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Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. We examined the anti-inflammatory effects of Ginkgo biloba extract (EGb) in interleukin-1 (IL-1)-stimulated human chondrocytes. Chondrocytes were prepared from cartilage specimens taken from patients with osteoarthritis who had received total hip or total knee replacement. The concentrations of chemokines and the degree of cell migration were determined by ELISA and chemotaxis assays, respectively. The activation of inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases (MAPKs), activator protein-1 (AP-1), and nuclear factor-kappaB (NF-κB) was determined by immunoblotting, immunohistochemistry, and electrophoretic mobility shift assay. We found that EGb inhibited IL-1-induced production of chemokines, which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and release of nitric oxide (NO). The EGb-mediated suppression of the iNOS-NO pathway correlated with the attenuation of activator protein-1 (AP-1) but not nuclear factor-kappaB (NF-κB) DNA-binding activity. Of the mitogen-activated protein kinases (MAPKs), EGb inhibited only c-Jun N-terminal kinase (JNK). Unexpectedly, EGb selectively caused degradation of c-Jun protein. Further investigation revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c-Jun and could be prevented by the proteosome inhibitor MG-132. The results imply that EGb protects against chondrocyte degeneration by inhibiting JNK activation and inducing ubiquitination-dependent c-Jun degradation. Although additional research is needed, our results suggest that EGb is a potential therapeutic agent for the treatment of OA. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acteoside enhances IL-10 production by DCs via activation of the aryl hydrocarbon receptor. • Acteoside acts on DCs to promote the differentiation of Foxp3+ regulatory T cells. • Acteoside alleviates the severity of syndromes of ovalbumin-induced allergic asthma. • Acteoside promotes Foxp3+ regulatory T cell expansion in an allergic asthma model. Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in directing T-cell responses and are involved in the pathogenesis of allergic asthma. Acteoside, an active phenylethanoid glycoside, is widely distributed in many medicinal plants. Herein, we explored the immunomodulatory effects of acteoside on bone marrow-derived DCs in vitro , and further investigated the immunosuppressive ability of acteoside to manipulate T helper type 2 (Th2)-mediated allergic asthma in mice. Following lipopolysaccharide activation, 50 μM of acteoside significantly reduced the production of proinflammatory mediators, including interleukin (IL)-12 and tumor necrosis factor (TNF)-α, whereas it enhanced secretion of the anti-inflammatory cytokine, IL-10, by DCs. However, these effects of acteoside on DCs were reversed by pretreatment with CH223191, an aryl hydrocarbon receptor (AhR) antagonist. Additionally, coculture of acteoside-treated DCs with CD4+ T cells promoted the generation of forkhead box P3-positive (Foxp3+) regulatory T cells (Tregs) via AhR activation. Using a murine asthma model, our results demonstrated that oral administration of 50 mg/kg of acteoside decreased levels of Th2-type cytokines, such as IL-4, IL-5, and IL-13, whereas the level of IL-10 and the frequency of CD4+Foxp3+ Tregs were augmented. Moreover, acteoside treatment markedly inhibited the elevated serum level of ovalbumin-specific immunoglobulin E, attenuated the development of airway hyperresponsiveness, and reduced inflammatory cell counts in bronchoalveolar lavage fluid. Additionally, histological results reveled that acteoside ameliorated pulmonary inflammation in asthmatic mice. Taken together, these results indicated that acteoside exhibits immunomodulatory effects on DCs and plays an anti-inflammatory role in the treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Allergic asthma is induced by T helper 2 (Th2) responses and allergen-specific immunoglobulin E (IgE). In asthma, regulatory T (Treg) cells play a crucial role in controlling immune homeostasis, and induction of Treg cells is a good strategy to treat Th2-mediated allergic asthma. Schisandrin B (Sch B), the main component isolated from Schisandra chinensis, reportedly possesses various pharmacological properties, but its immunomodulatory mechanism in allergic asthma remains unclear. In the present study, we explored whether Sch B exerts an antiallergic effect through modifying the function of dendritic cells (DCs) to regulate T-cell polarization and further investigated the immunomodulatory effects of Sch B in allergic asthma. Herein, an in vitro study revealed that 20 μM of Sch B-treated bone-marrow-derived DCs exhibited a semi-mature phenotype that secreted low amounts of proinflammatory cytokines including interleukin (IL)-12, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and expressed decreased levels of surface molecules of cluster of differentiation 80 (CD80) and CD86. Compared to fully mature DCs, these Sch B-treated DCs displayed a regulatory ability to promote CD4 + Foxp3 + Treg cell generation via upregulation of heme oxygenase (HO)-1 expression. Of note, in a murine model of ovalbumin (OVA)-induced asthma, levels of Th2-type cytokines such as IL-4, IL-5, and IL-13, and C-C motif chemokine 11 (CCL11) were dampened, whereas numbers of forkhead box P3 (Foxp3)-positive Treg cells were augmented in Sch B-treated mice. Moreover, administration of 5 mg/kg of Sch B alleviated the cardinal features of Th2-mediated allergic asthma, namely, serum OVA-specific IgE production, the development of airway hyperresponsiveness (AHR), and airway inflammation. Collectively, these findings indicate that the effectiveness of Sch B treatment against Th2-mediated allergic asthma was at least partially due to enhancement of DC induction of Treg cells, and Sch B can possibly be developed as an immunomodulatory adjuvant to treat allergic asthma., (Copyright © 2022 Elsevier B.V. All rights reserved.)