Table 1 Pharmacological activities of musk

Anti-inflammatory activity

Rat neutrophils

Glycoprotein musk-1

1, 10, 100 μg/mL

Slightly increasing PLA2 activity, significantly inhibiting ALOX5 activity, and significantly increasing COX activity

[41]

Rat neutrophils

Glycoprotein musk-1

1, 10, 100 μg/mL

Inhibiting the release of lysosomal enzymes

[42,43,44,45]

Rat neutrophils

Glycoprotein musk-1

1, 10, 100 μg/mL

Inhibiting the production of neutrophil platelet-activating factor and the activity of acetyl-CoA-dependent acetyltransferase

[46]

Rat neutrophils

Glycoprotein musk-1

1, 10, 100 μg/mL

Significantly inhibiting the chemotaxis of neutrophils

[47]

Carrageenin edema; Formalin arthritis; Adjuvant arthritis

Musk

0.5, 1.0, 5.0 mg/100 g, i.p.; 1.0, 5.0 mg/100 g, i.p.; 1.0, 5.0 mg/100 g, i.p

Reducing the histamine and S-HT contents of the inflamed tissues

[34]

HUVEC

Muscone

37.5, 75, 150 μg/mL

Decreasing expression of CAMs on HUVEC

[49]

IL-1β induced end-plate chondrocytes; Rat model of endplate degeneration

Muscone

6.25, 12.5, and 25 lmol/L; 10 mg/kg, p.o

Blocking the proinflammatory effect of IL-1β in vitro; inhibiting inflammatory cytokine expression in

degenerated IVDs, and prevent IVD degeneration in vivo

[52]

Murine BV2 microglial cells; adjuvant inflammatory pain model

Muscone

1, 2, 4, 8, 16 μM; 4, 8, 16 mg/kg

Suppressing microglial activation-mediated inflammatory response through the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome; inhibiting the CFA-induced NOX4, p-JAK2/p-STAT3, and NLRP3 inflammasome expression in the spinal cord of mice

[54]

Neuroprotective effects

Glutamate-induced PC12 cells

Muscone

0.1, 1, 10 μM

Attenuating ROS generation and Ca2 + influx, via NR1 and CaMKII-depended ASK-1/JNK/p38 signaling pathways

[61]

MCAO rat model

Muscone

1 mg/kg, i.g

Down-regulating the expression of EAAC1mRNA in the ischemic hippocampus

[62]

MCAO rat model

Muscone

1 mg/kg, i.g

Reducing NR1 protein expression, thereby reducing excitatory glutamate toxicity

[63]

MCAO rat model; oxygen–glucose deprivation cell model

Muscone

0.5, 1 mg/kg, i.g.; 0.9, 1.8 μM

Activating the PI3K/Akt signaling pathway

[67]

In vitro blood–brain barrier model

Muscone

8 μM

Inhibiting P-gp and MMP-9 expression

[59]

The traumatic brain injury model

Muscone

1.8 mg/kg, nasal administration

reducing the water content of brain tissue, alleviating cerebral edema, promoting secretion of BDNF and NGF by olfactory ensheathing cells

[71]

Traumatic brain injury rat model

Muscone

1.8 mg/kg, intranasal administration

Reducing cerebral edema and activating the PKA-CREB signal pathway

[72]

Complete cerebral ischemia/reperfusion rat model

Muscone

0.9, 1.8, 3.6 mg/kg, i.g

Reducing oxidative stress damage, delaying neuronal death effects, and inhibiting excitotoxicity caused by EAA

[64]

Pentylenetetrazol induced rat epilepsy model

Muscone

10, 50, 100 mg/kg, i.p

Inhibiting the c-Fos, c-jun expression

[73, 74]

PC12 cells; MCAO rat model

Muscone

100, 300 ng/mL; 0.08, 0.16 mg

Inhibiting apoptosis and Fas pathway

[66]

LPS-treated mice

Muscone

2 mg/kg, i.p

Repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade

[25]

Cardiovascular-protective effects

H₂O₂ induced H9c2 cardiomyocytes; H₂O₂ induced HUVEC

Musk

50 μg/mL

Scavenging ROS and improving the activity of intracellular antioxidant enzymes

[78, 79]

H₂O₂ induced HUVEC

Muscone

3, 15, 30 μg/mL

Stabilizing cell mitochondrial membrane potential, reducing cell permeability, and preventing Ca2⁺ influx

[80]

Myocardial infarction rat model

Muscone

2 mg/kg, i.g

Reducing the expression of transforming growth factor-β1, TNF-α, IL-1β and NF-κB

[82]

Myocardial infarction rat model

Muscone

2 mg/kg, i.g

Stimulating angiogenesis via upregulating HIF-1α and VEGFA

[83]

Myocardial infarction mice model

Muscone

2 mg/kg, i.g

Inhibiting NF-κB and NLRP3 inflammasome activation, thereby improving cardiac function

[84]

Neonatal rat cardiac myocytes

Muscone

0.215, 0.43 or 0.86 μg/mL

Alleviating the increase of lactic acid dehydrogenase release, malondialdehyde production, creatine kinase activity, caspase-3 activity, [Ca2 +]i, apoptosis rate and expression of Bax protein, and reduction of superoxide dismutase activity, MMP, and expression of Bcl-2 protein

[85]

Anti-cancer effects

Breast cancer mice model

Muscone

2 mg/kg, i.g

Reducing the expression of VEGF

[88]

HepG2 cells; xenograft liver cancer model

Muscone

0.663 μM; 0.1 mmol/kg, 0.2 ml/20 g bw

Increasing cellular apoptosis through endoplasmic reticulum stress responses and inducing autophagy through AMP kinase/mTOR complex 1 signaling pathway

[89]

Promoting effect on stem cell therapy

Human GMSCs

Muscone

3, 6, 9 mg/L

Increasing the proliferation and migration, promoting the adipogenic differentiation and inhibiting the osteogenic differentiation of GMSCs by inhibiting the Wnt/β-catenin signaling pathway

[93]

Skull bone defect rat model

Musk

42, 86, 168 mg/kg

Promoting stromal cell-derived factor 1 and monocyte chemotactic protein 1 expression to promote the migration of exogenous bone marrow mesenchymal stem cells to bone injury sites in rats

[97, 98]

Skull bone defect rat model

Musk

42 mg/kg

Increasing the level of SDF-1, HGF, and SCF, and expression of MCP-1 mRNA, FGF-2 mRNA, TGF-β mRNA, VEGF mRNA, and down-regulating the expression of EGF mRNA

[99,100,101,102]

Human GMSCs; alcohol-induced osteonecrosis of the femoral head

Muscone

1, 10, 25 μM; 1 mg/kg

Promoting ALP activity and mRNA expression of COL1 and OCN; restoring BV/TV ratio and bone density of necrotic femoral heads

[103]

Gentamicin-induced AKI

Muscone

3.0 mg/L

Up-regulating the expression of CXCR4 and CXCR7

[104]