Table 3.
Liver diseases and S. miltiorrhiza.
| Disease | Extract | Experimental Model | Dose; Duration | Efficacy | Mechanism | Reference |
|---|---|---|---|---|---|---|
| Alcoholic liver disease (ALD) |
Extractant unmentioned
(Danshen injection) |
(1) C57BL/6 mice (2) HepG2 (3) NCTC1469 |
(1) 3 g/kg; 4 weeks (2) 100, 200 µg/mL; 2 h (3) 150 µg/mL; 2 h |
Hepatoprotective effect against ALD | ↑ PPARα, CPT-1, CPT-2 ↓ 4-HNE |
[65] |
| Alcoholic liver fibrosis (ALF) | Pueraria lobata, Salvia miltiorrhiza, Schisandra chinensis, Silybum marianum extract (8:5:4:3) | SD rats | 0.333, 0.667, 1 g/kg; 30 days | Anti-fibrotic effect | ↑ MMP-13, Smad7 ↓ TIMP-1, TGF-β1, p-Smad2, p-Smad3 |
[66] |
| APAP-induced hepatotoxicity | Water |
(1) Primary SD rat hepatocytes (2) SD rat liver microsomes |
(1) 0.25, 1 mg/mL; 24 h (2) 0.25, 1 mg/mL; 24 h |
Antioxidant and anti-hepatotoxic effects | ↑ GSH/GSSG ratio ↓ CYP2E1 |
[68] |
| Hepatic sinusoidal obstruction syndrome (HSOS) | Extractant unmentioned | KM mice | 100, 200 mg/kg; N/A | Hepatoprotective effect on Gynura segetum-induced HSOS | ↓ TNF-α, VCAM-1, ICAM-1, NF-κB p65 | [69] |
| LPS-induced liver injury | Salvia miltiorrhiza, Carthamus tinctorius extract (5:2) | C57BL/6J mice | 3 g/kg; 30 min | Anti-inflammatory, anti-oxidative, and anti-apoptotic effects | ↑ Bcl-2 ↓ TNF-α, IL-6, p-NF-κB p65, p-IκBα, Bax |
[70] |
| Liver fibrosis | Ethanol | SD rats | 1, 2.5 mg/kg; 12 weeks | Anti-fibrotic effect against TAA-induced liver fibrosis | ↓ COL I (α), TIMP-1, α-SMA | [71] |
| Liver fibrosis | 90% ethanol | (1) C57BL/6 mice (2) NK cells (3) JS-1, NK cells (1:50) |
(1) 1.5, 3.0 g/kg; 4 weeks (2, 3) 50 µg/mL; 16 h |
Anti-fibrotic effect against CCl4-induced liver fibrosis | (1, 2) ↑ NKG2D, NKp46, IFN-γ (3) ↑ RAE-1ε, ↓ α-SMA |
[72] |
| Non-alcoholic steatohepatitis (NASH) | 70% ethanol |
(1) C57BL/6j mice (2, 3) LX-2 |
(1) 0.5, 1 mg/kg; 4, 6 weeks (2) 0.1, 0.5, 1 µg/mL; 24 h (3) 0.1, 1, 10, 100 µg/mL; 30 min |
Anti-inflammatory, anti-fibrotic, and antioxidant effects | ↓ TNF-α, TGF-β1, IL-1β, α-SMA, COL I, MMP-2, MMP-9, ROS | [73] |
| Non-alcoholic steatohepatitis (NASH) |
Artemisia iwayomogi, Amomum xanthioides, Salvia miltiorrhiza
water extract
(CGplus) |
C57/BL6J mice | 50, 100, 200 mg/kg; 5 days | Protection against the development of NASH | ↑ (p)-AMPK, ACADL, IL-10 ↓ TNF-α, IL-1β, IL-6, HMGCR, p-SREBP-1 |
[74] |
| Non-alcoholic fatty liver disease (NAFLD) |
Atrctylodes macrocephaly, Salvia miltiorrhiza, Radix Paeonia Alba, Rhizoma Alismatis, Fructus Schisandrae Chinensis powdered extract
(JPHX formula) |
Wistar rat | 0.60, 1.21, 2.42 g/kg; 8 weeks | Hepatoprotective effect against NAFLD | ↓ TG, TC, TNF-α, COL I, MMP-9, p-JNK | [75] |
PPAR-α, peroxisome proliferator-activated receptor alpha; CPT-1, carnitine palmitoyltransferase 1; CPT-2, carnitine palmitoyltransferase 2; 4-HNE, 4-hydroxynonenal; MMP-13, matrix metalloproteinase-13; TIMP-1, tissue inhibitor of metalloproteinase-1; SD, Sprague Dawley; ALF, alcohol liver fibrosis; APAP, acetaminophen; CYP2E1, cytochrome P450 2E1; KM, kunming mice; GSH/GSSG ratio, glutathione/glutathione disulfide ratio; VCAM-1, vascular cell adhesion molecule 1; ICAM-1, intercellular adhesion molecule-1; Bcl-2, B-cell lymphoma 2; TNF- α, tumor necrosis factor- α; IL-6, interleukin -6; MDA, malondialdehyde; p-NF-κB, phospho-nuclear factor kappa-light-chain-enhancer of activated B cells; p-IκBα, phospho-inhibitor of nuclear factor kappa B α; Bax, Bcl-2 associated X-protein; TAA, thioacetamide; TIMP-1, tissue inhibitor of metalloproteinases-1; α-SMA, alpha-smooth muscle actin; CCl4, carbon tetrachloride; NKG2D, natural killer group 2D; NKp46, natural killer p46; IFN-γ, interferon gamma; RAE-1ε, retinoic acid early-inducible protein 1 ε; TGF-β1, transforming growth factor beta 1; IL-1β, interleukin 1 beta; CRP, c-reactive protein; COL I, type I collagen; MMP-2, matrix metalloproteinase-2; MMP-9, matrix metalloproteinase-9; ROS, reactive oxygen species; (p)-AMPK, phospho-AMP-activated protein kinase; ACADL, acyl-CoA dehydrogenase long chain; HMGCR, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; p-SREBP-1, phospho-sterol regulatory element-binding protein 1; TG, triglycerides; TC, total cholesterol; p-JNK, phospho-c-Jun N-terminal kinase.