Table 1.
Medical plants and their effects in wound healing.
| Plant | Parts Used | Main Bioactive Components | In Vivo Wound Model, Doses and Routes of Administration | In Vitro Model and Doses | Biological Activity | Mechanism of Action | Ref. |
|---|---|---|---|---|---|---|---|
| Achillea millefolium | flower aerial parts | FLAVONOIDS (chlorogenic acid, apigenin, artemetin, luteolin, quercetina and shaftoside) |
Full-thickness incisional wound in Sprague-Dawley rats―topical: 3% acqueous extract (AAE). | Hs68, HaCaT, and RAW 264.7 cell line: 25–100 μg/mL AAE. |
Antibacterial Anti-inflammatory Re-epithelialization process |
Modulates the inflammatory cytokine and growth factor; activates Akt signaling pathways; stimulates collagen expression; stimulates keratinocyte differentiation and motility; reduces inflammatory mediators NO and PGE2. | [69] |
| Aloe vera | fleshy leaves | FLAVONOIDS (aloin, aleosin, emodin, rhein) POLYSACCHARIDES (acemannan, acetylated polymannan and glucomannan) |
Full-thickness wound in Wistar rats― topical: 25–50 mg/mL in gel. Full-thickness wounds in hairless mouse― topical: 0.1% and 0.5% w/w. Full-thickness wounds in mice― topical: 10 and 50 mg/kg. Burn wounds in BALB/c mice― Topical: aloe-emodin 1 × 10−8, 1 × 10−10 and 1 × 10−12% w/w. |
Fibroblast: 50, 100 and 150 μg/mL. HaCaT and Raw 264.7 cell line: 1, 5 and 10 µM aloesin. Primary epidermal keratinocytes and dermal fibroblasts: 2% and 3% |
Antibacterial Anti- Inflammatory Re-epithelialization process |
Modulates the inflammatory response; modulates signaling proteins phosphorylation; Stimulates collagen deposition and angiogenesis; Strongly promotes fibroblast proliferation and moderately stimulates keratinocyte migration. | [77,78,79,81,83,87] |
| Bletilla striata | root (tuber) | FLAVONOIDS (anthocyanins) POLYSACCHARIDES (glucomannan) TRITERPENOIDS STILBENOIDS (bibenzyl, bletilol D, bletilol E, dihydrophenanthrene and phenanthrene) |
Partial-thickness burn wound model in mice topical: 1 mg/mL BSP extract or BSP polysaccharides residue extract or Mix |
human mesangial cells (HMCs): 5, 10, and 20 μg/mL. | Antimicrobial and antiviral Antioxidative Anti-aging Anti-inflammatory Re-epithelialization process Hemostatic activity |
Promotes expression of mediators of the inflammatory response (TNF-α, IL-1β, and IFN-γ); increases NO and promotes neutrophils, monocytes, and macrophages chemotaxis; promotes epithelial cells growth and fibroblast proliferation. | [91,97,101,103] |
| Calendula officinalis | flowers | TRITERPENOIDS FLAVONOIDS (rosmarinic acid, caffeic acid, 5-O-caffeoylquinic acid, isorhamnetin-3-O-glucoside, isorhamnetin-3-O-rutinoside, kaempferol-3-O-rutinoside, quercetin-3-O-glucoside and quercetin-3-O-rutinoside) COUMARINES, QUINONES |
Full-thickness excisional wound in BALB/c―topical: 150 mg/kg BW ethanolic or water extract ointment. Metallic punch Wistar rats—topical: 100 uL of acqueous solution of 1% ethanolic extract. Incisional wound in Sprague-Dawley rats― topical: 5–10% gel. Full-thickness wound in Wistar rats topical: wound dressing in nanofibers with 2% CO extract. |
Human dermal fibroblasts: 100 ug/mL of extract. NIH-3T3, WI38, human dermal fibroblasts: 1:100–1:50 tinture for 0–60 min. human immortalised Keratinocytes: 10–50 ug/mL of hexanic, ethanolic or acqueous extracts. |
Anti- Inflammatory Re-epithelialization process |
Promotes expression of mediators of the inflammatory response; increases keratinocytes and fibroblasts proliferation; stimulates collagen production and angiogenesis; inhibits lipoxygenase activity; reduced glutathione levels. | [110,111,115,116,117,118,119] |
| Casearia sylvestris | leaves | TRITERPENOIDS (clerodane diterpenes) PHENOLIC ACIDS |
Full-thickness lesions― topical: 0.1, 0.3, 1.0 mg/site extract. Second degree burn in Wistar rats―topical: biofilm with 1 g of lyophilized extract or spray with extract. |
Anti-inflammatory | Reduces early and late edema; reduces myeloperoxidase activity. | [123,127,128] | |
| Crocus sativus | stigmi, stamen, flowers | CAROTENOIDS (crocin, crocetin, picrocrocin and safranal) MONO-TERPENOIDS FLAVONOIDS (kempherol and quercetin) PHENOLIC ACIDS |
Second degree burn in Wistar rats―topical: cream with 20% pollen saffron. Full thickness wound in Sprague-Dawley rats―topical: pomade with 20% saffron extract |
Fibroblasts from newborn mice: hydrogel with 160 mg/L crocin from saffron. Human dermal fibroblasts: 3.12–50 μg/mL for 6–24 h C2C12, MCF7, HCT116 cell lines:125 ug/mL of saffron anther extract |
Antioxidant Anti-inflammatory Re-epithelialization process |
Reduces the level of pro-inflammatory cytokines (TNF-α and IL-6) Increases level of anti-inflammatory cytokines (IL-4 and IL-10); Inhibits lipid peroxidation Enhances vascularization; increases fibroblasts proliferation. |
