Source: UNIV OF HAWAII submitted to
BENEFICIAL AND ADVERSE EFFECTS OF NATURAL. BIOACTIVE DIETARY CHEMICALS ON HUMAN HEALTH AND FOOD SAFETY (FROM W1122)
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0212347
Grant No.
(N/A)
Project No.
HAW00586-R
Proposal No.
(N/A)
Multistate No.
W-2122
Program Code
(N/A)
Project Start Date
Oct 1, 2007
Project End Date
Sep 30, 2012
Grant Year
(N/A)
Project Director
Nerurkar, P. V.
Recipient Organization
UNIV OF HAWAII
3190 MAILE WAY
HONOLULU,HI 96822
Performing Department
MOLECULAR BIOSCIENCES & BIOSYSTEMS
Non Technical Summary
Obesity-associated metabolic disorders are escalating world-wide. Changes in life style, such as dietary recommendations form the cornerstone of treatment. The essential challenge for nutritional science is to identify not only nutritious foods, but (functional foods%, that may provide health benefits beyond basic nutrition. The rationale for the proposed research is that understanding molecular events of functional foods has strong potential to identify effective nutritional intervention strategies and update dietary recommendation for a healthier living.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7021429101050%
7021429104050%
Goals / Objectives
1. Consumption of food-borne bioactive compounds can protect against human diseases such as cancer, inflammation, birth defects, and microbial infection. We will determine the mechanisms by which selected compounds exert their protective action. 2. Food-borne toxins and carcinogens are present per se or are induced by processing, preparations, and other post-harvest steps. We will identify mechanisms of action and develop biomarkers of natural and induced toxicants in food for human risk assessment and disease prevention. 3. Selected classes of bioactive compounds show potential for beneficial or adverse effects on human health. We will discover bioactive compounds that have beneficial or adverse effects on human health.
Project Methods
Investigate the ani-obesity, anti-diabetic and hypolipidemic properties of momordica charantia (bitter melon), using cell culture and animal model systems.

Progress 10/01/07 to 09/30/12

Outputs
OUTPUTS: Research findings on the health benefits of bitter melon was shared with scientific community and various health care practitioners in the form of oral presentations at various national and international scientific meetings including: 1. Medical symposium at Clinical School of the University of Tasmania, Hobart, Australia held on Oct 6, 2012 2. Masters in clinical Research course, JABSOM, University of Hawaii held on October 11, 2012. 3. Multistate meeting held in Fort Collins, Denver, CO held from Oct 23-26, 2012. Findings from this project were used as preliminary data to apply for two federal grants. PARTICIPANTS: One graduate and two undergraduate students were mentored and trained during this project period. TARGET AUDIENCES: Overweight individuals, diabetics, communities that are high risk for diabetes in Hawaii (Filipinos, Pacific Islanders, Native Hawaiians), scientific community, health care professionals, nutritionist, dietetics, holistic practitioners, individuals interested in prevention of diabetes. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our findings demonstrate that bitter melon not only improves obesity, diabetes, and systemic inflammation but also inhibits macrophage invasion and inflammation in the adipose tissue of mice fed high-fat diet (HFD). Adipose tissue inflammation is involved in the pathophysiology of insulin resistance and type 2 diabetes. Furthermore, bitter melon also reduced adipocytokines such as resistin, and leptin and increased adiponectin in HFD-fed mice.

Publications

  • Kumar, M., Roe, K., Nerurkar, P.V., Namekar, M., Orillo, B., Verma, S., and Nerurkar, V.R. 2012. Impaired virus clearance, compromised immune response and increased mortality in type 2 diabetic mice infected with West Nile virus. PLoS One. 7(8):e44682. doi: 10.1371/journal.pone.0044682. Epub 2012 Aug 31
  • Nerurkar, P.V., Nishioka, A., Eck, P.O., Johns, L.M., Volper, E., and Nerurkar, V.R. 2012. Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice. Br J Nutr. 108(2):218-28.


Progress 10/01/10 to 09/30/11

Outputs
OUTPUTS: The project resulted in four publications in peer-reviewed scientific journals with open access to public viewing. Research findings on the health benefits of bitter melon was shared with scientific community and various health care practitioners in the form of oral presentations at various national and international scientific meetings including, Functional Foods-Agriculture and Clinical Applications held on January 23, 2010 in Honolulu, HI; Experimental Biology Annual meeting held on April 24-28, 2010 in Anaheim, CA; He Huliau: A Turning Point - Eliminating Health Disparities in Native and Pacific Peoples: Metabolic Syndrome and Health Equity held on May 7 - 8, 2010 in Honolulu, HI; International Conference on Multidisciplinary Approaches to Diabetes Research and Health held on November 14-16, 2010, in Jaipur, India; 12th RCMI International Symposium on Health Disparities, held on December 6-9, 2010 in Nashville, TN. Findings on anti-cancer properties of bitter melon also shared with consumers in Hawaii and nation-wide through the news releases in various local and national news article including, but not limited to CTAHR news release, University of Hawaii news, Star Bulletin, Honolulu advertiser, and eHow.com internet news. Findings on neuroprotective effects of bitter melon were presented to the scientific community at monthly seminar held at the Queens Medical Center, Honolulu, HI held on January 14, 2011. Our findings about the anti-diabetic properties of noni were presented at the annual multistate meeting held in 2010 and 2011. PARTICIPANTS: Graduate students were trained under this project. TARGET AUDIENCES: Diabetics communities that are high risk for diabetes in Hawaii scientific community health care professionals nutritionist dietetics holistic practitioners PROJECT MODIFICATIONS: none

