Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China.
Research Center for Differentiation and Development of Basic Theory of TCM, University of Jiangxi TCM, Nanchang, PR China.
Phytomedicine. 2021 Jun;86:153077. doi: 10.1016/j.phymed.2019.153077. Epub 2019 Aug 23.
Immune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) as immune booster and help to control diseases with their healthy synergistic effect on immune system.
This study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study.
Computational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis.
AM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups.
A novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.
免疫系统在抵御各种致病微生物方面起着决定性的作用。黄芪（AM）和人参（PG）是两种在中药（TCM）中用作免疫增强剂的滋补草药，它们通过对免疫系统的健康协同作用帮助控制疾病。
本研究旨在通过动物和计算系统研究，探讨 AM 和 PG 对免疫系统的促进作用和分子机制，以及控制靶向疾病的作用。
采用吸收、分布、代谢和排泄（ADME）计算模型和基于加权整体相似性（WES）算法的模型以及 ClueGo 网络分析，寻找负责免疫调节的潜在生物活性化合物靶标和途径。通过进行长期给药小鼠的脏器指数分析、脾淋巴细胞增殖活性和 NK 细胞细胞毒性测定，验证 AM 和 PG 对免疫系统的作用。进行小鼠血浆代谢组学研究，探讨 AM 和 PG 对内源性代谢扰动的影响，并进行相关性分析。
AM 和 PG 同时表现出增强免疫系统功能的能力，包括增强脾脏和胸腺指数、脾淋巴细胞增殖和 NK 细胞细胞毒性。此外，通过分析潜在的生物活性化合物、酶作用和途径，还研究了 AM 和 PG 对免疫调节的不同分子机制。黄芪中的主要免疫相关化合物为槲皮素、芒柄花素和山奈酚，而人参中的主要免疫相关化合物为人参皂甙 Ra1、人参皂甙 Rh1 和山奈酚。发现了大约 10 个接近免疫调节的靶蛋白，包括乙酰胆碱酯酶（ACHE，AM 和 PG 的共同靶标）、鞘氨醇激酶 1（SPHK1）、胞嘧啶脱氨酶（CDA）和胆碱 O-乙酰转移酶（CHAT）。甘油磷脂代谢在 AM 和 PG 两组中均受到调节。嘧啶代谢和鞘脂代谢被认为是 AM 组的特殊途径。能量代谢和甘油脂代谢是 PG 组的特殊途径。
建立了一种新的综合分子机制分析方法，并应用于阐明 AM 和 PG 作为免疫调节的科学内涵，为 TCM 的临床实践提供了类似的草药滋补作用，为开发（免疫增强剂）使用 AM 和 PG 提供了新的研究思路。
