Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action
Abstract
:1. Salvia miltiorrhiza Bunge
2. Methods
2.1. Search Strategy
2.2. Study Selection Criteria
2.3. Data Extraction
3. Cancer
Cancer and S. miltiorrhiza
4. Cardiovascular Diseases
Cardiovascular Diseases and S. miltiorrhiza
5. Liver Diseases
Liver Diseases and S. miltiorrhiza
6. Nervous System Diseases
Nervous System Diseases and S. miltiorrhiza
7. Discussion
7.1. S. miltiorrhiza Exhibits Anti-cancer Activity by Inducing Apoptosis in Cancer Cells
7.2. S. miltiorrhiza Exerts Anti-inflammatory and Anti-fibrotic Effects in Modulating Cardiovascular Diseases
7.3. S. miltiorrhiza Exerts Several Effects in Modulating Liver Diseases
7.4. S. miltiorrhiza Acts on Multiple Targets and Exhibits a Neuroprotective Effect on Several Nervous System Diseases
7.5. Limitaions and Strong Points of This Study
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Glossary
4-HNE | 4-hydroxynonenal |
8 | 9-DHET |
8 | 9-dihydroxyeicosatrienoic acids |
8 | 9-EET |
8 | 9-epoxyeicosatrienoic acid |
ACADL | acyl-CoA dehydrogenase long chain |
AchE | acetylcholinesterase |
Acta2 | actin alpha 2 |
Akt | protein kinase B |
ALF | alcohol liver fibrosis |
AMPK | AMP-activated protein kinase |
AP-1 | activator protein-1 |
APAP | acetaminophen |
Apo | apolipoprotein |
APP | amyloid precursor protein |
ATF4 | activating transcription factor 4 |
BACE1 | β-secretase |
Bax | Bcl-2 associated X-protein |
Bad | Bcl-2 associated agonist of cell death |
Bcl-2 | B-cell lymphoma 2 |
Bcl-xl | B-cell lymphoma-extra large |
BDNF | brain derived neurotrophic factor |
BNP | brain natriuretic peptide |
BuChE | butyrylcholinesterase |
c-caspase-3 | cleaved caspase-3 |
c-PARP | cleaved poly ADP-ribose polymerase |
CCl4 | carbon tetrachloride |
CD11b | cluster of differentiation molecule 11B |
CDK | cyclin-dependent kinase |
ChAT | choline acetyltransferase |
CHOP | CCAAT-enhancer-binding protein homologous protein |
COL I | type I collagen |
COL III | type III collagen |
Col1a1 | collagen type I alpha 1 |
Col3a1 | collagen type 3 alpha 1 |
COX-2 | cyclooxygenase-2 |
CPTI | carnitine palmitoyltransferase I |
CRP | c-reactive protein |
CTN | compounds of tanshinone |
Cx43 | connexin 43 |
CYP2E1 | cytochrome P450 2E1 |
DBil | direct bilirubin |
eIF2 | eukaryotic initiation factor 2 |
eNOS | endothelial nitric oxide synthase. |
ERK | extracellular-signal-regulated-kinase |
ERK | extracellular signal-regulated kinase |
FATP | fatty acids transport protein |
fEPSP | field excitatory postsynaptic potential |
GDNF | glial cell line-derived neurotrophic factor |
GGT | gamma-glutamyl transpeptidase |
GSH/GSSG ratio | glutathione/glutathione disulfide ratio |
GSK-3β | glycogen synthase kinase-3β |
H3K36me3 | H3K36 trimethylation |
H3K4me3 | H3K4 trimethylation |
Hcy | homocysteine |
HDL-C | high-density lipoprotein cholesterol |
HIF1α | hypoxia-inducible factor 1α |
HMGCR | 3-hydroxy-3-methylglutaryl-coenzyme A reductase |
HO-1 | heme oxygenase-1 |
HQO-1 | NAD(P)H quinine oxidoreductase |
HSCs | hepatic stellate cells |
