Autoimmunity is a pathological chronic inflammatory state that arises when the immune system mistakenly targets healthy cells and tissues in the human body. Clinically, there are more than 80 types of autoimmune diseases described, including well-known conditions like psoriasis, rheumatoid arthritis, type I diabetes, multiple sclerosis, and Crohn’s disease. The incidence of autoimmune diseases in the human population is around 5−10% and continues to rise. Although current treatment options with immunosuppressant drugs like cyclosporine or biologic agents have shown excellent efficacy, they are often associated with unwanted side effects such as increased susceptibility to infections and malignancies, drug-drug interactions, cytokine release syndrome, hypersensitivity reactions, or anti-drug antibodies. Additionally, current drugs often lose efficacy over time, which leads to non-responsiveness, or to a lack of long-lasting relief of symptoms. Finally, the treatment of autoimmune diseases is very expensive and generates high treatment costs. Thus, there is a need for continued research into new therapies.
In the pathogenesis of chronic inflammation and autoimmune diseases enhanced activation and proliferation of T cells plays a crucial role. To address this issue, targeted therapies that specifically enhance inhibitory pathways in T cells are an attractive approach to treat human autoimmune diseases. Thus, the first aim of this study was to discover novel immune-modulating substances from plant extracts that specifically inhibit human T cell activation and proliferation. To achieve this goal, an in-house library of 600 extracts from plants endemic to Panama was screened for potential T cell inhibition. As one of the hits, an ethyl acetate extract from the aerial parts of Hyptis brachiata Briq. (Lamiaceae) was found to have strong inhibitory effects on T cell activation and proliferation. Seven aryltetralin lignans, five arylnaphthalene lignans, two flavonoids, three triterpenes, and cinnamyl cinnamate were isolated using an HPLC-based activity profiling approach. The aryltetralin lignans inhibited T cell proliferation in a concentration-dependent manner without inducing apoptosis. Additionally, the ethyl acetate extract and isolated triterpenes weakly lowered the secretion of inflammatory cytokines like IL-2 and TNF-α by activated T cells. The suppressive effects on activated T cells could be attributed to a synergistic interplay between the aryltetralin lignans and triterpenes. These findings suggest that the extract from Hyptis brachiata could be further investigated as a potential treatment for T cell-mediated inflammatory and autoimmune diseases. The findings of this study have been published in Biomedicine & Pharmacotherapy, 160 in 2023.
Another aspect of this work aimed to explore the potential use of saffron corms (Crocus sativus L., Iridaceae) that arise as a waste product from saffron cultivation. A 70% ethanol extract of the corms and a sugar-depleted methanol fraction of the extract have been found to inhibit the TNF-α/IFN-γ-induced gene expression and secretion of the chemokines IL-8, MCP-1, and RANTES in human HaCaT keratinocytes. The effects were in part stronger than those of the positive control hydrocortisone. These chemokines are responsible for monocyte and T cell attraction, as well as for keratinocyte proliferation, making them critical in wound healing and in the development of inflammatory skin diseases like psoriasis and atopic dermatitis. A series of unusual bidesmosidic glycosides of echinocystic acid, which bear a 3,16-dihydroxy-10-oxohexadecanoic acid residue attached to the glycosidic moiety at C-28, were isolated using centrifugal partition chromatography and different C18 and HILIC HPLC stationary phases. Two previously reported compounds, azafrines 1 and 2, and eight new congeners named as azafrines 3−10 were identified. Saffron saponins significantly inhibited TNF-α/IFN-γ-induced secretion of RANTES in human HaCaT cells at 1 μM (p