라즈베리 케톤

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.

1. Food Chem Toxicol. 2014 Oct;72:13-9. doi: 10.1016/j.fct.2014.06.020. Epub 2014 Jul 2. Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosylt

The Combined Effects of Exercise, Diet, and a Multi-Ingredient Dietary Supplement on Body Composition and Adipokine Changes in Overweight Adults.

1. J Am Coll Nutr. 2018 Feb;37(2):111-120. doi: 10.1080/07315724.2017.1368039. Epub 2017 Nov 7. The Combined Effects of Exercise, Diet, and a Multi-Ingredient Dietary Supplement on Body Composition and Adipokine Changes in Overweight Adults. Arent SM(1), Walker AJ(1), Pellegrino JK(1), Sanders DJ(1), McFadden BA(1), Ziegenfuss TN(2), Lopez HL(2). Author information: (1)a Center for Health and Human Performance, Rutgers University , New Brunswick , New Jersey , USA. (2)b The Center for Applied Health Sciences , Stow , Ohio , USA. BACKGROUND: Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes. METHODS: Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] × 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2). RESULTS: Significant decreases in weight (-2.6 ± 0.57 kg, p < 0.001), fat mass (-1.8 ± 0.20 kg; p < 0.001), and percentage body fat (-3.7% ± 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 ± 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 ± 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (-10.7 ± 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group. CONCLUSIONS: Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism. DOI: 10.1080/07315724.2017.1368039 PMID: 29111889 [Indexed for MEDLINE]

Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.

2. Growth Horm IGF Res. 2008 Aug;18(4):335-44. doi: 10.1016/j.ghir.2008.01.005. Epub 2008 Mar 5. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Harada N(1), Okajima K, Narimatsu N, Kurihara H, Nakagata N. Author information: (1)Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity. DOI: 10.1016/j.ghir.2008.01.005 PMID: 18321745 [Indexed for MEDLINE]

Injectable cell-targeting fiber rods to promote lipolysis and regulate inflammation for obesity treatment.

1. Biomater Sci. 2023 Aug 8;11(16):5663-5673. doi: 10.1039/d3bm00619k. Injectable cell-targeting fiber rods to promote lipolysis and regulate inflammation for obesity treatment. Tao X(1)(2), Liu Y(2)(3), Ding Z(2), Xie S(1)(2), Cao W(1)(2), Li X(1)(2). Author information: (1)Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, P.R. China. xhli@swjtu.edu.cn. (2)Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P.R. China. (3)Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P.R. China. Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of HaRChr fiber rods loaded with chrysin and grafted with hyaluronic acid and AtsFRk fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs). The hyaluronic acid grafts double the uptake levels of HaRChr by M1 macrophages to promote phenotype transformation from M1 to M2 through upregulating CD206 and downregulating CD86 expressions. ATS-mediated targeting and sustained release of raspberry ketone from AtsFRk increase the secretion of glycerol and adiponectin, and Oil red O staining shows much fewer lipid droplets in adipocytes. The combination treatment with AtsFRk and the conditioned media from HaRChr-treated macrophages elevates adiponectin levels, suggesting that M2 macrophages may secrete anti-inflammatory factors to stimulate adipocytes to produce adiponectin. Diet-induced obese mice showed significant weight losses of inguinal (49.7%) and epididymal (32.5%) adipose tissues after HaRChr/AtsFRk treatment, but no effect was observed on food intake. HaRChr/AtsFRk treatment reduces adipocyte volumes, lowers serum levels of triglycerides and total cholesterol and restores adiponectin levels to those of normal mice. In the meantime, HaRChr/AtsFRk treatment significantly elevates the gene expression of adiponectin and interleukin-10 and downregulates tissue necrosis factor-α expression in the inguinal adipose tissues. Thus, local injection of cell-targeting fiber rods and fragments demonstrates a feasible and effective antiobesity strategy through improving lipid metabolism and normalizing the inflammatory microenvironment. DOI: 10.1039/d3bm00619k PMID: 37432672 [Indexed for MEDLINE]

Hepatoprotective effect of Raspberry ketone and white tea against acrylamide-induced toxicity in rats.

2. Drug Chem Toxicol. 2022 Mar;45(2):722-730. doi: 10.1080/01480545.2020.1772279. Epub 2020 Jun 1. Hepatoprotective effect of Raspberry ketone and white tea against acrylamide-induced toxicity in rats. Hamdy SM(1), El-Khayat Z(2), Farrag AR(3), Sayed ON(1), El-Sayed MM(1), Massoud D(4)(5). Author information: (1)Chemistry Department, Biochemistry Division, Faculty of Science, Fayoum University, Fayoum, Egypt. (2)Medical Biochemistry Department, Medical Division, National Research Centre Cairo, Cairo, Egypt. (3)Pathology Department, Medical Division, National Research Centre, Cairo, Egypt. (4)Department of Biology, College of Science, Jouf University, Sakakah, Saudi Arabia. (5)Department of Zoology, Faculty of Science, Fayoum University, Faiyum, Egypt. The current investigation was accomplished to evaluate the hepatoprotective effect of White tea and Raspberry Ketone against toxicity induced by acrylamide in rats. Sixty adult male rats were divided randomly into group (I) control; group (II) rats received RK with dose (6 mg/kg/day); Group III: rats received 5 ml of WT extract/kg/day; Group IV rats received AA (5 mg/kg/day); Group V: rats administrated with both AA (5 mg/kg/day) and RK (6 mg/kg/day) and Group VI: rats administrated AA (5 mg/kg/day) and 5 ml of WT extract/kg/day. The biochemical assays exhibited a significant increase in serum levels of Adiponectin, AST, ALT, ALP of the group treated with acrylamide if compared to the control group and an improvement in their levels of groups V and VI. The histopathological and immunohistochemical findings confirm the biochemical observations. In conclusion, the present investigation proved that the supplementation of WT and RK enhanced the liver histology, immunohistochemistry and biochemistry against the oxidative stress induced by acrylamide. DOI: 10.1080/01480545.2020.1772279 PMID: 32482111 [Indexed for MEDLINE]

Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet.

