Skip to main content
. 2024 Nov 7;15:1470879. doi: 10.3389/fphar.2024.1470879

TABLE 1.

Summary of preclinical studies evaluating the effects of SCU in different diseases.

Model Main Target Disease Tissue Reference
Male SD rats MCAO-induced brain damage In vivo PARP↓, NAD↓ I/R injury Brain Zhang et al. (2009)
Female SD rats In vivo GAP43↑, PTN↓, JAK2↓, STAT↓ I/R injury Brain Niu et al. (2021)
Primary cortical neurons In vitro
SD rats MCAO-induced brain damage In vivo p65↓, p38↓, ROS↓, MDA↓, SOD↑, CAT↑ I/R injury Brain Zhang et al. (2022f)
GSH-Px↑, GSH↑, IL-1↓, IL-6↓, TNF-α↓
Rats MCAO-induced brain damage In vivo SOD↑, CAT↑, GSH↑, ROS↓ I/R injury Brain Guo et al. (2011a)
Rat cortical neurons In vitro
C57BL/6N mice MCAO-induced brain damage In vivo NOX1↓, NOX2↓, NOX4↓ I/R injury Brain Deng et al. (2022)
AR−/− mice
Male SD rats MCAO-induced brain damage In vivo eNOS↑, VEGF↓, bFGF↓, iNOS↓ I/R injury Brain Hu et al. (2005)
Male SD rats MCAO-induced brain damage In vivo and in vitro NOX2↓, 8-OHdG↓, 4-HNE↓, 3-NT↓ Sun et al. (2018c)
Primary astrocytes caspase-3↓, NeuN↓, connexin 43↑
Wistar rat, Neuronal cells Neuron damage induced by hydrogen peroxide In vitro cNOS↓, NO↑ Neuron damage Brain Liu et al. (2005)
SD rats MCAO-induced brain damage In vivo PKG↑ Cerebral ischemia Brain Chen et al. (2021b)
Rat brain microvascular In vitro NO↑, CD63↑, claudin 5↑, occludin↑, ZO1↑, LDH↓, ROS↓ Cerebral ischemia Brain Zhong et al. (2019)
Endothelial cells
Rats MCAO-induced brain damage In vivo XOD↓, ALT↓, AST↓, MDA↓ I/R injury Brain/Liver Yang et al. (2003)
BV-2 cells, TNC1 astrocytes MCAO-induced brain damage In vitro GFAP↑, Notch-1↑, NICD↑, HES-1↑, TNF-α↑, IL-1β↑, iNOS↑ Cerebral ischemia Brain Fang et al. (2015)
Male SD rats, BV-2 cells MCAO-induced brain damage In vivo and in vitro NF-κB↓, Notch-1↓, NICD↓, RBP-JK↓, Hes-1↓ MCP-1↓ Cerebral ischemia Brain Yuan et al. (2015)
Male SD rats MCAO-induced brain damage In vivo and in vitro p-p38↓, p-JNK↓, p-ERK1/2↑, iNOS↓, TNF-α↓, IL-1β↓ Cerebral ischemia Brain Chen et al. (2020)
BV-2 cells LPS induced BV-2 cells p-JNK↓, p-p38 MAPKs↓
SD rats MCAO-induced brain damage In vivo ACE↓, AT1R↓, Ang II↓, TNF-α↓, IL-6↓, IL-1β ↓ Cerebral ischemia Brain Wang et al. (2016a)
Male Wistar rats BCCAO-induced brain damage In vivo Glu↓, Asp↓, Gly↓, GABA↓, Tau↓, Ca 2+-ATPase↑ Cerebral ischemia Brain Tang et al. (2014)
Na +, K +-ATPase↑
SD rats In vitro p-VASP↑ Hypoxia Coronary artery Chen et al. (2015)
