In 3T3-L1 preadipocytes, raspberry ketone (1, 10, 20, and 50 μM) inhibits adipogenesis and lipid accumulation. Raspberry ketone (10 µM) increases the expression of ATGL, HSL, and CPT1B while significantly blocking the expression of C/EBPα, PPARγ, and aP2 [1].

In comparison to the high-fat diet-induced NASH model, Raspberry ketones (0.5%, 1%, or 2%), raise total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), ISI (insulin sensitivity index), PPAR- Level α, and LDLR, and decrease AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), IRI (insulin resistance index), glucose (GLU), INS (insulin sensitivity index), serum levels of LEP (leptin), and TNF-α. Increased SOD activity is another effect of raspberry ketone [2]. The PPAR-α agonistic activity of raspberry ketone may be the reason for its cardioprotective action against isoproterenol-induced myocardial infarction in rats [3].

Metabolism / Metabolites
Urinary analyses showed ketones in the urine of all treated animals at 7 and 13 weeks. The authors reported that this effect appeared within 12 hr in rats fed a diet containing 1% 4-(para-hydroxyphenyl)-2-butanone for-7 days, and disappeared within 9 hr when the rats were returned to normal diet. The ketonuria, which was possibly due to metabolites present in the urine, was considered not to be a toxic effect.
1. The metabolism of 4-(4-hydroxyphenyl)butan-2-one(raspberry ketone) was studied in rats, guinea-pigs and rabbits. 2. Following intragastric dosage (1 mmol/kg) urinary metabolite excretion was nearly complete within 24 hr, amounting to roughly 90% of the dose in all species. 3. The most prominent urinary metabolites were raspberry ketone and its corresponding carbinol, both largely conjugated with glucuronic acid and/or sulphate. The extent of ketone reduction was greatest in rabbits. 4. Oxidative metabolism included ring hydroxylation and side-chain oxidation. The latter pathway led to 1,2- and 2,3-diol derivatives. It is proposed that the latter undergo cleavage to furnish the C6-C3 and C6-C2 derivatives detected.
A ketone (probably acetone) was found in the urine of rats fed p-hydroxyphenylbutanone at 1% in the diet. After administration of a single 200-mg dose, rats excreted about 6% of the dose unchanged within 24 hr. A positive reaction for ketones being obtained only in urine produced between 1 and 6 hr after treatment.

Non-Human Toxicity Values
LD50 rat ip 0.7 g/kg for males and 0.35 g/kg for females /p-hydroxyphenylbutanone dissolved in propylene glycol/
LD50 rabbit acute oral and acute dermal 5 g/kg /p-hydroxyphenylbutanone dissolved in propylene glycol/
LD50 rat oral 1.32 g/kg for males and 1.40 g/kg for females /p-hydroxyphenylbutanone dissolved in propylene glycol/

[1]. Park KS. Raspberry ketone, a naturally occurring phenolic compound, inhibits adipogenic and lipogenic gene expression in 3T3-L1 adipocytes. Pharm Biol. 2015 Jun;53(6):870-5.

[2]. Raspberry ketone protects rats fed high-fat diets against nonalcoholic steatohepatitis. J Med Food. 2012 May;15(5):495-503.

[3]. Raspberry ketone protects against isoproterenol-induced myocardial infarction in rats. Life Sci. 2018 Feb 1;194:205-212.

Raspberry ketone is a ketone that is 4-phenylbutan-2-one in which the phenyl ring is substituted at position 4 by a hydroxy group. It is found in a variety of fruits including raspberries, blackberries and cranberries, and is used in perfumery and cosmetics. It has a role as a flavouring agent, a fragrance, a metabolite, a hepatoprotective agent, a cosmetic and an androgen antagonist. It is a member of phenols and a methyl ketone.
4-(4-Hydroxyphenyl)-2-butanone has been reported in Nidula niveotomentosa, Rheum palmatum, and other organisms with data available.