3. Nutr Res. 2019 Aug;68:19-33. doi: 10.1016/j.nutres.2019.05.005. Epub 2019 May 23. Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet. Kshatriya D(1), Li X(1), Giunta GM(2), Yuan B(3), Zhao D(3), Simon JE(3), Wu Q(3), Bello NT(4). Author information: (1)Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA; Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey New Brunswick, NJ, 08901, USA. (2)Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (3)New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (4)Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA; Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey New Brunswick, NJ, 08901, USA. Electronic address: ntbello@rutgers.edu. Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure. Copyright © 2019 Elsevier Inc. All rights reserved. DOI: 10.1016/j.nutres.2019.05.005 PMCID: PMC6823123 PMID: 31252376 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest The authors have no conflict of interests and declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Raspberry ketone preserved cholinergic activity and antioxidant defense in obesity induced Alzheimer disease in rats.

4. Biomed Pharmacother. 2018 Nov;107:1166-1174. doi: 10.1016/j.biopha.2018.08.034. Epub 2018 Aug 28. Raspberry ketone preserved cholinergic activity and antioxidant defense in obesity induced Alzheimer disease in rats. Mohamed HE(1), Abo-ELmatty DM(2), Mesbah NM(2), Saleh SM(2), Ali AA(3), Sakr AT(4). Author information: (1)Zagazig University, Department of Biochemistry, Faculty of Pharmacy, Egypt. (2)Suez Canal University, Department of Biochemistry, Faculty of Pharmacy, Egypt. (3)Zagazig University, Department of Pathology, Faculty of Veterinary Medicine, Egypt. (4)Ministry of Health, Zagazig, Sharkia, Egypt. Electronic address: amro.sakr@yahoo.com. Obesity is a proven risk factor for neurodegenerative disease like Alzheimer's disease (AD). Accumulating evidences suggested that nutritional interventions provide potential for prevention and treatment of AD. The present study aimed to investigate the effect of dietary treatment of obese rats with natural Raspberry ketone (RK) and their relationship with neurodegeneration. Obesity was first induced in 40 male Wistar rats (140-160 g) by feeding high fat diet (HFD) for 16 weeks. Obese rats were then assigned into 4 groups (n = 10 each). (O-AD) is obese induced AD group maintained on HFD for another 6 weeks. OCR is obese group received calorie restricted diet for 6 weeks. OCRRK is obese group received calorie restricted diet and RK (44 mg/kg body weight, daily, orally) for 6 weeks and OCRD is obese group received calorie restricted diet and orlistate (10 mg/kg body weight, daily orally) for 6 weeks. Another 10 normal rats received normal diet were used as normal control group (NC). Body weight, visceral white adipose tissue weight (WAT), lipid profile, oxidative stress markers, adiponectin, cholinergic activity and amyloid extracellular plaques were examined. In addition to histological changes in brain tissues were evaluated.Raspberry ketone (RK) via its antioxidant properties attenuated oxidative damage and dyslipidemia in O-AD group. It inhibited acetylcholinesterase enzyme (AchE) and hence increased acetylcholine level (Ach) in brain tissues of O-AD rats. It is also impeded the upregulation of beta-secretase-1 (BACE-1) and the accumulation of amyloid beta (Aβ) plaques which crucially involved in AD. The combination of CR diet with RK was more effective than CR diet with orlistate (antiobese drug) in abrogating the neurodegenerative changes induced by obesity. Results from this study suggested that concomitant supplementation of RK with calorie restricted regimen effectively modulate the neurodegenerative changes induced by obesity and delay the progression of AD. Copyright © 2018 Elsevier Masson SAS. All rights reserved. DOI: 10.1016/j.biopha.2018.08.034 PMID: 30257330 [Indexed for MEDLINE]

An optimized dose of raspberry ketones controls hyperlipidemia and insulin resistance in male obese rats: Effect on adipose tissue expression of adipocytokines and Aquaporin 7.

5. Eur J Pharmacol. 2018 Aug 5;832:81-89. doi: 10.1016/j.ejphar.2018.05.028. Epub 2018 May 19. An optimized dose of raspberry ketones controls hyperlipidemia and insulin resistance in male obese rats: Effect on adipose tissue expression of adipocytokines and Aquaporin 7. Mehanna ET(1), Barakat BM(2), ElSayed MH(3), Tawfik MK(4). Author information: (1)Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. (2)Department of Pharmacology & Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt; Department of Clinical Pharmacy, College of Clinical Pharmacy, Al-Baha University, Al-Baha, Saudi Arabia. (3)Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. (4)Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: dmon_kamal@yahoo.com. Obesity constitutes a major worldwide problem in which hyperlipidemia and insulin resistance represents adverse metabolic consequences of it. The present study was conducted to elucidate the role of raspberry ketones (RKs) in controlling body weight gain, hyperlipidemia and insulin resistance in male obese rats through affecting the expression of various adipocytokines. As Aquaporin-7 is co-related with the expression of various adipocytokines and has recently emerged as a modulator of adipocyte metabolism, the present study evaluated the effect of RKs on adipose tissue expression of aquaporin-7(AQP7) in high-fat (HF) diet-fed rats. Groups of male rats were assigned to normal, HF diet-fed control rats and RKs-treated (250 and 500 mg/kg) groups. RKs administration effectively abrogated hyperlipidemia and oxidative burden and enhanced insulin sensitivity. In addition, treatment with RKs ameliorated adipose tissue and liver indices and the reduced adipocyte diameters. Moreover, administration of the low dose of RKs ameliorated the expression of apelin and its receptor, and visfatin with upregulating adiponectin expression compared to HF diet control rats. However, both doses effectively downregulated leptin expression. It was obvious that both RKs doses revealed effectiveness in upregulating the AQP7 expression. The present data suggest the promising therapeutic role of RKs in HF diet-induced obesity that is likely attributable, at least in part, to upregulation of AQP7 expression. Copyright © 2018 Elsevier B.V. All rights reserved. DOI: 10.1016/j.ejphar.2018.05.028 PMID: 29787773 [Indexed for MEDLINE]

Raspberry ketone fails to reduce adiposity beyond decreasing food intake in C57BL/6 mice fed a high-fat diet.