SD rats, Rats with cerebral I/R treatment In vivo P-VASP↑, PKG↑ Hypoxia Brai Du et al. (2015)
HBMECs In vitro
Male SD rats, BV-2 cell MCAO-induced brain damage In vivo and in vitro cyclin B1↑, cyclin B1↑, cyclin D1↑, NT-3↑ Cerebral ischemia Brain Fang et al. (2016)
IGF-1↑, AP-2↑, PSD-95↑
Male SD rats In vivo eNOS↑, p-Erk5↑, KLF2↑ Subarachnoid hemorrhage Brain Li et al. (2016)
Male SD rats LPS-induced behavioral deficits In vivo ROS↓NLRP3, caspase-1, IL-1β↓ Depression Brain Bian et al. (2020)
Wistar rats In vivo IL-1β↓, IL-6↓, TNF-α↓, SOD↑, MAO↓ Depression Brain Guo et al. (2013)
Male C57BL/6 mice Depression-like behaviors In vivo TNFα↓, IL-1β↓, IL-6↓, iNOS↓, IL-4↑, BDNF↑ Depression Brain Lu et al. (2021)
Primary astrocytes induced by LPS In vitro
Male C57BL/6 mice In vivo GABAA Rα1↓, GABAAγ2↓, mEPSC↓ Anxiety disorders Brain Guo et al. (2021)
MCF-7 cells In vitro Aggregation of beta-amyloid↓ Alzheimer's disease Brain Zhu et al. (2009)
Male APPswe/PS1dE9 mice In vivo and in vitro Aβ aggregation↑, soluble Aβ oligomers↓, Aβ42↓, Aβ40↓ Alzheimer's disease Brain Zhang et al. (2020)
C57BL/6 mice
BV-2 cells In vitro NO↓, TNFα↓, IL-1β↓, ROS↓, iNOS↓, TNFα↓, IL-1β↓ Alzheimer's disease Brain Lu et al. (2021)
SH-SY5Y cells NF-κB↓, JNK↓, p38↓, IFN-γ↓, STAT1α↓
HT22 cell In vivo and in vitro Lactate dehydrogenase↓, lactate dehydrogenase↓, ROS↓, Aβ1‑42↑ Alzheimer's disease Brain Chiba et al. (2012)
Balb/c male mice p-Tau↓, ROS↓, Bcl-2↑, Bcl-xL↑, Bax↓, cleaved caspase-3↓
APP/PS1 transgenic mice In vivo and in vitro Aβ plaque↓, TNF-α↓, IL-6↓ Alzheimer's disease Brain Zeng et al. (2018)
WT mice, H-SY5Y cell line
Male SD rats Permanent bilateral In vivo Aβ (1-40) ↓, Aβ (1–42) ↓, Iba1↓ Vascular dementia Brain Shin et al. (2018)
Common carotid artery occlusion Alzheimer's disease
Male Wistar rats In vivo nAChR↑, nAChR α4↑, α7↑ Cognitive disorder Brain Guo et al. (2011b)
APP/PS1 transgenic mice In vivo SCFAs, IL-1β↓ Alzheimer's disease Brain Zhang et al., (2022c)
BALB/cmale mice In vivo MDA↓, SOD↑, IL-1β↓, IL-6↓, HO-1↓, NQO1↑, Nrf2↓ Alcohol induced brain injury Brain Zhang et al. (2022d)
BV-2 cells In vitro NF-κB-p65↓, TNF-α↓, IL-1β↓, IL-6↓, NO↓, TNF-α↓, IL-1β↓ neuroinflammation Brain You et al. (2018)
IL-6↓, iNOS↓, IκB↓, IKKβ↓, p38↓, JNK↓, AKT↓
Male albino Wistar rats In vivo MDA↓, SOD↑, GSH↑, AChE↓, NF-κB↓, TNFα↓, IL-6↓ Cognitive disorder Brain Baluchnejadmojarad et al. (2018)
Nrf2↑, beclin-1↓, LC3 II↓, mTOR↓, P62↓