HUVEC | human umbilical vein endothelial cell |
Hyp | hydroxyproline |
IBil | indirect bilirubin |
ICAM-1 | intercellular adhesion molecule-1 |
IDE | insulin-degrading enzyme |
IFN-γ | interferon gamma |
IL-10 | interleukin-10 |
IL-1β | interleukin 1 beta |
IL-6 | interleukin-6 |
Imp | importins |
iNOS | inducible nitric oxide synthase |
IκBα | inhibitor of nuclear factor kappa B α |
JNK | c-Jun N terminal kinase |
KM | kunming Mice |
LDL-C | low-density lipoprotein cholesterol |
Lp(a) | lipoprotein (a) |
LTP | Long-term potentiation |
MAPK | mitogen-activated protein kinase |
MBP | Myelin basic protein |
MCP-1 | monocyte chemoattractant protein-1 |
MDA | malondialdehyde |
miR-145 | microRNA-145 |
miR-21 | microRNA-21 |
MKP-1 | mitogen-activated protein kinase-1 |
MMP | matrix metalloproteinase |
MPO | myeloperoxidase |
MSCs | mesenchymal stem cells |
MyD88 | myeloid differentiation primary response 88 |
NF-H | neurofilament 200 |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
NKG2D | natural killer group 2D |
NKp46 | natural killer p46 |
NMDAR | N-methyl-d-aspartate receptor |
NR2C2 | nuclear receptor subfamily 2 group C member 2 |
Nrf2 | nuclear factor erythroid 2-related factor 2 |
NSCLC | non-small cell lung cancer |
OS | Olendlandia diffusa and Salvia miltiorrhiza extract |
PAI-1 | plasminogen activator inhibitor 1 |
PERK | protein kinase RNA-like endoplasmic reticulum kinase |
PKC | protein kinase C |
PKD1 | protein kinase D1 protein |
PPAR-α | peroxisome proliferator-activated receptor—alpha |
pPLCβ3 | phospho-phospholipase Cβ3 |
PR | tetraarsenic hexoxide |
PS1 | Presenilin-1 |
PTEN | phosphatase and tensin homolog deleted on chromosome ten |
RACK 1 | receptor of activated protein kinase C1 |
RAE-1ε | retinoic acid early-inducible protein 1 ε |
RAGE | receptor for advanced glycation endproducts |
ROS | reactive oxygen species. |
RXR | retinoid X receptor |
SD | Sprague Dawley |
sEH | soluble epoxide hydrolase |
SOD | superoxide dismutase |
SREBP-1 | sterol regulatory element-binding protein 1 |
STAT3 | signal transducer and activator of transcription 3 (Tyr705) |
TAA | thioacetamide |
TBil | total bilirubin |
TC | total cholesterol |
TG | triglycerides |
TGF-β1 | transforming growth factor beta 1 |
TIMP-1 | tissue inhibitor of metalloproteinase-1 |
TLR4 | toll-like receptor 4 |
TNF | tumor necrosis factor |
TXA2 | thromboxane A2 |
UA | uric acid |
VCAM-1 | vascular cell adhesion molecule 1 |
VEGFA | vascular endothelial growth factor A |
XIAP | X-linked inhibitor of apoptosis protein |
α-SMA | α-smooth muscle actin |
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Disease | Extract | Experimental Model | Dose; Duration | Efficacy | Mechanism | Reference |
---|---|---|---|---|---|---|
Breast cancer | 70% ethanol | MCF-7 | 50 µg/mL; 24 h | Inhibition of breast cancer cell invasiveness | ↓ MMP-9, p-ERK, p-JNK, p-p38, p-c-Jun | [30] |
Hepatocellular carcinoma | Astragalus and Salvia miltiorrhiza water/ethanol extract (71:1.85) | (1) SD rat (2) TGF-β1-stimulated HepG2 (3) BALB/c xenograft mouse model | (1) 60, 120, 240 mg/kg; 28 days (2) 20, 40, 80 µg/mL; 12, 24 h (3) 310 mg/kg; 28 days | Inhibition of hepatocellular carcinoma progression | ↑ Smad3C, miR-145 ↓ Smad3L, miR-21, p-ERK, p-JNK, p-p38 | [31] |
