Raspberry Ketone Research Articles

Pharmacophagy in insects: Ecological and evolutionary perspectives on the non‐nutritional use of plant specialized metabolites

AbstractHerbivorous insects can interact with plants in ways that go beyond nutrition, with plant specialized (secondary) metabolites (PSMs) mediating complex non‐nutritional relationships. While PSMs often function as anti‐herbivore defenses, many insects have evolved strategies to counteract and even exploit these compounds, using them for purposes such as their own defense against antagonists, enhanced mating success, or self‐medication. This review explores pharmacophagy, where insects actively seek and acquire specific PSMs from both food and non‐food plants for benefits unrelated to nutrition, across different insect orders such as Orthoptera, Lepidoptera, Hymenoptera, Coleoptera, Diptera, and Neuroptera. Key examples are provided for species taking up PSMs of different compound classes, including pyrrolizidine alkaloids, cardiac glycosides, neo‐clerodane diterpenoids, cucurbitacins, raspberry ketone, methyl eugenol, and other metabolites such as ethanol or resin. The insect species demonstrate unique adaptive uses of these non‐nutritional plant chemicals. We discuss the intra‐ and intergenerational transfer of pharmacophagously acquired PSMs among conspecifics and the methods for identifying and testing pharmacophagy, emphasizing the importance of interdisciplinary approaches that combine field observations, behavioral studies, and chemical analyses. The evolutionary pathways leading to pharmacophagy are considered, highlighting selective pressures such as predation, parasitism, and sexual selection. We also address the costs associated with pharmacophagy, including energetic demands and potential toxicity. Extending the discussion to non‐insect taxa suggests that pharmacophagy may be a broader ecological phenomenon. By establishing a comprehensive framework for understanding pharmacophagy, we aim to stimulate further research into this intriguing aspect of plant–insect interactions and highlight its potential applications in pest management, conservation, and human health.

Synthesis and Antifungal Activity of Raspberry Ketone Ester Derivatives as Potential Fungicides.

Raspberry ketone is an aromatic phenolic natural product with a variety of bioactivities. To discover novel fungicide molecules based on raspberry ketone, a total of 25 raspberry ketone ester derivatives were synthesized, and their chemical structures were well characterized. Among them, most compounds have not been reported except for compounds 3a and 3n. Compound 3f exhibited the most significant antifungal activity against Valsa mali with the EC50 of 16.430 µM, indicating that its antifungal activity was 234.6 folds more potent than that of raspberry ketone (EC50: 3854.401 µM). Compounds 3c and 3j displayed the broad-spectrum antifungal activity against three phytopathogenic fungi, which can be further optimized as the secondary lead compounds for the discovery of novel fungicide molecules. The structure-antifungal activity relationships indicated that acylation of the hydroxy group in the molecule of raspberry ketone could significantly improve its antifungal activity and the two methylene in the bridging chain is essential for its antifungal activity. This work will provide some reference for the development of novel fungicide candidates based on the natural product raspberry ketone.

Rational multienzyme architecture design with iMARS.

Rational multienzyme architecture design with iMARS.

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

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.

Dual Role of Raspberry Ketone as Antioxidant and Flavoring Agent in Citrus Flavors

Dual Role of Raspberry Ketone as Antioxidant and Flavoring Agent in Citrus Flavors

Exploring hydrophobic eutectic solvents based on raspberry ketone

Exploring hydrophobic eutectic solvents based on raspberry ketone

Optimization of Biocatalytic Rhododendrol Production from Biogenic Rhododendrol Glycosides.

An enzyme-catalyzed synthesis of rhododendrol, an intermediate in the production of raspberry ketone, was investigated. The approach involves the enzymatic hydrolysis of rhododendrol glycosides into rhododendrol and a glycosidic residue. Rhododendrol glycosides, which are naturally derived from the inner bark of birch trees-a renewable resource-vary considerably in composition depending on the origin of the plants. In this study, mixtures of betuloside and apiosylrhododendrin from natural resources were used in different proportions. An in-depth study was conducted to assess the feasibility of the process. A mathematical model was developed based on studies of the kinetics and operational stability of the enzyme. The model for betuloside hydrolysis catalyzed by β-glucosidase was validated in batch, repetitive batch, and ultrafiltration membrane reactors. The highest productivity, ranging from 83.9 to 94.5 g L-1 day-1, was achieved in the latter. After screening nearly 50 enzymes, RAPIDASE emerged as a solution for the hydrolysis of apiosylrhododendrin, and the model was validated in a batch reactor. Model-based optimization enabled the prediction of input parameters for different compositions of biogenic rhododendrol glycosides to obtain consistent process output metrics.

