Study on the anti-asthmatic effect of Ginseng-Schisandra herb pair and its mechanisms in regulating the PI3K-AKT signaling pathway

Abstract:Ethnopharmacological relevance: Ginseng-Schisandra herb pair is a classic representative one of the "combination of tonification and astringency" in traditional Chinese medicine. Ginseng tonifies lung Qi and benefits heart Qi, while Schisandra restrains the lung, nourishes the kidney, calms the mind and soothes the spirit. When they are used in combination, one can play a tonifying role and another can serve a astringency, with tonification but without stagnation and with astringency but without depression, so the combination can not only enhance the efficacy of replenishing Qi and nourishing Yin but also strengthen the effect of astringing and consolidating. However, the underlying mechanism and action of its combined use in the prevention and treatment of asthma remain unclear. Aim of the study: The anti-asthmatic effect of Ginseng-Schisandra herb pair was studied by both in vivo and in vitro experiments, its main active components were analyzed, and its mechanism of action was explored in this study.Materials and methods: An asthma model in mice was established by using ovalbumin (OVA) combined with aluminum hydroxide (Al(OH)3), so as to observe the anti-asthmatic effect of Ginseng-Schisandra herb pair and find its optimal compatibility ratio. Interleukin-4 (IL-4) combined with tumor necrosis factor-α (TNF-α) was employed to induce human bronchial epithelial cells (BEAS-2B) for simulating an in vitro asthma model, aiming to further verify the anti-asthmatic effect of the herb pair. Components in the herb pair extract were comprehensively analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and network pharmacology methods for identifying its bioactive components and predicting the anti-asthma mechanism, which were subsequently verified by Western blot and immunofluorescence techniques.Result: Ginseng-Schisandra herb pair could improve the behavior of asthmatic mice, alleviate the pathological damage of lung tissue, reduce the levels of inflammatory factors in the serum of asthmatic mice and the asthma model BEAS-2B cells, increase the activity of superoxide dismutase (SOD), and decrease the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). A total of 72 bioactive components were identified from the Ginseng-Schisandra herb pair extract, and the herb pair could inhibit the expression of PI3K-AKT pathway-related proteins in the lung tissue of asthmatic mice and BEAS-2B cells.Conclusion: Ginseng-Schisandra herb pair can effectively alleviate the airway inflammatory response and oxidative stress injury by regulating the PI3K-AKT signaling pathway in mice to exert an anti-asthmatic effect. Among different compatibility ratios and compared with single herbs, the 2:1 ratio of the herb pair exhibits the optimal therapeutic efficacy.