Investigation of natural compounds found in monk fruit and orange peel for human health benefits in Caenorhabditis elegans
Creators: name: Cai Shi, Denia
Publisher: name: No Publisher Supplied
Year: 2023

description: Traditional medicine (TM), which has been practiced for thousands of years, draws upon a vast collection of medicinal plants whose potential therapeutic benefits have not yet been fully explored. TM records and practices provide scientists with a starting point to investigate the extensive collection of medicinal plants with potential curative effects on human diseases. In the studies described in this dissertation, my core interests were to (i), study the possible health benefits of mogrosides (MG) and their effects on vitamin B12 deficiency and Alzheimer’s disease (AD); (ii), investigate the ability of modified citrus pectin (MCP) to prevent or ameliorate the adverse effects of cadmium chloride (CdCl₂)-treated Caenorhabditis elegans, with a focus on conserved signaling pathways that are implicated in mammalian cancer; and (iii), explore the possible effects of MG and MCP on the microbial interactions between Helicobacter pylori, Lacticaseibacillus casei, and Escherichia coli OP50 in the C. elegans. Vitamin B12 deficiency can lead to oxidative stress, which has been implicated in neurodegenerative diseases such as AD. MG are plant-derived triterpene glycosides that exhibit anti-inflammatory and antioxidant activity in animal cell lines and mouse models. Since amyloid-β toxicity is known to cause oxidative stress and damage to brain cells, we hypothesized that MG may have a protective effect against AD. In this study, we investigated the potential anti-AD effects of MG in vitamin B12-deficient wild-type N2 and transgenic CL2355 C. elegans expressing amyloid-β peptide. Our data indicated that MG have a beneficial effect on the lifespan and egg-laying rate of N2 and vitamin B12-deficient N2 worms. Additionally, these studies revealed that MG can effectively delay the onset of paralysis in CL2355 worms, as determined by a serotonin sensitivity assay. Our analysis showed that MG increases the expression of oxidative protective genes in N2 worms fed with vitamin B12-deficient OP50 bacterium. We conclude that MG may exert preventative, rather than curative, effects that counteract the detrimental vitamin B12-deficient environment in N2 and CL2355 C. elegans by modulating oxidation-related gene expression. Cadmium chloride (CdCl2) is a toxic compound that occurs in the environment from natural, agricultural, and industrial sources. Exposure to Cd2+ is known to promote malignant tumors such as lung cancer and leukemia. While the current medications for cadmium toxicity focus on treatments to promote excretion from the body, treatments to improve health after cadmium exposure are less well-studied. Modified citrus pectin (MCP) is a polysaccharide derived from citrus peels that has been shown to induce natural killer cell activity in myeloid leukemia cells and act as a natural chelation agent to help excrete toxic metals from healthy human subjects. We hypothesized that MCP might have a counteracting effect against CdCl2 toxicity that is mediated through cancer-related pathways. This study investigates the effects of MCP on CdCl2 toxicity in C. elegans, which shares several cancer-related pathways with mammals. The results indicated that MCP was able to significantly counter the toxic effects of CdCl2 on C. elegans' lifespan and development. Our studies suggest that the beneficial effects of MCP may result from its ability to mitigate the effects of CdCl2 on gene expression, particularly in conserved pathways associated with apoptosis, tumor induction and suppression and inflammation-related pathways. The human microbiome encompasses a complex community of microorganisms that reside both within and outside the human body. Because of the intricate relationship between the microbiome and human health, deciphering the microbiome's role in disease causality and progression can help us find a way to use the microbiome to prevent, manage and treat a broad spectrum of conditions. We proposed to study these intricate relationships by utilizing two bacteria: one that is known to cause gastrointestinal disease in humans (Helicobacter pylori) and one that has been used as a probiotic for overall health effects (Lacticaseibacillus casei). The effects of these bacterial supplements on C. elegans’ health and lifespan were assessed. Following this baseline study, we explored the effects of MG and MCP on C. elegans fed various combinations of H. pylori, L. casei and E.coli strain OP50, which usually serves as the sole microbiome bacterium for laboratory-raised N2 C. elegans. Based on assays for chemotaxis responses, as well as on measurements of length and body area, we find that L. casei and H. pylori do not provide an adequate supply of nutrients for C. elegans and may produce secondary metabolites that C. elegans avoid. Additionally, the chemotaxis assay shows that MCP and MG may have some counteracting effect against H. pylori as worms fed with these two compounds did not avoid the H. pylori + OP50 mixture. Our metabolomic findings also indicate that MG and H. pylori play a role in modulating the triglyceride and fatty acid pathways processes in C. elegans. Our study concluded that the interactions between H. pylori, OP50 and MG in C. elegans should be further studied to better understand these interactions.