Static and Dynamic Regulation of Precursor Supply Pathways to Enhance Raspberry Ketone Synthesis from Glucose in Escherichia coli.

Raspberry ketone (RK), a natural product derived from raspberry fruit, is commonly utilized as a flavoring agent in foods and as an active component for weight loss. Metabolic engineering has enabled microorganisms to produce RK more efficiently and cost-effectively. However, the biosynthesis of RK is hindered by an unbalanced synthetic pathway and a deficiency of precursors, including tyrosine and malonyl-CoA. In this study, we constructed and optimized the RK synthetic pathway in Escherichia coli using a static metabolic engineering strategy to enhance the biosynthesis of tyrosine from glucose, thereby achieving the de novo production of RK. Additionally, the synthetic and consumption pathways of malonyl-CoA were dynamically regulated by p-coumaric acid-responsive biosensor to balance the metabolic flux distribution between cell growth and RK biosynthesis. Following pathway optimization, the medium components and fermentation conditions were further refined, resulting in a significant increase in the RK titer to 415.56 mg/L. The optimized strain demonstrated a 32.4-fold increase in the RK titer while maintaining a comparable final OD600 to the initial strain. Overall, the implemented static and dynamic regulatory strategies provide a novel approach for the efficient production of RK, taking into account cell viability and growth.

Fully biobased unsymmetric bisphenols from condensation of lignin-derived monophenols for non-isocyanate polyurethane synthesis

Fully biobased unsymmetric bisphenols from condensation of lignin-derived monophenols for non-isocyanate polyurethane synthesis

A new raspberry ketone synthesis gene RinPKS4 identified in Rubus idaeus L. by transcriptome analysis.

Raspberry ketone accounts for the characteristic aroma of the raspberry fruit. In order to explore the genes involved in raspberry ketone synthesis, the transcriptome in fruit tissues of two red raspberry varieties "Polka" and "Orange legend", were sequenced and 24213 single genes were obtained. As the red raspberry fruit ripening, genes involved in flavonoid and anthocyanin synthesis were up-regulated, while those associated with lignin synthesis were down-regulated. A gene (RinPKS4) highly related to raspberry ketone synthesis was identified by transcriptome analysis, and RinPKS4 gene was over-expressed in raspberry in order to further understand the function of RinPKS4 gene in raspberry ketone synthesis. The results showed that the gene expression level of RinPKS4 in the leaf tissues of a transgenic lines increased by about 4-fold and the content of raspberry ketone increased by 42.64% compared with the wide type. This study lays a theoretical foundation for further study on the synthesis and regulation of raspberry ketone in red raspberry.

Preparation of self-preserving personal care cosmetic products using multifunctional ingredients and other cosmetic ingredients

The development of self-preserving personal care cosmetics represents a significant advancement in the cosmetics industry, offering safer and more natural alternatives to consumers. This study focused on the preparation of such formulations using multifunctional ingredients along with other cosmetic components. Five unique multifunctional ingredients (MFIs) were identified based on their antimicrobial properties: sodium coco PG-dimonium chloride phosphate, ricinoleic acid, palmitoleic acid, raspberry ketone, and sorbitan caprylate. Through meticulous experimentation, 150 combinations of MFIs were prepared and tested to understand their synergistic actions. From these trials, three synergistic antimicrobial compositions were determined: sodium coco PG-dimonium chloride phosphate: ricinoleic acid: raspberry ketone in the ratios 1:6.3:6.3 and 1:6.3:15.7. Sodium coco PG-dimonium chloride phosphate: palmitoleic acid: sorbitan caprylate at a ratio of 1:12.5:37.5. These synergistic compositions exhibited enhanced antimicrobial efficacy compared with their individual components, as evidenced by their lower Minimum Inhibitory Concentration values. Incorporating these formulations into three distinct personal care cosmetic products, including a color protection shampoo, body wash shower gel, and skin-lightening cream, the study further validated their effectiveness. A Preservation Challenge Test study revealed that all three antimicrobial compositions successfully preserved the cosmetic formulations for up to 28 days. This method of product preservation not only ensures consumer safety and stability but also reduces the need for potentially conventional preservatives. In conclusion, the appropriate use of multifunctional ingredients in combination with meticulous formulation techniques has led to the successful development of self-preserving personal care cosmetics. These formulations offer a promising avenue for the cosmetic industry, catering to the rising demand for natural, effective, and consumer-friendly cosmetic products.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-β and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Raspberry ketone loaded self nanoemulsifying system of cardamom oil: Assessment of phase behavior, dissolution rate and anti-hyperlipidemic activity

