title: Traditional Chinese medicine formulas for the treatment of osteoporosis: Implication for antiosteoporotic drug discovery.
abstract: BACKGROUND
  Osteoporosis is a chronic epidemic which can leads to enhanced bone fragility and consequent an increase in fracture risk. Traditional Chinese medicine (TCM) formulas have a long history of use in the prevention and treatment of osteoporosis. Antiosteoporotic TCM formulas have conspicuous advantage over single drugs. Systematic data mining of the existing antiosteoporotic TCM formulas database can certainly help the drug discovery processes and help the identification of safe candidates with synergistic formulations. In this review, the authors summarize the clinical use and animal experiments of TCM formulas and their mechanism of action, and discuss the potential antiosteoporotic activity and the active constituents of commonly used herbs in TCM formulas for the therapy of osteoporosis.
  
  
  METHODS
  The literature was searched from Medline, Pubmed, ScienceDirect, Spring Link, Web of Science, CNKI and VIP database from 1989 to 2015, and also collected from Chinese traditional books and Chinese Pharmacopoeia with key words such as osteoporosis, osteoblast, osteoclast, traditional Chinese medicine formulas to identify studies on the antiosteoporotic effects of TCM formulas, herbs and chemical constituents, and also their possible mechanisms.
  
  
  RESULTS
  Thirty-three TCM formulas were commonly used to treat osteoporosis, and showed significant antiosteoporotic effects in human and animal. The herb medicines and their chemical constituents in TCM formulas were summarized, the pharmacological effects and chemical constituents of commonly used herbs in TCM formulas were described in detail. The action mechanisms of TCM formulas and their chemical constituents were described. Finally, the implication for the discovery of antiosteoporotic leads and combinatory ingredients from TCM formulas were prospectively discussed.
  
  
  CONCLUSIONS
  Clinical practice and animal experiments indicate that TCM formulas provide a definite therapeutic effect on osteoporosis. The active constituents in TCM formulas are diverse in chemical structure, and include flavonoids, lignans, saponins and iridoid glycosides. Antiosteoporotic mechanism of TCM formulas and herbs involves multi regulatory pathways, such as Wnt/β-catenin, BMP/Smad, MAPK pathway and RANKL/OPG system. Phytochemicals from TCM formulas and their compositional herb medicines offer great potential for the development of novel antiosteoporotic drugs. The active ingredients in TCM formulas can be developed in combination as potent drugs, which may exhibit better antiosteoporotic effects compared to the individual compound.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Nai-Dan
authors.initials: ND
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Bao-Kang
authors.initials: BK
authors.lastname: Huang
authors.affiliation: Faculty of Science, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, LiverpoolL3 3AF, UK.
authors.forename: Khalid
authors.initials: K
authors.lastname: Rahman
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Jiang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Qin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: hailiangxin@163.com.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Xin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zqy1965@163.com.
authors.forename: Qiao-Yan
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Li
mesh_terms: D031002:Acer / Q000737:chemistry*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D019448:Ethnobotany; D020834:Ethnopharmacology; D006801:Humans; D008516:Medicine, Chinese Traditional; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D064209:Phytochemicals / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D010946:Plants, Medicinal
chemical_list: D050071:Bone Density Conservation Agents; D004365:Drugs, Chinese Herbal; D064209:Phytochemicals; D010936:Plant Extracts
keywords: Action mechanism; Active ingredients; AsperosaponinⅥ (PubChem CID: 71307450); Aucubin (PubChem CID: 91458); Catalpol (PubChem CID: 91520); Cinnamaldehyde (PubChem CID: 637511); Clinical use; Ecdysterone (PubChem CID: 271605); Emodin (PubChem CID: 3220); Ferulic acid (PubChem CID: 445858); Formononetin (PubChem CID: 5280378); Kaempferol (PubChem CID: 5280863); Osteoporosis; Sweroside (PubChem CID: 161036); Traditional Chinese medicine formulas