蜂王浆治疗更年期综合征及其相关机制的研究进展
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摘要
更年期综合征严重威胁更年期妇女健康,目前临床上常采用激素替代疗法进行治疗,虽疗效显著但存在诸多不良反应。蜂王浆作为一种天然物质具有广泛的生物学活性,能有效治疗更年期综合征。本文对蜂王浆治疗更年期泌尿生殖道疾病、精神障碍、绝经后骨质疏松及心血管疾病等方面的作用及其可能的机制进行综述,旨在为蜂王浆在更年期综合征治疗上的深入研究提供理论依据和新的思路。
Menopausal syndrome threatens the health of menopausal women seriously.At present,the hormone replacement is often applied in clinic,however,it also causes many adverse reactions.Royal jelly(RJ),a natural substance with diverse biological activities,can effectively improve menopausal syndrome.This article summarizes the effects and possible mechanisms of RJ in the treatment of menopausal urogenital diseases,mental disorders,postmenopausal osteoporosis and cardiovascular diseases,which will provide theoretical basis and new insights for the further study of RJ in treating menopausal syndrome.
Menopausal syndrome threatens the health of menopausal women seriously.At present,the hormone replacement is often applied in clinic,however,it also causes many adverse reactions.Royal jelly(RJ),a natural substance with diverse biological activities,can effectively improve menopausal syndrome.This article summarizes the effects and possible mechanisms of RJ in the treatment of menopausal urogenital diseases,mental disorders,postmenopausal osteoporosis and cardiovascular diseases,which will provide theoretical basis and new insights for the further study of RJ in treating menopausal syndrome.
引文
1 Lizcano F,et al.Estrogen deficiency and the origin of obesity during menopause[J].Bio Med Res Int,2014,2014:757461.
2 Han B,et al.Effect of Lepidium meyenii(Maca)ethanol extraction endocrine hormone levels in climacteric rats[J].Nat Prod Res Dev(天然产物研究与开发),2016,28:1207-1211.
3 Roberts H,et al.Managing the menopause:An update[J].Maturitas,2016,86:53-58.
4 Gemmell LC,et al.The management of menopause in women with a history of endometriosis:a systematic review[J].Hum Reprod Update,2017,23:481-500.
5 Mintziori G,et al.EMAS position statement:non-hormonal management of menopausal vasomotor symptoms[J].Maturitas,2015,81:410-413.
6 Fratini F,et al.Royal Jelly:An ancient remedy with remarkable antibacterial properties[J].Microbiol Res,2016,192:130-141.
7 Ramadan MF,et al.Bioactive compounds and health-promoting properties of royal jelly:A review[J].J Funct Foods,2012,4(1):39-52.
8 Mishima S,et al.Royal jelly has estrogenic effects in vitro and in vivo[J].J Ethnopharmacol,2005,101:215-220.
9 Nakaya M,et al.Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer cells[J].Biosci Biotechnol Biochem,2007,71:253-255.
10 Suzuki KM,et al.Estrogenic activities of fatty acids and a sterol isolated from royal jelly[J].Evid-Based Compl Alt,2008,5:295-302.
11 Brotman RM,et al.Association between the vaginal microbiota,menopause status,and signs of vulvovaginal atrophy[J].Menopause,2014,21:450-458.
12 Farrell AE.Genitourinary syndrome of menopause[J].Aust Fam Physician,2017,46:481-484.
13 Gandhi J,et al.Genitourinary syndrome of menopause:an overview of clinical manifestations,pathophysiology,etiology,evaluation,and management[J].Am J Obstet Gynecol,2016,215:704-711.
14 Yakoot M,et al.Effectiveness of a herbal formula in women with menopausal syndrome[J].Complement Med Res,2011,18:264-268.
15 Seyyedi F,et al.Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women:a clinical trial study[J].Electronic Physician,2016,8:3184-3192.
16 Koc AN,et al.Antifungal activity of the honeybee products against Candida spp.and Trichosporon spp[J].J Med Food,2011,14:128-134.
