Progress 04/15/17 to 04/14/22
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?We have been able to publish multiple papers related to mechanistic and pharmacokientic studies. In addition, we have been able to attend conferences to share the results of this data. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Overall our research has been able to characterie that Nrf2 is a critical target of rosemary extract in models of ulcerative colitis. We have been able to creat unique rosemary extracts that display different biolgoical activty against Nrf2 and AhR which are important targets in inflammatory bowel disease.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Veenstra JP, Johnson JJ. Rosemary ( Salvia rosmarinus): Health-promoting benefits and food preservative properties. Int J Nutr
. 2021;6(4):1-10. Epub 2021 Jun 24. PMID: 34651071 PMCID: PMC8513767
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Vemu B, Tocmo R, Nauman MC, Flowers SA, Veenstra JP, Johnson JJ. Pharmacokinetic characterization of carnosol from rosemary (Salvia Rosmarinus) in male C57BL/6 mice and inhibition profile in human cytochrome P450 enzymes. Toxicol Appl Pharmacol. 2021 Nov 15;431:115729. doi: 10.1016/j.taap.2021.115729. Epub 2021 Sep 27.
PMID: 34592323
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Tocmo R, Le B, Heun A, van Pijkeren JP, Parkin K, Johnson JJ. Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells. Free Radic Biol Med
. 2021 Feb 1;163:102-115. doi: 10.1016/j.freeradbiomed.2020.11.018. Epub 2020 Dec 9. PMID: 33310139 PMCID: PMC8647718 DOI: 10.1016/j.freeradbiomed.2020.11.018
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Tocmo R, Veenstra JP, Huang Y, Johnson JJ. Covalent Modification of Proteins by Plant-Derived Natural Products: Proteomic Approaches and Biological Impacts. Proteomics. 2021 Feb;21(3-4):e1900386. doi: 10.1002/pmic.201900386. Epub 2020 Dec 31. PMID: 32949481 PMCID: PMC8494383 DOI: 10.1002/pmic.201900386
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Veenstra JP, Johnson JJ. Oregano (Origanum vulgare) extract for food preservation and improvement in gastrointestinal health. Int J Nutr
. 2019;3(4):43-52. doi: 10.14302/issn.2379-7835.ijn-19-2703. Epub 2019 Apr 9. PMID: 31080888 PMCID: PMC6508890 DOI: 10.14302/issn.2379-7835.ijn-19-2703
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Yan M, Vemu B, Veenstra J, Petiwala SM, Johnson JJ. Carnosol, a dietary diterpene from rosemary (Rosmarinus officinalis) activates Nrf2 leading to sestrin 2 induction in colon cells. Integr Mol Med
. 2018 Aug;5(4):10.15761/IMM.1000335. doi: 10.15761/IMM.1000335. Epub 2018 Aug 15. PMID: 30972223 PMCID: PMC6453141 DOI: 10.15761/IMM.1000335
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2019
Citation:
14. Johnson, JJ. Mangosteen (Garcinia mangostana) fruit and selected xanthones to disrupt prostate cancer. Presentation type: Oral Presentation. 3rd International Conference on Natural Products for Cancer Prevention and Therapy at Erciyes University. December 18-20, 2019. Kayseri, Turkey
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2019
Citation:
Johnson JJ. Phytochemicals, biological activity and dosing considerations. University of Santo Tomas. September 11, 2019. University of Santo Tomas, Manila, Philippines.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2019
Citation:
Johnson JJ. Health Promoting Properties of Phytochemicals from Rosemary (Rosmarinus officinalis) for Cancer and Inflammatory Bowel Disease. Conference on Applications of Preventive Nutrition. February 18, 2019 Rome, Italy.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2018
Citation:
Johnson JJ. Discovering new pharmacotherapy strategies inspired by natural products. Harvest Pharmaceuticals, September 10, 2018 in Changsha, China
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Johnson JJ. How to use clinical knowledge to direct translational research. 8th International Xiangya Clinical Pharmacy Forum. September 8, 2018. Changsha China
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2021
Citation:
Identification of Sestrin 2 Modulators from Rosemary (Salvia rosmarinus) in Colitis and Colon Cancer
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Progress 04/15/21 to 04/14/22
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?We are in the process of preparing an additional manuscripts that we will be submitting a peer reviewed journal for publication. This will be completed in the next several months. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Our goal was to publish the pharmacokinetic results of rosemary phytochemicals which we have been able to complete with 2 publications. In addition, we have created 3 unique fractions of rosemary and evaluated these fractions for activation of Nrf2 and AhR. Both of these targets (NRF2 adn AhR) are important in regulating inflammatory expression. We have been able to utilize a cell based approach to quantify how unique fractions display different biological activity acgainst these targets. In addition, we have isolated 15 unique phytochemicals that we are working on purifying for pharmacological assays.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Johnson JJ and Veenstra JP. Rosemary ( Salvia rosmarinus): Health-promoting benefits and food preservative properties. Int J Nutr . 2021;6(4):1-10.