Impacts
Besides bitter melon, we are also exploring the anti-diabetic properteis of Morinda citrifolia (noni). We have recently demonstrated that noni improves not only glucose and lipid metabolism, but also prevent weight gain in mice fed high-fat-diet (HFD) containing 58% fat. Mechanistic studies indicate a role for chronic inflammation in pathophysiology of obesity and T2D. Our data demonstrates that noni improves HFD-associated systemic inflammation by reducing secretions of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), interferon-gamma (INFγ), interleukin 6 (IL-6). Furthermore, noni also improved hepatic inflammation in HFD-fed mice.

Publications

  • Nerurkar, P.V., Nishioka, A., Eck, P.O., Johns, L.M., Volper, E., and Nerurkar, V.R. (2011). Regulation of Glucose Metabolism via Hepatic FoxO1 by Morinda Citrifolia (Noni) in HFD-Induced Obese Mice. British J Nutr. 10(1):1-11.
  • Ru, P., Steele, R., Nerurkar, P., Phillips, N.J., Ray, R.B. (2011). Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model. Cancer Prev Res. (Phila)4(12):2122-2130.
  • Nerurkar, P.V.*, Johns, L.M., Buesa, L.M., Kipyakwai, G., Volper, E., Sato, R., Shah, P., Feher, D., Williams, P.G., Nerurkar, V.R. (2011). Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. Journal of Neuroinflammation. 8(1):64-72.
  • Snee, S.L., Nerurkar, V.R., Dooley, D.A., Efird, J.T., Shovic, A.C., and Nerurkar, P.V. (2011). Strategies to improve palatability and increase consumption intentions for Momordica charantia (bitter melon): a vegetable commonly used for diabetes management. Nutr J. 28(10): 78-85.


Progress 10/01/09 to 09/30/10

Outputs
OUTPUTS: The project resulted in three publications in peer-reviewed scientific journals with open access to public viewing. Research findings on the health benefits of bitter melon was shared with scientific community and various health care practitioners in the form of oral presentations at various national and international scientific meetings including, Functional Foods-Agriculture and Clinical Applications held on January 23, 2010 in Honolulu, HI; Experimental Biology Annual meeting held on April 24-28, 2010 in Anaheim, CA; He Huliau: A Turning Point - Eliminating Health Disparities in Native and Pacific Peoples:Metabolic Syndrome and Health Equity held on May 7 - 8, 2010 in Honolulu, HI; International Conference on Multidisciplinary Approaches to Diabetes Research and Health held on November 14-16, 2010, in Jaipur, India; 12th RCMI International Symposium on Health Disparities, held on December 6-9, 2010 in Nashville, TN. Findings on anti-cancer properties of bitter melon also shared with consumers in Hawaii and nation-wide through the news releases in various local and national news article including, but not limited to CTAHR news release, University of Hawaii news, Star Bulletin, Honolulu advertiser, and eHow.com internet news. PARTICIPANTS: Training -provided for undergraduate and graduate students TARGET AUDIENCES: Hawaii residents, specifically ethnic minorities such as Native Hawaiians, Pacific Islanders and Filipinos who have the highest rates and incidences of type 2 diabetes. Pharmaceutical industry for drug development. Agricultural community. Health care Professionals such as dieticians and nutritionists. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our results indicate that both bitter melon and noni were able to alleviate high-fat-diet (HFD)-induced diabetes and hyperlipidemia in mice fed a 58% fat diet for 16 weeks. These basic findings have been extrapolated to human studies and we are currently testing the long-term safety of bitter melon in healthy obese individuals. Our collaborative studies further demonstrated that bitter melon was an effective anti-cancer agent against breast cancer using human cancer cells in culture. Disparities in breast cancer incidence as well as type 2 diabetes (T2D)is evident by the fact that Native Hawaiians have the highest incidence as well as mortality rates compared to other ethnic groups in Hawaii. Bitter melon is available throughout the year in Hawaii in local super markets, China town as well as farmer's market. Bitter melon is also added to various ethnic food dishes cooked in many households as well as in restaurants. Therefore, it is easy in Hawaii to adopt a diet rich in bitter melon that may have a far-reaching impact on health benefits among Hawaii's population. Bitter melon being is easily grown in tropical climate and added value of health benefits can also add to its crop value and generate agricultural revenues, boosting the economy. Bitter melon also offers an affordable complementary treatment option in developing worlds.