17 Khanjani S,et al.Effect of conjugated estrogen in stress urinary incontinence in women with menopause[J].Int J Clin Med,2017,8:375-385.
18 Alreshoodi FM,et al.Antimicrobial activity of royal jelly[J].Anti-Infective Agents,2015,13(1):50-59.
19 Yu LP,et al.Study on bacteriostasis of three bee products in vitro[J].Apiculture of China(中国蜂业),2009,60(3):13-16.
20 Fratini F,et al.Royal jelly:An ancient remedy with remarkable antibacterial properties[J].Microbio Res,2016,192:130-141.
21 Girard R,et al.Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity[J].Sci Rep,2017,7:44917.
22 Anniverno R,et al.Depressive syndrome in perimenopausal,menopausal and postmenopausal patients.An Italian multicentre observational study[J].J Psychopathol,2017,23:19-25.
23 Morita H,et al.Effect of royal jelly ingestion for six months on healthy volunteers[J].Nutrition J,2012,11(1):77.
24 Minami A,et al.Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly[J].Climacteric,2016,19:568-573.
25 Rocha BA,et al.17β-estradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-βknockout(BERKO)mice[J].Psychopharmacol,2005,179:637-643.
26 Walf AA,et al.Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol's modulation of affective and sexual behavior,respectively[J].Neuropsychopharmacol,2008,33:431-440.
27 Jacome LF,et al.Estradiol and ERβagonists enhance recognition memory,and DPN,an ERβagonist,alters brain monoamines[J].Neurobiol Learn Mem,2010,94:488-498.
28 Luine VN,et al.Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density[J].Front Neuroendocrinol,2012,33:388-402.
29 Suzuki KM,et al.Estrogenic activities of fatty acids and a sterol isolated from royal jelly[J].Evid-Based Compl Alt,2008,5:295-302.
30 Moutsatsou P,et al.Fatty acids derived from royal jelly are modulators of estrogen receptor functions[J].PLo S One,2010,5(12):e15594.
31 Chen D,et al.Effect of major royal jelly proteins on spatial memory in aged rats:metabolomics analysis in urine[J].JAgr Food Chem,2017,65:3151-3159.
32 Ito S,et al.Antidepressant-like activity of 10-hydroxy-trans-2-decenoic acid,a unique unsaturated fatty acid of royal jelly,in stress-inducible depression-like mouse model[J].Evid-Based Compl Alt.2012,2012:139-140.
33 Hattori N,et al.Royal jelly and its unique fatty acid,10-hydroxy-trans-2-decenoic acid,promote neurogenesis by neural stem/progenitor cells in vitro[J].Biomed Res,2007,28:261-266.
34 Hattori N,et al.Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases[J].Biomed Res,2007,28:139-146.
35 Furukawa S.Stimulatory effects of royal jelly on the generation of neuronal and glial cells-expectation of protection against some neurological disorders[J].Foods and Food Ingredients J.Jpn,2008,213:620-626.
36 Hattori N,et al.Royal jelly facilitates restoration of the cognitive ability in trimethyltin-intoxicated mice[J].Evid-Based Compl Alt,2011,2011:165968.
37 Li CL,et al.Effects of royal jelly on the sleep of mice[J].Shandong Animal Sci and Veter Med(山东畜牧兽医),2014,12:6-7.
38 Yan JH(闫继红),et al.Study on the effect of royal jelly compound capsule on improving sleep in mice[J].Apiculture of China(中国蜂业),2003,54(6):9.
39 Park HM,et al.Royal jelly increases collagen production in rat skin after ovariectomy[J].J Med Food,2012,15:568-575.
40 Hidaka S,et al.Royal jelly preventsosteoporosis in rats:beneficial effects in ovariectomy model and inbone tissue culture model[J].Evid-Based Compl Alt,2006,3:339-348.
41 Kafadar IH,et al.Royal jelly and bee pollendecrease bone loss due to osteoporosis in an oophorectomized ratmodel[J].Eklem Hastalik Cerrahisi,2012,23:100-105.
