Raspberry ketone inhibits adipogenesis in 3T3-L1 adipocytes by targeting adipogenic transcription factors (PPARγ, C/EBPα) and lipogenic enzymes (FAS, ACC)[1]
Raspberry ketone protects against nonalcoholic steatohepatitis (NASH) by regulating hepatic lipid metabolism and inflammatory signaling pathways (e.g., NF-κB)[2]
Raspberry ketone alleviates isoproterenol-induced myocardial infarction by targeting oxidative stress (SOD, CAT) and apoptotic signaling (Bcl-2/Bax/caspase-3)[3]

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].

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In 3T3-L1 preadipocytes induced to differentiate, Raspberry ketone (10-100 μM) dose-dependently inhibited adipocyte differentiation: 100 μM reduced lipid accumulation by ~60% (oil red O staining) and downregulated mRNA levels of adipogenic genes PPARγ (~50%), C/EBPα (~45%), and lipogenic genes FAS (~55%), ACC (~40%) (RT-PCR)[1]
Western blot analysis showed Raspberry ketone (50-100 μM) decreased PPARγ and C/EBPα protein expression by ~40-50% in differentiated 3T3-L1 adipocytes, with no significant cytotoxicity at concentrations up to 100 μM (MTT assay)[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].

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In Sprague-Dawley rats fed a high-fat diet (HFD) for 8 weeks, Raspberry ketone (200 mg/kg/day, oral gavage) reduced body weight gain by ~25%, hepatic triglyceride (TG) content by ~40%, and serum ALT/AST levels by ~30-35% vs. HFD controls; it also downregulated hepatic TNF-α (~50%) and IL-6 (~45%) mRNA (RT-PCR) and improved hepatic steatosis (histology score from 3.5 to 1.5)[2]
In Wistar rats with isoproterenol-induced myocardial infarction (85 mg/kg, s.c. for 2 days), Raspberry ketone (100 mg/kg/day, oral gavage for 14 days before isoproterenol injection) reduced serum CK-MB (~40%) and LDH (~35%) levels, increased myocardial SOD activity (~30%) and decreased MDA content (~45%) vs. model controls; it also upregulated Bcl-2 (~50%) and downregulated Bax (~40%)/cleaved caspase-3 (~45%) protein levels (western blot), and reduced myocardial infarct size (~35%) (TTC staining)[3]

Lipogenic enzyme activity assay (FAS/ACC): Differentiated 3T3-L1 adipocytes treated with Raspberry ketone (10-100 μM) were lysed; FAS activity was measured by mixing lysate with acetyl-CoA, malonyl-CoA, and NADPH, incubating at 37°C for 30 min, and measuring NADPH oxidation at 340 nm; ACC activity was detected by quantifying acetyl-CoA carboxylation using [14C]-acetyl-CoA and counting radioactivity[1]
Hepatic inflammatory cytokine detection (TNF-α/IL-6): Livers from HFD-fed rats treated with Raspberry ketone were homogenized; TNF-α and IL-6 levels were measured by ELISA: homogenate supernatant was mixed with capture antibody-coated plates, incubated at 4°C overnight, washed, incubated with detection antibody, and absorbance measured at 450 nm[2]
Myocardial oxidative stress enzyme assay (SOD/CAT): Myocardial tissue from isoproterenol-treated rats was homogenized; SOD activity was measured by inhibiting nitrite formation from hydroxylamine, and CAT activity by monitoring H2O2 decomposition at 240 nm[3]

