Natural Formulations: Novel Viewpoint for Scleroderma Adjunct Treatment

Table 2

In vitro, in vivo, and clinical interventions of natural therapeutics for scleroderma treatment.

Samples	Inducer	Type of study	Outcome	Ref.
Abscisic acid	—	In vitro/dermal fibroblast	↓Collagen, ↑MMP-1, ↑TIMP-1, ↓migration	[154]
Activin	—	In vivo/clinical trial	↓ICAM-1, ↓VCAM-1, ↓E-selectin, ↓MDA	[156]
Astragalus polysaccharide	BLM	In vivo/mice	↓Collagen, ↓TGF-β1, ↓MCP-1, ↓Smad2, ↓Smad3	[158]
Bee venom	—	In vivo/clinical trial	↓NRS for itch intensity, ↓NRS for sleep disturbance	[160]
Bromelain	—	In vivo/clinical trial	↓Depigmentation area, ↑food intake, ↑improvement of hand and foot activity	[172]
Curcumin	BLM	In vivo/mice; In vitro/SLF	↑SLF apoptosis	[161]
Dipropyltetrasulfide	—	In vivo/mice; In vitro/mouse dermal fibroblast	↓α-SMA, ↓AOPP, ↓pSmad2/3, ↓B cells, ↓T cells, ↓IL-4, ↓IL-13, ↑GSH	[163]
Geniposide	BLM	In vivo/mice; In vitro/HUVECs	↓End MT, ↓α-SMA, ↓phospho-mTOR, ↓phospho-S6, ↓Slug, ↓Snail, ↓Twist, ↑CD31, ↑E-cadherin	[165]
HSc025	BLM	In vivo/mice; In vitro/human dermal fibroblasts	↓Collagen, ↓hypodermal thickness, ↓hydroxyproline, ↓α-SMA, ↓fibrosis	[166]
Magnesium lithospermate	—	In vitro/human dermal fibroblast	↓Collagen	[168]
Nimbolide	BLM	In vivo/mice	↓Skin thickness, ↓NO, ↓TNF-α, ↓IL-1β, ↓p-NF-κB, ↓TGF-β1, ↓Smad2/3, ↓α-SMA, ↓N-cadherin, ↑GSH	[170]
Tanshinone IIA	IL-17A	In vitro/DVSMCs	↓Proliferation, ↓collagen 1 and 3, ↓migration, ↓ERK phosphorylation	[175]
Withaferin A	BLM	In vivo/mice	↓Skin thickness, ↓E-cadherin, ↓α-SMA, ↓fibronectin, ↓hydroxyproline, ↓collagen, ↓p-Akt, ↓TGF-β1, ↓Smad2/3, ↓p-NF-κB, ↓p65, ↓IKKβ, ↓TNF-α, ↓IL-1β, ↓NO, ↓iNOS, ↑FOXO3a, ↑GSH	[177]

Abbreviations: AOPP = advanced oxidation protein products; BLM = bleomycin; HUVECs = human umbilical vein endothelial cells.