The immune response is a multifaceted process involving both innate and adaptive components. The innate immune response encompasses the initial defense mechanisms mediated by macrophages and natural killer cells, while the adaptive immune response involves T and B lymphocytes1. Macrophages play a crucial role in tissue immune responses through phagocytosis and non-specific protection against bacterial infections2. Activation of phagocytic cells is essential for initiating inflammation, which involves the release of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), along with other inflammatory mediators like nitric oxide (NO) and prostaglandin E2 (PGE2)3,4. Inducible nitric oxide synthase (iNOS) is responsible for generating NO during the immune response, while cyclooxygenases (COX-1 and − 2) produce PGE2 by converting arachidonic acid. Given the role of NO and PGE2 as key pro-inflammatory mediators in macrophages, enhancing their production could be a beneficial strategy for boosting the immune system5,6. Lipopolysaccharide (LPS) is a potent inflammatory stimulant commonly used in screening for anti-inflammatory and immune-enhancing compounds. Previous studies have utilized high doses of LPS (e.g., 0.1-1 µg/ml) to induce acute inflammation in RAW264.7 macrophage cells for screening anti-inflammatory agents7–9. Conversely, low doses of LPS (e.g., 1–10 ng/ml) are used as a positive control to stimulate murine macrophages in screening for immune-boosting agents10.
Stress-induced immunosuppression refers to the suppression or weakening of the body's immune response as a result of exposure to stressors, which can be psychological, physiological, or environmental. One of the mechanisms through which stress induces immunosuppression is by activating the hypothalamic-pituitary-adrenal axis, leading to the release of stress hormones such as cortisol11. Cortisol, also known as hydrocortisone (HCOR) when supplied as a drug, is a steroid hormone produced by the adrenal glands in response to stress12. It plays a pivotal role in regulating various physiological processes, including metabolism, inflammation, and immune function13,14. Especially, when released into the bloodstream, cortisol binds to glucocorticoid receptors on immune cells, thereby suppressing immune responses15.
Chemotherapy is a fundamental component of cancer treatment, yet it carries the risk of inducing immunosuppression, which can potentially impact patient outcomes. While chemotherapy effectively targets cancer cells, it can also affect rapidly dividing cells in the immune system, including leukocytes and bone marrow precursors, leading to compromised immune function16,17. Consequently, patients may experience heightened susceptibility to infections, delayed wound healing, and other immune-related complications. Managing and monitoring immune function during chemotherapy are crucial to mitigate the risk of infections and other adverse effects, underscoring the importance of comprehensive patient care.
Socheongryong-tang (SCRT) has traditionally been used as an herbal medicine formula for managing bronchitis, asthma, rhinitis, and cold-related symptoms across East Asia, including Korea, China, and Japan17,18. SCRT composes 8 herbal components: Pinellia ternata Rhizoma, Paeonia lactiflora Pall. Radix, Ephedra sinica Stadf. Herba, Zingiber officinale Rosc. Rhizoma, Glycyrrhiza glabra L. Radix, Cinnamomum cassia Blume. Ramulus, Asarum sieboldii F. Maekawa Radix, and Schizandra chinensis Fructus18. The major components of SCRT include 6-gingerol, liquiritigenin, and glycyrrhizin, as well as phenylpropanoids such as cinnamic acid, cinnamaldehyde, and coumarin; monoterpene glycosides such as paeoniflorin and albiflorin; lignans including schizandrin, gomisin A, and gomisin N; and alkaloids including ephedrine and pseudoephedrine19–21.
In this study, we aimed to investigate the immunomodulatory properties of SCRT aqueous extract and elucidate its underlying mode of action in macrophages. Our findings provide a molecular trait for the reversal of stress- or chemotherapy-induced immunosuppression by SCRT for the first time, and could be used to help in the development of pharmaceuticals aimed at manipulating immunomodulation.