3T3-L1 adipocyte differentiation assay: 3T3-L1 preadipocytes were seeded in 6-well plates (2×10⁴ cells/well) and cultured in DMEM with 10% FBS. At 80% confluence, differentiation was induced with DMEM containing 10% FBS, 0.5 mM IBMX, 1 μM dexamethasone, and 10 μg/mL insulin; Raspberry ketone (10-100 μM) was added simultaneously. After 8 days, cells were stained with oil red O (0.5% in isopropanol) for 30 min, washed, and lipid accumulation quantified by extracting dye with isopropanol and measuring absorbance at 510 nm[1]
RT-PCR for adipogenic genes: Total RNA from Raspberry ketone-treated 3T3-L1 cells was extracted; cDNA was synthesized, and PCR amplified with primers for PPARγ, C/EBPα, FAS, ACC, and GAPDH (internal control). PCR products were separated by agarose gel electrophoresis and densitometry quantified[1]
Western blot for adipogenic proteins: Cell lysates from Raspberry ketone-treated 3T3-L1 cells were separated by SDS-PAGE, transferred to PVDF membranes, probed with anti-PPARγ, anti-C/EBPα, and anti-β-actin antibodies, and visualized by chemiluminescence[1]

HFD-induced NASH model: Male Sprague-Dawley rats (6 weeks old) were randomized into 3 groups: normal diet (ND), HFD (45% fat), HFD + Raspberry ketone (200 mg/kg/day). Raspberry ketone was dissolved in 0.5% carboxymethyl cellulose (CMC) and administered by oral gavage once daily for 8 weeks. Body weight was measured weekly; at sacrifice, serum and liver samples were collected for biochemical and histological analysis[2]
Isoproterenol-induced myocardial infarction model: Male Wistar rats (8 weeks old) were divided into 3 groups: control, model (isoproterenol 85 mg/kg, s.c. on days 14 and 15), model + Raspberry ketone (100 mg/kg/day). Raspberry ketone was dissolved in saline and given by oral gavage once daily for 14 days (before isoproterenol injection). On day 16, rats were sacrificed; serum and myocardial tissue were collected for enzyme activity and histological[3]

Metabolism / Metabolites
Urinary analysis revealed ketone bodies in the urine of all tested animals at weeks 7 and 13. The authors reported that ketone bodies appeared within 12 hours of rats being fed a diet containing 1% 4-(p-hydroxyphenyl)-2-butanone for 7 consecutive days and disappeared within 9 hours after resuming a normal diet. This ketonuria is likely caused by metabolites present in the urine and is not considered a toxic effect. 1. This study investigated the metabolism of 4-(4-hydroxyphenyl)butanone (raspberry ketone) in rats, guinea pigs, and rabbits. 2. Following gavage administration (1 mmol/kg), urinary metabolite excretion was almost complete within 24 hours in all species, representing approximately 90% of the administered dose. 3. The most significant metabolites in urine were raspberry ketone and its corresponding methanol, both primarily bound to glucuronic acid and/or sulfate. Ketone reduction was most pronounced in rabbits. 4. Oxidative metabolism included cyclic hydroxylation and side-chain oxidation. The side-chain oxidation pathway generates 1,2- and 2,3-diol derivatives. It is presumed that the latter undergoes cleavage to generate the detected C6-C3 and C6-C2 derivatives. A ketone (likely acetone) was found in the urine of rats fed a diet containing 1% p-hydroxyphenylbutanone. Following a single 200 mg dose, rats excreted approximately 6% of the unchanged drug within 24 hours. A positive reaction for the ketone was detected only in urine produced 1 to 6 hours after administration.

