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Traditional Japanese Formula Kigikenchuto Accelerates Healing of Pressure-Loading Skin Ulcer in Rats

By Mari Kimura, Naotoshi Shibahara, Hiroaki Hikiami, Toshiko Yoshida, Michiko Jo, Maria Kaneko, Tatsuya Nogami, Makoto Fujimoto, Hirozo Goto and Yutaka Shimada


We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing. Immunohistochemically, KKT increased CD-31-positive vessels in early phase and increased α-smooth muscle actin-(α-SMA-) positive fibroblastic cells in early phase and decreased them in late phase of wound healing. By Western blotting, KKT showed the potential to decrease inflammatory cytokines (MCP-1, IL-1β, and TNF-α) in early phase, decrease vascular endothelial growth factor in early phase and increase it in late phase, and modulate the expression of extracellular protein matrix (α-SMA, TGF-β1, bFGF, collagen III, and collagen I). These results suggested the possibility that KKT accelerates pressure ulcer healing through decreases of inflammatory cytokines, increase of angiogenesis, and induction of extracellular matrix remodeling

Topics: Research Article
Publisher: Hindawi Publishing Corporation
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Provided by: PubMed Central

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  1. (2009). A chronic pressure ulcer model in the nude mouse,” Wound Repair and Regeneration,
  2. (1997). A comparison of two dressings in the management of chronic wounds,”
  3. (2000). A cost analysisofdiabetic lower-extremity ulcers,”
  4. (1998). a g a s a k a ,H .T o s a ,T .T a s u m i ,Y .S h i m a d a ,a n dT .I t o u , “Four cases report of intractable pressure ulcers effectively treated with Kigi-kenchu-to-ka-bushi,”
  5. (2006). a n e k o ,A .H a s h i m o t o ,N .U m e h a r a ,a n dM .T e z u k a b , “Effects of a new wound dressing material SG-01 in an experimental rat skin burn and decubitus ulcer model,”
  6. (2004). Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds,”
  7. (2003). C h e n ,K .M .L e i f e r m a n ,M .R .P i t t e l k o w ,M .T .O v e r
  8. (2004). Case reports of diabetic foot successfully treated with Kigi-kenchu-to with additional ingredients,”
  9. (1998). Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia,”
  10. (1992). Control of scarring in adult wounds by neutralising antibody to transforming growth factor β,”
  11. (1985). Cutaneous tissue repair: basic biologic considerations.
  12. (2006). Cytokine expression profile over time in severely burned pediatric patients,”
  13. (2005). D e s n e v e s ,B .E .T o d o r o v i c ,A .C a s s a r ,a n dT .C .C r o w e , “Treatment with supplementary arginine, vitamin C and zinc inpatientswithpressureulcers:arandomisedcontrolledtrial,”
  14. (2010). Dermal transforming growth factor-β responsiveness mediates wound contraction and epithelial closure,”
  15. (2000). Dissolution profiles of principal ingredients in Kampo medicinal powders by highperformance liquid chromatography,”
  16. (1998). e t m a r ,L .F .B r o w n ,M .P .S c h ¨ on et al., “Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice,”
  17. (1994). Effects of prostaglandin E1 on human keratinocytes and dermal fibroblasts: a possible mechanism for the healing of skin ulcers,”
  18. Efficacy of vitamin supplementation in situations with wound healing disorders: results from clinical intervention studies,” Current Opinion in Clinical Nutrition andMetabolicCare,vol.12,no.6,pp.588–595,2009.
  19. (1961). Etiology of decubitus ulcers,”
  20. (2010). Evaluating the effect of the new incentive system for high-risk pressure ulcer patients on wound healing and cost-effectiveness: a cohort study,”
  21. (2009). International Guidelines. Pressure Ulcer Prevention: Prevalence and Incidence in Context. A Consensus Document,
  22. (2000). Ischemiareperfusion injury in chronic pressure ulcer formation: a skin model
  23. (2001). K n i g h t ,R .P .T a y l o r ,A .A .P o l l i a c k ,a n dD .L .B a d e r , “Establishingpredictive indicators forthe status ofloaded soft tissues,”
  24. (1996). M a s ta n dG .S .S c h u l t z ,“ I n t e r a c t i o n so fc y t o k i n e s , growth factors, and proteases in acute and chronic wounds,” Wound Repair and Regeneration,
  25. (2004). Mechanical compressioninduced pressure sores in rat hindlimb: muscle stiffness, histology, and computational models,”
  26. (1997). Mechanismsoftissuerepair: fromwoundhealingtofibrosis,”
  27. (2009). Nutritional support in the treatment and prevention of pressure ulcers: an overview of studies with an arginine enriched oral nutritional supplement,”
  28. (2007). o g a m i ,T .H o s h i ,M .K i n o s h i t a ,T .A r a i ,M .T a k a m a ,a n d I.Takahashi,“Vascularendothelialgrowthfactorexpressionin rat skin incision wound,” Medical Molecular Morphology,v o l .
  29. (2001). P e i r c e ,T .C .S k a l a k ,J .M .R i e g e r ,T .L .M a c d o n a l d ,a n dJ . Linden, “Selective A2A adenosine receptor activation reduces skin pressure ulcer formation and inflammation,”
  30. (2007). Persistent ischemia impairs myofibroblast development in wound granulationtissue:anewmodel ofdelayed wound healing,”Wound Repair and Regeneration,
  31. (2009). Radix Astragali extract promotes angiogenesis involving vascular endothelial growth factor receptor-related phosphatidylinositol 3-kinase/aktdependent pathway in human endothelial cells,”
  32. (2004). t a d l e r ,R .Y .Z h a n g ,P .O s k o u i ,M .S .W h i t t a k e r ,a n dR .J . Lanzafame, “Development of a simple, noninvasive, clinically relevant model of pressure ulcers in the mouse,”
  33. (2008). The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo,”
  34. (2003). The etiology of pressure ulcers: skin deep or muscle bound?”
  35. (2008). The loss of MCP-1 attenuates cutaneous ischemia-reperfusion injury in a mouse model of pressure ulcer,”
  36. (2010). The mechanisms underlying fibroblast apoptosis regulated by growth factors during wound healing,”
  37. (2005). Tissue repair, contraction, andthe myofibroblast,”Wound Repair and Regeneration,
  38. (2009). Wound healing activity of aqueous extract of Radix paeoniae root,”
  39. (2008). Wound repair and regeneration,”
  40. (2007). Y.Akasaka,I.Ono,A.Tominagaetal.,“Basicfibroblastgrowth factor in an artificial dermis promotes apoptosis and inhibits expression of α-smooth muscle actin, leading to reduction of wound contraction,”