42 Kaku M,et al.Royal jelly affects collagen crosslinking in bone of ovariectomized rats[J].J Funct Foods,2014,7:398-406.
43 Yanagita M,et al.Osteoinductive and antiinflammatory effect of royal jelly on periodontal ligament cells[J].Biomed Res,2011,32:285-291.
44 Narita Y,et al.Royal jelly stimulates boneformation:physiologic and nutrigenomic studies with mice and celllines[J].Biosci Biotechnol Biochem,2006,70:2508-2514.
45 Niu K,et al.Royal jelly prevents the progression of sarcopenia in aged mice in vivo and in vitro[J].J Gerontol A Biol Sci Med Sci,2013,68:1482-1492.
46 Matthews KA,et al.Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition[J].J Am Coll Cardiol,2009,54:2366-2373.
47 Tan DH.Experimental study of Gan Lu San on climacteric syndrome[D].Shenyang:Shenyang Pharmaceutical University(沈阳药科大学),2005.
48 Lambrinoudaki I,et al.Greek-origin royal jelly improves the lipid profile of postmenopausal women[J].Gynecol Endocrinol,2016,32:835-839.
49 Sengupta A,et al.Hypolipidemic effect of mustard oil enriched with medium chain fatty acid and polyunsaturated fatty acid[J].Nutrition,2011,27:1183-1193.
50 Xu Q,et al.Medium-chain fatty acids enhanced the excretion of fecal cholesterol and cholic acid in C57BL/6J mice fed a cholesterol-rich diet[J].Biosci Biotechnol Biochem,2013,77:1390-1396.
51 Xue C,et al.Chinese hypertriglycerideamic subjects of different ages responded differently to consuming oil with mediumand long-chain fatty acids[J].Biosci Biotechnol Biochem,2009,73:1711-1717.
52 Xue C,et al.Consumption of medium-and long-chaintriacylglycerols decreases body fat and blood triglyceride in Chinese hypertriglyceridemic subjects[J].Eur J Clin Nutr,2009,63:879-886.
53 Kashima Y,et al.Identification of a novel hypocholesterolemic protein,major royal jelly protein 1,derived from royal jelly[J].PLo S One,2014,9:e105073.
54 Chiu HF,et al.Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults[J].Pharm Biol,2017,55:497-502.
55 Münstedt K,et al.Royal jelly increases high density lipoprotein levels but in older patients only[J].J Altern Complem Med,2009,15:329-330.
56 Pourmoradian S,et al.Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female:a randomized clinical trial[J].Chin J Integr Med,2014,20:347-352.
57 Pourmoradian S,et al.Effects of royal jelly supplementation on body weight and dietary intake in type 2 diabetic females[J].Health Promot Perspect,2012,2:231-235.
58 Viuda-Martos M,et al.Functional properties of honey,propolis,and royal jelly[J].J Food Sci,2008,73:117-124.
59 Wu AX.Hypolipidemic of Royal Jelly And Royal Jelly Protein[D].Fuzhou:Fujian Agriculture and Forestry University(福建农林大学),2012.
60 Tokunaga KH,et al.Antihypertensive effect of peptides from royal jelly in spontaneously hypertensive rats[J].Biol Pharm Bull,2004,27:189-192.
61 Vittek J.Effect of royal jelly on serum lipids in experimental animals and humans with atherosclerosis[J].Cell Mol Life Sci,1995,51:927-935.
62 You TH,et al.Recent advances on active substances of antiaging and its mechanisms[J].Nat Prod Res Dev(天然产物研究与开发),2015,27:1985-1990.
63 Yang Y,et al.Cissus quadrangularis prevented the ovariectomy induced oxidative stress in the femur of adult albino rats[J].Biomed Pharmacother,2016,81:416-423.
64 Qiu BM,et al.Effect of Kun Geng Xin capsule on serum SOD,LPO and MDA in climacteric model rats[J].Laboratory Medicine(检验医学),2016:304-305.
65 Inoue S,et al.Royal jelly prolongs the life span of C3H/He Jmice:correlation with reduced DNA damage[J].Exp Gerontol,2003,38:965-969.