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Vemu B, Tocmo R, Nauman MC, Flowers SA, Veenstra JP, Johnson JJ. Pharmacokinetic characterization of carnosol from rosemary (Salvia Rosmarinus) in male C57BL/6 mice and inhibition profile in human cytochrome P450 enzymes. Toxicol Appl Pharmacol. 2021 Nov 15;431:115729. doi: 10.1016/j.taap.2021.115729.
|
Progress 04/15/20 to 04/14/21
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?We are in the process of preparing an additional manuscripts that we will be submitting a peer reviewed journal for publication. This will be completed in the next several months. What do you plan to do during the next reporting period to accomplish the goals?For the final phase of the project we are refining cell culture based experiments to allow us to more accurately compare the different constituents in rosemary extract for modulation of key signaling pathways relevant to inflammatory bowel disease. We are continuing to isolate individual compounds to determine key diterpenes and establish structure activity relationships.
Impacts
What was accomplished under these goals?
Our long-term goal is to determine how a rosemary extract used as a food preservative modulates Nrf2 (a major regulator of antioxidant response and inflammation), for the prevention of ulcerative colitis, to improve overall GI health. The objective here is to determine how polyphenolic diterpenes (e.g. carnosol and carnosic acid) can modulate Nrf2 1) directly and/or 2) indirectly (i.e. Unfolded Protein Response Pathway). Also, in vivo efficacy of rosemary extract in an ulcerative colitis animal model will be determined.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Veenstra JP, Vemu B, Tocmo R, Nauman MC, Johnson JJ. Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis. Nutrients
. 2021 Feb 27;13(3):773. doi: 10.3390/nu13030773.
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Progress 04/15/19 to 04/14/20
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?We are in the process of preparing two additional manuscripts that we will be submitting a peer reviewed journal for publication. This will be completed in the next several months. What do you plan to do during the next reporting period to accomplish the goals?For the final phase of the project we are refining cell culture based experiments to allow us to more accurately compare the different constituents in rosemary extract for modulation of key signaling pathways relevant to inflammatory bowel disease. We are continuing to isolate individual compounds to determine key diterpenes and establish structure activity relationships.
Impacts
What was accomplished under these goals?
We have been able to successfully complete experiments relevant to cell culture as outlined in a recent publication. Free Radic Biol Med. 2021 Feb 1;163:102-115. We are beginning to outline these experiments using individual phytochemicals from Rosemary. One key componenet is that we are making different chemical fractions using rosemary extract to perform these experiments. Once chemical seperation has been completed we will perform these experiments to evaluate the benefits on tight junction protein expression in colon models. We have finished analysis of an animal experiment using the DSS colitis model and submitted this for publication. Depending on the review, we may be required to perform additional experiments to address reviewer comments.
Publications
- Type:
Journal Articles
Status:
Submitted
Year Published:
2021
Citation:
Veenstra JP, Vemu B, Tocmo R, Nauman MC, Pharmacokinetic analysis of carnosic acid and carnosol in standardized rosemary extract and the effect on the disease activity index of DSS-induced colitis.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Tocmo R, Pena-Fronteras J, Calumba KF, Mendoza M, Johnson JJ. Valorization of pomelo (Citrus grandis Osbeck) peel: A review of current utilization, phytochemistry, bioactivities, and mechanisms of action. Compr Rev Food Sci Food Saf. 2020 Jul;19(4):1969-2012. doi: 10.1111/1541-4337.12561.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Tocmo R, Le B, Heun A, van Pijkeren JP, Parkin K, Johnson JJ. Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells. Free Radic Biol Med. 2021 Feb 1;163:102-115. doi: 10.1016/j.freeradbiomed.2020.11.018.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Tocmo R, Veenstra JP, Huang Y, Johnson JJ. Covalent Modification of Proteins by Plant-Derived Natural Products: Proteomic Approaches and Biological Impacts. Proteomics. 2020 Sep 19:e1900386. doi: 10.1002/pmic.201900386.