Hepatocellular carcinoma | Astragalus and Salvia miltiorrhiza water/ethanol extract (71:1.85) | (1) SD rat (2) HSCs, HepG2 | (1) 60, 120, 240 mg/kg; 12, 16 weeks (2) 20, 40, 80 µg/mL; 24 h | Inhibition of hepatocellular carcinoma | (1) ↑ pSmad3C ↓ p-ERK, p-JNK, p-p38, pSmad3L, Smad4, Imp 7/8, PAI-1 (2) ↑ p38 ↓ p-ERK, p-JNK | [32] |
Multiple myeloma and myeloid leukemia | 99.9% ethanol | U266, U937 | 25, 50, 100, 200 µg/mL; 24 h | Induction of apoptosis | ↑ miR-216b, p-ATF4, p-eIf2, p-PERK, ROS, CHOP, c-PARP, c-caspase-3 ↓ c-Jun | [33] |
Non-small cell lung cancer (NSCLC) | Methanol extract (CTN-compounds of tanshinone) | (1) Glc-82 (2) BALB/c mice | (1) 20, 40 µg/mL; 24 h (2) 40 mg; 22 days | Induction of apoptosis | ↑ p53, p21, c-caspase-3, -9, c-PARP1, PTEN, Bax ↓ Bcl-2, Bcl-xl, p-Akt | [34] |
Non-small cell lung cancer (NSCLC) | Oldenlandia diffusa, Salvia miltiorrhiza 50% EtOH extract (5:2) | (1) A549, H460 (2) HUVECs (3) H460 xenograft model | (1,2) PR 2.5 µg/mL + OS 180 µg/mL; 24 h (3) PR 125 µg/kg + OS 20 mg/kg; 18 days | Antiangiogenic and apoptotic effects | ↑ c-caspase-3 ↓ p-STAT3, pro-PARP, Bcl-2, cyclin E, cyclin A, CDK2, E2F1, p-ERK, p-Akt, COX-2, SOCS-1, p-Src, VEGF, p-VEGFR2 | [35] |
Oral cancer | Double-distilled water, 95% ethanol or 1:1 water/ethanol | (1) HSC-3, OC-2 (2) BALB/cNU mice | (1) 10, 25, 50 µg/mL; 48, 72 h (2) 50, 100 mg/kg; 34 days | Inhibition of oral squamous carcinoma cell proliferation | ↑ c-caspase-3 ↓ XIAP, survivin | [36] |
Oral cancer | 95% ethanol | (1) SAS, SCC25, Oec-ml (2) KB, KB7D, KB tax, KB100, KB Vin, KB Vin 10 (3) SAS xenograft animal model | (1) 0.625, 1.25, 2.5, 5, 10, 20, 30 µg/mL; 24 h (2) 2.5, 5, 10, 20, 40, 80 µg/mL; 24 h (3) 10 mg/kg; 32 days | Inhibition of proliferation of oral cancer cell | ↑ c-caspase-3 ↓ XIAP | [37] |
Prostate cancer | Acetonitrile | (1) PC-3 (2) PC-3 xenograft mouse model | (1) 20 µg/mL; 24, 48, 72 h (2) 100 mg/kg; 6 weeks | Inhibitory effect on the growth of prostate cancer cell | ↑ ROS, c-caspase-3, -9, c-PARP, p21 ↓ Bcl-2, CDK2, CDK4, cyclin D1 | [38] |
Various cancers | 100% ethanol or 100% acetone | AGS, A549, HCT116, LNCaP, MCF7 | 5, 10, 20, 40 µg/mL; 24 h | Inhibitory effect on the growth of cancer cells | [39] | |
Multidrug-resistant cancer | Dichloromethane-methanol (1:1) | CCRF-CEM | (1) 3, 10, 30 µg/mL; 1 h (2) 5, 10, 20, 40 µg/mL; N/A (3) 20 µg/mL; 24, 2 h | Cytotoxicity towards multidrug-resistant cancer cells | ↑ ROS, p-JNK, p-ERK1/2, p-p38, c-caspase-3, -7, -9, c-PARP ↓ p65 translocation | [40] |
Disease | Extract | Experimental Model | Dose; Duration | Efficacy | Mechanism | Reference |
---|---|---|---|---|---|---|
Coronary heart disease (CHD) | Extractant unmentioned (Danshen pills) | Patients | 810 mg/day; 3 months | Reduction of the CHD risk | ↑ HDL-C, ApoA, ApoB, ApoE, TBil, IBil ↓ TG, TC, LDL-C, Lp(a), GGT, DBil, UA, Hcy | [48] |
