题名

Evaluation of selected traditional Chinese medical extracts for bone mineral density maintenance: A mechanistic study

DOI

10.1016/j.jtcme.2017.07.004

作者

John F. Rebhun;Qin Du;Molly Hood;Hailing Guo;Kelly M. Glynn;Hao Cen;Jeffrey D. Scholten;Feng Tian;Min Gui;Minjie Li;Yongfang Zhao

关键词

Epimedium brevicornu ; Drynaria fortunei ; Osteoporosis ; Estrogenic ; Anti-inflammatory

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

9卷3期(2019 / 07 / 01)

页次

227 - 235

内容语文

英文

中文摘要

Objective: To investigate the development of a minimal traditional Chinese medicine (TCM) formula using selected TCM ingredients and evaluating their biological activity with bone-specific in vitro tests. Finally, determining if the minimal formula can maintain bone mineral density (BMD) in a low bone mass (LBM)/osteoporosis (OP) model system. Methods and results: Sixteen different TCM plant extracts were tested for estrogenic, osteogenic and osteoclastic activities. Despite robust activation of the full-length estrogen receptors α and β by Psoralea corylifolia and Epimedium brevicornu, these extracts do not activate the isolated estrogen ligand binding domains (LBD) of either ERα or ERβ; estrogen (17-β estradiol) fully activates the LBD of ERα and ERβ. E. brevicornu and Drynaria fortunei extracts activated cyclic AMP response elements (CRE) individually and when combined these ingredients stimulated the production of osteoblastic markers Runx2 and Bmp4 in MC3T3-E1 cells. E. brevicornu, Salvia miltiorrhiza, and Astragalus onobrychis extracts inhibited the Il-1β mediated activation of NF-kβ and an E. brevicornu/D. fortunei combination inhibited the development of osteoclasts from precursor cells. Further, a minimal formula containing the E. brevicornu/ D. fortunei combination with or without a third ingredient (S. miltiorrhiza, Angelica sinensis, or Lycium barbarum) maintained bone mineral density (BMD) similar to an estradiol-treated control group in the ovariectomized rat; a model LBM/OP system. Conclusion: A minimal formula consisting of TCM plant extracts that activate CRE and inhibit of NF-kβ activation, but do not behave like estrogen, maintain BMD in a LBM/OP model system.