Male C57BL/6 mice In vivo and in vitro nestin↑, Tuj-1↑, ERK1/2↑ Cognitive disorder Brain Wang et al. (2017)
Neural stem cells
Male Wistar albino rats Metanil yellow induced In vivo GFAP↓, cleaved caspase-3↓, MDA↓, SOD↑, GSH↑ Gliosis Brain Tawfeek et al. (2021)
Male SD rats In vivo TLR4↓, NF- κ B p65↓, TNF- α↓, IL-1 β↓, IL-18↓ Hypertension Brain Chen et al. (2013)
Bax↓, cleaved-caspase-3 p17↓, Mcl1↑
Male SD rats In vivo CTn-T↓, CTn-I↓, AST↓, LDH↓, SOD↑, CAT↑GSH↑ Myocardial infarction Heart Huang et al. (2018)
Caspase3↓, Caspase9↓, cytochrome C↓, NGAL↓, NFκB↓, IL-1β↓
P53↓, IL-6↓, Bcl2↑, MDA↓, iNOS↓, Bax↓
Male Wistar rats In vivo FN1↓, TGFβ1↓, CFs↓, p38-MAPK↓, ERK1/2↓ Cardiac fibrosis Heart Pan et al. (2011)
Male SD rats In vivo LVWI↓, RVWI↓, type I and type III collagen↓, MVD↑, CD31↑ Cardiac fibrosis Heart Zhou et al. (2014)
α-sma ↓, Jagged1↑, Notch 1↑, Hes1↑
C57BL/6 mice In vitro and in vivo CaMKII↓, β-MHC↑, ANP↑ Cardiac hypertrophy Heart Pan et al. (2010)
Cardiac myocytes
SD rats, H9c2 cells In vitro and in vivo NLRP3↓, mTORC1↓, p-Akt↑, Casp-1↓, IL-1β↓ Myocardial I/R injury Heart Xu et al. (2020)
Rats, endothelial cell In vitro and in vivo P-JAK↓, P-STAT3↓ Myocardial I/R injury Heart Lin et al. (2014)
HCMECs In vitro JAK2↓, p-JAK2↓, STAT3↓, p-STAT3↓ Myocardial ischemia Heart Chen et al. (2019)
H9c2 cells In vitro JAK/STAT3↑, Bcl2↑, VEGF↑, MMP2↑, MMP9↑, TNFα↓ Myocardial I/R injury Heart Wang et al. (2016b)
IL-8↓, CK ↓, NO↑, ROS↓, SOD ↑, MDA ↓, STAT3↑, Bcl2↑
VEGF↑, MMP2↑, MMP9↑, IL-1β↓, IL-6↓
HCMECs In vitro EIF6↓, HSPD1↑, CCT6A↑ Anoxia Heart Shi et al. (2015)
HCMECs, SD rats MIR model In vitro and in vivo PKG-I↑, PKG-Iα↑ Myocardial I/R injury Heart Li et al. (2015)
Male SD rats LPS induced lung injury In vivo ROS↓, SOD↓, IL-1β↑, IL−18↑, IL−6↑, IL−4↑, IL−10↑, MDA↓ Lung injury Lung Fan et al. (2022)
Mice Injected with a dose of LPS In vivo TNF-α↓, iNOS↓, c-Fos↓, iNOS↓, NF-kappaB↓, IkBa↓, GSH↑ Lung injury Lung Tan et al.(2010)
Male albino rats Rat Model of Bilateral In vivo iNOS↑, Bax↑, Bcl2↓, COX2↓ Posterior limb I/R injury Lung Ibrahim et al. (2019)
Hind Limb I/R
HBE-16 cell In vitro MUC5AC↓, p-PKC↓, ERK1/2↓ Airway mucus secretion Lung Jiang et al. (2011b)
HBE-16 cell, Male SD rats In vivo and in vitro MUC5AC↓, PKC↓, ERK1/2↓ Airway mucus secretion Lung Jiang et al. (2011a)
Male BALB/c mice BLM-induced In vivo and in vitro p-p65/p65 ratio↓, IκBα↓NLRP3↓, caspase-1↓, caspase-11↓, IL-1β↓ Pulmonary fibrosis Lung Peng et al. (2020)
A549 cell, RLE-6TN cell IL-18↓, fibronectin↓, vimentin↓, N-cadherin↓, MMP-2↓, MMP-9↓
