen et al, 2016 ); decreasing the recurrent attack rate of asthma and allergic rhinitis ( Yang and Yu, 2008 ); inhibiting the rhinovirus infection in human tracheal epithelial cells ( Yamaya et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, BZYQT has been reported with multiple effects on respiratory diseases, for example, reducing systemic inflammation, improving the exercise capacity, lung function, and quality of life for COPD patients ( Shinozuka et al, 2007 ; Chen et al, 2016 ); decreasing the recurrent attack rate of asthma and allergic rhinitis ( Yang and Yu, 2008 ); inhibiting the rhinovirus infection in human tracheal epithelial cells ( Yamaya et al, 2007 ). Our previous study demonstrated that BZYQT could negatively regulate the pulmonary immune system from the aspect of antigen-specific antibody responses ( Liu et al, 2019 ). However, the potential effects of BZYQT on pulmonary inflammation are still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation

Yamamoto

Chen

et al. 2022

Front. Pharmacol.

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Pulmonary inflammation caused by respiratory tract viral infections is usually associated with acute exacerbation of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Therefore, maintaining the pulmonary immune homeostasis is particular important for prevention of the acute exacerbation. Bu-Zhong-Yi-Qi-Tang (BZYQT), a traditional Chinese medicine formula, has been broadly used to improve respiratory and gastrointestinal disorders in China for over 700 years. Previously, we have found the regulatory activity of BZYQT on the lower respiratory immune system, while its potential effects during pulmonary inflammation remain unknown. Thus, the current study focused on deciphering its immunomodulatory effect and potential mechanism against pulmonary inflammation by using a viral RNA analogue, poly (I:C), induced murine pulmonary inflammation model and BEAS-2B cell model coupled with network pharmacology. Inflammatory cells in the bronchoalveolar lavage fluid were counted through microscope examination according to the cell’s morphology and staining characteristics; protein and gene levels of inflammatory mediators were determined with Elisa and quantitative PCR, respectively; network pharmacology was conducted based on 46 BZYQT-related potential bioactive components, pulmonary inflammation and immune-related targets. Our results indicated that the recruitment of neutrophils and the expression of Adgre1 (encoding the F4/80, which is a macrophage marker) in the lung induced by poly (I:C) were significantly reduced after BZYQT treatment, and these effects were further demonstrated to be related to the interference of leukocyte transendothelial migration from the decreased levels of CXCL10, IL-6, TNF-α, CXCL2, ICAM-1, VCAM-1, and E/P-selectins. Furthermore, BZYQT inhibited the CXCL10, TNF-α, and IFN-β expression of poly (I:C)-challenged BEAS-2B cells in a dose-dependent manner. Through integrating results from network pharmacology, experiments, and the published literature, isoliquiritigenin, Z-ligustilide, atractylenolide I, atractylenolide III, formononetin, ferulic acid, hesperidin, and cimigenoside were presumed as the bioactive components of BZYQT against pulmonary inflammation. Overall, our findings demonstrated that BZYQT possesses a pronounced immunomodulatory effect on poly (I:C)-induced pulmonary inflammation, which provides a pharmacological basis for BZYQT in the treatment of respiratory disorders.

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Section: Potential Bioactive Components In Bzyqtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation

Yamamoto

Chen

et al. 2022

Front. Pharmacol.

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“…HET has been used to enhance the immune system in respiratory disorders [23,24] and to improve the nutritional status associated with chronic diseases [25]. Thus, many studies have investigated the immunopharmacological activities of HET [26,27,28].…”

Section: Introductionmentioning

confidence: 99%

Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model

Cai

Yang

2019

Nutrients

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Hochu-ekki-to (Bojungikgi-Tang (BJIGT) in Korea; Bu-Zhong-Yi-Qi Tang in Chinese), a traditional herbal prescription, has been widely used in Asia. Hochu-ekki-to (HET) is used to enhance the immune system in respiratory disorders, improve the nutritional status associated with chronic diseases, enhance the mucosal immune system, and improve learning and memory. Amyotrophic lateral sclerosis (ALS) is pathologically characterized by motor neuron cell death and muscle paralysis, and is an adult-onset motor neuron disease. Several pathological mechanisms of ALS have been reported by clinical and in vitro/in vivo studies using ALS models. However, the underlying mechanisms remain elusive, and the critical pathological target needs to be identified before effective drugs can be developed for patients with ALS. Since ALS is a disease involving both motor neuron death and skeletal muscle paralysis, suitable therapy with optimal treatment effects would involve a motor neuron target combined with a skeletal muscle target. Herbal medicine is effective for complex diseases because it consists of multiple components for multiple targets. Therefore, we investigated the effect of the herbal medicine HET on motor function and survival in hSOD1G93A transgenic mice. HET was orally administered once a day for 6 weeks from the age of 2 months (the pre-symptomatic stage) of hSOD1G93A transgenic mice. We used the rota-rod test and foot printing test to examine motor activity, and Western blotting and H&E staining for evaluation of the effects of HET in the gastrocnemius muscle and lumbar (L4–5) spinal cord of mice. We found that HET treatment dramatically inhibited inflammation and oxidative stress both in the spinal cord and gastrocnemius of hSOD1G93A transgenic mice. Furthermore, HET treatment improved motor function and extended the survival of hSOD1G93A transgenic mice. Our findings suggest that HET treatment may modulate the immune reaction in muscles and neurons to delay disease progression in a model of ALS.

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A network pharmacological approach to investigate the pharmacological effects of CZ2HF decoction on Alzheimer's disease

Wei

Gao

Xu³

et al. 2021

Ibrain

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BackgroundAlzheimer's disease (AD) is the most common type of dementia, which brings tremendous burden to the sufferers and society. However, ideal tactics are unavailable for AD. Our previous study has shown that CZ2HF, a Chinese herb preparation, mitigates cognitive impairment in AD rats; whereas, its detailed mechanism has not been elucidated.MethodsPublic databases were applied to collect and identify the chemical ingredients of eight herbs in CZ2HF. Criteria of absorption, distribution, metabolism, and excretion was used to screen oral bio‐availability and drug‐likeness. STITCH database and Therapeutic Target Database were applied to decipher the relationship between compounds and genes related to AD. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology term analyses were used to identify the involved signaling pathways. Cytoscape was adopted to establish the networks The molecular docking was used to validate the interactions between the candidate compounds and their potential targets.Results914 compounds were identiﬁed in eight herbal medicines of CZ2HF. Among them, 9 compounds and 28 genes were highly involved in the pathologic process of AD. Furthermore, the mechanism of CZ2HF to AD was based on its anti‐inflammatory effects mainly through lipopolysaccharide‐mediated signaling pathway and TNF signaling pathway. Core genes in this network were TNF, ICAM1, MMP9 and IL‐10.ConclusionThis study predicts the active compounds in CZ2HF and uncovers their protein targets using holistic network pharmacology methods. It will provide a insight into the underlying mechanism of CZ2HF to AD from a multi‐scale perspective.

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Mucosal immunomodulatory evaluation and chemical profile elucidation of a classical traditional Chinese formula, Bu-Zhong-Yi-Qi-Tang

Cited by 20 publications

References 28 publications

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation

Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model

A network pharmacological approach to investigate the pharmacological effects of CZ2HF decoction on Alzheimer's disease

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