Iron-mediated myocardial fibrosis | Water | Kunming mice | 3, 6 g/kg; 7 weeks | Protective effect on cardiac fibrosis induced by chronic iron overload | ↑ SOD ↓ TGF- β1, MMP-9, COL I, COL III | [49] |
Myocardial infarction (MI) | Extractant unmentioned (Danshen injection) | BALA/c mice | 3, 6 g/kg; 4 weeks | Beneficial effect on cardiac angiogenesis and cardiac function | ↑ HIF1α, VEGFA | [50] |
Myocardial infarction (MI) | Water | SD rats | 1.5 mL/kg; 14 days | Anti-inflammatory and anti-cardiac remodeling effects | ↑ Bcl-2/Bax ↓ MMP-2, MMP-9, iNOS, MPO | [51] |
Myocardial infarction (MI) | Salvia miltiorrhiza and Carthamus tinctorius extract (ratio unmentioned) | Wild-type C57BL/6 mice | 3 µL/g; 3 weeks | Inhibition of inflammation and fibrosis | ↑ IL-10 ↓ H3K4me3, H3K36me3, IL-1β, TNF, IL-6, COL I, COL III, α-SMA, Col1a1, Col3a1, Acta2 | [52] |
Myocardial infarction (MI) | Salvia miltiorrhiza Bunge and Astragalus mongholicus extract (1:1) | SD rats | 20 mg/kg/day; 8 weeks | Inhibition of myocardial fibrosis and ventricular remodeling | ↓ PKD1 | [53] |
Myocardial ischemia | Salvia miltiorrhiza Bunge and Panax notoginseng water extract (1:1) | SD rats | 1.2 mg/kg; 28 days | Regulatory effect on lipid metabolism disorder induced by myocardial ischemia | ↑ ApoA-I, FATP, CPTI, PPARα, RXR ↓ TG, LDL, Apo-B, HMGCR, NR2C2 | [54] |
Post-MI complications | Salvia miltiorrhiza Bunge and Panax notoginseng powdered water extract (1:1) | SD rats | 0.6, 0.9, 1.2 g/kg; 4 weeks | Inhibition of infarct border zone remodeling and ventricular arrhythmias | ↑ Cx43 ↓ TGF-β1, COL I, COL III, α-SMA, p-Smad3, BNP, MCP-1 | [55] |
Ischemia-reperfusion injury, cardiac hypertrophy, hypertension, and inflammation | 75% ethanol | sEH, 8,9-EET | IC50: 86.5 µg/mL | Cardiovascular protective and anti-inflammatory effects | ↓ sEH activity, 8,9-DHET | [56] |
Myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation injuries | Salvia miltiorrhiza and ligustrazine injection (1:50) | SD rats | 6.8, 20.4, 61.2 mg/kg/day; 3 days | Alleviation of I/R injury in cardiomyocytes and inhibition of apoptosis | ↑ Bcl-2/Bax, p-Akt, p-eNOS, SOD ↓ caspase-3, MDA | [57] |
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 miltiorrhizawater 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] |
Disease | Extract | Experimental Model | Dose; Duration | Efficacy | Mechanism | Reference |
---|---|---|---|---|---|---|
Alzheimer’s disease (AD) | Water | SH-SY5Y cells | 0.01, 0.1, 0.2 mg/mL; 2 h | Neuroprotection against Aβ25-35-induced neurotoxicity | ↓ ROS, Bax/Bcl-2, cytochrome c, caspase-3 | [92] |
Alzheimer’s disease (AD) | Water | Human recombinant GSK-3β | IC50: 7.77±1.38 μg/mL | Inhibition of AD | ↓ GSK-3β | [93] |
Alzheimer’s disease (AD) | 50% ethanol | Wistar rats | 200 mg/kg; 28 days | Improvement of long-term memory of rats | ↓ AChE, BuChE, BACE1 | [94] |
Alzheimer’s disease (AD) | Salvia miltiorrhiza, Panax Notoginseng, Borneol extract (450:141:8) | Kunming mice | 0.405, 0.81 g/kg; 7 days | Neuroprotective, anti-inflammatory, neurotrophic effects on learning and memory in Aβ25-35-induced mice | ↑ ChAT, BDNF, RACK1 ↓ IL-6, TNF-α | [95] |