|
Progress 04/15/18 to 04/14/19
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?We have successfuly published two papers relevant to the study of mediterranean herbs on gastroinestinal health during the last cycle. In addition, we have been fortunate to present our research at different scientific meetings in the United States and worldwide (Italy, Phillipines, and China). What do you plan to do during the next reporting period to accomplish the goals?We are planning on continuing our pharmacokinetic studies to understand the biotransformation of carnosol and carnosic acid in the mouse model. In addition, we are furthering our studies on understanding the regulation of sestrin 2 in cell culture models. We are planning on performing additional in vivo efficacy studies using DSS to further understand the optimal dosing of rosemary extract in mice.
Impacts
What was accomplished under these goals?
Based on the results of our previous in vivo animal model we utilized different conditions to evaluate rosemary extract. We employed a DSS colitis model evaluating rosemary extract. For this intervention, two different doses were employed that included 10 mg/kg and 100 mg/kg of rosemary extract in a mouse model. In addition, we reduced the exposure to DSS. Samples were collected for inflammatory and protein markers that included TNF-alpha, interleukin-8, tight junction proteins (ZO1, AFAD, ZO2, ZO3, CDSAP, occludin, JAM A, Claudin 1, and Claudin 2), unfolded protein response proteins (PERK, IRE-1, NRF2, BiP, NFkB, Sestrin 2and CHOP), and Caspase 3. Prior to euthanasia mice were administered FITC orally to determine the gastrointestinal permeability to establish if the FITC reached the bloodstream. Blood was collected, plasma separated, and FITC was quantified in the different mice. We have also developed experiments using colon cells and macrophage cells to understand the mechanism of action of the compounds in rosemary extract. For example, immune cells can be stimulated with an irritant (i.e. DSS, TNF-alpha) and determine if rosemary extract can control the inflammatory response. Another experiment that we are developing is to establish if the cell membrane can be protected with these agents using an instrument to quantify the electrical potential of the cell membrane. Data collected included an analysis mRNA and protein using qPCR and western blot. In addition, we have performed pharmacokinetic studies of orally administered rosemary extract in mice using 100 mg/kg, carnosic acid 100 mg/kg, carnosic acid 40 mg/kg, and carnosol 100 mg/kg. This work in volved setting up and validating an LC-MS/MS assay capable of detecting carnosol and carnosic acid and their respective internal standards. We were able to overcome significant obstacles that occurred during the assay development. Specifically, we had great difficulty in preventing the carryover of carnosic acid from one sample to another. Currently, the data is being analyzed now to establish the 24 hour pharmacokinetic profile.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Veenstra JP and Johnson JJ. Oregano (Origanum vulgare) extract for food preservation and improvement in gastrointestinal health. Int J Nutr. 2019; 3(4): 43-52
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Yan M, Vemu B, Veenstra J, Petiwala SM, Johnson JJ. Carnosol, a dietary diterpene from rosemary (Rosmarinus officinalis) activates Nrf2 leading to sestrin 2 induction in colon cells. Integr Mol Med. 2018 Aug;5(4).
|
Progress 04/15/17 to 04/14/18
Outputs
Target Audience:
Nothing Reported
Changes/Problems:We do not anticipate any major changes as our experimental methods are working as we propoosed in the original applicaiton. What opportunities for training and professional development has the project provided?As a member of the Pharmacognosy graduate program at UIC I have been able to have a graduate student participate and learn the experiments described above. This work and project is supporting his career development evaluating food components and small molecules for preventing and or treating colitis/inflammatory bowel disease. How have the results been disseminated to communities of interest?This is the first year of the project and currently has been presented with other researchers at our institution. We are in the process of preparing two manuscripts that we will be submitting a peer reviewed journal for publication. This will be completed in the second year. We will also be presenting the research at a conference related to the food components and inflammation. What do you plan to do during the next reporting period to accomplish the goals?We are continuing experiments as described above to idenfity novel mechanism of action. Optimization and modifying the animal model will allow us to further define the potential of rosemary extract increasing key proteins related to preventing and or treating colitis/inflammaotry bowel disease. We will be submitting our work for publication to peer reviewed journals and anticpate at least 2 publications. We will present our work at a conference related to colitis and inflammatory bowel disease.