HK-2 cells, Wistar rats In vitro and in vivo HO-1↑, SCr↓, BUN↓, KIM-1↓, ROS↓ I/R injury kidney Dai et al. (2022)
HK-2 cells In vitro NGAL↓, Kim-1↓, cystatin C↓, IL-18↓, NLRP3↓, CCN1↑ Hyperuricemia kidney Li et al. (2020a)
Male C57BL/6 mice In vivo
Male C57BL/6 mice In vivo BUN↑, CRE↑, TNF-α↓, IL-6↓, Cleaved caspase-3↓ Chemotherapy toxicity kidney Sun et al. (2019)
Cleaved PARP↓, p53↓, Bax/Bcl-2↓, LC3-II/LC3-I↑, Atg7↑
p62↓JNK↓, ERK↓, p38↓, stat3↓
HepG2 cells Acid-treated HepG2 cells In vivo XBP1↓, SREBP-1c↓, IRE1α↓ NAFLD Liver Zhang et al. (2022e)
C57/BL6 mice HFD-induced In vitro
HepG2 cells In vitro CD36↓, Fasn↓, ACC↓, AKT↑, mTOR↓, n-SREBP-1c↓ Hepatocyte lipid metabolism Liver Han and Wang (2018)
Male C57BL/6 mice In vivo
Mice HFD-induced In vivo and in vitro SREBP-1c↓, mTOR↓ Hepatocyte lipid metabolism Liver Luan et al. (2020)
HepG2 cells PA-treated HepG2 cells
Male C57BL/6 mice HFD induced mice In vivo and in vitro PPARγ↑, PGC-1α↑, Nrf2↑, HO-1↑, GST↑, NQO1↑ NAFLD Liver Zhang et al. (2018)
HepG2 cells Oleic acid induced cells NF-κB↓, Keap1↓
SD rats HFD-induced In vivo Nrf2, HO-1, and PI3K, and AKT ↑HO-1, NQO1, and Nrf2↑ NAFLD Liver Fan et al. (2017)
subjected to chronic stress
BALB/c mice CCl4-induced liver injury In vivo AST↓, ALT↓, TBIL↓, IL-1β↓, TNF-α↓, CYP2E1↓, IκBα/NF-κB↓ Hepatotoxicity Liver Miao et al. (2021)
S180 tumor-bearing mic DB-induced liver injury In vivo MPO↑, IκB↓, NF-κB p65↓, TNF-α↓, IL-6↓, IFN-γ↓, MDA↓, GPx↑ Hepatotoxicity Liver Niu et al. (2015)
Male ICR mice Induced by concanavalin A In vivo ALT↓, AST↓, TNF-α↓, iNOS↓, c-Fos↓, c-Jun↓, iNOS↓, IkappaB↑ Hepatitis autoimmune Liver Tan et al. (2007)
Male Wistar rats Se-treated rats In vivo MDA↑, GSH-Px↑, TR↑ Hepatotoxicity Liver Eltayeb et al. (2004)
HL-7702 Under hypoxic condition In vitro ROS↓, MDA↓, SOD↑, bcl-2↑, Keap1↓ Nrf2↑, HO-1↑, NQO1↑, Nrf2↓ I/R injury Liver Wu and Jia (2019)
Chondrocytes In vitro MMP1↓, MMP13↓, ADAMTS-5↓, Wnt3a↓, Frizzled7↓ Osteoarthritis Bones and joints Liu et al. (2020)
C57BL/6 male mice In vivo Collagen II↑, Aggrecan↑
C57BL/6 mice In vivo and in vitro MMP-13↓, ADAMTS-5↓, COX-2↓, iNOS↓, IL-6↓, Osteoarthritis Bones and joints Luo et al. (2020)
Chondrocytes TNF-α↓, PGE2↓, IL-1β↓, NF-κB↑, Nrf2↑
BL6/C57 male mice In vivo and in vitro TNF-α↓, IL-1β↓, iNOS↓, MMP13↓, ADAMTS-5↓ Osteoarthritis Bones and joints Wang et al. (2019)
Chondrocyte cells COX-2↓, IL-6↓, NO↓