主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. (2011).SPSS Statistics for Windows, Version 20.0 [computer program]. Version 20.0. Armonk, NY2011..
  2. Ba, F,Pang, PK,Davidge, ST,Benishin, CG(2004).The neuroprotective effects of estrogen in SK-N-SH neuroblastoma cell cultures.Neurochem Int,44(6),401-411.
  3. Bauer W, Aub JC, Albright F. Studies of calcium and phosphorus metabolism : V. A study of the bone Trabeculae as a readily available reserve supply of calcium. J Exp Med. 1929;49(1):145-162.
  4. Berthois, Y,Katzenellenbogen, JA,Katzenellenbogen, BS(1986).Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture.Proc Natl Acad Sci,83(8),2496-2500.
  5. Bunone, G,Briand, PA,Miksicek, RJ,Picard, D(1996).Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation.EMBO J.,15(9),2174-2183.
  6. Choi, HJ,Park, YR,Nepal, M(2010).Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kB signaling pathways.Eur J Pharmacol,636(1),28-35.
  7. Chopra, B,Dhingra, AK,Dhar, KL(2013).Psoralea corylifolia L. (Buguchi)dFolklore to modern evidence: review.Fitoterapia,90,44-56.
  8. Dell'Agli, M,Galli, GV,Dal Cero, E(2008).Potent inhibition of human phosphodiesterase-5 by icariin derivatives.J Nat Prod.,71(9),1513-1517.
  9. Dunn, OJ(1964).Multiple comparisons using rank sums.Technometrics,6(3),241-252.
  10. Finkelstein, JS,Klibanski, A,Schaefer, EH,Hornstein, MD,Schiff, I,Neer, RM(1994).Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency.N. Engl J Med.,331(24),1618-1623.
  11. Franceschi, RT,Xiao, G,Jiang, D,Gopalakrishnan, R,Yang, S,Reith, E(2003).Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation.Connect tissue Res,44(1),109-116.
  12. Fu, Q,Jilka, RL,Manolagas, SC,O'Brien, CA(2002).Parathyroid hormone stimulates receptor activator of NFkappa B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein.J Biol Chem,277(50),48868-48875.
  13. Ghisletti, S,Meda, C,Maggi, A,Vegeto, E(2005).17b-estradiol inhibits inflammatory gene expression by controlling NF-kB intracellular localization.Mol Cell Biol,25(8),2957-2968.
  14. Glazier, MG,Bowman, MA(2001).A review of the evidence for the use of phytoes-trogens as a replacement for traditional estrogen replacement therapy.Archives Intern Med.,161(9),1161-1172.
  15. Hsieh, T-P,Sheu, S-Y,Sun, J-S,Chen, M-H(2011).Icariin inhibits osteoclast differentiation and bone resorption by suppression of MAPKs/NF-kB regulated HIF-1a and PGE 2 synthesis.Phytomedicine,18(2),176-185.
  16. Hsieh, TP,Sheu, SY,Sun, JS,Chen, MH,Liu, MH(2010).Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression.Phytomedicine,17(6),414-423.
  17. Huang, JC,Sakata, T,Pfleger, LL(2004).PTH differentially regulates expression of RANKL and OPG.J bone mineral Res official J Am Soc Bone Mineral Res,19(2),235-244.
  18. Investigators, WGftWsHI(2002).Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.Jama,288(3),321-333.
  19. Jang, SN,Choi, YH,Choi, MG(2006).Prevalence and associated factors of osteoporosis among postmenopausal women in Chuncheon: Hallym Aging Study (HAS).J Prev Med public health,39(5),389-396.
  20. Jin, Q,Lee, C,Lee, JW(2014).2-Phenoxychromones and prenylflavonoids from Epimedium koreanum and their inhibitory effects on LPS-induced nitric oxide and interleukin-1b production.J Nat Prod,77(7),1724-1728.
  21. Juppner, H,Abou-Samra, AB,Freeman, M(1991).A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide.Science,254(5034),1024-1026.
  22. Kalu, DN.(1984).Evaluation of the pathogenesis of skeletal changes in ovariectomized rats.Endocrinology,115(2),507-512.
  23. Kameda, T,Mano, H,Yuasa, T(1997).Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts.J Exp Med,186(4),489-495.
  24. Kanis, JA,McCloskey, EV,Johansson, H,Oden, A,Melton, LJ, 3rd,Khaltaev, N(2008).A reference standard for the description of osteoporosis.Bone,42(3),467-475.
  25. Khosla, S,Westendorf, JJ,Oursler, MJ(2008).Building bone to reverse osteoporosis and repair fractures.J Clin Invest,118(2),421.
  26. Kim, JM,Choi, JS,Kim, YH(2013).An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells.J Cell physiology,228(3),617-626.