6. Food Funct. 2017 Apr 19;8(4):1512-1518. doi: 10.1039/c6fo01831a. Raspberry ketone fails to reduce adiposity beyond decreasing food intake in C57BL/6 mice fed a high-fat diet. Cotten BM(1), Diamond SA, Banh T, Hsiao YH, Cole RM, Li J, Simons CT, Bruno RS, Belury MA, Vodovotz Y. Author information: (1)Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, 1787 Neil Avenue, Columbus, OH 43210, USA. belury.1@osu.edu. As the incidence of obesity continues to increase, identifying novel nutritional therapies to enhance weight loss are needed. Raspberry ketone (RK; 4-(4-hydroxyphenyl) butan-2-one) is a bioactive phytochemical that is marketed as a weight loss supplement in the United States, yet there is scant scientific evidence demonstrating that RK promotes weight loss. The aim of the current study was to investigate the effect of RK on accumulation of adipose mass, hepatic lipid storage, and levels of plasma adiponectin in mice fed a high-fat (HF) diet. Mice were individually housed and fed a HF control diet (45% kcal from fat) for two weeks to induce weight gain, then assigned to HF control, high-dose (1.74% wt/wt) raspberry ketone (HRK), low-dose (0.25% wt/wt) raspberry ketone (LRK), or a pair-fed group (PF) fed similar food intake to LRK mice. Following five weeks of feeding, mice fed LRK and HRK diets showed reduced food intake and body weight compared to mice maintained on control diet. When normalized to body weight, mice fed HRK diet exhibited decreased inguinal fat mass and increased liver mass compared to the control group. Hepatic steatosis was lowest in mice fed HRK diet, whereas LRK diet did not have an effect when compared to the PF group. Plasma adiponectin concentration was unaffected by RK and pair-feeding. Our findings demonstrate that RK supplementation has limited benefit to adipose loss beyond reducing energy intake in mice fed a high-fat diet. The present study supports the need for appropriate study design when validating weight-loss supplements. DOI: 10.1039/c6fo01831a PMID: 28378858 [Indexed for MEDLINE]

Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women.

7. J Int Soc Sports Nutr. 2013 Apr 19;10(1):22. doi: 10.1186/1550-2783-10-22. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women. Lopez HL(1), Ziegenfuss TN, Hofheins JE, Habowski SM, Arent SM, Weir JP, Ferrando AA. Author information: (1)The Center for Applied Health Sciences, 4302 Allen Road, STE 120, Stow, OH, 44224, USA. hl@appliedhealthsciences.org. BACKGROUND: Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy. OBJECTIVE: To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program. METHODS: Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure. RESULTS: Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P < 0.01), fat mass (METABO -7.8 vs. placebo -2.8%, P < 0.001), lean mass (METABO +3.4% vs. placebo +0.8%, P < 0.03), waist girth (METABO -2.0% vs. placebo -0.2%, P < 0.0007), hip girth (METABO -1.7% vs. placebo -0.4%, P < 0.003), and energy levels per anchored visual analogue scale (VAS) (METABO +29.3% vs. placebo +5.1%, P < 0.04). During the first 4 weeks, effects/trends for maintaining elevated serum leptin (P < 0.03) and decreased serum resistin (P < 0.08) in the METABO group vs. placebo were also observed. No changes in systemic hemodynamics, clinical blood chemistries, adverse events, or dietary intake were noted between groups. CONCLUSIONS: METABO administration is a safe and effective adjunct to an eight-week diet and exercise weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in placebo. Ongoing studies to confirm these results and clarify the mechanisms (i.e., biochemical and neuroendocrine mediators) by which METABO exerts the observed salutary effects are being conducted. DOI: 10.1186/1550-2783-10-22 PMCID: PMC3639826 PMID: 23601452

Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes.

8. Planta Med. 2010 Oct;76(15):1654-8. doi: 10.1055/s-0030-1249860. Epub 2010 Apr 27. Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Park KS(1). Author information: (1)Nutrition & Functional Food Research Team, Korea Food & Drug Administration, Seoul, Korea. parkks71@kfda.go.kr Raspberry ketone (RK) is a natural phenolic compound of the red raspberry. The dietary administration of RK to male mice has been reported to prevent high-fat diet-induced elevation in body weight and to increase lipolysis in white adipocytes. To elucidate a possible mechanism for the antiobesity action of RK, its effects on the expression and the secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 were investigated. Treatment with 10 µM of RK increased lipolysis significantly in differentiated 3T3-L1 cells. An immunoassay showed that RK increased both the expression and the secretion of adiponectin, an adipocytokine mainly expressed and secreted by adipose tissue. In addition, treatment with 10 µM of RK increased the fatty acid oxidation and suppressed lipid accumulation in 3T3-L1 adipocytes. These findings suggest that RK holds great promise as an herbal medicine since its biological activities alter the lipid metabolism in 3T3-L1 adipocytes. © Georg Thieme Verlag KG Stuttgart · New York. DOI: 10.1055/s-0030-1249860 PMID: 20425690 [Indexed for MEDLINE]

High-titer de novo raspberry ketone production in Yarrowia lipolytica via precursor supply engineering and fed-batch fermentation optimization.

9. Bioresour Technol. 2026 May;447:134232. doi: 10.1016/j.biortech.2026.134232. Epub 2026 Feb 15. High-titer de novo raspberry ketone production in Yarrowia lipolytica via precursor supply engineering and fed-batch fermentation optimization. Li Y(1), Niu S(1), Wang Z(1), Wang Y(1), Zhang X(1), Deng Y(1), Zhou S(2). Author information: (1)School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Synthetic Biology of Jiangsu Province, Jiangnan University, Wuxi 214122, China. (2)School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Synthetic Biology of Jiangsu Province, Jiangnan University, Wuxi 214122, China. Electronic address: zhoush@jiangnan.edu.cn. Raspberry ketone (RK) is a high-value aroma compound, yet de novo microbial production is constrained by an imbalanced supply of l-tyrosine and malonyl-CoA. Here, Yarrowia lipolytica was engineered for high-titer RK biosynthesis from glucose. A multi-copy RK pathway was integrated into the 26S rDNA locus. Deregulating and strengthening the shikimate pathway increased l-tyrosine formation, while reinforcing the pentose phosphate pathway and improving the conversion of L-tyrosine to p-coumaric acid (PCA) enhanced the supply of erythrose 4-phosphate, NADPH, and PCA, thereby alleviating l-tyrosine accumulation. To relieve malonyl-CoA limitation, we strengthened β-oxidation, introduced a non-carboxylative malonyl-CoA route, and reduced neutral lipid storage, improving RK production by 1.49-fold. In a 5-L fed-batch process optimized for carbon feeding, initial medium, and nitrogen supplementation, RK reached 7.24 g/L, representing a 42.5-fold improvement over the initial shake-flask strain and, based on published studies to date, the highest reported de novo RK titer in microbial fermentation. Copyright © 2026 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.biortech.2026.134232 PMID: 41702516 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Hepatoprotective activity of raspberry ketone against streptozotocin-induced type 2 diabetes in male rats.

