Analgesic Mechanism of Sinomenine against Chronic Pain

Table 1

The modulatory properties of sinomenine on neuroimmune regulators.

Substance	Type	Effect by sinomenine	Model/site of expression	Reference
Glutamate	Molecule	Decrease concentration	Brain extracellular fluid	[12]
GABA	Molecule	Decrease concentration	Brain extracellular fluid	[12]
Serotonin	Molecule	Increase concentration	Brain extracellular fluid	[13, 14]
Dopamine	Molecule	Increase concentration	Brain extracellular fluid	[13, 14]
cAMP	Molecule	Decrease concentration	Brain extracellular fluid	[13]
Opioid μ receptor	Protein	Dose-dependent activation	Chinese hamster ovary cell	[9]
Adenosine A2A receptor	Protein	Upregulation	Lung tissue in mice with acute lung injury	[15]
P2X3 receptor	Protein and mRNA	Downregulation	Dorsal root ganglia in rats with type 2 diabetes melitus	[16]
Dopamine D2 receptor	Protein and mRNA	Upregulation	Astrocytes in the middle cerebral artery occlusion (MCAO) mouse model	[17]
mIL-2R	Protein	Inhibit expression	Peripheral blood mononuclear cells	[18]
Histamine	Molecule	Potent release stimulation	Tissue mast cells	[19]
NO	Molecule	Reduce production	Microglial cells	[20]
			Macrophages	[21]
nNOS	Protein	Reduce activity	Cerebral cortex in morphine-dependent, naloxone-precipitated withdrawal rats	[13, 14]
iNOS	mRNA	Downregulation	Microglial cells	[22]
COX-2	mRNA	Downregulation	Microglial cells	[21]
Prostaglandin E2	Protein	Reduce expression	Microglial cells	[22]
			Macrophages	[21]
TNF	Protein and mRNA	Downregulation	Microglial cells	[22]
			RBL-2H3 cells	[23]
			Synoviocytes	[24]
INF-γ	Protein	Reduce production	Spleen cells	[25]
			Serum from mesangial proliferative nephritis patients	[18]
IL-6	Protein	Reduce production	Macrophages	[26]
		Enhance production	Peripheral blood mononuclear cells	[27]
IL-1 and IL1-β	Protein	Reduce production	Serum of CIA rats/macrophages	[28]
IL-4	Protein	Reduce production	Antigen-activated RBL-2H3 cells	[23]
IL-5	Protein	Reduce production	Spleen cells	[25]
IL-8	Protein	Inhibit production	Peripheral blood mononuclear cells	[27]
IL-18	mRNA	Downregulation	Brain tissue	[17]
IL-13	mRNA	Downregulation	Human synovial sarcoma	[28]
IL-10	Protein	Upregulation	Rat serum	[29]
IL-17A	Protein	Downregulation	Rat serum	[29]
Leukotriene C4	Lipophilic molecule	Reduce production	Macrophages	[21]
NF-κB	Protein	Inhibition activity	Monocyte-derived dendritic cells	[30]
			Macrophage and synoviocytes	[24]
P38 MAPK	Protein	Reduce phosphorylation	Antigen-activated RBL-2H3 cells	[23]
ERK	Protein	Activation	Macrophages	[2]
β-Hexosaminidase	Protein	Reduce release	Mast cell mediated by FcεRI	[23]
HO-1	Protein	Induce expression	Rat liver tissue	[31]
TGF-β	Protein	Enhance secretion	Spleen cells	[32]
VCAM-1	Molecule	Reduce production	Fibroblast-like synoviocytes	[33]
CCL2	Protein	Inhibit expression	Fibroblast-like synoviocytes	[33]
CXCL8	Protein	Inhibit expression	Fibroblast-like synoviocytes	[33]
T-bet	mRNA	Downregulation expression	Peripheral blood mononuclear cells	[18]
MMP-2 and MMP-9	Protein and mRNA	Inhibit activity and downregulation	Rat paw tissues	[26]
TIMP-1 and TIMP-3	Protein and mRNA	Enhance activity and upregulation	Rat paw tissues	[26]
ROS	Molecule	Reduce production	Microglial cells	[22]
Nrf2	Protein	Upregulation	Spinal cord in rats with spinal cord injury	[34]
NADPH oxidase	Protein	Inhibition of activity	Microglial cells	[22]
IκB-α	mRNA and protein	Downregulation and inhibit phosphorylation	Macrophages and synoviocytes	[24]
P-NMDAR1 and NMDAR1	Protein	Reduce expression	Morphine-treated SH-SY5Y cells	[35]
P-CAMKII and CAMKII	Protein	Reduce expression	Morphine-treated SH-SY5Y cells	[35]
PKB	Protein	Reduce phosphorylation	Antigen-activated RBL-2H3 cells	[23]
Gab2	Protein	Reduce phosphorylation	Antigen-activated RBL-2H3 cells	[23]
P-CREB and CREB	Protein	Reduce expression	Morphine-treated SH-SY5Y cells	[35]

GABA, γ-amino butyric acid; cAMP, cyclic adenosine monophosphate; mIL-2R, membrane interleukin-2 receptor; NO, nitric oxide; nNOS, neuronal nitric oxide synthase; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; TNF, tumor necrosis factor; INF-γ, interferon-γ; IL-6, interleukin 6; IL-1, interleukin 1; IL1-β, interleukin 1-β; IL-4, interleukin 4; IL-5, interleukin 5; IL-8, interleukin 8; IL-18, interleukin 18; IL-13, interleukin 13; IL-10, interleukin 10; IL-17A, interleukin 17A; NF-κB, transcription factor nuclear factor kappa B; P38 MAPK, p38 mitogen-activated protein kinase; ERK, extracellular-regulated protein kinase; HO-1, heme oxygenase-1; TGF-β, transforming growth factor-β; VCAM-1, vascular cell adhesion molecule-1; CCL2, C-C motif ligand 2; CXCL8, C-X-C motif chemokine ligand 8; T-bet, T-box transcription factor expressed in T-cells; MMP-2, matrix metalloproteinase 2; MMP-9, matrix metalloproteinase 9; TIMP-1, tissue inhibitor of metalloproteinase 1; TIMP-3, tissue inhibitor of metalloproteinase 3; ROS, reactive oxygen species; Nrf2, nuclear factor erythroid-2-related factor 2; NADPH, nicotinamide adenine dinucleotide phosphate; IκB-α, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; P-NMDAR1, phosphor-N-methyl-D-aspartate receptor 1; NMDAR1, N-methyl-D-aspartate receptor 1; P-CAMKII, phosphor-calmodulin-dependent protein kinase II; CAMKII, calmodulin-dependent protein kinase II; PKB, protein kinase B; Gab2, GRB2-associated-binding protein 2; P-CREB, phosphor-cAMP-response element-binding protein; CREB, cAMP-response element-binding protein.