title: Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-κB inhibition.
abstract: OBJECTIVE
  Guang-Pheretima, the live form of the earthworm Pheretima aspergillum, is a traditional Chinese medicine commonly used for the treatment of asthma, cough, stroke, epilepsy and other diseases due to its anti-inflammatory, anti-asthmatic, anti-seizure, thrombolytic and diuretic properties. Although Guang-Pheretima is effective in the relief of asthma, its pharmacological activity and the underlying molecular mechanisms are not fully understood. Hence, we investigated the effects of a Pheretima aspergillum decoction (PAD) against inflammation in a model of ovalbumin (OVA)-induced asthma in BALB/c mice, as well as the nuclear factor-κB (NF-κB) pathway involved in this process.
  
  
  METHODS
  OVA was used to sensitize and challenge the airway of the mice, and PAD was administrated by gavage. We measured airway hyperresponsiveness (AHR) in the mice 24h following a final methacholine challenge with whole-body plethysmography. The bronchoalveolar lavage fluid (BALF), serum and pulmonary tissues were collected 48h after the last challenge. The levels of inflammatory factors and the related mRNAs were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. The number of differential inflammatory cells in the BALF was counted. Serum total and OVA-specific IgE levels were measured with ELISA. The activation of NF-κB signaling in the lung was detected by western blotting. In addition, the lung tissues were stained with hematoxylin and eosin or periodic acid Schiff stain for histopathological examination.
  
  
  RESULTS
  PAD treatment significantly alleviated AHR in the asthmatic mice, decreased the mRNA and protein levels of IL-4, IL-5 and IL-13 and downregulated IgE. In addition, PAD treatment attenuated mucus secretion and infiltration of inflammatory cells in the lung while inhibiting the activation of NF-κB signaling.
  
  
  CONCLUSIONS
  PAD effectively inhibited the activation of NF-κB signaling in the lungs of mice with OVA-induced asthma, and mitigated AHR and Th2 type inflammatory reactions. Therefore, PAD may serve as a drug candidate for asthma treatment.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Chuan-Qi
authors.initials: CQ
authors.lastname: Huang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: liwei-li@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Guan-Wen
authors.initials: GW
authors.lastname: Mo
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Qiu-Feng
authors.initials: QF
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gong
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Hai-Mei
authors.initials: HM
authors.lastname: Zhu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Qing-Zhong
authors.initials: QZ
authors.lastname: Zeng
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009835:Oligochaeta / Q000737:chemistry*; D010047:Ovalbumin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014020:Tissue Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D014020:Tissue Extracts; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Airway; Asthma; Choline (PubChem CID: 305); Earthworm; Hypoxanthine (PubChem CID: 790); OVA; Traditional Chinese medicine; l-alanine (PubChem CID: 5950); l-leucine (PubChem CID: 6106); l-lysine (PubChem CID: 5962); l-valine (PubChem CID: 6287)