10. PLoS One. 2025 Jun 9;20(6):e0324940. doi: 10.1371/journal.pone.0324940. eCollection 2025. Hepatoprotective activity of raspberry ketone against streptozotocin-induced type 2 diabetes in male rats. Fouad D(1), Elnagar DM(1), Eid G(1), Shuker E(1). Author information: (1)Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia. Type 1 diabetes encompasses a spectrum of metabolic disorders marked by insulin deficiency, resulting in elevated blood glucose levels, commonly referred to as hyperglycemia. This persistent condition often precipitates lipid profile abnormalities, causing cholesterol alterations, low-and high-density lipoproteins, and triglycerides. The liver is particularly vulnerable to increased oxidative stress and inflammatory responses, which activate the transcription of pro-apoptotic genes and ultimately contribute to hepatocyte damage. This study analyzed the potential therapeutic role of raspberry ketone (RK), a natural antioxidant with antiapoptotic and anti-inflammatory properties, in male albino rats with induced type 2 diabetes. Fifty rats were equally divided into five groups: control, rats orally administered 200 mg /kg Body Weight (BW) RK for 5 days, diabetic rats intramuscularly injected once with 60 mg/kg BW streptozotocin, streptozotocin-induced diabetic rats orally administered 200 mg/kg BW RK for 5 days, and streptozotocin-induced diabetic rats orally administered 100 mg/kg metformin. Streptozotocin treatment significantly affected blood biochemical parameters, lipid profiles, oxidative stress markers, immunotoxicity biomarkers, and DNA damage biomarkers. Conversely, RK efficiently ameliorated the toxic effects of streptozotocin on the liver by reducing the pathological and biochemical changes associated with diabetes through its antioxidant and anti-inflammatory properties. Therefore, incorporating RK into the diet of diabetic patients can help prevent hepatocyte damage associated with diabetes. In conclusion, oral administration of RK exerts hepatoprotective effects by offering antioxidant, antiapoptotic, and anti-inflammatory properties against streptozotocin-induced type 1 diabetes in male rats. Copyright: © 2025 Fouad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.1371/journal.pone.0324940 PMCID: PMC12148097 PMID: 40489503 [Indexed for MEDLINE] Conflict of interest statement: The authors have declared that no competing interests exist.

Ameliorative Effect of Raspberry Ketone on Hypothalamic Inflammation in High Fat Diet-Induced Obese Mice.

11. J Nutr Sci Vitaminol (Tokyo). 2024;70(6):496-502. doi: 10.3177/jnsv.70.496. Ameliorative Effect of Raspberry Ketone on Hypothalamic Inflammation in High Fat Diet-Induced Obese Mice. Yao Z(1), Zhu Z(2)(3), Chen X(2), Li X(2)(3)(4)(5). Author information: (1)College of Health Industry, Sichuan Tourism University. (2)Key Laboratory of Sichuan Cuisine Artificial Intelligence, Sichuan Tourism University. (3)Cuisine Science Key Laboratory of Sichuan Province, Sichuan Tourism University. (4)College of Culinary, Sichuan Tourism University. (5)State Key Laboratory of Food Science and Resource, Nanchang University. This study aimed to investigate the regulatory effects of raspberry ketone on hypothalamic inflammation and its mechanism. Mouse microglia cells (BV2 cells) were cultured in vitro with palmitic acid (100 μM) to induce inflammation model and then incubated with raspberry ketone (5, 20, 50 μM) alone or raspberry ketone (50 μM) and the specific inhibitor of uncoupling protein 2 (UCP2), genipin (10 μM), to test the role of UCP2 in raspberry ketone regulatory of inflammation. Meanwhile, C57BL/6J mice were fed a high-fat diet containing raspberry ketone (0.2%, wt/wt) for 16 wk or 7 d to observe the effects of raspberry ketone on the body weights and hypothalamic inflammation of mice. The expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1beta (IL-1β) and tumour necrosis factor alpha (TNF-α), were detected using RT-qPCR, Elisa, and Western blotting, respectively. At the cellular level, raspberry ketone reduced the content of inflammatory factors in BV2 cells and in the cell culture medium. Genipin inhibited the anti-inflammatory effect of raspberry ketone on BV2 cells. At the animal level, after 16 wk of feeding, raspberry ketone-containing diets significantly reduced the body weight of mice, but had no significant effect on the mRNA expression level of hypothalamic inflammatory factors. On the other hand, 7 d of raspberry ketone gavage significantly reduced mRNA and protein expression of hypothalamic inflammatory factors. The results of this study suggest that raspberry ketone could regulate high-fat diet-induced obesity in mice, and the specific mechanism may be to inhibit hypothalamic inflammation in mice by regulating UCP2 gene expression. DOI: 10.3177/jnsv.70.496 PMID: 39756970 [Indexed for MEDLINE]

Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase/sphingosine-1-phosphate and toll-like receptor 4 pathways.

12. J Pharm Pharmacol. 2023 Jul 5;75(7):985-994. doi: 10.1093/jpp/rgad044. Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase/sphingosine-1-phosphate and toll-like receptor 4 pathways. Abdelraheem KM(1), Younis NN(2), Shaheen MA(3), Elswefy SE(2)(4), Ali SI(2). Author information: (1)Biochemistry Department, Faculty of Pharmacy, Sinai University - Qantara Branch, Ismailia, Egypt. (2)Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. (3)Histology and Cell Biology Department, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt. (4)Biochemistry Department, Faculty of Pharmacy, Delta University for Sciences and Technology, Gamasa, Egypt. OBJECTIVES: To investigate the therapeutic role of calorie-restricted diet (CR) and raspberry ketone (RK) in non-alcoholic fatty liver disease (NAFLD) and the implication of sphingosine kinase-1 (SphK1)/sphingosine-1-phosphate (S1P) and toll-like receptor 4 (TLR4) signalling. METHODS: NAFLD was induced by feeding rats high-fat-fructose-diet (HFFD) for 6 weeks. Rats were then randomly assigned to three groups (n = 6 each); NAFLD group continued on HFFD for another 8 weeks. CR group was switched to CR diet (25% calorie restriction) for 8 weeks and RK group was switched to normal diet and received RK (55 mg/kg/day; orally) for 8 weeks. Another six rats were used as normal control. KEY FINDINGS: HFFD induced a state of NAFLD indicated by increased fat deposition in liver tissue along with dyslipidemia, elevated liver enzymes, oxidative stress and inflammation. Either CR diet or RK reversed these changes and decreased HFFD-induced elevation of hepatic SphK1, S1P, S1PR1 and TLR4. Of notice, RK along with a normal calorie diet was even better than CR alone in most studied parameters. CONCLUSIONS: SphK1/S1P and TLR4 are interconnected and related to the establishment of HFFD-induced NAFLD and can be modulated by RK. Supplementation of RK without calorie restriction to patients with NAFLD unable to follow CR diet to achieve their treatment goals would be a promising therapeutic modality. © The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/jpp/rgad044 PMID: 37167472 [Indexed for MEDLINE]

The combined effect of Raspberry Ketone with Resveratrol against oxidative stress and steatohepatitis in rats: Pharmacokinetic and pharmacodynamic studies.

