Cimicifuga heracleifolia is therapeutically similar to black cohosh in relieving menopausal symptoms: evidence from pharmacological and metabolomics studies
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摘要
In the market of botanical dietary supplements, Cimicifuga heracleifolia(CH) has always been considered as an adulterated species of Cimicifuga racemosa(CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized(OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography(Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry(GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.
In the market of botanical dietary supplements, Cimicifuga heracleifolia(CH) has always been considered as an adulterated species of Cimicifuga racemosa(CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized(OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography(Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry(GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.
In the market of botanical dietary supplements, Cimicifuga heracleifolia(CH) has always been considered as an adulterated species of Cimicifuga racemosa(CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized(OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography(Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry(GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.
引文
[1]Nelson HD.Menopause[J].Lancet,2008,371(9614):760-770.
[2]Takahashi TA,Johnson KM.Menopause[J].Med Clin North Am,2015,99(3):521-534.
[3]Go H,Ryuk JA,Lee HW,et al.Palmiwon attenuates hepatic lipid accumulation and hyperlipidemia in a menopausal rat model[J].Menopause,2015,22(8):872-884.
[4]Tella SH,Gallagher JC.Prevention and treatment of postmenopausal osteoporosis[J].J Steroid Biochem Mol Biol,2014,142:155-170.
[5]Gordon JL,Girdler SS.Hormone replacement therapy in the treatment of perimenopausal depression[J].Curr Psychiatry Rep,2014,16(12):517.
[6]Beral V.Ovarian cancer and hormone replacement therapy in the Million Women Study[J].Lancet,2007,369(9574):1703-1710.
[7]Bae JM,Kim EH.Hormone replacement therapy and risk of breast cancer in Korean women:a quantitative systematic review.[J].J Prev Med Public Health,2015,48(5):225-230.
[8]Eden JA.Menopausal status,adipose tissue,and breast cancer risk:impact of estrogen replacement therapy[J].Horm Mol Biol Clin Investig,2013,14(2):57-63.
[9]Bai W,Henneicke-von Zepelin HH,Wang S,et al.Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms:a randomized,double blind,parallel-controlled study versus tibolone[J].Maturitas,2007,58(1):31-41.
[10]Sun Y,Yu Q,Shen Q,et al.Black cohosh ameliorates metabolic disorders in female ovariectomized rats[J].Rejuvenation Res,2016,19(3):204-214.
[11]Da YM,Niu KY,Liu SY,et al.Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?[J].Biol Res,2017,50(1):11.
[12]Leach MJ,Moore V.Black cohosh(Cimicifuga spp.)for menopausal symptoms[J].Cochrane Database Syst Rev,2012,9(9):CD007244.
[13]Merchant S,Stebbing J.Black cohosh,hot flushes,and breast cancer[J].Lancet Oncol,2015,16(2):137-138.
[14]Pharmacopoeia of The People’s Republic of China[S].2015:73-74.
[15]Li JX,Liu J,He CC,et al.Triterpenoids from Cimicifugae rhizoma,a novel class of inhibitors on bone resorption and ovariectomy-induced bone loss[J].Maturitas,2007,58(1):59-69.
[16]Ahn BS,Yang M,Jang H,et al.Evaluation of the antiosteoporotic potential of Cimicifuga heracleifolia in female mice.[J].Phytother Res,2012,26(5):663-668.
[17]Jiang B,Ma C,Motley T,et al.Phytochemical fingerprinting to thwart black cohosh adulteration:a 15 Actaea species analysis[J].Phytochem Anal,2011,22(4):339-351.
[18]Li JX,Yu ZY.Cimicifugae rhizoma:from origins,bioactive constituents to clinical outcomes[J].Curr Med Chem,2006,13(24):2927-2951.
[19]Ma C,Kavalier AR,Jiang B,et al.Metabolic profiling of Actaea species extracts using high performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry[J].J Chromatogr A,2011,1218(11):1461-1476.
[20]Zhao DS,Jiang LL,Fan YX,et al.Investigation of Dioscorea Bulbifera Rhizome-induced hepatotoxicity in rats by a multisample integrated metabolomics approach[J].Chem Res Toxicol,2017,30(10):1865-1873.
[21]Liu FJ,Liang D,Miao LY,et al.Liver-specific metabolomics characterizes the hepatoprotective effect of saponin-enriched Celosiae Semen extract on mice with nonalcoholic fatty liver disease[J].J Func Foods,2018,42:185-194.
[22]Jayagopal V,Albertazzi P,Kilpatrick ES,et al.Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes[J].Diabetes Care,2002,25(10):1709-1714.
[23]Suliga E,Koziel D,Ciesla E,et al.Factors associated with adiposity,lipid profile disorders and the metabolic syndrome occurrence in premenopausal and postmenopausal women[J].PLoS One,2016,11(4):e0154511.
[24]Bendsen NT,Haugaard SB,Larsen TM,et al.Effect of trans-fatty acid intake on insulin sensitivity and intramuscular lipids-a randomized trial in overweight postmenopausal women[J].Metabolism,2011,60(7):906-913.
