title: Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing.
abstract: BACKGROUND
  Astragali Radix (AR) and Rehmanniae Radix (RR) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic foot ulcer.
  
  
  OBJECTIVE
  In our previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was found effective in enhancing diabetic wound healing in rats through the actions of tissue regeneration, angiogenesis promotion and inflammation inhibition. The aims of the present study were to investigate the herb-herb interaction (or the possible synergistic effect) between AR and RR in NF3 to promote diabetic wound healing and to identify the principal herb in the formula by evaluating the potencies of individual AR and RR in different mechanistic studies.
  
  
  METHODS
  A chemically induced diabetic foot ulcer rat model was used to examine the wound healing effect of NF3 and its individual herbs AR and RR. For mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration assays were adopted to investigate the anti-inflammatory, granulation formation and angiogenesis-promoting activities of the herbal extracts, respectively.
  
  
  RESULTS
  In the foot ulcer animal model, neither AR nor RR at clinical relevant dose (0.98g/kg) promoted diabetic wound healing. However, when they were used in combination as NF3, synergistic interaction was demonstrated, of which NF3 could significantly reduce the wound area of rats when compared to water group (p<0.01). For anti-inflammation and granulation formation, AR was more effective than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells.
  
  
  CONCLUSIONS
  AR plays a preeminent role in the anti-inflammatory and fibroblast-proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3 to exert its overall wound-healing as well as the underlying angiogenesis-promoting effects. The results of present study justified the combined usage of AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated that AR is the principal herb in this herbal formula.
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Kit-Man
authors.initials: KM
authors.lastname: Lau
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Lai
authors.forename: Cheuk-Lun
authors.initials: CL
authors.lastname: Liu
authors.forename: Jacqueline Chor-Wing
authors.initials: JC
authors.lastname: Tam
authors.forename: Ming-Ho
authors.initials: MH
authors.lastname: To
authors.forename: Hin-Fai
authors.initials: HF
authors.lastname: Kwok
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lau
authors.forename: Chun-Hay
authors.initials: CH
authors.lastname: Ko
authors.forename: Ping-Chung
authors.initials: PC
authors.lastname: Leung
authors.forename: Kwok-Pui
authors.initials: KP
authors.lastname: Fung
authors.forename: Simon Kar-Sing
authors.initials: SK
authors.lastname: Poon
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D027883:Astragalus Plant / Q000737:chemistry; D027885:Astragalus propinquus; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D017719:Diabetic Foot / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D032267:Rehmannia / Q000737:chemistry; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D009569:Nitric Oxide; C027492:Huang Qi