title: Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.
abstract: OBJECTIVE
  Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health.
  
  
  METHODS
  In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library.
  
  
  RESULTS
  The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts.
  
  
  CONCLUSIONS
  In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes.
authors.affiliation: Nutrilite Health Institute, Amway R&D, 5600 Beach Boulevard, Buena Park, CA 90622, United States; Yumei Consulting, Inc., P.O. Box 821, Huntington Beach, CA 92648, United States.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Nutrilite Health Institute, Amway R&D, 5600 Beach Boulevard, Buena Park, CA 90622, United States.
authors.forename: Valentina
authors.initials: V
authors.lastname: Kazlova
authors.affiliation: Nutrilite Health Institute, Amway R&D, 5600 Beach Boulevard, Buena Park, CA 90622, United States; The Himalaya Drug Company, Makali, Tumkur Road, Bangalore 562123, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Nutrilite Health Institute, Amway R&D, 5600 Beach Boulevard, Buena Park, CA 90622, United States.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Murray
authors.affiliation: Access Business Group, 7575 East Fulton Avenue, Ada, MI 49355, United States.
authors.forename: David
authors.initials: D
authors.lastname: Fast
authors.affiliation: Access Business Group, 7575 East Fulton Avenue, Ada, MI 49355, United States.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Nutrilite Health Institute, Amway R&D, 5600 Beach Boulevard, Buena Park, CA 90622, United States. Electronic address: kevin.gellenbeck@amway.com.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Gellenbeck
mesh_terms: D001862:Bone Resorption / Q000378:metabolism*; D019587:Dietary Supplements; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause
chemical_list: D010936:Plant Extracts
keywords: Bone morphogenetic protein 2; Botanical extracts; Microarray analysis; Receptor activator of nuclear factor kappa-B ligand