SW1353 cells In vitro IL-6↓, AKT↓, mTOR↓, p-mTOR↓, CH25H↓ Osteoarthritis Bones and joints Ju et al. (2021)
CYP7B1↓, ABCA1↑, APOA-1↑
Human Enucleus In vivo and in vitro ROS↓, NF-κB↓, MAPK↓, TNF-α↓, NLRP3↓ Intervertebral Bones and joints Wang et al. (2022b)
Pulposus Cells disc degeneration
Male SD rats
SD rats In vivo and in vitro ATG5↑, Rab8a↑, PI3K↑, PTEN↑, Akt↑ Intervertebral Bones and joints Hu et al. (2022)
Nucleus pulposus cells disc degeneration
Male DBA/1J mice collagen‑induced arthritis In vivo IL‑1β↓, IL‑6↓, TNF‑α↓, Caspase‑3/-9↓Bax/Bcl‑2↓TLR4↓NF‑κB↓ Arthritis Bones and joints Zhang et al., (2017)
Raw264.7 cell line In vivo and in vitro RANKL↓, MAPK↓, NF-κB↓, JNK1/2↓, p38↓, ERK1/2↓, IκBα↓ Arthritis Bones and joints Zhao et al. (2016)
C57BL/6 male mice
Osteoblasts female SD rats In vivo and in vitro ALP secretion↑, intracellular calcium ion influx↑ Osteoporosis Bones and joints Wang et al. (2018)
calcium deposition↑, CXCR4↑, p65↑
3T3-L1 cells In vitro PPARγ↓ C/EBPα↓ Obesity Metabolic disease Lu et al. (2013)
db/db mice db/m+ mice In vivo Nrf2↑, HO-1↑, IL-1β↓, IL-2↓, IL- 4↑ Diabetic Nephropathy Diabetic complication Liu et al. (2019b)
C57BL/6 male mice In vitro and in vivo laudin-1↑, claudin-19↑, NFκB↓, TNF-α↓, p-ERK 1/2↓, Nrf2↑ Diabetic retinopathy Diabetic complication Mei et al. (2019)
WT mice and HRECs
Human retinal endothelial cells In vitro VEGF↓, p-ERK↓, p-FAK↓, p-Src↓ Diabetic retinopathy Diabetic Long et al. (2019)
Rats In vivo complication
Male Wistar rats In vivo MDA↓, ROS↓, Bcl-2↑, BAX↓, VEGF↑ Testicular Damages Diabetic Long et al. (2015)
complication
Male SD rats In vivo blood glucose↓, TC↓, TG↓ LDL↓, HDL↑, LDH1↓, CK↓, Diabetic cardiomyopathy Diabetic Su et al. (2022)
Beclin-1↑, LC3-II↑ complication
Male Swiss mice HFD-induced In vivo CK-MB↓, Troponin↓, BNP↓, SOD↑, CAT↑, GPx↑, GST↑, Nrf2↓ Diabetic cardiomyopathy Diabetic Huo et al. (2021)
Nqo-1↓, Ho-1↓, Tlr4↓, Myd88↓, Nf-κb↓, IL-6↓, TNf-α↓, IKKβ↑ complication
Cyt-c↓, Parp 1↓, bcl-2↑, caspase-3↓, caspase-9↓, Bax↓
HUVECs In vitro Bcl-2↓, Bax↓ Cyt c↓, ROS↑, SOD↑, SOD2↑, LC3 II↑, Beclin 1↑ Diabetic Diabetic Xi et al. (2021)
Atg 5↑, PINK1↑, Parkin↑, Mitofusin2↑ cardiomyopathy complicatio
Male C57/B6 mice In vivo NLRP3↓, NF-κB↓, p-AKT↓, Nrf2↓, HO-1↓, EF↓, LVVd↓ Diabetic Diabetic Xu et al. (2021)
CK↓, Col I↓, TGF-β1↓, SOD↑, CAT↑, GSH-Px↑, MDA↓ cardiomyopathy complication
ROS↓, IL-1β↓, IFN-γ↓, IL-6↓, MCP-1↓, TNF-α↓, IL-18↓
LDH↓, cTnI↓
LO2 Induced by Hcy In vivo and in vitro Hcy↓, TG↓, CHO↓, LDL↓, ALT↓, AST↓, insulin↓, CBS↓, CSE↓ Diabetic Diabetic Wang et al. (2020)