[25]Lenora J,Ivaska KK,Gerdhem P.Use of bone turnover markers in osteoporosis[J].Clin Rev Bone Miner Metab,2009,8(1):1-14.
[26]Ma B,Zhang Q,Wang GJ,et al.GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats[J].Acta Pharmacol Sin,2011,32(2):270-278.
[27]Zhao G,Etherton TD,Martin KR,et al.Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects[J].Am J Clin Nutr,2007,85(2):385-391.
[28]Gortan Cappellari G,Losurdo P,Mazzucco S,et al.Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause[J].JNutr Biochem,2013,24(1):371-379.
[29]Lands WEM.Control of prostaglandin biosynthesis[J].Prog Lipid Res,1981,20:875-883.
[30]Longo AB,Ward WE.PUFAs,Bone mineral density,and fragility fracture:findings from human studies.[J].Adv Nutr,2016,7(2):299-312.
[31]Ma B,Liu J,Zhang Q,et al.Metabolomic profiles delineate signature metabolic shifts during estrogen deficiency-induced bone loss in rat by GC-TOF/MS[J].PLoS One,2013,8(2):e54965.
[32]Lin Y,Berg AH,Iyengar P,et al.The hyperglycemia-induced inflammatory response in adipocytes:the role of reactive oxygen species[J].J Biol Chem,2005,280(6):4617-4626.
[33]Xue L,Wang Y,Liu L,et al.A HNMR-based metabonomics study of postmenopausal osteoporosis and intervention effects of Er-Xian Decoction in ovariectomized rats[J].Int J Mol Sci,2011,12(11):7635-7651.
[34]Confavreux CB.Bone:from a reservoir of minerals to a regulator of energy metabolism[J].Kidney Int,2011,79:S14-S19.
[35]You YS,Lin CY,Liang HJ,et al.Association between the metabolome and low bone mineral density in Taiwanese women determined by 1H NMR spectroscopy[J].J Bone Miner Res,2014,29(1):212-222.
[36]Auro K,Joensuu A,Fischer K,et al.A metabolic view on menopause and ageing[J].Nat Commun,2014,5:4708.
[37]Liu YR,Huang RQ,Xiao BK,et al.1H NMR metabolic profiling analysis offers evaluation of Nilestriol treatment in ovariectomised rats[J].Mol Cell Endocrinol,2014,387(1-2):19-34.
[38]Conigrave AD,Brown EM,Rizzoli R.Dietary protein and bone health:roles of amino acid-sensing receptors in the control of calcium metabolism and bone homeostasis[J].Annu Rev Nutr,2008,28:131-155.
[39]Zhang L,Wang Y,Xu Y,et al.Metabonomic analysis reveals efficient ameliorating effects of acupoint stimulations on the menopause-caused alterations in mammalian metabolism[J].Sci Rep,2014,4:3641.
[40]Pernow Y,Thoren M,Saaf M,et al.Associations between amino acids and bone mineral density in men with idiopathic osteoporosis[J].Bone,2010,47(5):959-965.
[2]Takahashi TA,Johnson KM.Menopause[J].Med Clin North Am,2015,99(3):521-534.
[3]Go H,Ryuk JA,Lee HW,et al.Palmiwon attenuates hepatic lipid accumulation and hyperlipidemia in a menopausal rat model[J].Menopause,2015,22(8):872-884.
[4]Tella SH,Gallagher JC.Prevention and treatment of postmenopausal osteoporosis[J].J Steroid Biochem Mol Biol,2014,142:155-170.
[5]Gordon JL,Girdler SS.Hormone replacement therapy in the treatment of perimenopausal depression[J].Curr Psychiatry Rep,2014,16(12):517.
[6]Beral V.Ovarian cancer and hormone replacement therapy in the Million Women Study[J].Lancet,2007,369(9574):1703-1710.
[7]Bae JM,Kim EH.Hormone replacement therapy and risk of breast cancer in Korean women:a quantitative systematic review.[J].J Prev Med Public Health,2015,48(5):225-230.
[8]Eden JA.Menopausal status,adipose tissue,and breast cancer risk:impact of estrogen replacement therapy[J].Horm Mol Biol Clin Investig,2013,14(2):57-63.
[9]Bai W,Henneicke-von Zepelin HH,Wang S,et al.Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms:a randomized,double blind,parallel-controlled study versus tibolone[J].Maturitas,2007,58(1):31-41.
[10]Sun Y,Yu Q,Shen Q,et al.Black cohosh ameliorates metabolic disorders in female ovariectomized rats[J].Rejuvenation Res,2016,19(3):204-214.
[11]Da YM,Niu KY,Liu SY,et al.Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?[J].Biol Res,2017,50(1):11.
[12]Leach MJ,Moore V.Black cohosh(Cimicifuga spp.)for menopausal symptoms[J].Cochrane Database Syst Rev,2012,9(9):CD007244.
[13]Merchant S,Stebbing J.Black cohosh,hot flushes,and breast cancer[J].Lancet Oncol,2015,16(2):137-138.
[14]Pharmacopoeia of The People’s Republic of China[S].2015:73-74.