[141,142,144,145] |
| Curcuma longa | rhizomes | CURCUMINOIDS (bisdemethoxycurcumin, curcumin and demethoxycurcumin) |
Full-thickness wound in Balb/c mice―topical: gel 3% curcumin Full-thickness wound in W rats―topical: PCL nanofibers 10% curcumin Full-thickness wound in W. Rats―topical: PVA nanofibers 1% curcumin Full thickness wound model in SD rats―topical: 100–200 ug/mL curcumin nanoparticle loaded dermal patch |
Rat BMSCs bone marrow mesenchymal stem cells: 10 μM curcumin Mouse 3T3 fibroblast: PCL nanofibers 10% curcumin Swiss 3T6 cell lines PVA nanofibers 1% curcumin HADF cells: 100–200 ug/mL curcumin nanoparticles |
Antioxidant Radical-Scavenging Anti-inflammatory Re-epithelialization process |
Regulates many genes implicated in the initiation of inflammatory responses (NF-(κ)B, AKT, PI3K, IKK); enhances fibroblast migration, granulation tissue formation, collagen deposition; increases TGF-β production; increases fibroblast proliferation. | [167,169,171,175,177] |
| Glycyrrhiza glabra | root, leaves | FLAVONOIDS TERPENOIDS (glycyrrhizic acid, saponins and triterpene) CHALCONES (glycyglabrone & licochalcone C) |
Sprague Dawley rats wound―topical: 3% extract in crem. Guinea pig full-thickness wound―topical: 5% and 10% extract in cream. |
3T3 Cell Line: 1–25 μg/mL extract | Antimicrobial Anti-inflammatory Antioxidant Re-epithelialization process |
Increases collagen deposition; increases the wound healing rate; reduces superoxide anion; inhibits NO production; increases fibroblast proliferation. | [189,190,191] |
| Malva sylvestris | flowers, leaves, root, whole plant | POLYSACCHARIDES FLAVONOIDS (malvidin, malvin, delphinidin, genistein; myricetin, apigenin, quercetin and kaempferol) TERPENOIDS (monoterpenes, diterpenes, sesquiterpenes and nor-terpenes) |
BALB/c mice cut wound– topical: 1% extract in cream. Second degree burn wound in rats―topical: 1–5–10% extract in cream. Diabetic streptozotocin induced wound in W rats—topical: 5–20% extract containing nanofibers |
Mesenchimal Stem cells: 5–20% extract containing nanofibers |
Antibacterial Antioxidant Anti-ageing Anti-inflammatory |
Modulates the inflammatory response; Increases collagen deposition; Enhances vascularization; increases the wound healing rate. | [200,201,202] |
| Plantago L. | leaves | MONOTERPENOIDS (aucubin, acteoside, calceorioside B, catalpol, homoplantaginin and plantamajoside) |
Oral epithelial cell line H400: 0.1 mg/mL extract L229 fibroblast cell line: 0.2–1 ug/mL extract Macrophages: 50–200 ug/mL |
Antibacterial Antioxidant Anti-inflammatory |
Inhibits NO production; reduces superoxide anion; reduces pro-inflammatory cytochine level (PGE2, TNF-α); decreases fibroblasts H2O2 cytotoxicity | [206,207] | |
| Salvia officinalis | aerial parts | TERPENES (1,8-cineole) OXY-SESQUITERPENES (camphor, nonacosane and pentacosane viridiflorol) |
BALB/c mice excisional splinting model―topical: 0.5% w/w dry extract in cream. BALB/c mice full-thickness wounds―topical: 2% and 4% essential oil ointment Wistar rats wound models: topical: 1%, 3% and 5%. hydroalcoholic extract Excision on Streptozotocin-induced diabetic rats: topical: 0.5% and 1% essential oil |
Human dermal fibroblasts and epidermal keratinocytes: 0.031% extract | Anti-inflammatory Antimicrobial Antioxidant |
Reduces pro-inflammatory cytokines; downregulates mRNA expression levels of IL-6, IL-1 β and TNF-α augments fibroblast proliferation via enhancing cyclin-D1 expression. |
[216,221,222,223,224] |
| Rosmarinus officinalis | leaves, flowers roots, stems | FLAVONOIDS (diosmin, eriocitrin, genkwanin isoscutellarein 7-O-glucoside, hispidulin 7-O-glucosidehesperidin and luteolin 3-O-β-D-glucuronide) |
full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice―topical: 100% essential oil - intraperitoneal injection: 0.2 mL, 10% (v/v) Excision on Streptozotocin-induced diabetic rats: topical: 100% essential oil. full thickness excision wound in Sprague Dawley rats -topical: 10% rosemary essential oil in chitosan |
RAW 264.7 murine macrophage cells: 5–10 μg/mL hydroalcoholic extract | Antimicrobial Antioxidant Anti-inflaflammatory |
Inhibits NO production; reduces inflammatory cytokines expression (IL-1β, IL-6, TNF-α); reduces expression of iNOS, COX-2, P-IκB and NF-κB/p65. | [228,230,232,234,235] |
Akt: Protein Kinase B; NO: Nitric Oxide; TNF-α: Tumor necrosis factor alpha; IL: Interleukin; IFN-γ: Interferon gamma; NF-(κ)B: Nuclear Factor Kappa B; PI3K: Phosphoinositide 3-kinase; IKK: IkappaB Kinase; TGF-β: Transforming Growth Factor beta; PGE2: Prostaglandin E; H2O2: Hydrogen peroxide; iNOS: Inducible Nitric Oxide Synthase; COX-2: Cyclooxygenase-2; P-IκB: Phosphorylated Inhibitor kappaB.