Male SD rats High-fat induced MTHFR↓, folic acid↑, VitB6↑, VitB12↑ Liver Injury complication
PC-9, H1975, Hela cells In vitro p-ERK1/2↑ ERK1/2↓, p-AKT↓, AKT↓, LC3-II↓ Lung cancer Cancer Sun et al. (2018a)
HepG2, Beas-2B cells p-ERK1/2↑, p-AKT↓
A549 cells In vitro G0/G1↓, AKT↓, mTOR↓, BCL-XL↓, STAT3↓, p-STAT3↓, 4EBP1↑ Lung cancer Cancer Cao et al. (2019)
A549 cells In vitro ROS↑, caspase-3↑, TGF-β1↓ Lung cancer Cancer Zhang et al. (2021)
HepG2 and MHCC97-H cells In vitro EMT↓, p-JAK2↓, p-STAT3↓ E‐cadherin↑, snail↓, vimentin↓ Liver cancer Cancer Liu et al. (2019a)
HepG2 and SK-Hep1 cells In vitro STAT3↓, Girdin↓, AKT↓ Liver cancer Cancer Ke et al. (2017)
Male BALB/c nude mice In vivo
C57BL/6 male mice CAC caused by AOM/DSS In vivo and in vitro NF-κB↓, SHH↓, Ptch1↓, Smo↓, Gli1↓ Colorectal cancer Cancer Zeng et al. (2022)
SW480 cells
SW620, HCT116, LOVO In vitro and in vivo ephrinb2↓, ephB6↓, ephA1↓ Colorectal cancer Cancer Zhu et al. (2017)
HT29 cells and Balb/c nude mice
HT-29 CSC cells In vitro and in vivo Lgr5↓, c-Myc↓, CK20↓, Nanog↓, Gli1↓, CD133↓, Lgr5↓ Colorectal cancer Cancer Lei et al. (2020)
Nude mice Gli1↓, Ptch1↓, c-Myc↓, Ki-67↓, CK20↓
HCT116 p53+/+ (wild-type) In vitro caspase-6↑ Colorectal cancer Cancer Chan et al. (2009)
p53-/- (knockout) cells
Male C57BL/6 mice Induced by azoxymethane and In vivo Wnt/β-catenin↓, TNF-α↓, IL-6↓, Bax↑ Colorectal cancer Cancer Zeng et al. (2021)
HT-29 cells dextran sulfate sodium In vitro Bcl-2↓, GSK-3β↓, cyclin D1↓
Mice In vivo p38 MAPK↓, TNFR2+Tregs↓, CD8+T↑ Colorectal cancer Cancer Chen et al. (2022)
WEHI-13VAR and CT26 cell In vitro
HCT‑116 cells In vitro Bcl‑2↓, Bax↑, caspase‑3↑, p-p53↑ Colorectal cancer Cancer Yang et al. (2017)
AGS In vitro and in vivo LDH↓, G0-G1↑S↓, G2-M↓, SOD↑, GSH↑, CAT↑, MDA↓, 8-OHdG↓ Gastric cancer Cancer Sun and Meng (2022)
MGC-803 and AGS In vitro PI3K↓, PTEN↑ Gastric cancer Cancer Li et al. (2021)
SAS cells In vitro and in vivo MMP-2 and -9↓, integrin αvβ6↓, c-JUN↓ Oral squamous cell carcinoma Cancer Li et al. (2013)
Athymic Balb/ca nude mice
SAS and HSC-4 cells In vitro E-cadherin↑, αvβ6 integrin↓ Oral squamous cell carcinoma Cancer Li et al. (2010)
C57BL/6J mice In vivo retinal thinning and reduced visual behavioral deficits Glaucoma Eye Pang and Clark (2020)
Female C57BL/6 mice LPS-primed macrophages In vivo and in vitro NLRP3↓, IL-1β↓, caspase-1 ↓ Sepsis Multiple Organ Liu et al. (2017)