Publications

  • Nerurkar, P., Ray, R. B. Bitter melon: antagonist to cancer. Pharm Res. 2010 Jun;27(6):1049-53. Epub 2010 Mar 3. PMID: 20198408
  • Ray, R.B., Raychoudhuri, A., Steele, R., Nerurkar, P. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Res. 2010 Mar 1;70(5):1925-31. Epub 2010 Feb 23. PMID: 20179194
  • Nerurkar, P.V.*, Lee, Y-K and Nerurkar, V.R. Y-K. Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes. BMC Complement Altern Med. 2010 10: 34-41. Epub 2010 July 01. PMCID: 2911406


Progress 10/01/08 to 09/30/09

Outputs
OUTPUTS: Activities: Earlier studies from our laboratory indicated that bitter melon (BM) improves high-fat diet (HFD)-associated obesity and insulin resistance. Current mechanistic studies demonstrated that BM regulates glucose metabolism and ameliorates insulin resistance by modulating ER stress and gluconeogenesis pathway. Grant was instrumental in training one undergraduate student Events: the data was presented at local and national meetings. PARTICIPANTS: Grant was instrumental in training one undergraduate student. TARGET AUDIENCES: Minority populations, Pacific Islanders, obese and diabetic individuals PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Our findings confirm the anti-diabetic potency of BM fruit juice in diet-induced diabetic mice. The data obtained from this grant was instrumental in applying for federal (NIH-R01) grant.

Publications

  • Snee LS, Nerurkar VR, Dooley D, Efird J, Shovic A, Nerurkar PV. Feasibility study to increase palatability and consumption of Momordica charantia (Bitter Melon). J Med Food, (submitted 2009).
  • Nerurkar PV, Lee YK and Nerurkar VR. Momordica Charantia (Bitter Melon) Inhibits Primary Human Adipocyte Differentiation by Modulating Adipogenic genes. J Complementary Alternative Medicine (submitted 2009).
  • Nerurkar PV, Eck PO, Shah P and Nerurkar VR. Effect of Momordica charantia (bitter melon) on drug metabolizing enzymes in primary human hepatocytes. Manuscript in preparation, 2009.
  • Nerurkar PV, Lee YK, Adeli K and Nerurkar VR. Momordica charantia (bitter melon) improves hepatic insulin signaling. ASBMB Annual Meeting, San Diego, CA, April 4-6, 2008.
  • Shah P, Eck PO, Nerurkar VR and Nerurkar PV. Effect of Momordica charantia (bitter melon) on drug metabolizing enzymes. 20th Annual CTAHR Student Research Symposium, University of Hawaii at Manoa, April, 2008.
  • Pratibha V. Nerurkar, Yun-Kyung Lee and Vivek R. Nerurkar. Momordica Charantia (Bitter Melon) Improves Adipose Tissue Insulin Signaling in Mouse Fed a High-Fat-Diet. In: Abstracts of the 11th RCMI International Symposium on Health Disparities, Honolulu, HI, December 2008.


Progress 10/01/07 to 09/30/08

Outputs
OUTPUTS: The project facilitated mentoring of Ph.D. student, Dr. Yun-Kyung Lee who is currently a post-doc at National Institutes of Health, Bethesda, MD. Data generated from this project is used by the PI in her undergraduate Biochemistry class as examples of how "bench-side research can be extrapolated to bedside" and advance classroom knowledge of basic fundamentals and principles of biochemistry. PARTICIPANTS: Individuals - Dr. Pratibha Nerurkar (PI) Training - Ms. Yun-Kyung Lee graduate student (did not receive stipend from this project) TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our findings indicate that bitter melon prevents obesity-associated metabolic disorders such as diabetes and hyperlipidemia. Bitter melon is available through out the year in Hawaii and is a staple among ethnic minorities such as Filipinos. Functional foods such as bitter melon therefore will be readily acceptable among culturally sensitive population and will offer a cost-effective treatment or preventive strategy in developing nations.

Publications

  • Nerurkar PV*, Lee Y-K, Motosue M, Adeli K and Nerurkar VR. Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions. British J Nutri, 2008; 100: 751-759.
  • Invited Review Nerurkar PV* and Nerurkar VR. Is Sirt1 the magic target for diabetes Cell Science Reviews, 2008; 4: 50-56.
  • Invited Commentary Nerurkar PV* Cancer and Sirt1 regulation Cell Science Reviews, 2008; 4: 82-96.
  • Snee LS, Nerurkar VR, Dooley D, Efird J, Shovic A, Nerurkar PV*. Feasibility study to increase palatability and consumption of Momordica charantia (Bitter Melon). Appetite, Submitted Nov 2008, reviewed Feb 2009, to be submitted with revisions, March 2009.