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Therapeutic Uses
EXPL THER Melanogenesis inhibition by raspberry ketone (RK) from Rheum officinale was investigated both in vitro in cultivated murine B16 melanoma cells and in vivo in zebrafish and mice. In B16 cells, RK inhibited melanogenesis through a post-transcriptional regulation of tyrosinase gene expression, which resulted in down regulation of both cellular tyrosinase activity and the amount of tyrosinase protein, while the level of tyrosinase mRNA transcription was not affected. In zebrafish, RK also inhibited melanogenesis by reduction of tyrosinase activity. In mice, application of a 0.2% or 2% gel preparation of RK applied to mouse skin significantly increased the degree of skin whitening within one week of treatment. In contrast to the widely used flavoring properties of RK in perfumery and cosmetics, the skin-whitening potency of RK has been demonstrated in the present study. Based on our findings reported here, RK would appear to have high potential for use in the cosmetics industry.
EXPL THER The decrease in the bone mass associated with osteoporosis caused by ovariectomy, aging, and other conditions is accompanied by an increase in bone marrow adipose tissue. The balance between osteoblasts and adipocytes is influenced by a reciprocal relationship. The development of modalities to promote local/systemic bone formation by inhibiting bone marrow adipose tissue is important in the treatment of fractures or metabolic bone diseases such as osteoporosis. In this study, we examined whether raspberry ketone [4-(4-hydroxyphenyl)butan-2-one: RK], which is one of the major aromatic compounds of red raspberry and exhibits anti-obesity action, could promote osteoblast differentiation in C3H10T1/2 stem cells. Confluent C3H10T1/2 stem cells were treated for 6 days with 10-100 ug/mL of RK in culture medium containing 10 nM all-trans-retinoic acid (ATRA) or 300 ng/mL recombinant human bone morphogenetic protein (rhBMP)-2 protein as an osteoblast-differentiating agent. RK in the presence of ATRA increased alkaline phosphatase (ALP) activity in a dose-dependent manner. RK in the presence of rhBMP-2 also increased ALP activity. RK in the presence of ATRA also increased the levels of mRNAs of osteocalcin, alpha1(I) collagen, and TGF-betas (TGF-beta1, TGF-beta2, and TGF-beta3) compared with ATRA only. RK promoted the differentiation of C3H10T1/2 stem cells into osteoblasts. However, RK did not affect the inhibition of early-stage adipocyte differentiation. Our results suggest that RK enhances the differentiation of C3H10T1/2 stem cells into osteoblasts, and it may promote bone formation by an action unrelated to adipocyte differentiation.
EXPL THER 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. 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. 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-a, IL-6) and markers of health including heart rate and blood pressure. 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. 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. /Multi-ingredient supplement containing raspberry ketone/
EXPL THER 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 uM 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 uM 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.
EXPL THER Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK) is a major aromatic compound of red raspberry (Rubus idaeus). The structure of RK is similar to the structures of capsaicin and synephrine, compounds known to exert anti-obese actions and alter the lipid metabolism. The present study was performed to clarify whether RK helps prevent obesity and activate lipid metabolism in rodents. To test the effect on obesity, our group designed the following in vivo experiments: 1) mice were fed a high-fat diet including 0.5, 1, or 2% of RK for 10 weeks; 2) mice were given a high-fat diet for 6 weeks and subsequently fed the same high-fat diet containing 1% RK for the next 5 weeks. RK prevented the high-fat-diet-induced elevations in body weight and the weights of the liver and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric). RK also decreased these weights and hepatic triacylglycerol content after they had been increased by a high-fat diet. RK significantly increased norepinephrine-induced lipolysis associated with the translocation of hormone-sensitive lipase from the cytosol to lipid droplets in rat epididymal fat cells. In conclusion, RK prevents and improves obesity and fatty liver. These effects appear to stem from the action of RK in altering the lipid metabolism, or more specifically, in increasing norepinephrine-induced lipolysis in white adipocytes.

C10H12O2

164.2011

164.083

5471-51-2

21648

White to off-white solid powder

1.1±0.1 g/cm3

292.2±15.0 °C at 760 mmHg

81-85 °C(lit.)

122.9±13.0 °C

0.0±0.6 mmHg at 25°C

1.535

0.94

1

2

3

12

146

0

NJGBTKGETPDVIK-UHFFFAOYSA-N

InChI=1S/C10H12O2/c1-8(11)2-3-9-4-6-10(12)7-5-9/h4-7,12H,2-3H2,1H3

4-(4-hydroxyphenyl)butan-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~609.01 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (15.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)