Medicinal Plants for the Treatment of Hypertrophic Scars

Table 2

Antihypertrophic scar displaying phytochemicals widely distributed in medicinal plants.

Phytochemicals	Observation	Dose	Effect	Mechanism of action	References
10-Hydroxycamptothecin (HCPT)	In vivo	0.01~0.1 mg/mL	Decrease of the area of epidural scar tissue and the number of fibroblasts. Reduction of epidural adhesion and inhibitory proliferation of RESF	Inhibition of topoisomerase I	[5]
Angelica naphtha	In vitro	1~16 mg/L	Antiproliferation of HSFBs and induction of HSFBs apoptosis	Inhibition of G0/G1 and G2/M phases, promotion of S phase, and reduction of collagen protein in fibroblasts	[32]
Asiaticoside	In vivo; In vitro	25~50 mg/mL; Local injection; 25~1000 μM; 300 μg/mL	Reduction of scar hyperplasia of HSRE; Decrease of hypertrophic index; Promotion of keratinocytes migration; Anti-proliferation of HSFBs	Inhibition of the mRNA expression of TGF-β1, RhocA, ROCK-I, and CTGF, facilitation of TGF-β3 mRNA expression, and decrease of the expression of types I/III collagen and TIMP-1 proteins	[33–36]
Matrine	In vitro	0.01~5.00 g/L	Antiproliferation and induction of apoptosis in HSFBs	Promotion of G2-M phase, inhibition of lactate dehydrogenase and Hyp and enhancement of I/III collagen ratio	[37]
Quercetin	In vivo	0.05%~1%, w/o; Local Application	Inhibition of scarring in hairless mice	Increase of the protein and mRNA expression of MMP-1 and enhancement of the phosphorylation of JNK and ERK	[38]
	In vitro	10~40 μM	Antiproliferation of HSkF
Emodin	In vitro	50~200 μg/mL	Antiproliferation of HSFBs	Inhibition of G0/G1 phase, increase of intracellular calcium, and decrease of collagen synthesis	[39–41]
Resveratrol	In vitro; In vivo	25~400 μM; 150~400 μM Local injections	Antiproliferation of HSFBs; Reduction of hypertrophic scar index	Inhibition of the mRNA expression of type I/type III procollagens	[42]
Tan IIA	In vitro	20~80 μg/mL; 0.05~0.15 mg/mL	Antiproliferation of HSFBs; Induction of HSFBs apoptosis	Facilitation of nuclei shrinkage, condensation and fragmentation, blockage of HSFBs from G1 to S phases, downregulation of MDA content and XOD activity, increase of T-SOD and GSH-Px activity, and promotion of MMP-1 mRNA expression	[43–45]
Curcumin	In vitro	12.5~100 μM	Antiproliferation of HSFBs	Inhibition of procollagen 1 mRNA expression Reduction of hypertrophic index and collagen fiber area density	[46]
	In vivo	0.5~2.0 mM, 0.1 mL/d Local injections
Dihydroartemisinin	In vivo	180 mg/kg	Inhibition of HSRE scarring	Inhibition of collagen fibers and hypertrophic index	[47]
		10 mL intragastric administration	Antifibroblast proliferation of HSRE
Arteannuin	In vitro	0.103~0.206 mg/mL	Antiproliferation of HSFBs	Congregation of nuclear chromatin, promotion of calcium concentration, increase of G0-G1 phase, and reduction of collagen levels and hypertrophic index of HSRE	[48–51]
	In vivo	60 mg/mL/2 d	Decrease of HSRE scarring
		20 μL local injection	Antiproliferation of mastocyte
Panax notoginseng saponins (PNS)	In vitro	400~800 μg/mL	Antiproliferation of HSFBs	Inhibition of G2-M and G0-G1 phases, increase of S phase, reduction of the protein expression of TGF-β1 and α-SMA, and inhibition of intracellular free calcium concentration	[52, 53]
Oleanolic Acid	In vivo	Topical application of 2.5, 5, and10% for 28 consecutive days	Inhibition of hypertrophic scarring, induction of apoptosis, and reduction of scar elevation index	Inhibition of the mRNA expression of TGF-β1 mRNA, MMP-1, TIMP-1, and P311. Increase of the mRNA expression of MMP-2, caspase-3, and caspase-9. Reduction of the protein expression of TGF-β1 and collagen I/collagen III	[54]
Hirudin	In vitro	1~50 μM	Promotion of apoptosis	Increase of Gl phase and inhibition of S phase Enhancement of the protein expression of MMP-2, MMP-9, and p27, reduction of the protein expression of cyclin E and TGF-β1, and inhibition of the mRNA expression of I/III procollagens	[55]
Xiamenmycin	In vivo	10 mg/kg·d^−1, intraperitoneal injection for 10 days	Attenuation of hypertrophic scarring and suppression of local inflammation in a mechanical stretch-induced mouse mode	Reduction of CD^4+ lymphocyte and monocyte/macrophage retention in fibrotic foci Blockage of fibroblast adhesion with monocytes.; Inactivation of FAK, p38, and Rho guanosine triphosphatase signaling	[56]
	In vitro	5–30 μg/mL	Inhibition of proliferation of HSFBs