13. J Biochem Mol Toxicol. 2023 Jun;37(6):e23336. doi: 10.1002/jbt.23336. Epub 2023 Apr 3. The combined effect of Raspberry Ketone with Resveratrol against oxidative stress and steatohepatitis in rats: Pharmacokinetic and pharmacodynamic studies. Verma S(1)(2), Goand UK(1)(2), Rathaur S(1), Garg R(1)(2), Katekar R(1)(2), Gayen JR(1)(2)(3). Author information: (1)Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, India. (2)Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. (3)Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India. Raspberry Ketone (RK) and Resveratrol (RSV) are natural phenolic antioxidants and anti-inflammatory agents. However, its combined pharmacokinetic and pharmacodynamics potentials are not reported. The study aims to assess the combined effect of RK with RSV to protect rats from carbon-tetrachloride (CCl4) induced oxidative stress and NASH. The toxicant CCl4 was employed at a concentration of 1 mL/kg as a 1:1 (v/v) mixture with olive oil twice weekly for 6 weeks to induce liver toxicity. Animal treatment was followed for 2 weeks. Silymarin was used as a standard control drug to compare the hepatoprotective effect of RK and RSV. Hepatic histology, oxidative stress, MMP, reduced glutathione (GSH), plasma levels of SGOT, SGPT, and lipid profile (total cholesterol and triglycerides) were measured. Anti-inflammation genes (IL-10), and fibrotic genes (TGF-β) were also examined in liver tissue. Oral administration of combined RK with RSV (50 + 50 mg/kg for 2 weeks) showed significantly more hepatoprotection by significantly decreasing elevated plasma markers and lipid profile than alone RK and RSV (100 mg/kg daily for 2 weeks). It also significantly alleviated the hepatic lipid peroxidation, restoring the activities of GSH levels in the liver. RT-PCR and Immunoblotting studies confirmed that significantly upregulation of anti-inflammation genes and protein expression (MMP-9) ameliorated the disease. Pharmacokinetic studies confirmed more synergistic stability in simulated gastric-intestinal fluids (FaSSGF, FaSSIF) and rat liver microsomes (CYP-450, NADPH oxidation & glucuronidation. Moreover, coadministration of drugs augmented the relative bioavailability, Vd/ F (L/Kg), and MRT0-∞( h), which leads to more efficacy. This pharmacokinetic and pharmacodynamic reveals a new adjuvant therapy for the treatment of steatohepatitis. © 2023 Wiley Periodicals LLC. DOI: 10.1002/jbt.23336 PMID: 37009719 [Indexed for MEDLINE]

Rhododendrol, a reductive metabolite of raspberry ketone, suppresses the differentiation of 3T3‑L1 cells into adipocytes.

14. Mol Med Rep. 2023 Feb;27(2):51. doi: 10.3892/mmr.2023.12938. Epub 2023 Jan 12. Rhododendrol, a reductive metabolite of raspberry ketone, suppresses the differentiation of 3T3‑L1 cells into adipocytes. Uramaru N(1), Kawashima A(1), Osabe M(1), Higuchi T(1). Author information: (1)Division of Pharmaceutical Health Biosciences, Nihon Pharmaceutical University, Saitama 362‑0806, Japan. Obesity is a serious medical condition worldwide, and a major risk factor for type 2 diabetes, metabolic syndrome, cancer and cardiovascular disease. In addition to changes in dietary habits and physical activity, consuming supplements to maintain good health and prevent obesity is important in modern society. Raspberry ketone (RK) is a natural phenolic ketone found in the European red raspberry (Rubus idaeus L.) and is hypothesized to prevent obesity when administered orally. The present study found that RK was reduced to rhododendrol (ROH) in human liver microsomes and cytosol. The present study investigated whether the metabolite ROH had anti‑adipogenic effects using mouse 3T3‑L1 cells. The effects of ROH or RK on lipid accumulation during differentiation of 3T3‑L1 pre‑adipocyte into adipocyte were determined using Oil Red O staining. CCAAT enhancer‑binding protein α (C/EBPα) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were examined using reverse transcription‑quantitative PCR and western blotting analysis, respectively. The present study revealed that ROH suppressed lipid accumulation in the cells, similar to RK. In addition, ROH suppressed the mRNA expression levels of C/EBPα and PPARγ in 3T3‑L1 adipocytes. Furthermore, ROH suppressed PPARγ protein expression in 3T3‑L1 adipocytes. These findings suggested that ROH is an active metabolite with an anti‑adipogenic effect, which may contribute to the anti‑obesity effect of orally administered RK. The present study indicated that it is important to understand the biological activity of the metabolites of orally administered compounds. DOI: 10.3892/mmr.2023.12938 PMCID: PMC9879071 PMID: 36633126 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.

Metabolic gene signature in white adipose tissue of oral doses raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] that prevent diet-induced weight gain and induce loss of righting reflex.

15. Food Chem Toxicol. 2023 Jan;171:113540. doi: 10.1016/j.fct.2022.113540. Epub 2022 Nov 30. Metabolic gene signature in white adipose tissue of oral doses raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] that prevent diet-induced weight gain and induce loss of righting reflex. Kshatriya D(1), Hao L(2), Bello NT(3). Author information: (1)Department of Animal Sciences, Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (2)Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (3)Department of Animal Sciences, Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. Electronic address: ntbello@rutgers.edu. Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a synthetic flavoring agent and dietary supplement for weight control. This study investigated the metabolic signature of oral doses of RK that prevent weight gain or promote loss of righting reflex (LORR) in C57Bl/6J mice. Daily RK 200 mg/kg prevented high-fat diet (HFD; 45% Kcal fat) fed weight gain (∼8% reduction) over 35 days. RNA-seq of inguinal white adipose tissue (WAT) performed in males revealed 12 differentially expressed genes. Apelin (Apln) and potassium voltage-gated channel subfamily C member (Kcnc3) expression were elevated with HFD and normalized with RK dosing, which was confirmed by qPCR. Acute RK 640 mg/kg produced a LORR with a <5 min onset with a >30 min duration. Acute RK 200 mg/kg increased gene expression of Apln, Kcnc3, and nuclear factor erythroid 2-related factor 2 (Nrf2), but reduced acetyl-COA carboxylase (Acc1) and NAD(P)H quinone dehydrogenase 1 (Nqo1) in inguinal WAT. Acute RK 640 mg/kg elevated interleukin 6 (Il 6) and heme oxygenase 1 (Hmox1) expression, but reduced Nrf2 in inguinal and epididymal WAT. Our findings suggest that RK has a dose-dependent metabolic signature in WAT associated with either weight control or LORR. Copyright © 2022 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.fct.2022.113540 PMCID: PMC9793719 PMID: 36460224 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Raspberry ketone promotes FNDC5 protein expression via HO-1 upregulation in 3T3-L1 adipocytes.

