Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Psoriasis, Anti-inflammatory Saponins, RORγt inhibitor

Abstract

Psoriasis is considered as a chronic autoimmune condition that resulted in a rapid proliferation of skin cells due to inflammation which causes red scaling on the skin’s surface. To this date there is still no cure for psoriasis. Treatment often involves creams and ointments. Inflammation of the epidermal layer of the skin is due to the hyperactivity of T cells that release various proinflammatory cytokines such as IL-17 that act as a core downstream element in the development of psoriasis. Furthermore, nuclear receptor retinoid-related orphan receptor gamma t (RORγt) has a vital function in the development of Th-17 cells along with the production of IL-17 in immune cells. Suppressing the development of RORγt with the use of secondary metabolites as inhibitors might prevent the production of IL-17 thus, blocking the inflammation in the epidermis layer of the skin and preventing the development of psoriasis. With the use of various antiinflammatory saponins and digoxin as a reference inhibitor for RORγt, the affinity, molecular interactions, and toxicity of ligand to receptor were compared via in silico analysis. The result showed that the top five most ideal anti-inflammatory saponins that can surpass the inhibitory effect of digoxin to RORγt were spirostane, taraxasterol, ganoderic acid SZ, faradiol, and oleanolic acid. Various interactions, such as van der Waals interactions, alkyl, and pi-alkyl interactions, were observed between several amino acids of the receptor and the top five anti-inflammatory saponins. Modified structures of the top five most ideal anti-inflammatory saponins enhanced their inhibitory property against the RORγt receptor. Though digoxin had better physicochemical properties in some aspects, the top five anti-inflammatory saponins did not violate Lipinski’s rule of five for evaluation of metabolites characteristics based on solubility and permeability for the drug development and enhancement process. Thus, this study can be used for the foundation of further drug development and long-term treatment of psoriasis via inhibition of RORγt for psoriasis patients as a prevention for the development of the disease and might be cure as well.

First Advisor

Tabitha L. Amora

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