Non-Human Toxicity Values
Rat intraperitoneal LD50: Male 0.7 g/kg, Female 0.35 g/kg (p-hydroxyphenylbutanone soluble in propylene glycol) / Rabbit acute oral and acute dermal LD50: 5 g/kg (p-hydroxyphenylbutanone soluble in propylene glycol) / Rat oral LD50: Male 1.32 g/kg, Female 1.40 g/kg (p-hydroxyphenylbutanone soluble 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 compound with the structure 4-phenylbut-2-one, in which the 4-position of the benzene ring is replaced by a hydroxyl group. It is found in various fruits, including raspberries, blackberries, and cranberries, and is used in the perfume and cosmetics industries. Raspberry ketone has a variety of uses, including as a flavoring agent, fragrance, metabolite, hepatoprotective agent, cosmetic ingredient, and androgen antagonist. It belongs to the phenolic class of compounds and is also a methyl ketone. 4-(4-hydroxyphenyl)-2-butanone has been reported to exist in Nidula niveotomentosa, Rheum palmatum, and several other organisms with relevant data.
Therapeutic Uses
Exploratory Study: This study investigated the inhibitory effect of raspberry ketone (RK) on melanin production in cultured mouse B16 melanoma cells in vitro and in zebrafish and mice in vivo. In B16 cells, RK inhibits melanin production by posttranscriptionally regulating tyrosinase gene expression, leading to a downregulation of both cellular tyrosinase activity and protein levels, while tyrosinase mRNA transcription levels remain unaffected. In zebrafish, RK also inhibits melanin production by reducing tyrosinase activity. In mice, application of 0.2% or 2% RK gel formulations to the skin significantly improved skin whitening within one week. Unlike the flavoring properties of RK, which are widely used in perfumes and cosmetics, this study confirms the skin-whitening efficacy of RK. Based on the results reported here, RK has significant application potential in the cosmetics industry.
Exploring treatments for osteoporosis caused by oophorectomy, aging, and other factors leads to decreased bone mass and increased bone marrow adipose tissue. The balance between osteoblasts and adipocytes is mutually influential. Methods to promote local/systemic bone formation by inhibiting bone marrow adipose tissue are crucial for treating fractures or metabolic bone diseases such as osteoporosis. This study investigated whether raspberry ketone [4-(4-hydroxyphenyl)butan-2-one: RK] (one of the main aromatic compounds of raspberry, with anti-obesity effects) could promote osteoblast differentiation of C3H10T1/2 stem cells. Confluent C3H10T1/2 stem cells were cultured for 6 days in a medium containing 10-100 μg/mL RK, with 10 nM all-trans retinoic acid (ATRA) or 300 ng/mL recombinant human bone morphogenetic protein (rhBMP)-2 protein added simultaneously as an osteoblast differentiation agent. In the presence of ATRA, RK increased alkaline phosphatase (ALP) activity in a dose-dependent manner. In the presence of rhBMP-2, RK also increased ALP activity. Compared to ATRA alone, RK, in the presence of ATRA, also increased the mRNA levels of osteocalcin, α1(I) type collagen, and TGF-β (TGF-β1, TGF-β2, and TGF-β3). RK promoted the differentiation of C3H10T1/2 stem cells into osteoblasts. However, RK did not affect the inhibition of early adipocyte differentiation. Our results suggest that RK enhances the differentiation of C3H10T1/2 stem cells into osteoblasts and may promote bone formation through effects independent of adipocyte differentiation.
Exploring Treatment: Many commercially available natural products claim to reduce weight and fat, but few have undergone product-specific studies to demonstrate their safety and efficacy. This study aimed to evaluate the safety and efficacy of a multi-ingredient supplement with raspberry ketone, caffeine, capsaicin, garlic, ginger, and lime (Citrus aurantium, brand name: Prograde Metabolism [METABO]) as an adjunct to an eight-week weight loss program. A randomized, placebo-controlled, double-blind study was conducted, randomly assigning 70 obese but otherwise healthy participants to either the METABO group or the placebo group for eight weeks, followed by daily supplementation, a low-calorie diet, and exercise. The study examined changes in body composition, serum levels of adipokines (adiponectin, resistin, leptin, TNF-α, IL-6), and health indicators including heart rate and blood pressure. Among the 45 participants who completed the study, significant differences were observed in the following areas: weight (METABO -2.0% vs. placebo -0.5%, P<0.01), body fat mass (METABO -7.8% vs. placebo -2.8%, P<0.001), lean body mass (METABO +3.4% vs. placebo +0.8%, P<0.03), waist circumference (METABO -2.0% vs. placebo -0.2%, P<0.0007), hip circumference (METABO -1.7% vs. placebo -0.4%, P<0.003), and energy level calculated using the Anchored Visual Analogue Scale (VAS) (METABO +29.3% vs. placebo +5.1%, P<0.04). During the initial 4 weeks, serum leptin levels remained elevated (P<0.03) and serum resistin levels decreased (P<0.08) in the METABO group compared to the placebo group, with related effects/trends observed. No changes were observed in systemic hemodynamics, clinical blood chemistry parameters, adverse events, or dietary intake between the two groups. METABO can serve as a safe and effective adjunct to an 8-week diet and exercise weight loss program, enhancing improvements in body composition, waist circumference, and hip circumference. Adherence to the 8-week weight loss program also resulted in beneficial changes in body fat percentage in the placebo group. Further research is underway to confirm these results and elucidate the mechanisms by which METABO exerts these beneficial effects (e.g., biochemical and neuroendocrine mediators). /Multi-component supplement containing raspberry ketone/
EXPL THER Raspberry ketone (RK) is a natural phenolic compound found in red raspberries. RK supplementation in male mice has been reported to prevent weight gain induced by a high-fat diet and promote lipolysis in white adipocytes. To elucidate the possible mechanisms of RK's anti-obesity effect, this study investigated the effects of RK on adiponectin expression and secretion, lipolysis, and fatty acid oxidation in 3T3-L1 cells. The results showed that 10 μM RK treatment significantly promoted lipolysis in differentiated 3T3-L1 cells. Immunoassay revealed that RK increased the expression and secretion of adiponectin (a cytokine primarily expressed and secreted by adipose tissue). Furthermore, 10 μM RK treatment also promoted fatty acid oxidation in 3T3-L1 adipocytes and inhibited lipid accumulation. These findings suggest that raspberry ketone (RK) has significant potential as a medicinal herb due to its ability to alter lipid metabolism in 3T3-L1 adipocytes. Raspberry ketone (4-(4-hydroxyphenyl)butan-2-one; RK) is the main aromatic compound of red raspberry (Rubus idaeus). The structure of RK is similar to that of capsaicin and synephrine, both of which are known to have anti-obesity effects and alter lipid metabolism. This study aimed to elucidate whether raspberry ketone (RK) helps prevent obesity and activate lipid metabolism in rodents. To test its effects on obesity, we designed the following in vivo experiments: 1) Mice were fed a high-fat diet containing 0.5%, 1%, or 2% RK for 10 weeks; 2) Mice were first fed a high-fat diet for 6 weeks, followed by the same high-fat diet containing 1% RK for 5 weeks. RK prevented the weight gain induced by the high-fat diet, as well as the increase in weight of liver and visceral adipose tissue (epididymis, retroperitoneum, and mesentery). RK also reduced the increase in the weight of these tissues and liver triglyceride content induced by the high-fat diet. RK significantly enhanced norepinephrine-induced lipolysis and promoted the translocation of hormone-sensitive lipases from the cytosol to lipid droplets, thereby improving lipid metabolism in rat epididymal adipocytes. In conclusion, RK can prevent and improve obesity and fatty liver. These effects appear to stem from the alterations in lipid metabolism caused by raspberry ketone (RK), more specifically, its enhancement of norepinephrine-induced lipolysis in white adipocytes.

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Raspberry ketone is a naturally occurring phenolic compound, mainly isolated from the fruit of raspberry (Rubus idaeus)[1].
The anti-adipogenic mechanism of raspberry ketone in 3T3-L1 cells involves downregulation of PPARγ/C/EBPα, key transcription factors for adipocyte differentiation, thereby inhibiting the expression of adipogenic genes and lipid accumulation[1].
In high-fat diet-induced non-alcoholic steatohepatitis (NASH) rats, raspberry ketone exerts a hepatoprotective effect by reducing hepatic lipid deposition and inhibiting inflammatory response[2].
Raspberry ketone alleviates myocardial infarction by enhancing antioxidant capacity (increasing SOD/CAT activity) and inhibiting cardiomyocyte apoptosis (upregulation). Bcl-2, downregulation of Bax/caspase-3)[3]

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.)