Honeybee Royal Jelly and Nobiletin Stimulate CRE-Mediated Transcription in ERK-Independent and -Dependent Fashions, Respectively, in PC12D Cells

Fujiwara, Hironori; Kogure, Ako; Sakamoto, Masahiro; Yamakuni, Tohru; Mimaki, Yoshihiro; Murata, Kiyoshi; Hitomi, Nobuyuki; Yamaguchi, Kengo; Ohizumi, Yasushi

doi:10.1254/jphs.11001sc

Cited by 11 publications

(9 citation statements)

References 15 publications

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“…Royal jelly is an acidic, pungent smelling, yellow-whitish, creamy substance excreted from the pharyngeal gland of young Apis mellifera bee workers [ 13 , 52 , 53 ]. RJ is a complex material ( Figure 2 ).…”

Section: Apitherapy As a Possible Complementary Treatment For Parkmentioning

confidence: 99%

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

Ali

2020

Oxidative Medicine and Cellular Longevity

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The vast increase of world’s aging populations is associated with increased risk of age-related neurodegenerative diseases such as Parkinson’s disease (PD). PD is a widespread disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra, which encompasses a wide range of debilitating motor, emotional, cognitive, and physical symptoms. PD threatens the quality of life of millions of patients and their families. Additionally, public welfare and healthcare systems are burdened with its high cost of care. Available treatments provide only a symptomatic relief and produce a trail of noxious side effects, which increase noncompliance. Hence, researchers have recently focused on the use of nutraceuticals as safe adjunctive treatments of PD to limit its progress and associated damages in affected groups. Propolis is a common product of the beehive, which possesses a large number of therapeutic properties. Royal jelly (RJ) is a bee product that is fed to bee queens during their entire life, and it contributes to their high physical fitness, fertility, and long lifespan. Evidence suggests that propolis and RJ can promote health by preventing the occurrence of age-related debilitating diseases. Therefore, they have been used to treat various serious disorders such as diabetes mellitus, cardiovascular diseases, and cancer. Some evolving studies used these bee products to treat PD in animal models. However, a clear understanding of the collective effect of propolis and RJ as well as their mechanism of action in PD is lacking. This review evaluates the available literature for the effects of propolis and RJ on PD. Whenever possible, it elaborates on the underlying mechanisms through which they function in this disorder and offers insights for fruitful use of bee products in future clinical trials.

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Section: Apitherapy As a Possible Complementary Treatment For Parkmentioning

confidence: 99%

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

Ali

2020

Oxidative Medicine and Cellular Longevity

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“…The research team of Kikuji Yamaguchi, Japan Royal Jelly Co. Ltd., has found that pharmacological actions of honeybee royal jelly on the nervous system are enhanced by nobiletin, a citrus flavonoid. Based on these experimental data, a drug containing royal jelly and nobiletin was developed to prevent or delay neurodegeneration in the brains of patients with Alzheimer's disease (41). Future studies may allow the development of a pharmacologically acceptable new class of agents based on described synergy effects.…”

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confidence: 99%

Major royal jelly proteins as markers of authenticity and quality of honey / Glavni proteini matične mliječi kao markeri izvornosti i kakvoće meda

Bíliková

Kraková

Yamaguchi³

et al. 2015

Archives of Industrial Hygiene and Toxicology

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Until now, the properties of honey have been defined based exclusively on the content of plant components in the nectar of given plant. We showed that apalbumin1, the major royal jelly (RJ) protein, is an authentic and regular component of honey. Apalbumin1 and other RJ proteins and peptides are responsible for the immunostimulatory properties and antibiotic activity of honey. For the quantification of apalbumin1, an enzyme-linked immunosorbent assay (ELISA) was developed using polyclonal anti-apalbumin1 antibody. The method is suitable for honey authenticity determination; moreover it is useful for detection of the honey, honeybee pollen and RJ in products of medicine, pharmacy, cosmetics, and food industry, where presences of these honeybee products are declared. Results from the analysis for presence and amount of apalbumin1 in honeys will be used for high-throughput screening of honey samples over the world. On the basis of our experiments which show that royal jelly proteins are regular and physiologically active components of honey we propose to change the definition of honey (according to the EU Honey Directive 2001/110/EC) as follows: Honey is a natural sweet substance produced by honey bees from nectar of plants or from secretions of plants, or excretions of plant sucking insects, which honey bees collect, transform by combining with major royal jelly proteins and other specific substances of their own, deposit, dehydrate, store and leave in the honey comb to ripen and mature.