Raspberry ketone loaded self nanoemulsifying system of cardamom oil: Assessment of phase behavior, dissolution rate and anti-hyperlipidemic activity

Attractiveness, longevity, and release rates of multilure wafers for trapping males of the oriental fruit fly and melon fly (Diptera: Tephritidae).

Invasive fruit flies (Diptera: Tephritidae) pose a serious threat to the production and export of many commercially important fruits and vegetables. Detection of the agricultural pests Bactrocera dorsalis (Hendel) and Zeugodacus cucurbitae (Coquillett) relies heavily on traps baited with male-specific attractants. For B. dorsalis, traps are typically baited with liquid methyl eugenol (ME), and for Z. cucurbitae, traps are baited with liquid cue-lure (CL). Operating large-scale trapping networks is costly, consequently, there is much interest in identifying ways to maintain network sensitivity while reducing costs. One cost-cutting approach is the possibility of combining different male lures in the same dispenser, thus reducing the number of traps requiring servicing. The chief objective of this study was to compare captures of B. dorsalis and Z. cucurbitae males in Jackson traps baited with polymeric wafers impregnated with both ME and raspberry ketone (RK, a hydrolyzed form of CL) versus traps baited with liquid ME or CL freshly applied to cotton wicks. Captures were measured when the ME/RK wafers had been weathered for 12, 18, or 24wk. Captures of B. dorsalis and Z. cucurbitae males were similar between fresh lure and weathered wafers over all trapping periods, with a single exception apparently due to the lessened potency of the associated killing agent. The residual amount and release rate of ME and RK from the wafers were also measured to examine possible relationships between wafer chemistry and trap catch. The possible implications of the present results to area-wide trapping programs are discussed.

Bioproduction of high-value raspberry ketone by submerged fermentation of Nidula niveo-tomentosa

Bioproduction of high-value raspberry ketone by submerged fermentation of Nidula niveo-tomentosa

Raspberry Ketone Prevents LPS-Induced Depression-Like Behaviors in Mice by Inhibiting TLR-4/NF-κB Signaling Pathway via the Gut-Brain Axis.

Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food-derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)-induced depressed mice and elucidates its potential mechanisms, focusing on the gut-brain axis. Through behavioral tests, RK exerts a notable preventive effect on LPS-induced depression-like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short-chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR-4/NF-κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse-associated proteins. The current study provides compelling evidence that RK effectively inhibits the TLR-4/NF-κB pathway via the gut-brain axis, leading to the improvement of LPS-induced depression-like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.

Comparative Responses of Two Major Cucurbit Pests, Zeugodacus cucurbitae and Zeugodacus tau to Phenylbutanoid Male Lures.

Zeugodacus cucurbitae and Z. tau are two major fruit fly pests of cucurbitaceous plants in the tropical and subtropical regions. The former species has a broader host range and wider world distribution than the latter. With global climate change, Z. tau shows great potential for geographical expansion with several invasion records in recent years. Males of both species are attracted to cue lure (CL) (and raspberry ketone (RK), a deacetyl derivative of CL), a common male lure used in fruit fly population detection, monitoring and control programs. Males of both species are also known to respond to zingerone (ZN), which are produced by some rainforest orchids. Previous studies have shown that fruit fly-male lure interactions are unique to species and lure types, and significantly impact the success of a lure-based fruit fly control program. We seek to compare the attraction of Z. cucurbitae and Z. tau males to CL, RK and ZN via Probit behavioral assays. Our results showed that CL is more attractive to Z. cucurbitae and Z. tau males than RK, while ZN is a poor lure for both species. Attraction Z. tau to CL is slightly lower than Z. cucurbitae, but the former is at least 1.71 times less attractive to RK than the latter. Together with published information on species' sexual development, our current study indicates a lure-based control program via male annihilation technique for Z. tau will be more challenging than Z. cucurbitae and should incorporate other integrated pest management strategies for a desirable outcome.

