Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China; Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
J Ethnopharmacol. 2023 Jun 12;309:116300. doi: 10.1016/j.jep.2023.116300. Epub 2023 Mar 2.
Shaoyao-Gancao Tang (SGT) is a traditional Chinese medicine formulation. It has been used to treat kinds of pain and to alleviate asthma in clinic. However, the mechanism of action is not known.
To investigate the anti-asthma effect of SGT involving modulation of the T-helper type 1 (Th1) Th1/Th2 ratio in the gut-lung axis and alteration of the gut microbiota (GM) in rats with ovalbumin (OVA)-induced asthma.
The main constituents of SGT were analyzed by high-performance liquid chromatography (HPLC). A model of asthma was established in rats by OVA-induced allergen challenge. Rats suffering from asthma (RSAs) were treated with SGT (2.5, 5.0 and 10.0 g/kg), dexamethasone (1 mg/kg) or physiologic saline for 4 weeks. The level of immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF) and serum was determined by enzyme-linked immunosorbent assay. Histology of lung and colon tissues was investigated using staining (hematoxylin and eosin and periodic acid-Schiff). The Th1/Th2 ratio and levels of cytokines (interferon (IFN)-γ and interleukin (IL)-4) in the lung and colon were detected by immunohistochemistry. The GM in fresh feces was analyzed by 16 S rRNA gene sequencing.
Twelve main constituents (gallic acid, albiflorin, paeoniflorin, liquiritin apioside, liquiritin, benzoic acid, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid, isoliquiritigenin and glycyrrhetinic acid) of SGT were simultaneously determined by HPLC. SGT treatment (5.0 and 10.0 g/kg) was found to reduce the IgE level (a vital marker of hyper-responsiveness) in BALF and serum, improve typical morphological changes (inflammatory-cell infiltration and goblet cell metaplasia) in the lung and colon, alleviate airway remodeling (including bronchiostenosis and basement membrane-thickening) in the lung, significantly decrease the IL-4 level and increase the IFN-γ level in the lung and colon, which led to restoration of the IFN-γ/IL-4 ratio. The dysbiosis and dysfunction of GM in RSAs were modulated by SGT. The abundance of bacteria of the genera Ethanoligenens and Harryflintia was increased in RSAs and was decreased upon SGT treatment. The abundance of Family_XIII_AD3011_group was decreased in RSAs and increased upon SGT treatment. Moreover, SGT therapy increased the abundance of bacteria of the genera Ruminococcaceae_UCG-005 and Candidatus_Sacchrimonas, and decreased that of Ruminococcus_2 and Alistipes.
SGT ameliorated rats with OVA-induced asthma via regulation of the Th1/Th2 ratio in the lung and gut, and modulated the GM.
芍药甘草汤（SGT）是一种中药方剂。它已被用于治疗各种疼痛和缓解哮喘的临床。然而，其作用机制尚不清楚。
研究 SGT 对哮喘的治疗作用，涉及调节肠道-肺轴中的辅助性 T 细胞 1（Th1）Th1/Th2 比值和改变肠道微生物群（GM）在卵清蛋白（OVA）诱导的哮喘大鼠中。
采用高效液相色谱法（HPLC）分析 SGT 的主要成分。通过 OVA 诱导的变应原攻击建立哮喘模型。哮喘大鼠（RSAs）用 SGT（2.5、5.0 和 10.0 g/kg）、地塞米松（1 mg/kg）或生理盐水治疗 4 周。通过酶联免疫吸附试验测定支气管肺泡灌洗液（BALF）和血清中免疫球蛋白（Ig）E 的水平。用苏木精-伊红和过碘酸-Schiff 染色法观察肺和结肠组织的组织学变化。通过免疫组化检测肺和结肠中 Th1/Th2 比值和细胞因子（干扰素（IFN）-γ和白细胞介素（IL）-4）水平。通过 16S rRNA 基因测序分析新鲜粪便中的 GM。
采用 HPLC 同时测定 SGT 的 12 种主要成分（没食子酸、白芍苷、丹皮酚、甘草苷、甘草苷、苯甲酸、异甘草苷、异甘草苷、甘草素、甘草酸、异甘草素和甘草次酸）。发现 SGT 治疗（5.0 和 10.0 g/kg）可降低 BALF 和血清中的 IgE 水平（高反应性的重要标志物），改善肺和结肠的典型形态变化（炎性细胞浸润和杯状细胞化生），减轻肺气道重塑（包括支气管狭窄和基底膜增厚），显著降低肺和结肠中的 IL-4 水平，增加 IFN-γ 水平，从而恢复 IFN-γ/IL-4 比值。SGT 调节了 RSAs 肠道微生物群的失调和功能障碍。RSAs 中 Ethanoligenens 和 Harryflintia 属细菌的丰度增加，而 SGT 治疗后则减少。RSAs 中 Family_XIII_AD3011_group 的丰度降低，而 SGT 治疗后则增加。此外，SGT 治疗增加了 Ruminococcaceae_UCG-005 和 Candidatus_Sacchrimonas 属细菌的丰度，降低了 Ruminococcus_2 和 Alistipes 属细菌的丰度。
SGT 通过调节肺和肠道中的 Th1/Th2 比值和调节肠道微生物群来改善 OVA 诱导的哮喘大鼠。
