title: Rehmanniae Radix in osteoporosis: A review of traditional Chinese medicinal uses, phytochemistry, pharmacokinetics and pharmacology.
abstract: BACKGROUND
  Emerging clinical usage and pharmacological effects have been achieved in using Rehmanniae Radix either singly or in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM) in the recent years. This study is aimed to provide a comprehensive review about the historical TCM interpretation of the action of Rehmanniae Radix in osteoporosis, its usage in clinical trials and osteoporotic models, its main phytochemical constituents, and its pharmacokinetics.
  
  
  METHODS
  Several databases included PubMed, China Knowledge Resource Integrated Database, China Science and Technology Journal Database, National Science and Technology Library and the Web of Science Database were consulted to locate the publications pertaining to Rehmanniae Radix. The initial inquiry was conducted for the presence of the following terms combinations in the abstracts: Rehmanniae Radix, Dihuang, phytochemistry, pharmacokinetics, osteoporosis, bone, osteoclast and osteoblast. About 330 research papers and reviews were consulted.
  
  
  RESULTS
  In TCM, Rehmanniae Radix exerts the anti-osteoporotic effect via regulating the functions of kidney and liver as well as improving blood circulation. 107 clinical trials are identified that used Rehmanniae Radix in combination with other herbs to treat post-menopausal, senile and secondary osteoporosis. Most of the clinical trials are characterized by high efficacy and no obvious adverse effects. However, the efficacies of these clinical trials are limited because of small patient sample size, short treatment duration and poor clinical design. In addition, TCM herbs under the clinical study are not clear because of a lack of standardization and authentication. The pharmacokinetics data demonstrate that the ingredients of Rehmanniae Radix are widely distributed after administration, and that catalpol and ajugol as well as acetoside are supposed to be the active constituents. More than 140 individual compounds have been currently isolated from this plant and reported to show pleiotropic effects on various diseases. Rehmanniae Radix displays bone protecting features in the osteoporosis models via the delicate balance between osteoclastogenesis and osteoblastogenesis through single herb extracts and its isolated compounds.
  
  
  CONCLUSIONS
  The successful inclusion of Rehmanniae Radix in clinical trials and preclinical studies for the management of osteoporosis has attracted rising attentions for identifying potential anti-osteoporotic candidates from this plant and clinical existing TCM formulas, which will further speed up anti-osteoporosis drug discovery processes. Properly designed and well controlled prospective studies are still needed to further demonstrate bone protective actions and safe use of this herb and its ingredients.
authors.affiliation: Chinese Material Medica School, Beijing University of Chinese Medicine, Beijing 100102, China.
authors.forename: Chenyue
authors.initials: C
authors.lastname: Liu
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Ma
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Ruyuan
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Beijing Research Institute of Chinese Medicine and Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8549, USA.
authors.forename: Shangang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: The First Affiliated Hospital of He'nan TCM College, Zhengzhou 45000, China.
authors.forename: Jinfa
authors.initials: J
authors.lastname: Tang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Niu
authors.affiliation: The Research Institute of McGill University Health Center, Montreal, Quebec, Canada H4A 3J1.
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: dongwei1006@gmail.com.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: gaosihua1216@163.com.
authors.forename: Sihua
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008516:Medicine, Chinese Traditional / Q000379:methods; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D032267:Rehmannia / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal; D010936:Plant Extracts
keywords: Ajugol, CID 6325127; Catalpol, CID 91520; Clinical trial; Gentisic acid, CID 3469; Oleanolic acid, CID 10494; Osteoporosis; Pharmacokinetics; Pharmacology; Phytochemistry; Rehmaglutin A, CID 5320903; Rehmaglutin B, CID 14413769; Rehmaglutin C, CID 21637649; Rehmaglutin D, CID 5320906; Rehmaionoside A, CID 10023290; Rehmaionoside B, CID 10430488; Rehmaionoside C, CID 11740990; Rehmanniae Radix; Rehmannioside A, CID 78407230; Rehmannioside B, CID 101654196; Rehmannioside C, CID 101654197; Rehmannioside D, CID 92044472; Versulin, CID 5280443; and geniposide, CID 107848