Oolonghomobisflavans from Oolong Tea: A Pathway to Healthy Aging and Alzheimer's disease Intervention
ABSTRACT:
Oxidative stress can accelerate age-related pathologies and has been extensively studied in the progression of neurodegenerative diseases. Alzheimer’s disease (AD) is a common debilitating neurodegenerative disease with limited treatment options. Amyloid-β (Aβ) and tau fibrils are well-established hallmarks of AD, which can induce oxidative stress, neuronal cell death, and are linked to disease pathology. Therefore, strategies to protect against oxidative stress are needed to promote healthy aging and delay AD. Tea polyphenols are widely considered excellent antioxidant agents which can contribute to human health and longevity. However, the identification of the active biomolecules in complex tea extracts that promote health and longevity are not fully known. Previous work in our lab identified the oxidative stress resistance properties and neuroprotective effects of oolong tea and its compounds, oolonghomobisflavans (OFs) in neuronal cells culture (Neuro-2a and HT22) and Caenorhabditis elegans models. Our recent results showed that OFs prolongs lifespan and improves healthspan positively correlated with the stress resistance via DAF-16/FOXO and SKN-1/NRF2 signaling pathways. Additionally, OFs displayed protective effects against Aβ- and polyQ-induced neuro/proteotoxicity. Utilizing transcriptomic approaches, OFs treatment has a remarkable impact on the expression of genes that promote oxidative stress responses, cellular proteostasis and signaling that help maintain homeostasis. We further identified a significant improvement multiple health benefits over the lifespan in human tau expressing C. elegans. Correspondingly, OFs treatment clearly disaggregated the tau fibril in brain-derived tau Paired Helical Filament which are protein fibrils typically found in Alzheimer’s disease. The results from this study will provide new evidence supporting the neuroprotective effects of OFs, unique bioactive compounds from oolong tea, and reveal a new therapeutic strategy for targeting AD and other neurodegenerative diseases. The findings from this study will hold significant biological relevance, as they elucidate the potential molecular mechanisms by which oolong tea may contribute to the treatment of Alzheimer’s disease, and establish oolonghomobisflavans as a promising new class of compounds that support healthy aging.
Therapeutic potential of Appalachian Natural Products for cancer and age-related diseases
ABSTRACT:
The incidence of cancer increases with age, making it one of the most extensively studied age-related diseases. Despite significant progress in cancer treatment, conventional chemotherapies have limited positive effect on patient survival. Therefore, there is a need to identify effective therapeutic agents to improve cancer treatment outcomes alongside with other age-related diseases. The Appalachian region is rich in medical plants, many of which are poorly studied or remain understudied. Exploring the bioactivity of Appalachian natural products could enhance our knowledge of traditional herbal medicine and potentially develop therapeutic strategies for cancer treatment and promote healthy aging. The hypothesis of this study is to investigate the anticancer and longevity effects of Appalachian natural products by using human carcinoma cells and Caenorhabditis elegans model. 10 crude extracts including Lousewort, Teasel cutleaf, Garlic mustard, Ground ivy, American water willow, Poison hemlock, Wingstem, Common milkweed, Evening primrose, and Wild ramp will be sent to the National Cancer Institute to screen anticancer activity in 60 different human tumor cell lines, such as lung, colon, brain, ovary, breast, prostate and kidney cancers. If promising results are found, we will future identify cytotoxicity and molecular mechanism in individual cell lines. Oxidative stress play a crucial role in cancer development and the aging process. The free-living soil nematode Caenorhabditis elegans (C. elegans) is a valuable model for studying pharmacological influences of oxidative stress and age-related diseases. We will examine the metabolic health benefits and longevity effects of crude extracts. Antioxidant effects including the survival rate under oxidative stress and intracellular reactive oxygen species (ROS) levels will be assessed. Longevity effects will be determined through pharyngeal pumping function, pigment accumulation (lipofuscin), and lifespan assay. To examine the molecular mechanisms, we will perform transcriptomic and proteomic analyses on cancer cells and C. elegans treated with crude extracts. Machine learning will be employed to identify signaling pathways and target proteins affected by the treatment, which will be confirm through western blot analysis. Gas/liquid chromatography-mass spectrometry (GLC-MS) and high-performance liquid chromatography (HPLC) will be used to identify and characterize the phytochemical compounds in the extract. AI-based modeling will be utilized to predict structure-activity relationship between bioactive compounds and their bioactivity. These novel findings are expected to identify the medical value of Appalachian natural products and elucidate their mechanisms of action, contributing to the development of therapeutic treatments for cancer and age-related diseases.
