Date of Award
2-8-2022
Document Type
Dissertation
Degree Name
Molecular Biosciences, Ph.D.
First Advisor
Fabricio Medina-Bolivar
Committee Members
Asela Wijeratne; Jianfeng Xu; Sun-Ok Lee; Viswanathan Rajagopalan
Call Number
LD 251 .A566d 2021 H37
Abstract
Stilbenoids are a non-flavonoid class of polyphenols that are important for their potential medicinal applications. Resveratrol, ione of the most well-studied compounds of this group, has various medicinal properties including anti-inflammatory, antioxidant, anti-cancer and many other properties. Prenylated stilbenoids which include arachidin-1 and arachidin-3 are produced as a defense response to biotic and abiotic stresses in peanut (Arachis hypogaea). Prenylation has been shown to enhance the biological activities of polyphenolic compounds and thus arachidins may have higher anti-inflammatory activity than resveratrol in addition to many other potential health applications. However, the molecular mechanism of the arachidins as an anti-inflammatory and cardioprotective compounds has not been elucidated yet. First, the present study identified the anti-inflammatory function and mechanism of the prenylated stilbenoid arachidin-3 in a mouse macrophage cell line. Specifically, arachidin-3 showed significant inhibition of IL-6, IL-1β and prostaglandin levels in lipopolysaccharide (LPS)-induced macrophage cells. Arachidin-3 also inhibited the translocation of nuclear transcription factor NF-κB p65 into the nucleus and thus regulated the expression of genes related to inflammation. Arachidin-3 also regulated JNK (c-Jun N-terminal Kinase) activity and HMGB-1 (High mobility group box 1) translocation. Secondly, for the first time, the study demonstrated the cardioprotective effect of prenylated stilbenoids in cardiomyoblast cell line and in vivo models. Using the cardiac oxidative injury model, it was demonstrated that prenylated stilbenoids arachidin-1, arachidin-3, and also a prenylated stilbenoid-enriched peanut hairy root extract can significantly prevent oxidative injury-related cell death in rat cardiomyoblast cells. Furthermore, the study has identified the potential target molecules of prenylated stilbenoids for cardioprotection. Finally, using propylthiouracil (PTU)-induced hypothyroidism rat model of cardiac injury, this study has identified the potential cardioprotective functions as well as key signaling pathways of the mechanism of prenylated stilbenoids. Arachidin-3 and peanut hairy root extract showed improved left ventricular (LV) function, cardiac muscle contraction, and oxidative phosphorylation when compared to the hypothyroidism-induced rat. Together, the present study increased our understanding of the anti-inflammatory and cardioprotective function of the prenylated stilbenoids and carries important translational implications for the application of prenylated stilbenoids for anti-inflammation and cardioprotection.
Rights Management
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Hasan, Md Rokib, "Unraveling The Anti-Inflammatory and Cardioprotective Mechanism of Prenylated Stilbenoids from Peanut Hairy Root Cultures In Vitro And In Vivo" (2022). Student Theses and Dissertations. 281.
https://arch.astate.edu/all-etd/281
Included in
Molecular Biology Commons, Pharmacy and Pharmaceutical Sciences Commons, Plant Sciences Commons