16. Chin J Physiol. 2022 Mar-Apr;65(2):80-86. doi: 10.4103/cjp.cjp_95_21. Raspberry ketone promotes FNDC5 protein expression via HO-1 upregulation in 3T3-L1 adipocytes. Tsai YC(1), Chen JH(2), Lee YM(3), Yen MH(3), Cheng PY(2). Author information: (1)Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan; Department of Medicine, Taipei Medical University, Taipei; Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. (2)Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan. (3)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. Obesity is a global health problem and a risk factor for cardiovascular diseases and cancers. Exercise is an effective intervention to combat obesity. Fibronectin type III domain containing protein 5 (FNDC5)/irisin, a myokine, can stimulate the browning of white adipose tissue by increasing uncoupling protein 1 (UCP1) expression, and therefore may represent a link between the beneficial effects of exercise and improvement in metabolic diseases. Thus, upregulating the endogenous expression of FNDC5/irisin by administering medication would be a good approach for treating obesity. Herein, we evaluated the efficacy of raspberry ketone (RK) in inducing FNDC5/irisin expression and the underlying mechanisms. The expression of brown fat-specific proteins (PR domain containing 16 (PRDM16), CD137, and UCP1), heme oxygenase-1 (HO-1), FNDC5, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in differentiated 3T3-L1 adipocyte was analyzed by western blotting or immunofluorescence. The level of irisin in the culture medium was also assayed using an enzyme-linked immunosorbent assay kit. Results showed that RK (50 μM) significantly induced the upregulation of FNDC5 protein in differentiated 3T3-L1 adipocytes; however, the irisin level in the culture media was unaffected. Moreover, RK significantly increased the levels of PGC1α, brown adipocyte markers (PRDM16, CD137, and UCP1), and HO-1. Furthermore, the upregulation of PGC1α and FNDC5 and the browning effect induced by RK were significantly reduced by SnPP or FNDC5 siRNA, respectively. In conclusion, RK can induce FNDC5 protein expression via the HO-1 signaling pathway, and this study provides new evidence for the potential use of RK in the treatment of obesity. DOI: 10.4103/cjp.cjp_95_21 PMID: 35488673 [Indexed for MEDLINE] Conflict of interest statement: None

Potential metabolic activities of raspberry ketone.

17. J Food Biochem. 2022 Jan;46(1):e14018. doi: 10.1111/jfbc.14018. Epub 2021 Dec 16. Potential metabolic activities of raspberry ketone. Li X(1), Wei T(1), Wu M(1), Chen F(1)(2), Zhang P(1), Deng ZY(1), Luo T(1). Author information: (1)State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China. (2)School of Public Health, Nanchang University, Nanchang, China. Novel food and food compounds interventions have attracted a lot of attention nowadays for the prevention and treatment of metabolic diseases. Raspberry ketone (RK) is aromatic compound found within red fruits and berries, has been used as an over-the-counter product for weight loss. However, actually, the effect of RK on weight loss is still controversial, and the mechanism is largely unknown. Besides, in vivo and in vitro studies have demonstrated the beneficial effect of RK on the development of other metabolic diseases. In this review, we comprehensively highlighted the synthesis, bioavailability, and metabolism of RK, and summarized the progress made in our understanding of the potential biological activities of RK, including antiobesity, antidiabetes, cardioprotection, and hepatoprotection, as well as their underlying mechanisms. This paper provides a critical overview about the current findings and proposes the future studies in the area of RK on human health. PRACTICAL APPLICATIONS: Raspberry ketone (RK) has been used for weight control for years, but this effect is controversial considering food intake. Additionally, RK is beneficial for T2DM, liver and heart injury. The underlying mechanisms of the protective effect of RK including accelerating fatty acid oxidation, balancing serum glucose level, anti-inflammation, antioxidant process, and so on. In this context, we provide a comprehensive analysis of the benefits of RK against many metabolic diseases and discuss the underlying molecular mechanisms. We hope our work will be helpful for further researches on RK and improve its public recognition. © 2021 Wiley Periodicals LLC. DOI: 10.1111/jfbc.14018 PMID: 34913499 [Indexed for MEDLINE]

Influence of Diet-Induced Obesity on the Bioavailability and Metabolism of Raspberry Ketone (4-(4-Hydroxyphenyl)-2-Butanone) in Mice.

18. Mol Nutr Food Res. 2020 Apr;64(8):e1900907. doi: 10.1002/mnfr.201900907. Epub 2020 Feb 25. Influence of Diet-Induced Obesity on the Bioavailability and Metabolism of Raspberry Ketone (4-(4-Hydroxyphenyl)-2-Butanone) in Mice. Zhao D(1)(2), Yuan B(1)(3), Kshatriya D(4)(5), Polyak A(1), Simon JE(1)(2), Bello NT(4)(2)(5), Wu Q(1)(2)(3). Author information: (1)New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, School of Environmental and Biological Sciences , Rutgers University, New Brunswick, NJ, 08901, USA. (2)New Jersey Institute for Food, Nutrition and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (3)Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ, 08901, USA. (4)Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. (5)Nutritional Sciences Graduate Program, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. OBJECTIVES: Raspberry ketone (RK) is the primary aroma compound in red raspberries and a dietary supplement for weight loss. This work aims to 1) compare RK bioavailability in male versus female, normal-weight versus obese mice; 2) characterize RK metabolic pathways. METHODS: Study 1: C57BL/6J male and female mice fed a low-fat diet (LFD; 10% fat) receive a single oral gavage dose of RK (200 mg kg-1 ). Blood, brain, and white adipose tissue (WAT) are collected over 12 h. Study 2: Male mice are fed a LFD or high-fat diet (45% fat) for 8 weeks before RK dosing. Samples collected are analyzed by UPLC-MS/MS for RK and its metabolites. RESULTS: RK is rapidly absorbed (Tmax  ≈ 15 min), and bioconverted into diverse metabolites in mice. Total bioavailability (AUC0-12 h ) is slightly lower in females than males (566 vs 675 nmol mL-1 min-1 ). Total bioavailability in obese mice is almost doubled that of control mice (1197 vs 679 nmol mL-1 min-1 ), while peaking times and elimination half-lives are delayed. Higher levels of RK and major metabolites are found in WAT of the obese than normal-weight animals. CONCLUSIONS: RK is highly bioavailable, rapidly metabolized, and exhibits significantly different pharmacokinetic behaviors between obese and control mice. Lipid-rich tissues, especially WAT, can be a direct target of RK. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. DOI: 10.1002/mnfr.201900907 PMCID: PMC7329366 PMID: 32052560 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest The authors declare no conflict of interest.

Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet.

19. Biomed Pharmacother. 2019 Feb;110:500-509. doi: 10.1016/j.biopha.2018.11.079. Epub 2018 Dec 7. Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet. Attia RT(1), Abdel-Mottaleb Y(2), Abdallah DM(3), El-Abhar HS(4), El-Maraghy NN(2). Author information: (1)Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), 11835, Cairo, Egypt. Electronic address: reem.tarek@fue.edu.eg. (2)Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), 11835, Cairo, Egypt. (3)Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 12613 Cairo, Egypt. (4)Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), 11835, Cairo, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 12613 Cairo, Egypt. AIM: Obesity is a continually growing pandemic leading to many diseases that affect the overall quality of life. The widely marketed Garcinia cambogia (GC) and Raspberry ketone (RK) were used in this study. Despite their known dietetic effect, however, the metabolomic/signaling pathways involved in this effect are not fully elucidated. Hence, our study comprehends the possible trajectories of their combination against obesity and insulin resistance in addition to exploring their combination merit. MATERIALS AND METHODS: Adult male Wistar rats were divided into 5 groups; viz., normal diet (ND), high fat fructose diet (HFFD), HFFD+GC (600mg/kg), HFFD+RK (55mg/kg) and HFFD+GC+RK. To assess our aim, we determined their effect on body weight, IPGTT, glucose homeostasis (glucose, insulin, HOMA IR), lipid profile parameters and SREBP-1c, oxidative stress markers, insulin and leptin signaling pathways (p-IRS-1/p-AKT/GLUT-4, and leptin/STAT-3), as well as liver and adipose tissue histopathology. RESULTS: GC/RK combinationcaused weight loss, corrected the disturbed glucose and insulin homeostasis, raised serum levels of HDL anddecreased all other lipid profile parameters. They also increased Nrf-2 expression, ad GSH, as well as p-IRS-1/p-Akt/GLUT-4 cue, while they decreased MDA, leptin/STAT-3 and SREBP-1c content compared to the HFFD group. Furthermore, the GC/RK combination abolished apoptosis, fatty changes and inflammation in hepatocytes and decreased sclerotic blood vessels and congestion in adipose tissue. CONCLUSION: Our study highlights the involvement ofp-IRS-1/p-Akt/GLUT-4, leptin/STAT-3 and SREBP-1c signaling trajectories in the beneficial combination of GC and RK, besides, the efficient rebalance of the redox status, insulin resistance and tissue fat deposition confirmed histopathologically. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved. DOI: 10.1016/j.biopha.2018.11.079 PMID: 30530230 [Indexed for MEDLINE]

Suppression of isoproterenol-induced cardiotoxicity in rats by raspberry ketone via activation of peroxisome proliferator activated receptor-α.

20. Eur J Pharmacol. 2019 Jan 5;842:157-166. doi: 10.1016/j.ejphar.2018.10.034. Epub 2018 Oct 26. Suppression of isoproterenol-induced cardiotoxicity in rats by raspberry ketone via activation of peroxisome proliferator activated receptor-α. Khan V(1), Sharma S(1), Bhandari U(1), Sharma N(2), Rishi V(2), Haque SE(3). Author information: (1)Department of Pharmacology, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India. (2)National Agri-Food Biotechnology Institute, SAS Nagar, Punjab 140306, India. (3)Department of Pharmacology, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address: sehaq@jamiahamdard.ac.in. The peroxisome proliferator-activated receptor-α (PPAR-α) controls the lipid and glucose metabolism and also affects inflammation, cell proliferation and apoptosis during cardiovascular disease. Raspberry ketone (RK) is a red raspberry (Rubusidaeus, Family-Rosaceae) plant constituent, which activates PPAR-α. This study was conducted to assess the cardioprotective action of RK against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups (six rats/group). Rats were orally administered with RK (50, 100 and 200 mg/kg, respectively) and fenofibrate (standard, 80 mg/kg) for 28 days and ISO was administered (85 mg/kg, subcutaneously) on 27th and 28th day. Administration of ISO in rats significantly altered hemodynamic and electrocardiogram patterns, total antioxidant capacity, PPAR-α, and apolipoprotein C-III levels. These myocardial aberrations were further confirmed during infarct size, heart weight to body weight ratio and immunohistochemical assessments (caspase-3 and nuclear factor-κB). RK pretreatment (100 and 200 mg/kg) significantly protected rats against oxidative stress, inflammation, and dyslipidemia caused by ISO as demonstrated by change in hemodynamic, biochemical and histological parameters. The results so obtained were quite comparable with fenofibrate. Moreover, RK was found to have binding affinity with PPAR-α, as confirmed by docking analysis. PPAR-α expression and concentration was also found increased in presence of RK which gave impression that RK probably showed cardioprotection via PPAR-α activation, however direct binding study of RK with PPAR-α is needed to confirm this assumption. Copyright © 2018 Elsevier B.V. All rights reserved. DOI: 10.1016/j.ejphar.2018.10.034 PMID: 30431010 [Indexed for MEDLINE]

Raspberry ketone induces brown-like adipocyte formation through suppression of autophagy in adipocytes and adipose tissue.

