Herb Pair of Glycyrrhiza Radix–Platycodonis Radix Alleviates Respiratory Syncytial Virus Pneumonia in Mice by Modulating Lipid Metabolism and Inhibiting Inflammation

Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix (GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix (PR, Platycodon grandiflorum A. DC) and its potential mechanism for treating respiratory syncytial virus (RSV) pneumonia in mice. Materials and Methods: Aqueous extracts of GR-PR with different ratios (1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of inflammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung inflammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin (SM) and ceramide (CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced inflammation and apoptosis, along with decreased mRNA levels of caspase-1, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3), and toll-like receptor 3 (TLR3), and protein expression of NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin-1β (IL-1β), IL-18, gasdermin D (GSDMD), nuclear factor kappa-B (NF-κB), Bcl2-associated X protein (BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.