Herbal Combinational Medication of Glycyrrhiza glabra, Agastache rugosa Containing Glycyrrhizic Acid, Tilianin Inhibits Neutrophilic Lung Inflammation by Affecting CXCL2, Interleukin-17/STAT3 Signal Pathways in a Murine Model of COPD

Nutrients. 2020 Mar 27;12(4):926. doi: 10.3390/nu12040926.

Abstract

Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction. This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients. GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative. TN is a major flavonoid that is present in AR. It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent. The COPD in the mice model was induced by a challenge with CFA and DEP. BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD. The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid. It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-α, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-α mRNA expression in the lung tissue. Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone. The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN). In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway. Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD.

Keywords: Agastacha rugosa; COPD; CXCL-2; Glycyrrhiza glabra; IL-17; STAT3.

MeSH terms

  • Agastache*
  • Animals
  • Chemokine CXCL2 / analysis
  • Chemokine CXCL2 / genetics
  • Chemokine CXCL2 / metabolism
  • Disease Models, Animal
  • Flavonoids / pharmacology
  • Glycosides / pharmacology
  • Glycyrrhiza*
  • Glycyrrhizic Acid / pharmacology
  • Interleukin-17 / analysis
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Pneumonia / metabolism
  • Polymerase Chain Reaction
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • STAT3 Transcription Factor / analysis
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Flavonoids
  • Glycosides
  • Il17a protein, mouse
  • Interleukin-17
  • Plant Extracts
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • tilianin
  • Glycyrrhizic Acid