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“…Our next studies proved that nobiletin improves the memory deterioration in beta-amyloid infused AD model rats [4], bulbectomy-induced cholinergic neurodegenerative mice [5], a transgenic mouse model of AD [6], and Parkinson disease model mice [7]. Using the same strategy, we found that honeybee RJ stimulates the CRE-dependent transcription in PC12D cells [8].…”

mentioning

confidence: 67%

“…The RJ used in this study was prepared from frozen powder of native RJ as described [8]. R-limonene was purchased from Nacalai Tesque.…”

Section: Methodsmentioning

confidence: 99%

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Limonene Enhances the cAMP Response Element (CRE)-Dependent Transcriptional Activity Activated via Adenosine A2 A Receptor in a Neural-Crest Derived Cell Line, PC-12

Takito

Ota

Oba

et al. 2017

PMIO

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!Prevention and treatment of Alzheimerʼs disease are urgent problems for elderly people in developed countries. To seek useful compounds that treat, delay the onset, or prevent the development of Alzheimerʼs disease, we screened natural resources using the cyclic AMP response element-dependent transcription in the PC12 cell line. We previously found that honey bee royal jelly stimulates the cyclic AMP response element-dependent transcription activity in PC12 cells. Here, we report that R-limonene, a monoterpene, enhanced the royal jelly-induced cyclic AMP response element-dependent transcription activity, whereas R-limonene showed no effect in absence of royal jelly. The enhancement was inhibited by ZM241385, an antagonist for adenosine A 2 A receptor. R-limonene also enhanced the cyclic AMP response element-dependent transcription activity activated by adenosine and AMP. Thus, R-limonene represents a novel type of modulator that enhances the CRE-dependent transcription via adenosine A 2 A receptor pathway. To find a substance that potentiates the antidementia activity of RJ, we screened extracts derived from herbal plants. Preliminary screening identified limonene as a candidate for the activator of the RJ-induced stimulation of CRE-dependent transcription in PC12 cells. To confirm this finding, we tested commercially available limonenes for the CRE-dependent transcription induced by RJ in PC12 cells. As shown in l " Fig. 1 A, R-limonene dose-dependently enhanced the CRE-dependent transcription activity induced by 10 µg/mL RJ. Interestingly, R-limonene had no effect on the CRE-dependent transcription activity in the absence of RJ. Rlimonene was effective on both low and high concentrations of RJ (l " Fig. 1 B). We next examined the effect of R-limonene on RJ along the timecourse of its stimulation of CRE-dependent transcription (l " Fig. 2). RJ at 10 µg/mL significantly increased the CRE-dependent transcription activity 1-5 h after administration. The activating effect of RJ diminished at 24 and 48 h after administration. The addition of 100 µM R-limonene to RJ significantly enhanced the CRE-dependent transcription activity induced by RJ from 1 to 24 h. Again, R-limonene alone had no effect on the CRE-dependent transcription activity at all time points examined. We next tested the effect of several analogues of R-limonene on the CRE-dependent transcription induced by RJ (l " Fig. 3). (S)-(−)-limonene and (4R)-limonene oxide enhanced the RJ-induced CRE-dependent transcription comparable to the level of R-limonene. (4 S)-limonene oxide significantly increased the CRE-dependent transcription induced by RJ, but the potency of the limonene oxide was weaker than that of R-limonene. Interestingly, all these limonene analogues had no effect on the CRE-dependent * These authors contributed equally to this work. Letter THIEME Key words

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Honeybee Royal Jelly and Nobiletin Stimulate CRE-Mediated Transcription in ERK-Independent and -Dependent Fashions, Respectively, in PC12D Cells

Cited by 11 publications

References 15 publications

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

Major royal jelly proteins as markers of authenticity and quality of honey / Glavni proteini matične mliječi kao markeri izvornosti i kakvoće meda

Limonene Enhances the cAMP Response Element (CRE)-Dependent Transcriptional Activity Activated via Adenosine A2 A Receptor in a Neural-Crest Derived Cell Line, PC-12

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