Evidence-Based Complementary and Alternative Medicine

Review Article

Medicinal Plants for the Treatment of Hypertrophic Scars

Table 1

The components from medicinal plants with antihypertrophic scar activity.


Component	Botanical name	Family	Medicinal part	Observation	Dose	Effect	Mechanism of action	References

Madecassoside	Centella asiatica	Umbelliferae	Whole plant	In vitro	10~100 μM	Antiproliferation of HSFBs Promotion of apoptosis Diminishment of scar formation Facilitation of wound healing	Inhibition of HKF migration, F-actin filaments protein, and cytoskeletal protein. Promotion of nuclear shrinkage and mitochondrial membrane depolarization Condensation of chromatin and fragment of nuclei Inhibitory phosphorylation of p38, PI3K, AKT, and cofilin. Activation of caspase-3/caspase-9 Facilitation of Bax mRNA expression and decrease of Bcl-2 and MMP-13 mRNA expression	[11, 12]

Genistein	Glycine max	Leguminosae	Fruit	In vitro	25~100 μg/mL	Anti-proliferation of HSFBs Suppression of mitosis Promotion of apoptosis	Inhibition of TPKs, increase of caspase-3, and decreases of α-SMA and Bcl-2 protein Enhancement of Bax protein Inhibition of types I/III precollagen mRNA expression, down-regulation of collagen I/III mRNA, reduction of PCNA expression, and inhibitory phosphorylation of c-Raf, MEK1/2, ERK1/2, and p38 Induction of morphology changes of apoptosis cells Inhibitory transdifferentiation of fibroblasts into myofibroblasts	[13–17]
Genistein	Glycine max	Leguminosae	Fruit	In vitro	37~370 µM		Decrease of G₀-G₁ phase and increase of G₂-M phase Increase of C-JUN mRNA expression and decrease of FOS-B mRNA expression in skin keratinocytes Inhibitory mRNA expression of C-JUN and C-FOS in human fibroblasts In keloid fibroblasts, decrease of C-JUN and C-FOS mRNA expression at 37 µM, but enhancement at 370 µM	[13–17]

Astragaloside IV	Astragalus Membranaceus	Leguminosae	Root	In vitro	12.5~200 μM	Antiproliferation of HSFBs	Decrease of collagen I/collagen III and TGF-β₁ secretion	[18]

Tetrandrine	Stephania tetrandra	Menispermaceae	Root	In vitro	10~80 μM	Antiproliferation of HSFBs	Inhibition of TGF-β₁ mRNA transcription, promotion of Smad7 and MMP-1 mRNA expression, and inhibition of Smad2 mRNA expression Decrease of protein expression of collagen I/collagen III, Bcl-2, and MKP-1. Reduction of total collagen volume and S phase, increase of G₀/G₁ phase, and prevention of G₀/G₁ into G₂ phase Inhibitory phosphorylation of MEK1/2 and ERK1/2	[19–22]
				In vivo	1~10 mg/L
				Local injection	0.5~2 mg/L 50 mg/mL, 20 μL

Aloe-emodin	Rheum palmatum	Polygonaceae	Root, rhizome	In vitro	20~80 mg/L	Antiproliferation of HSFBs	Increase of S phase	[23]

5F	Pteris semipinnata	Pteridaceae	Whole plant	In vitro	20~80 μg/mL	Antiproliferation of HPS	Blockage of fibroblasts from G₁ to S phase Decreased protein expression of TGF-β₁ and type I collagen, increase of caspase-3, and reduction of total collagen and fibroblasts PCNA protein (cyclin) Inhibitory mRNA expression of type I/type III procollagen in SSSF	[24–26]
				In vivo	10~40 mg/L	Reduction of PS volume
				In vivo	40~120 mg/L	Antiproliferation of SSSF
				Local injection	20~80 mg/L	Promotion of HPS apoptosis Decrease of hypertrophic index	Reduction of collagen fiber content

Oxymatrine	Sophora japonica	Leguminosae	Root	In vitro	0.125~1.0 mg/mL 2 μM	Antiproliferation of KFb and HFb Promotion of KFb apoptosis	Increase of S phase, inhibitory mRNA expression of collagen I/collagen III and reduction of protein expression of Smad3 and ERK₁ Promotion of Smad7 protein expression Inhibition of p-Smad3 and nuclear translocation of Smad3	[27, 28]

Ginsenoside Rg3 (G-Rg3)	Panax ginseng	Araliaceae	Root, rhizome	In vivo Local injection	3 mg/mL, 0.1 mL	Inhibition of HS Decrease of scar tissue fibrosis	Increase of protein expression of PCNA, Bax, caspase-3, and Cyt-c Decrease of Bcl-2 protein expression	[29, 30]

Osthole	Cnidium monnieri	Apiaceae	Fruit	In vitro	5~50 μM	Antiproliferation of HSFBs and Induction of apoptosis	Promotion of Bax mRNA expression and inhibition of Bcl-2 mRNA expression Decreases of TGF-β₁ protein expression and facilitation of HSFBs shrinkage, chromatin condensation, membrane blebbing, apoptotic body formation, and DNA ladder formation	[31]