21. J Nutr Biochem. 2018 Jun;56:116-125. doi: 10.1016/j.jnutbio.2018.01.017. Epub 2018 Feb 13. Raspberry ketone induces brown-like adipocyte formation through suppression of autophagy in adipocytes and adipose tissue. Leu SY(1), Tsai YC(2), Chen WC(3), Hsu CH(4), Lee YM(5), Cheng PY(6). Author information: (1)Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. (2)Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan; Department of Medicine, Taipei Medical University, Taipei; Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. (3)Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan. (4)Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. (5)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. (6)Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan. Electronic address: pycheng@mail.ndmctsgh.edu.tw. Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase). RK significantly reduced the expression of the autophagy-related protein Atg12 and increased the expression of p62 and heme oxygenase 1 (HO-1). Additionally, these effects of RK were reversed by the HO-1 inhibitor SnPP (20 μM). In addition, RK (160 mg/kg, gavage, for 8 weeks) significantly reduced body weight gain (Ovx+RK, 191.8 ± 4.6 g vs. Ovx, 223.6 ± 5.9; P < .05), food intake, the amount of inguinal adipose tissue (Ovx+RK, 9.05 ± 1.1 g vs Ovx, 12.9 ± 0.92 g; P < .05) and the size of white adipocytes in Ovx rats. Moreover, compared to expression in the Ovx group, the levels of browning-specific proteins were significantly higher and the levels of autophagy-related proteins were significantly lower in the Ovx+RK group. Therefore, this study elucidated the mechanism associated with RK-induced WAT browning and thus provides evidence to support the clinical use of RK for obesity treatment. Copyright © 2018. Published by Elsevier Inc. DOI: 10.1016/j.jnutbio.2018.01.017 PMID: 29525531 [Indexed for MEDLINE]

Raspberry Ketone Reduced Lipid Accumulation in 3T3-L1 Cells and Ovariectomy-Induced Obesity in Wistar Rats by Regulating Autophagy Mechanisms.

22. J Agric Food Chem. 2017 Dec 20;65(50):10907-10914. doi: 10.1021/acs.jafc.7b03831. Epub 2017 Dec 11. Raspberry Ketone Reduced Lipid Accumulation in 3T3-L1 Cells and Ovariectomy-Induced Obesity in Wistar Rats by Regulating Autophagy Mechanisms. Leu SY(1), Chen YC(2), Tsai YC(3)(4)(5), Hung YW(6), Hsu CH(7), Lee YM(8), Cheng PY(2). Author information: (1)Graduate Institute of Life Sciences, National Defense Medical Center , 114 Taipei, Taiwan. (2)Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center , 114 Taipei, Taiwan. (3)Department of Obstetrics and Gynecology, Chi-Mei Medical Center , Tainan, Taiwan. (4)Department of Medicine, Taipei Medical University , 11031 Taipei, Taiwan. (5)Department of Sport Management, Chia Nan University of Pharmacy and Science , 71710 Tainan, Taiwan. (6)Institute of Preventive Medicine, National Defense Medical Center , Taipei, Taiwan. (7)Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center , 114 Taipei, Taiwan. (8)Department of Pharmacology, National Defense Medical Center , 114 Taipei, Taiwan. This study aimed to determine the antiobesity effects of raspberry ketone (RK), one of the major aromatic compounds contained in raspberry, and its underlying mechanisms. During adipogenesis of 3T3-L1 cells, RK (300 μM) significantly reduced lipid accumulation and downregulated the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferation-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS). RK also reduced the expression of light chain 3B (LC3B), autophagy-related protein 12 (Atg12), sirtuin 1 (SIRT1), and phosphorylated-tuberous sclerosis complex 2 (TSC2), whereas it increased the level of p62 and phosphorylated-mammalian target of rapamycin (mTOR). Daily administration of RK decreased the body weight (ovariectomy [Ovx] + RK, 352.6 ± 5 vs Ovx, 386 ± 5.8 g; P < 0.05), fat mass (Ovx + RK, 3.2 ± 0.05 vs Ovx, 5.0 ± 0.4 g; P < 0.05), and fat cell size (Ovx + RK, 6.4 ± 0.6 vs Ovx, 11.1 ± 0.7 × 103 μm2; P < 0.05) in Ovx-induced obesity in rats. The expression of PPARγ, C/EBPα, FAS, and FABP4 was significantly reduced in the Ovx + RK group compared with that in the Ovx group. Similar patterns were observed in autophagy-related proteins and endoplasmic reticulum stress proteins. These results suggest that RK inhibited lipid accumulation by regulating autophagy in 3T3-L1 cells and Ovx-induced obese rats. DOI: 10.1021/acs.jafc.7b03831 PMID: 29164883 [Indexed for MEDLINE]

Heme oxygenase-1 mediates anti-adipogenesis effect of raspberry ketone in 3T3-L1 cells.

23. Phytomedicine. 2017 Jul 15;31:11-17. doi: 10.1016/j.phymed.2017.05.005. Epub 2017 May 22. Heme oxygenase-1 mediates anti-adipogenesis effect of raspberry ketone in 3T3-L1 cells. Tsai YC(1), Yang BC(2), Peng WH(2), Lee YM(3), Yen MH(3), Cheng PY(4). Author information: (1)Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan; Department of Medicine, Taipei Medical University, Taipei; Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. (2)Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan. (3)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. (4)Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan. Electronic address: pycheng@mail.ndmctsgh.edu.tw. BACKGROUND: Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Raspberry ketone (RK), a major aromatic compound in red raspberry, was recently reported to possess anti-obesity effects. However, its mechanisms are unclear. AIM: Adipogenesis plays a critical role in obesity and, therefore, this study aimed to investigate the effect and mechanisms of action of RK on adipogenesis in 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3T3-L1 preadipocytes were differentiated in medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Adipocyte lipid contents were determined using oil-red O staining while adipogenic transcription factor and lipogenic protein expressions were determined using western blotting. RESULTS: RK (300-400µM) strongly inhibited lipid accumulation during 3T3-L1 preadipocyte differentiation into adipocytes. RK reduced the CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferation-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4) expressions and increased heme oxygenase-1 (HO-1), Wnt10b, and β-catenin expressions in 3T3-L1 adipocytes. Additionally, RK inhibited lipid accumulation, and adipogenic transcription factor and lipogenic protein expressions were all decreased by inhibiting HO-1 or β-catenin using tin protoporphyrin (SnPP) or β-catenin short-interfering RNA (siRNA), respectively. Furthermore, Wnt10b and β-catenin expressions were negatively regulation by SnPP. CONCLUSION: RK may exert anti-adipogenic effects through modulation of the HO-1/Wnt/beta-catenin signaling pathway. Copyright © 2017 Elsevier GmbH. All rights reserved. DOI: 10.1016/j.phymed.2017.05.005 PMID: 28606512 [Indexed for MEDLINE]