66 Nagai T,et al.Antioxidant properties of enzymatic hydrolysates from royal jelly[J].J Med Food,2006,9:363-367.
67 Cavusoglu K,et al.Royal jelly(honey bee)is a potential antioxidant against cadmium-induced genotoxicity and oxidative stress in albino mice[J].J Med Food,2009,12:1286-1292.
68 Narita Y,et al.Effects of long-term administration of royal jelly on pituitary weight and gene expression in middle-aged female rats[J].Biosci Biotechnol Biochem,2009,73:431-433.
69 Kanno J,et al.The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses:phase 1[J].Environ Health Persp,2001,109:785-794.
70 Minami A,et al.Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly[J].Climacteric,2016,19:568-573.
71 Shahinian VB,et al.Risk of fracture after androgen deprivation for prostate cancer[J].N Engl J Med,2005,352:154-164.
2 Han B,et al.Effect of Lepidium meyenii(Maca)ethanol extraction endocrine hormone levels in climacteric rats[J].Nat Prod Res Dev(天然产物研究与开发),2016,28:1207-1211.
3 Roberts H,et al.Managing the menopause:An update[J].Maturitas,2016,86:53-58.
4 Gemmell LC,et al.The management of menopause in women with a history of endometriosis:a systematic review[J].Hum Reprod Update,2017,23:481-500.
5 Mintziori G,et al.EMAS position statement:non-hormonal management of menopausal vasomotor symptoms[J].Maturitas,2015,81:410-413.
6 Fratini F,et al.Royal Jelly:An ancient remedy with remarkable antibacterial properties[J].Microbiol Res,2016,192:130-141.
7 Ramadan MF,et al.Bioactive compounds and health-promoting properties of royal jelly:A review[J].J Funct Foods,2012,4(1):39-52.
8 Mishima S,et al.Royal jelly has estrogenic effects in vitro and in vivo[J].J Ethnopharmacol,2005,101:215-220.
9 Nakaya M,et al.Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer cells[J].Biosci Biotechnol Biochem,2007,71:253-255.
10 Suzuki KM,et al.Estrogenic activities of fatty acids and a sterol isolated from royal jelly[J].Evid-Based Compl Alt,2008,5:295-302.
11 Brotman RM,et al.Association between the vaginal microbiota,menopause status,and signs of vulvovaginal atrophy[J].Menopause,2014,21:450-458.
12 Farrell AE.Genitourinary syndrome of menopause[J].Aust Fam Physician,2017,46:481-484.
13 Gandhi J,et al.Genitourinary syndrome of menopause:an overview of clinical manifestations,pathophysiology,etiology,evaluation,and management[J].Am J Obstet Gynecol,2016,215:704-711.
14 Yakoot M,et al.Effectiveness of a herbal formula in women with menopausal syndrome[J].Complement Med Res,2011,18:264-268.
15 Seyyedi F,et al.Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women:a clinical trial study[J].Electronic Physician,2016,8:3184-3192.
16 Koc AN,et al.Antifungal activity of the honeybee products against Candida spp.and Trichosporon spp[J].J Med Food,2011,14:128-134.
17 Khanjani S,et al.Effect of conjugated estrogen in stress urinary incontinence in women with menopause[J].Int J Clin Med,2017,8:375-385.
18 Alreshoodi FM,et al.Antimicrobial activity of royal jelly[J].Anti-Infective Agents,2015,13(1):50-59.
19 Yu LP,et al.Study on bacteriostasis of three bee products in vitro[J].Apiculture of China(中国蜂业),2009,60(3):13-16.
20 Fratini F,et al.Royal jelly:An ancient remedy with remarkable antibacterial properties[J].Microbio Res,2016,192:130-141.
21 Girard R,et al.Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity[J].Sci Rep,2017,7:44917.
22 Anniverno R,et al.Depressive syndrome in perimenopausal,menopausal and postmenopausal patients.An Italian multicentre observational study[J].J Psychopathol,2017,23:19-25.
