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

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.

Hypericum ascyron L. extract reduces particulate matter‐induced airway inflammation in mice

“…A volume of 100 μl of CFD was administered to each mouse. CFD consists of coal (5 mg/ml), fly ash (10 mg/ml), and diesel exhaust particles (DEP; 5 mg/ml), as previously described (Kim et al, 2020). CFD was intratracheally administered on days 4, 7, and 10.…”

The potential of glycyrrhizin and licorice extract in combating COVID-19 and associated conditions

“…( Ashfaq et al, 2017 , Omar et al, 2012 , Oyama et al, 2016 , Soufy et al, 2012 , Bailly and Vergoten, 2020 , Tong et al, 2020 , Velvizhiv and Annapurani, 2018 , Vispute, 2011 , Wang et al, 2015 , Wu et al, 2019 , Xu et al, 2018 , Zakaryan et al, 2017 , Zhang et al, 2018 , Chen et al, 2017 , Dao et al, 2011 , Editorial 2020 , Hazlett et al, 2019 , Aipire et al, 2020b , Hirabayashi et al, 1991 , Kim et al, 2020 , Lee et al, 2018 , Liu et al, 2019 , Liu et al, 2020 , Long et al, 2013 , Maksoud et al, 2019 )…”

Modulation of neutrophil (dys)function by Ayurvedic herbs and its potential influence on SARS-CoV-2 infection

“… Bromhexine a derivative of A. vasica has mucolytic activity In vivo: 400mg/kg p.o. for 8 days in male Wistar rats Increases adhesion of neutrophils to nylon fibers Yastimadhu (Glycyrrhiza glabra) Pitta-anila-asra jith (mitigates pitta-vata-rakta), Shothahara (anti-inflammatory), Ruchya (enhances taste), Rasayana (rejuvenation) a) Antimicrobial b) Immunomodulatory c) Antithrombotic Antitussive, expectorant, antimicrobial, antiviral, anti-oxidant, anti-inflammatory, immune-modulatory activity [ 66 , 122 , [194] , [195] , [196] , [197] ] In vitro: 25-100μg/ml in RAW 264.7 macrophages stimulated with LPS Inhibits LPS-induced TNF-α, IL-1β, IL-6 production In vitro: 50-200μg/ml in LPS-stimulated mouse endometrial epithelial cells Glycyrrhizin inhibits LPS-induced TNF-α, IL-1β, NO & PGE 2 production In vitro: 200, 40, 8mg/l in LPS-induced macrophage cell line of RAW264.7 Glycyrrhizin acid supresses IL-1β, IL-3, IL-5, IL-10, IL-12, IL-13 & TNF- α (LPS stimulated) In vivo: 50 to 100mg/kg p.o. for 11 days in Male BALB/c mice.…”

“…Interestingly, independent studies have shown that above mentioned herbs such as T . chebula [ 52 ] , P. niruri [ 65 ] , V.vinifera [ 55 ], G.glabra [ 66 ], J.adhatoda [ 63 ] and A.sativum [ 67 ] significantly modulated neutrophil functions in disease conditions.…”

“…In two different experimental models of induced thrombosis in rats, intravenous administration of GL showed dose-dependent reduction in thrombus size and hypercoagulability [ 122 ]. Interestingly, independent studies have shown Phyllantus [ 65 ], Vitis [ 123 ], Ginger [ 89 ] and glycyrrhiza [ 66 ] significantly modulates neutrophil function. Taken together, these Ayurvedic herbs might help both to inhibit NETs production and its consequences on platelet aggregation in COVID-19 pathogenesis.…”