  27. Klinge, CM(2001).Estrogen receptor interaction with estrogen response elements.Nucleic acids Res,29(14),2905-2919.
  28. Mok, SK,Chen, WF,Lai, WP(2010).Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells.Br J Pharmacol,159(4),939-949.
  29. Nakamura, T,Imai, Y,Matsumoto, T(2007).Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts.Cell,130(5),811-823.
  30. Nelson, HD,Helfand, M,Woolf, SH,Allan, JD(2002).Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services Task Force.Ann Intern Med,137(6),529-541.
  31. Powell, WF, Jr,Barry, KJ,Tulum, I(2011).Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses.J Endocrinol,209(1),21-32.
  32. Rajgopal, A,Missler, SR,Scholten, JD(2016).Magnolia officinalis (Hou Po) bark extract stimulates the Nrf2-pathway in hepatocytes and protects against oxidative stress.J Ethnopharmacol,193,657-662.
  33. Rajgopal, A,Rebhun, JF,Burns, CR,Scholten, JD,Balles, JA,Fast, DJ(2015).Immunomodulatory effects of Lippia sidoides extract: induction of IL-10 through cAMP and p38 MAPK-dependent mechanisms.J Med food,18(3),370-377.
  34. Rebhun, JF,Glynn, KM,Missler, SR(2015).Identification of glabridin as a bioactive compound in licorice (Glycyrrhiza glabra L.) extract that activates human peroxisome proliferator-activated receptor gamma (PPARgamma).Fitoterapia,106,55-61.
  35. Rebhun, JF,Roloff, SJ,Velliquette, RA,Missler, SR(2015).Identification of evodiamine as the bioactive compound in evodia (Evodia rutaecarpa Benth.) fruit extract that activates human peroxisome proliferator-activated receptor gamma (PPAR-gamma).Fitoterapia,101,57-63.
  36. Riancho, JA,Hernandez, JL(2012).Pharmacogenomics of osteoporosis: a pathway approach.Pharmacogenomics,13(7),815-829.
  37. Rossouw, JE,Anderson, GL,Prentice, RL(2002).Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.Jama,288(3),321-333.
  38. Saini, V,Marengi, DA,Barry, KJ(2013).Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH.J Biol Chem,288(28),20122-20134.
  39. Songlin, P,Ge, Z,Yixin, H(2009).Epimedium-derived flavonoids promote osteo-blastogenesis and suppress adipogenesis in bone marrow stromal cells while exerting an anabolic effect on osteoporotic bone.Bone,45(3),534-544.
  40. Srivastava, S,Weitzmann, MN,Cenci, S,Ross, FP,Adler, S,Pacifici, R(1999).Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD.J Clin Invest,104(4),503-513.
  41. Srivastava, S,Weitzmann, MN,Kimble, RB(1998).Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1.J Clin Invest,102(10),1850-1859.
  42. Stein, B,Yang, MX(1995).Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta.Mol Cell Biol,15(9),4971-4979.
  43. Strickson, S,Campbell, DG,Emmerich, CH(2013).The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system.Biochem J.,451(3),427-437.
  44. Wang, Z-q,Li, J-l,Sun, Y-l(2013).Chinese herbal medicine for osteoporosis: a systematic review of randomized controlled trails.Evidence-Based Complementary Altern Med,27-48.
  45. Weitzmann, MN,Pacifici, R(2006).Estrogen deficiency and bone loss: an inflammatory tale.J Clin Invest,116(5),1186-1194.
  46. Xin, D,Wang, H,Yang, J(2010).Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.Phytomedicine,17(2),126-131.
  47. Xu, H,Lawson, D,Kras, A,Ryan, D(2005).The use of preventive strategies for bone loss.Am J Chin Med,33(02),299-306.
  48. Zeng, K-W,Fu, H,Liu, G-X,Wang, X-M(2010).Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-kB and JNK/p38 MAPK pathways.Int Immunopharmacol,10(6),668-678.
  49. Zhai, YK,Guo, X,Pan, YL(2013).A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy.Die Pharm,68(9),713-722.
  50. Zhang, G,Qin, L,Hung, W(2006).Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption.Bone,38(6),818-825.
  51. Zhang, G,Qin, L,Shi, Y(2007).Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.J bone mineral Res official J Am Soc Bone Mineral Res,22(7),1072-1079.
  52. Zhao, J,Ohba, S,Shinkai, M,Chung, U-i,Nagamune, T(2008).Icariin induces osteogenic differentiation in vitro in a BMP-and Runx2-dependent manner.Biochem bio-physical Res Commun,369(2),444-448.