Study on the Therapeutic Effects of Ginsenoside Rh2 in Asthma Improvement

Ginsenoside Rh2, a protopanaxadiol-type saponin derived from Panax ginseng, exhibits a broad spectrum of biological activities; however, its specific mechanisms in asthma remain elusive. In this study, we systematically evaluated the therapeutic efficacy of Rh2 against asthma using both in vitro and in vivo models. A lipopolysaccharide (LPS)-induced in vitro cell model was established and treated with low, medium, and high doses of Rh2 (1, 5, and 10 μg/mL). Concurrently, an in vivo asthma model was constructed via ovalbumin (OVA) sensitization and administered with three doses of Rh2 (2.5, 5, and 10 mg/kg). The results demonstrated that Rh2 significantly suppressed pro-inflammatory cytokines (interleukin-4 [IL-4], interleukin-5 [IL-5], interleukin-13 [IL-13], interleukin-33 [IL-33], and tumor necrosis factor-α [TNF-α]) and upregulated anti-inflammatory factors (interferon-γ [IFN-γ] and interleukin-10 [IL-10]) in both experimental models. Furthermore, Rh2 inhibited the expression of key inflammatory pathway proteins, including suppression of tumorigenicity 2 (ST2), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and c-Jun N-terminal kinase (JNK). Transcriptomic and metabolomic analyses revealed that Rh2 primarily modulates the TNF-α signaling pathway, cytokine–cytokine receptor interaction, pyrimidine metabolism, and glycine, serine, and threonine metabolism. Integrated analysis further identified significant correlations between differentially expressed genes (C-X-C motif chemokine ligand 2 [CXCL2], C-X-C motif chemokine ligand 17 [CXCL17], and leukemia inhibitory factor [LIF]) and differential metabolites (cytosine, L-histidine, and creatine). Collectively, these findings suggest that ginsenoside Rh2 ameliorates asthma by modulating cytokine interactions and amino acid metabolism.