Table 1.
Wound healing effects of Centella asiatica and asiatic acid in different phases of skin repair process.
| Inflammatory Phase of Acute Wound Healing | |||
|---|---|---|---|
| Experimental Model | Wound Healing Effect | Cellular and Molecular Mechanism | Reference |
| Excision Wounds | CAE complexed with HP-β-CD healed completely the excising wound in rats after 14 days. | The authors attributed the wound healing effect of CAE to presence of asiaticoside that stimulates keratinization, increases the tensile strength and synthesis of collagen and inhibits the inflammatory phase. | [37] |
| Phthalic anhydride (PA)-induced atopic dermatitis | CAE attenuated the development of PA-induced atopic dermatitis. | CAE (1, 2, 5 µg/mL) inhibited mast cells and infiltration of inflammatory cells, expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, CAE potently inhibited NF-κB DNA binding activities in RAW264.7macrophage cells. |
[47] |
| Excision Wounds | CAE reduced the wound area and wound healing period of full-thickness wounds | CAE (100 mg/kg) increase the NOS activity and the levels of TGF-β. | [50] |
| Imiquimod-induced psoriasis | Asiatic acid reduced imiquimod-induced inflammation | Asiatic acid (100 mg/kg) inhibited the increase in serum levels of IL-17A and IL-23 induced by imiquimod | [53] |
| Incision, Burn and Diabetic wounds | CAE and Aa reduced the inflammation and accelerated the wound healing | CAE and Aa reduced inflammatory cells recruitment and reduced pro-inflammatory (e.g., TNF-α, IL-1β and IL-6) levels. | [48,52] |
| Proliferative phase of acute wound healing | |||
| Human Fibroblast cells | CAE and Aa promoted granulation tissue formation and increased the tensile strength | CAE and Aa stimulated fibronectin and collagen synthesis | [58,61] |
| Excision and Incision Wound | CAE and Aa promoted a decrease in the wound area and faster healing of excision wound in rats | CAE and Aa increased collagen synthesis and fibroblast proliferation | [37,39] |
| Incision Wound | CAE accelerated the wound healing of rat incision model | CAE increased cellular proliferation, protein and collagen content of granulation tissues | [54] |
| Open wound | The topical formulation of CAE applied 3 times daily for 24 days wounds promoted epithelialized faster and higher the rate of wound contraction to open wounds in rats | CAE increased cellular proliferation and collagen synthesis | [56] |
| Dexamethasone-suppressed incision wound | Animals treated with CAE showed faster wound contraction than untreated animals | CAE enhanced wound breaking strength, granulation tissue weights, granulation tissue breaking stretch | [57] |
| Remodelling phase of acute wound healing | |||
| Human Fibroblast | Aa induced collagen I synthesis | Aa induced human collagen I synthesis through TGFβ receptor I kinase (TβRI kinase)-independent Smad signaling | [43] |
| Burn wound | Aa decreased wound area and faster healing | C. asiatica and its bioactive glycoside raised TGF-β 1, TβRII and procollagen type I and type III expression | [39] |
| Tongue wounds | CAE increase wound contraction and faster oral tissue regeneration on the healing process | C. asiatica was effective to promote collagen deposition and extracellular matrix accumulation | [66] |
| Incision Wound | CAE and Aa accelerated the wound healing process | CAE and Aa stimulated extracellular matrix accumulation, maintenance of granulation tissue, increase of collagen synthesis and tensile strength force | [45,60] |
| Chronic wound healing | |||
| Streptozotocin-induced diabetes | As facilitated the healing process of diabetic rats | Asiatic acid increased hydroxyproline content, tensile strength, collagen content, maturation and cross linking of collagen and epithelization | [67] |
| Type 2 diabetic patients | CAE, was effective in the wound healing promotion and suppress the scar in diabetic wound patients. | _ | [49,67,68] |