23 Morita H,et al.Effect of royal jelly ingestion for six months on healthy volunteers[J].Nutrition J,2012,11(1):77.
24 Minami A,et al.Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly[J].Climacteric,2016,19:568-573.
25 Rocha BA,et al.17β-estradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-βknockout(BERKO)mice[J].Psychopharmacol,2005,179:637-643.
26 Walf AA,et al.Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol's modulation of affective and sexual behavior,respectively[J].Neuropsychopharmacol,2008,33:431-440.
27 Jacome LF,et al.Estradiol and ERβagonists enhance recognition memory,and DPN,an ERβagonist,alters brain monoamines[J].Neurobiol Learn Mem,2010,94:488-498.
28 Luine VN,et al.Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density[J].Front Neuroendocrinol,2012,33:388-402.
29 Suzuki KM,et al.Estrogenic activities of fatty acids and a sterol isolated from royal jelly[J].Evid-Based Compl Alt,2008,5:295-302.
30 Moutsatsou P,et al.Fatty acids derived from royal jelly are modulators of estrogen receptor functions[J].PLo S One,2010,5(12):e15594.
31 Chen D,et al.Effect of major royal jelly proteins on spatial memory in aged rats:metabolomics analysis in urine[J].JAgr Food Chem,2017,65:3151-3159.
32 Ito S,et al.Antidepressant-like activity of 10-hydroxy-trans-2-decenoic acid,a unique unsaturated fatty acid of royal jelly,in stress-inducible depression-like mouse model[J].Evid-Based Compl Alt.2012,2012:139-140.
33 Hattori N,et al.Royal jelly and its unique fatty acid,10-hydroxy-trans-2-decenoic acid,promote neurogenesis by neural stem/progenitor cells in vitro[J].Biomed Res,2007,28:261-266.
34 Hattori N,et al.Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases[J].Biomed Res,2007,28:139-146.
35 Furukawa S.Stimulatory effects of royal jelly on the generation of neuronal and glial cells-expectation of protection against some neurological disorders[J].Foods and Food Ingredients J.Jpn,2008,213:620-626.
36 Hattori N,et al.Royal jelly facilitates restoration of the cognitive ability in trimethyltin-intoxicated mice[J].Evid-Based Compl Alt,2011,2011:165968.
37 Li CL,et al.Effects of royal jelly on the sleep of mice[J].Shandong Animal Sci and Veter Med(山东畜牧兽医),2014,12:6-7.
38 Yan JH(闫继红),et al.Study on the effect of royal jelly compound capsule on improving sleep in mice[J].Apiculture of China(中国蜂业),2003,54(6):9.
39 Park HM,et al.Royal jelly increases collagen production in rat skin after ovariectomy[J].J Med Food,2012,15:568-575.
40 Hidaka S,et al.Royal jelly preventsosteoporosis in rats:beneficial effects in ovariectomy model and inbone tissue culture model[J].Evid-Based Compl Alt,2006,3:339-348.
41 Kafadar IH,et al.Royal jelly and bee pollendecrease bone loss due to osteoporosis in an oophorectomized ratmodel[J].Eklem Hastalik Cerrahisi,2012,23:100-105.
42 Kaku M,et al.Royal jelly affects collagen crosslinking in bone of ovariectomized rats[J].J Funct Foods,2014,7:398-406.
43 Yanagita M,et al.Osteoinductive and antiinflammatory effect of royal jelly on periodontal ligament cells[J].Biomed Res,2011,32:285-291.
44 Narita Y,et al.Royal jelly stimulates boneformation:physiologic and nutrigenomic studies with mice and celllines[J].Biosci Biotechnol Biochem,2006,70:2508-2514.
45 Niu K,et al.Royal jelly prevents the progression of sarcopenia in aged mice in vivo and in vitro[J].J Gerontol A Biol Sci Med Sci,2013,68:1482-1492.
46 Matthews KA,et al.Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition[J].J Am Coll Cardiol,2009,54:2366-2373.
47 Tan DH.Experimental study of Gan Lu San on climacteric syndrome[D].Shenyang:Shenyang Pharmaceutical University(沈阳药科大学),2005.