Predicting Bulk Density for Agglomerated Raspberry Ketone via Integrating Morphological and Size Metrics Using Artificial Neural Networks

The bulk density of the particles, which is directly related to transportation and storage costs, is an important basic characteristic of products as well as an important parameter in many processing systems. This work quantified the relationship between the tapped bulk density of raspberry ketone with different degrees of agglomeration and morphological metrics (particle shape descriptors and roughness descriptors) and size metrics (size descriptors) and developed an artificial neural network (ANN) prediction model for the tapped bulk density of raspberry ketone. Samples prepared under different conditions were sieved and remixed, the tapped bulk density of the particles was then measured, and the descriptor features of the particles were obtained by combining them with image processing. The dimensions of the variables were decreased by principal component analysis and variance processing. To overcome the hyperparameter estimation of the heuristic-based artificial neural networks, the network model architectures were optimized by a neural architecture search strategy combining two-objective optimization. The results demonstrated that the tapped bulk density of raspberry ketone products is not only related to the descriptors of particle size and shape but also has a non-negligible relationship with particle roughness descriptors. The performance of the optimal ANN model demonstrated that the model can well predict the tapped bulk density of raspberry ketone with different degrees of agglomeration. The ANN model obtained by extracting morphology and size metrics through online image analysis can be used to measure the tapped bulk density in real-time and has the potential to be used for developing model-based online process monitoring.

A review on natural phenylbutanoid attractants: Occurrence, distribution, and role in nature, especially in relation to Dacini fruit fly behavior and pollination.

The natural occurrence, distribution (within a plant) and roles of four phenylbutanoid compounds (anisyl acetone, cue-lure, raspberry ketone and zingerone) are elucidated for the Asia-Pacific and Oceania regions. These phenylbutanoids may act individually or in combination to attract true fruit fly males belonging to a tribe Dacini of subfamily Dacinae (Diptera: Tepritidae). Of special interest are the mutualistic interactions between the Dacini fruit fly males and the tropical daciniphilous (attracting exclusively Dacini fruit flies) orchids - leading to cross pollination for the orchids and enchanced mating success for the flies. When offered to male flies, anisyl acetone and cue-lure are generally converted to raspberry ketone. Upon consumption, raspberry ketone and zingerone are individually sequestered in the male rectal (pheromonal) gland unchanged. Attracted male flies readily imbibe the phenylbutanoid(s) in the floral synomone to compliment the endogenously synthesized male sex pheromonal components - to enhance attraction of conspecific females during courtship as well as attract conspecific males to form 'leks'. The phenylbutanoid(s) may also act as an allomone to deter vertebrate predators, especially geckos, besides possessing antimicrobial and antioxidant activities. Cue-lure, raspberry ketone and zingerone are important attractants/lures used in pest surveillance and mass trapping under the integrated pest management (IPM) program against quarantine Dacini fruit fly pest species, particularly Bactrocera tryoni and Zeugodacus cucurbitae.

Exploring the antidepressant potential of raspberry ketone: Behavioural and neurochemical insights in a chronic unpredictable mild stress-induced depression model

Objectives: This research investigates the potential antidepressant properties of raspberry ketone (RK) using a chronic unpredictable mild stress-induced depression model in mice. Materials and Methods: Through a comprehensive examination encompassing behavioural and neurochemical assessments, the study reveals promising outcomes. RK administration results in significant enhancements in locomotor activity, reductions in immobility time and improvements in sucrose preference, indicative of antidepressant-like effects. Results: RK treatment leads to elevated levels of dopamine and serotonin, coupled with a decrease in inflammatory cytokines, suggesting a multifaceted mechanism underlying its therapeutic potential. Conclusion: These findings underscore the promise of RK as a novel antidepressant agent, with implications for developing alternative and potentially more tolerable treatments for depression. Further, exploration into its mechanisms and clinical applicability is warranted.