Compound K (CK) is a secondary ginsenoside biotransformed from ginseng. This review discusses the function of CK as a potential ligand of the glucocorticoid receptor and a regulator of macrophage inflammatory responses. We provide findings on the ability of CK to inhibit the activation of M1 macrophages and promote the activation and differentiation of M2 macrophages. In addition, the effect of inhibiting the inflammasome response was collected. We summarized the evidences that CK is effective in the treatment of various inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, dermatitis, asthma, chronic obstructive pulmonary disease, sepsis associated encephalopathy, atherosclerosis, inflammatory bowel disease, and diabetes. These findings suggest the potential of CK as a therapeutic agent that can resolve inflammation and restore homeostasis.

Allergic rhinitis (AR) is a common upper-airway inflammatory disease of the nasal mucosa caused by immunoglobulin (IgE)-mediated inflammation. AR causes various painful clinical symptoms of the nasal mucosa that worsen the quality of daily life, necessitating the urgent development of therapeutic agents. Herein, we investigated the effects of Caesalpinia sappan Linn. heartwood water extract (CSLW), which has anti-inflammatory and antioxidant properties, on AR-related inflammatory responses. We examined the anti-inflammatory and anti-allergic effects of CSLW in ovalbumin (OVA)-induced AR mice and in primary human nasal epithelial cells (HNEpCs). Administration of CSLW mitigated allergic nasal symptoms in AR mice, decreased total immune cell and eosinophil counts in nasal lavage fluid, and significantly reduced serum levels of OVA-specific IgE, histamine, and Th2 inflammation-related cytokines. CSLW also inhibited the infiltration of several inflammatory and goblet cells, thereby ameliorating OVA-induced thickening of the nasal mucosa tissue. We found that CSLW treatment significantly reduced infiltration of eosinophils and production of periostin, MUC5AC, and intracellular reactive oxygen species through the Keap1/Nrf2/HO-1 pathway in HNEpCs. Thus, our findings strongly indicate that CSLW is a potent therapeutic agent for AR and can improve the daily life of patients by controlling the allergic inflammatory reaction of the nasal epithelium.

Background: Regulatory T cells (Tregs) are living drugs with feasibility, tolerability, and therapeutic benefits. Although Tregs are linked to asthma prognosis through inflammation regulation, no therapeutic agents specifically designed to manage asthma by upregulating Tregs have been developed to date.Methods: We screened a library of 250 natural products using a cytometric bead array. Among the selected candidates, gRb1 was identified for further investigation. The effects of gRb1 on Treg and Th17 populations were evaluated in mouse asthma models and human PBMCs from both healthy donors and asthma patients using flow cytometry and cytokine analysis.Results: In inflammatory conditions, ginsenoside Rb1 (gRb1, a major ginseng component) increased IL‐10‐ and TGF‐β‐expressing Treg populations and decreased the Th17 population; activated phospho‐STAT5 and NFAT1 in Tregs; inhibited NFAT1 activation in conventional T cells (Tconvs); increased Treg proliferation and Tconv–Treg differentiation, inhibiting Tconv proliferation; and reduced inflammatory cytokine secretion by Tconvs. In asthma model mice, suppression of asthma symptoms by gRb1 was associated with elevated Treg and lower Th17, Th1, and Th2 counts. gRb1 treatment of stimulated PBMCs from patients with asthma and healthy donors increased IL‐10‐ and TGF‐β‐expressing Treg populations and decreased IL‐17A‐, IL‐22‐, IFN‐γ‐, and TNF‐α‐expressing T‐cell populations.Conclusions: gRb1 alleviate asthma by shifting the Treg–inflammatory T cell balance. These findings suggest a strategy for enhancing Treg activity through treatment with gRb1. This may provide a novel therapeutic approach for asthma and related disorders.

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We investigated the inhibitory effects of water- and ethanol-extracted GJ (GJW and GJE, respectively) in an ovalbumin-induced AR mouse model and in splenocytes, differentiated Th2 cells, and primary human nasal epithelial cells (HNEpCs). Administering GJW and GJE to ovalbumin-induced AR mice improved clinical symptoms including behavior (sneezing and rubbing), serum cytokine levels, immune cell counts, and histopathological marker levels. Treatment with GJW and GJE reduced the secretion of Th2 cytokines in Th2 cells isolated and differentiated from the splenocytes of these mice. To investigate the underlying molecular mechanisms of AR, we treated IL-4/IL-13-stimulated HNEpCs with GJW and GJE; we found that these extracts significantly reduced the production of mitochondrial reactive oxygen species via the uncoupling protein-2 and periostin, a biomarker of the Th2 inflammatory response. Our results suggest that GJ extracts may potentially serve as therapeutic agents to improve the symptoms of AR by regulating the Th2 inflammatory response of the nasal epithelium.

High expression alleles of the innate cytokine, macrophage migration inhibitory factor (MIF), are associated with the development or the severity of autoimmune inflammatory diseases, including rheumatoid arthritis. Numerous studies support MIF’s role in activating inflammatory pathways and MIF inhibition reduces joint pathology in different experimental models of arthritis. We examined the impact of gene deletion of MIF or its cognate receptor CD74 in the T cell–dependent model of collagen-induced arthritis (CIA) and observed the complete absence of arthritis development, suggesting an unforeseen role for MIF/CD74 signaling in the development of arthritogenic T cells. While MIF has been shown in model systems to contribute to T cell activation by augmenting innate responses, fewer than 1% of T lineage cells express CD74 in naive spleens and lymph nodes, and its functional consequences in pathogenic T cell subpopulations have not been studied. We found CD74+ T cells to expand during CIA and to increase in number within joint synovium, where they express an effector memory phenotype and recapitulate CIA development upon transfer into naive mice. We further found evidence for the presence of CD74+ T cells in the circulation and joint synovium of patients with rheumatoid arthritis. MIF-dependent, CD74+ T cells may contribute to the chronicity of rheumatoid synovitis and to disease relapse in previously inflamed joints.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and cutaneous dry skin. Here, we investigated whether topical application of NI-01 composed of six herbal medicines has a therapeutic effect on AD in vivo. Twelve marker compounds of NI-01 were analyzed by high-performance liquid chromatography with a photodiode array detector for quality control. To induce AD, house dust mite extract was applied to the shaved dorsal skin and ear surfaces of NC/Nga mice twice a week for 6 weeks. NI-01 (1, 2, or 4 mg/mouse) was applied daily to the site for experiment periods. The coefficient of determination of each compound showed good linearity (≥ 0.9999). The recovery rate of the 12 marker components was 96.77%–105.17%; intra and interday precision and repeatability were ≤ 1.40%. Topical application of NI-01 reduced house dust mite induced AD symptoms. The increased expressions of interleukin-4 and intercellular adhesion molecule-1 caused by house dust mites were markedly suppressed in NI-01-treated mice. Corticosterone levels significantly decreased, whereas serotonin levels increased with NI-01 application. These results suggest that NI-01 alleviates AD symptoms by inhibiting infiltration of inflammatory cells, thereby decreasing AD-related stress. NI-01 could be beneficial for the treatment of AD-like skin diseases.