[15]Li JX,Liu J,He CC,et al.Triterpenoids from Cimicifugae rhizoma,a novel class of inhibitors on bone resorption and ovariectomy-induced bone loss[J].Maturitas,2007,58(1):59-69.
[16]Ahn BS,Yang M,Jang H,et al.Evaluation of the antiosteoporotic potential of Cimicifuga heracleifolia in female mice.[J].Phytother Res,2012,26(5):663-668.
[17]Jiang B,Ma C,Motley T,et al.Phytochemical fingerprinting to thwart black cohosh adulteration:a 15 Actaea species analysis[J].Phytochem Anal,2011,22(4):339-351.
[18]Li JX,Yu ZY.Cimicifugae rhizoma:from origins,bioactive constituents to clinical outcomes[J].Curr Med Chem,2006,13(24):2927-2951.
[19]Ma C,Kavalier AR,Jiang B,et al.Metabolic profiling of Actaea species extracts using high performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry[J].J Chromatogr A,2011,1218(11):1461-1476.
[20]Zhao DS,Jiang LL,Fan YX,et al.Investigation of Dioscorea Bulbifera Rhizome-induced hepatotoxicity in rats by a multisample integrated metabolomics approach[J].Chem Res Toxicol,2017,30(10):1865-1873.
[21]Liu FJ,Liang D,Miao LY,et al.Liver-specific metabolomics characterizes the hepatoprotective effect of saponin-enriched Celosiae Semen extract on mice with nonalcoholic fatty liver disease[J].J Func Foods,2018,42:185-194.
[22]Jayagopal V,Albertazzi P,Kilpatrick ES,et al.Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes[J].Diabetes Care,2002,25(10):1709-1714.
[23]Suliga E,Koziel D,Ciesla E,et al.Factors associated with adiposity,lipid profile disorders and the metabolic syndrome occurrence in premenopausal and postmenopausal women[J].PLoS One,2016,11(4):e0154511.
[24]Bendsen NT,Haugaard SB,Larsen TM,et al.Effect of trans-fatty acid intake on insulin sensitivity and intramuscular lipids-a randomized trial in overweight postmenopausal women[J].Metabolism,2011,60(7):906-913.
[25]Lenora J,Ivaska KK,Gerdhem P.Use of bone turnover markers in osteoporosis[J].Clin Rev Bone Miner Metab,2009,8(1):1-14.
[26]Ma B,Zhang Q,Wang GJ,et al.GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats[J].Acta Pharmacol Sin,2011,32(2):270-278.
[27]Zhao G,Etherton TD,Martin KR,et al.Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects[J].Am J Clin Nutr,2007,85(2):385-391.
[28]Gortan Cappellari G,Losurdo P,Mazzucco S,et al.Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause[J].JNutr Biochem,2013,24(1):371-379.
[29]Lands WEM.Control of prostaglandin biosynthesis[J].Prog Lipid Res,1981,20:875-883.
[30]Longo AB,Ward WE.PUFAs,Bone mineral density,and fragility fracture:findings from human studies.[J].Adv Nutr,2016,7(2):299-312.
[31]Ma B,Liu J,Zhang Q,et al.Metabolomic profiles delineate signature metabolic shifts during estrogen deficiency-induced bone loss in rat by GC-TOF/MS[J].PLoS One,2013,8(2):e54965.
[32]Lin Y,Berg AH,Iyengar P,et al.The hyperglycemia-induced inflammatory response in adipocytes:the role of reactive oxygen species[J].J Biol Chem,2005,280(6):4617-4626.
[33]Xue L,Wang Y,Liu L,et al.A HNMR-based metabonomics study of postmenopausal osteoporosis and intervention effects of Er-Xian Decoction in ovariectomized rats[J].Int J Mol Sci,2011,12(11):7635-7651.
[34]Confavreux CB.Bone:from a reservoir of minerals to a regulator of energy metabolism[J].Kidney Int,2011,79:S14-S19.
[35]You YS,Lin CY,Liang HJ,et al.Association between the metabolome and low bone mineral density in Taiwanese women determined by 1H NMR spectroscopy[J].J Bone Miner Res,2014,29(1):212-222.
[36]Auro K,Joensuu A,Fischer K,et al.A metabolic view on menopause and ageing[J].Nat Commun,2014,5:4708.
[37]Liu YR,Huang RQ,Xiao BK,et al.1H NMR metabolic profiling analysis offers evaluation of Nilestriol treatment in ovariectomised rats[J].Mol Cell Endocrinol,2014,387(1-2):19-34.
[38]Conigrave AD,Brown EM,Rizzoli R.Dietary protein and bone health:roles of amino acid-sensing receptors in the control of calcium metabolism and bone homeostasis[J].Annu Rev Nutr,2008,28:131-155.
[39]Zhang L,Wang Y,Xu Y,et al.Metabonomic analysis reveals efficient ameliorating effects of acupoint stimulations on the menopause-caused alterations in mammalian metabolism[J].Sci Rep,2014,4:3641.
[40]Pernow Y,Thoren M,Saaf M,et al.Associations between amino acids and bone mineral density in men with idiopathic osteoporosis[J].Bone,2010,47(5):959-965.