48 Lambrinoudaki I,et al.Greek-origin royal jelly improves the lipid profile of postmenopausal women[J].Gynecol Endocrinol,2016,32:835-839.
49 Sengupta A,et al.Hypolipidemic effect of mustard oil enriched with medium chain fatty acid and polyunsaturated fatty acid[J].Nutrition,2011,27:1183-1193.
50 Xu Q,et al.Medium-chain fatty acids enhanced the excretion of fecal cholesterol and cholic acid in C57BL/6J mice fed a cholesterol-rich diet[J].Biosci Biotechnol Biochem,2013,77:1390-1396.
51 Xue C,et al.Chinese hypertriglycerideamic subjects of different ages responded differently to consuming oil with mediumand long-chain fatty acids[J].Biosci Biotechnol Biochem,2009,73:1711-1717.
52 Xue C,et al.Consumption of medium-and long-chaintriacylglycerols decreases body fat and blood triglyceride in Chinese hypertriglyceridemic subjects[J].Eur J Clin Nutr,2009,63:879-886.
53 Kashima Y,et al.Identification of a novel hypocholesterolemic protein,major royal jelly protein 1,derived from royal jelly[J].PLo S One,2014,9:e105073.
54 Chiu HF,et al.Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults[J].Pharm Biol,2017,55:497-502.
55 Münstedt K,et al.Royal jelly increases high density lipoprotein levels but in older patients only[J].J Altern Complem Med,2009,15:329-330.
56 Pourmoradian S,et al.Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female:a randomized clinical trial[J].Chin J Integr Med,2014,20:347-352.
57 Pourmoradian S,et al.Effects of royal jelly supplementation on body weight and dietary intake in type 2 diabetic females[J].Health Promot Perspect,2012,2:231-235.
58 Viuda-Martos M,et al.Functional properties of honey,propolis,and royal jelly[J].J Food Sci,2008,73:117-124.
59 Wu AX.Hypolipidemic of Royal Jelly And Royal Jelly Protein[D].Fuzhou:Fujian Agriculture and Forestry University(福建农林大学),2012.
60 Tokunaga KH,et al.Antihypertensive effect of peptides from royal jelly in spontaneously hypertensive rats[J].Biol Pharm Bull,2004,27:189-192.
61 Vittek J.Effect of royal jelly on serum lipids in experimental animals and humans with atherosclerosis[J].Cell Mol Life Sci,1995,51:927-935.
62 You TH,et al.Recent advances on active substances of antiaging and its mechanisms[J].Nat Prod Res Dev(天然产物研究与开发),2015,27:1985-1990.
63 Yang Y,et al.Cissus quadrangularis prevented the ovariectomy induced oxidative stress in the femur of adult albino rats[J].Biomed Pharmacother,2016,81:416-423.
64 Qiu BM,et al.Effect of Kun Geng Xin capsule on serum SOD,LPO and MDA in climacteric model rats[J].Laboratory Medicine(检验医学),2016:304-305.
65 Inoue S,et al.Royal jelly prolongs the life span of C3H/He Jmice:correlation with reduced DNA damage[J].Exp Gerontol,2003,38:965-969.
66 Nagai T,et al.Antioxidant properties of enzymatic hydrolysates from royal jelly[J].J Med Food,2006,9:363-367.
67 Cavusoglu K,et al.Royal jelly(honey bee)is a potential antioxidant against cadmium-induced genotoxicity and oxidative stress in albino mice[J].J Med Food,2009,12:1286-1292.
68 Narita Y,et al.Effects of long-term administration of royal jelly on pituitary weight and gene expression in middle-aged female rats[J].Biosci Biotechnol Biochem,2009,73:431-433.
69 Kanno J,et al.The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses:phase 1[J].Environ Health Persp,2001,109:785-794.
70 Minami A,et al.Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly[J].Climacteric,2016,19:568-573.
71 Shahinian VB,et al.Risk of fracture after androgen deprivation for prostate cancer[J].N Engl J Med,2005,352:154-164.