Genoprotective effects of royal jelly (RJ) treatments against doxorubicin (DXR), a potent genotoxic chemotherapeutic compound in human lymphocytes were investigated using the sister chromatid exchange (SCE) assay, and their molecular mechanisms were examined by Western blot. Results showed that RJ pretreatments at 0.005 and 0.05 mg/mL significantly decreased DXR-induced SCE levels by 1.2-fold (p<0.05), compared to DXR treatment alone. Co-treatment of RJ (5 mg/mL) with DXR (0.2 μg/mL) increased the ratios of BCL2/BAX (1.5-fold), NRF2/BAX (1.3-fold), and hTERT/BAX (1.1-fold) compared to the DXR alone, suggesting its power in enhancing cell survival, antioxidative potentials, and longevity over cell death. The study suggested that RJ protected human cells from DXR-induced genotoxicity, possibly mediated through anti-apoptotic, anti-oxidative, and anti-aging properties of RJ. However, lower doses of RJ co-treatments enhanced DXR toxicity. Further, in vivo molecular study is required to validate this in vitro study.
TownsendGF, MorganJF, TolnaiS, HazlettB, MortonHJ, ShuelRW. (1960) Studies on the in vitro antitumor activity of fatty acids. I. 10- Hydroxy-2-decenoic acid from royal jelly. Cancer Research, 20, 503–510.
2.
Salazar-OlivoLA, Paz-GonzalezV. (2005) Screening of biological activities present in honeybee (Apis mellifera) royal jelly. Toxicology In Vitro, 19, 645–651.
3.
KamakuraM, SuenobuN, FukushimaM. (2001) Fifty-seven-kDa protein in royal jelly enhances proliferation of primary cultured rat hepatocytes and increases albumin production in the absence of serum. Biochemical and Biophysical Research Communications, 282, 865–874.
4.
AndritoiuCV, AndritoiuV, CuciureanuM, Nica-BadeaD, BibireN, PopaM. (2014) Effect of apitherapy products against carbon tetrachloride-induced toxicity in Wistar rats. Romanian Journal of Morphology and Embryology, 55, 835–847.
5.
MohamedAA, GalalAA, ElewaYH. (2015) Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain. Acta Histochemica, 117, 649–658.
6.
YaparK, CavusogluK, OrucE, YalcinE. (2009) Protective effect of royal jelly and green tea extracts effect against cisplatin-induced nephrotoxicity in mice: a comparative study. Journal of Medicinal Food, 12, 1136–1142.
7.
MalekinejadH, AhsanS, Delkhosh-KasmaieF, CheraghiH, Rezaei-GolmishehA, Janbaz-AcyabarH. (2016) Cardioprotective effect of royal jelly on paclitaxel-induced cardio-toxicity in rats. Iranian Journal of Basic Medical Sciences, 19, 221–227.
8.
YangF, TevesSS, KempCJ, HenikoffS. (2014) Doxorubicin, DNA torsion, and chromatin dynamics. Biochimica et Biophysica Acta, 1845, 84–89;
9.
LattSA. (1974) Sister chromatid exchanges, indices of human chromosome damage and repair: detection by fluorescence and induction by mitomycin C. Proceedings of the National Academy of Sciences of the United States of America, 71, 3162–3166.
10.
GreenbergRA, O'HaganRC, DengH, XiaoQ, HannSR, AdamsRR, LichtsteinerS, ChinL, MorinGB, DePinhoRA. (1999) Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene, 18, 1219–1226.
11.
CerniC. (2000) Telomeres, telomerase, and myc. An update. Mutation Research, 462, 31–47.
12.
LarsenCJ. (1994) [The BCL2 gene, prototype of a gene family that controls programmed cell death (apoptosis)]. Annales De Genetique, 37, 121–134.
13.
HayesJD, Dinkova-KostovaAT. (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends in Biochemical Sciences, 39, 199–218.
14.
RyterSW, AlamJ, ChoiAM. (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiological Reviews, 86, 583–650.
15.
JenkhetkanW, ThitiorulS, JansomC, RatanavalachaiT. (2017) Molecular and cytogenetic effects of Thai royal jelly: modulation through c-MYC, h-TERT, NRF2, HO-1, BCL2, BAX and cyclins in human lymphocytes in vitro. Mutagenesis, 32, 525–531.
16.
KorsmeyerSJ, ShutterJR, VeisDJ, MerryDE, OltvaiZN. (1993) Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Seminars in Cancer Biology, 4, 327–332.
17.
InoueS, Koya-MiyataS, UshioS, IwakiK, IkedaM, KurimotoM. (2003) Royal Jelly prolongs the life span of C3H/HeJ mice: correlation with reduced DNA damage. Experimental Gerontology, 38, 965–969.
18.
DetienneG, De HaesW, ErnstUR, SchoofsL, TemmermanL. (2014) Royalactin extends lifespan of Caenorhabditis elegans through epidermal growth factor signaling. Experimental Gerontology, 60, 129–135.
19.
Valiollahpoor AmiriM, DeldarH, Ansari PirsaraeiZ. (2016) Impact of supplementary royal jelly on in vitro maturation of sheep oocytes: genes involved in apoptosis and embryonic development. Systems Biology in Reproductive Medicine, 62, 31–38.
20.
GhanbariE, NejatiV, KhazaeiM. (2016) Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats. International Journal of Reproductive Biomedicine, 14, 519–526.
21.
SiliciS, EkmekciogluO, EraslanG, DemirtasA. (2009) Antioxidative effect of royal jelly in cisplatin-induced testes damage. Urology, 74, 545–551.
22.
El-AidyWK, EbeidAA, Sallam AelR, MuhammadIE, AbbasAT, KamalMA, SohrabSS. (2015) Evaluation of propolis, honey, and royal jelly in amelioration of peripheral blood leukocytes and lung inflammation in mouse conalbumin-induced asthma model. Saudi Journal of Biological Sciences, 22, 780–788.
23.
A.O.A.C. (Association of Official Analytical Chemist) (2006) In Official methods of analysis of the AOAC International. 18th Ed. HorwitizW. (Ed). AOAC International, Washington DC. USA.
24.
BatistaAG, FerrariAS, da CunhaDC, da SilvaJK, CazarinCB, CorreaLC, PradoMA, Carvalho-SilvaLB, EstevesEA, Marostica JuniorMR. (2016) Polyphenols, antioxidants, and antimutagenic effects of Copaifera langsdorffii fruit. Food Chemistry, 197 PtB, 1153–1159.
25.
De Garcia-AmoedoLH, Almeida-MuradianLB. (2003) Determination of trans-10-hydroxy-2-decenoic acid (10-HDA) in royal jelly from Sao Paulo State, Brazil. Food Science and Technology, 23(Suppl), 62-65. 25] ButsatS, SiriamornpunS. (2010) Phenolic acids and antioxidant activities in husk of different Thai rice varieties. Food Science and Technology International, 16, 329–336.
26.
ChiewchanwitT, AuWW. (1994) Cytogenetic effects of 2-methoxyethanol and its metabolite, methoxyacetaldehyde, in mammalian cells in vitro. Mutation Research, 320, 125–132;
27.
RatanavalachaiT, ThitiorulS and NandhasriP. (2008) In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes. Songklanakarin Journal of Science and Technology, 30, 583–389.
28.
WhortonEBJr., TiceRR, StetkaDG. (1984) Statistical design, analysis, and inference issues in studies using sister chromatid exchange. Basic Life Sciences, 29 PtA, 431–440.
