Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, Jilin 132013, People's Republic of China.
Affiliated Hospital of Beihua University, Jilin, Jilin 132011, People's Republic of China.
Clin Interv Aging. 2020 Jan 29;15:97-110. doi: 10.2147/CIA.S237601. eCollection 2020.
Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. , a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism.
D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue.
Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes.
Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.
衰老 是生物自发且不可避免的现象,它会导致组织和器官逐渐恶化。与衰老相关的退化过程之一是免疫衰老,这会导致免疫系统功能发生变化,包括免疫细胞和相关细胞因子。适当调节免疫反应可以改善与年龄相关的免疫衰老过程,从而实现健康衰老。 作为一种中药,千百年来一直被用作药物和营养补充剂。此前有报道称,木脂素单体化合物 木脂内酯具有免疫调节作用。因此,本研究旨在进一步探讨木脂内酯是否也能调节衰老模型小鼠的免疫功能及其潜在机制。
D-半乳糖(D-gal)常用于动物的免疫衰老诱导剂。在本研究中,通过连续 42 天皮下注射 D-gal(220 mg/kg)构建小鼠模型。然后,采集血液和脾脏组织样本,分析观察细胞因子水平、免疫球蛋白水平、白细胞数量、巨噬细胞吞噬活性以及脾脏组织的组织学变化、淋巴细胞增殖能力和生化参数。
木脂内酯显著提高了衰老小鼠血清中 IL-2、IL-4、IFN-γ、lgG、lgM 和 lgA 的水平,降低了 TNF-α和 IL-6 的含量,增加了白细胞数量、吞噬活性、淋巴细胞增殖和脾脏指数。木脂内酯还显著提高了 SOD 和 GSH-Px 的活性,降低了 MDA 和 8-OHdG 在脾脏组织中的含量,上调了 Nrf2、HO-1 和 Bcl2 的表达,下调了 Keap1、Caspase-3 和 Bax 的表达,减少了脾淋巴细胞的凋亡。
木脂内酯通过激活 Nrf2/ARE 通路及其下游酶的抗氧化能力,以及通过调节 Caspase-3 和 Bcl2 与 Bax 的比值来发挥抗凋亡作用,部分恢复了 D-gal 诱导的衰老小鼠下降的免疫功能。