title: A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.
abstract: Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow cytometric analysis revealed that NF3 could boost circulating EPC levels for local wound vessel incorporation. Immunohistochemical analysis showed that NF3 could significantly augment blood vessel density, VEGF and eNOS expression, and attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3 significantly stimulated MMP activity involved in angiogenesis. Our study shows, for the first time, the beneficial effects of NF3 in wound healing and post-ischemic neovascularization in diabetes.
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Jacqueline Chor-Wing
authors.initials: JC
authors.lastname: Tam
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Chun-Hay
authors.initials: CH
authors.lastname: Ko
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Kit-Man
authors.initials: KM
authors.lastname: Lau
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Ming-Ho
authors.initials: MH
authors.lastname: To
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Hin-Fai
authors.initials: HF
authors.lastname: Kwok
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Yuet-Wa
authors.initials: YW
authors.lastname: Chan
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Wing-Sum
authors.initials: WS
authors.lastname: Siu
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Etienne-Selloum
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lau
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Wai-Yee
authors.initials: WY
authors.lastname: Chan
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Ping-Chung
authors.initials: PC
authors.lastname: Leung
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Kwok-Pui
authors.initials: KP
authors.lastname: Fung
authors.affiliation: Faculté de Pharmacie, Université de Strasbourg, France. Electronic address: valerie.schini-kerth@unistra.fr.
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address: claralau@cuhk.edu.hk.
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D017719:Diabetic Foot / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006614:Hindlimb; D007511:Ischemia / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Astragalus membranaceus; Chinese medicines; Diabetic foot; Hindlimb ischemia; Rehmannia glutinosa; Wound healing