Alzheimer’s disease (AD) | Salvia miltiorrhiza, Panax Notoginseng, Borneol ethanol extract (450:141:8) | SD rats | 520 mg/kg; 14 days | Improvement of spatial learning and memory in Aβ25-35-induced rat model of AD | ↑ IDE ↓ APP, PS1 | [96] |
Brain Ischemic Stroke | Water | (1) MSCs (2) SD rats | (1) 10 µg/mL (2) 50 mg/kg; 2 weeks | Anti-apoptosis and improvement of cell survival | ↑ Bcl-2, p-Akt, p-ERK ↓ Bax, caspase-3 | [97] |
Cerebral Ischemia (Acute) | 80% ethanol | Wistar rats | 5.25, 10.5, 21 mg/kg; 15 days | Neuroprotective effect against cerebral ischemic injury | ↑ HO-1, HQO-1, Nrf-2 ↓ RAGE, MMP-9, COX-2, TNF-α, ICAM-1 | [98] |
Cerebral Ischemia (Permanent) | Supercritical CO2 and 95% ethanol | SD rats | (1)15, 7.5, 3.75 mg/kg/day; 3 days (2) 0.44, 4.4, 44 mg/L; 10 min | Attenuation of cerebral ischemic injury through inhibitory effects on thrombosis formation and platelet aggregation in rats | ↓ TXA2, p-PLCβ3, p-PKC | [99] |
Cerebral Ischemia | Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius water extract—Ratio unmentioned | Kunming mice | (1) 20 g/kg; 5 days (2) 20 g/kg; 28 days | Recovery of cognitive impairment and Neuroprotection against cerebral ischemic injury | ↑ Bcl-2, BDNF ↓ IL-1β, IL-6, TNF-α, Bax | [100] |
Dementia | Extractant unmentioned | SD rats | 5 mL/kg/day; 4 weeks | Improvement of learning and memory abilities in streptozotocin-induced diabetic rats | ↑ MKP-1 | [101] |
Dementia, Vascular | Water | Wister rats | 200 mg/kg/day; 22 days | Protection against damage to the white matter and hippocampus after bilateral common carotid artery occlusion | ↑ MBP ↓ TNF-α, IL-1β, IL-6, TLR4, MyD88 | [102] |
Ethanol-induced Amnesia | 70% ethanol | CD-1 mice | (1) 200 mg/kg; 30 min (2) 10, 100 µg/mL; 20 min | Blockage of ethanol-induced synaptic dysfunction | ↑ LTP, NMDAR-dependent fEPSP | [103] |
Spinal cord injury (SCI) | 75% ethanol | SD rats | 12.5 g/kg; 8 days | Beneficial effects on the recovery of locomotor function after SCI | ↑ NF-H, BDNF, CD11b | [104] |
Temporal Lobe Epilepsy (TLE) | Extractant unmentioned Salvia miltiorrhiza Bunge, Panax notoginseng, Borneol—Ratio unmentioned | SD rats | 85 mg/kg; 90 days | Neuroprotection on a kainic acid-induced TLE and cognitive impairment in rats | ↑ GDNF, Bcl-2/Bax | [105] |
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Jung, I.; Kim, H.; Moon, S.; Lee, H.; Kim, B. Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action. Antioxidants 2020, 9, 857. https://doi.org/10.3390/antiox9090857
Jung I, Kim H, Moon S, Lee H, Kim B. Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action. Antioxidants. 2020; 9(9):857. https://doi.org/10.3390/antiox9090857
Chicago/Turabian StyleJung, Inyong, Hyerin Kim, Seongcheol Moon, Hyuk Lee, and Bonglee Kim. 2020. "Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action" Antioxidants 9, no. 9: 857. https://doi.org/10.3390/antiox9090857
APA StyleJung, I., Kim, H., Moon, S., Lee, H., & Kim, B. (2020). Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action. Antioxidants, 9(9), 857. https://doi.org/10.3390/antiox9090857