Impacts
What was accomplished under these goals?
Sales of food preservatives in 2014 passed $2.5 billion with more than $905 million of these sales in natural food preservatives. Among the general public there is a belief that synthetic preservatives such as BHT (Butylated hydroxytoluene) or BHA (Butylated hydroxyanisole) are toxic. This sentiment may have some merit given that multiple studies have raised awareness about the increased risk associations of synthetic preservatives that directly impact the health of the gastrointestinal tract [9]. Interestingly, all the natural preservatives on the market are evaluated for safety/toxicity, however, the potential to promote gastrointestinal health is unknown. One ingredient used extensively as a natural preservative is rosemary (Rosmarinus officinalis) extract. Rosemary has been shown to have potent antioxidant properties and has been proposed as an antioxidant preservative for many years Our long-term goal is to understand how a standardized rosemary extract used as a food preservative modulates Nrf2 (a major regulator of antioxidant response and inflammation), for the prevention of ulcerative colitis, to improve overall GI health. The objective here is to determine how polyphenolic diterpenes (e.g. carnosol and carnosic acid) can increase Nrf2 1) directly and/or 2) indirectly (i.e. PERK). The potential of dietary rosemary extract as a food preservative to prevent intestinal disease, especially ulcerative colitis, that impacts the lining of the intestine, will be determined. 1. Major activities completed / experiments conducted Established a colitis animal model in our laboratory for investigating rosemary extract. Briefly, mice are pre-treated with a highly characterized rosemary extract for 7 days, then treated with dextran sodium sulfate for 7 days. The mice gastrointestinal tract was removed following euthanasia to establish a disease activity index. Samples were also collected to analyze by for inflammatory and protein markers including TNF-alpha, interleukin-8, tight junction proteins (ZO1, AFAD, ZO2, ZO3, CDSAP, occludin, JAM A, Claudin 1, and Claudin 2), unfolded protein response proteins (PERK, IRE-1, NRF2, BiP, NFkB, Sestrin 2and CHOP), and Caspase 3. Prior to euthanasia mice were administered FITC orally to determine the gastrointestinal permeability to establish if the FITC reached the bloodstream. Blood was collected, plasma separated, and FITC was quantified in the different mice. We have also developed experiments using colon cells and macrophage cells to understand the mechanism of action of the compounds in rosemary extract. For example, immune cells can be stimulated with an irritant (i.e. DSS, TNF-alpha) and determine if rosemary extract can control the inflammatory response. Another experiment that we are developing is to establish if the cell membrane can be protected with these agents using an instrument to quantify the electrical potential of the cell membrane. For both our cell and animal experiments we are continuing our work to fine tune the protocols to allow for additional promising compounds to be evaluated. 2. Data Collected A preliminary colitis animal model experiment with rosemary extract found significant protection of the gastrointestinal tract. Rosemary extract was found to to Reduce the disease activity index (DAI) compared to mice not receiving rosemary extract Reduce the gastrointestinal permeability compared to mice not receiving rosemary extract Increase the expression of key proteins including PERK, IRE1, Nrf2, BiP, NFkB, and CHOP 3. Summary of Statistics and Discussion of results The results suggest of this preliminary experiment suggest that rosemary extract was able to protect the mouse colon in a colitis (i.e. inflammation bowel disease) animal model. Data was analyzed to determine if the results were statistically significant. Statistically significant changes were observed with rosemary extract for Reducing the Disease activity index Reducing gastrointestinal permeability as evidenced by oral FITC treatment Increase the expression of key proteins including PERK, IRE1, Nrf2, BiP, NFkB and CHOP 4. Key outcomes or other accomplishments realized. Change in knowledge - improved skills The above animal experiments have allowed us to improve our skills in evaluating promising agents for preventing and or treating colitis and inflammatory bowel disease. The animal model and assays are quite versatile and could be used to continue evaluating for food components as well as promising drug leads. We are developing promising cell culture experiments that will allow for a more effective approach to screening the mechanism of action of small molecules for preventing colitis.
Publications
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