Table 3.

The Relevant Studies on the Pharmacological Effects of Matrine Through the NF-κB Signaling Pathway

Disease	Drugs	Cell Line/Animal Model	Action Mechnism	Reference
Acute lung injury	Matrine	NR8383; LPS-induced lung injury mouse model	Inhibited the NF-κB inflammatory cascade, down-regulating the inflam-mation mediator TNF-α, IL-6 and HMGB1, and suppressed MPO and MDA activity, thereby attenuated ROS and tissue oxidative stress	[76]
Breast cancer		MCF-7, BT-474, MDA-MB-231	Reduced the expression of IKK β, play an anti-tumor effect on breast cancer cells through NF-κB signaling pathway	[77]
HCC		SMMC-7721	Suppressed the expression of MMP-9 and NF-κB, inhibited HCC cells invasion by downregulation the NF-κB signaling pathway	[78]
Pancreatic cancer		PANC-1	Up-regulated E-cadherin expression and down-regulated the levels of ROS, N-cadherin, Vimentin, MMP-2, MMP-9, pP65 and pIκBα, inhibited pancreatic cells invasion and epithelial-mesenchymal transition through ROS/NF-κB/MMPs pathway	[79]
Cancers		A549, DU145, MIAPaca-2	Negatively regulated HER2 and CXCL12-induced CXCR4 expression, down-regulated expression of MMP-9/2 and NF-κB, blocking the cancer metastasis through the negative regulation of CXCR4 and MMP-9/2	[80]
Prostate cancer		DU-145, PC-3	Decreased the expression levels of p65, p-p65, ikk-α/β, p-ikk-α/β, iKB-α and p-iKB-α, indicating the NF-κB signaling pathway was involved in the inhibition of prostate cancer	[81]
		DU145, PC3; DU145 and PC-3 xenograft tumor model in BALB/c nude mice	Reduced the expression levels of MMP-9, MMP-2 and p-p65, inhibited invasion of castration-resistant prostate cancer (CRPC) by downregulating MMP-2/9 through NF-κB pathway	[82]
Gastric cancer		MNK45	Inhibited gastric cancer cell growth via controlling NF-κB subunit proteins, CIAP, XIAP, and p-ERK	[83]
Leukemia		K562, K562/ADR	Increased caspase-9 activity, reduced the expression of p-NF-κB, Survivin, and Bcl-xl, suppressed ABCB1 drug transport and facilitated the intrinsic apoptosis pathway through inhibiting NF-κB, enhanced the effect of anticancer drugs on K562/ADR cells	[84]
Osteosarcoma		SaOS-2, U2OS, MG-63; U2OS xenograft tumor model in BALB/c nude mice	Decrease the expression of MMP-2 and 9, reduce the nuclear translocation of p50 and p65, and the phosphorylation level of IκB-β and ERK 1/2, and act by down-regulating the NF-κB signaling pathway	[85]
Spinal cord injury		PC12	Reversed LPS-decreased miR-9 level to attenuate the loss of viability, stimulation of apoptosis, and release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), inhibited LPS-evoked JNK and NF–κB pathways via a miR-9-dependent way	[86]
Multiple sclerosis		Encephalomyelitisl Wistar rat model	Reduced inflammatory infiltration and demyelination, and the production of inflammatory factors including TNF-α, IL-6, and IL-1β, significantly reduced the expression of HMGB1, TLR, MyD88, TRAF6, and the p-NF-κB p65, increased the level of IκB-α, the direct inhibitory effect of MAT on HMGB1/TLR4/NF-κB signaling in macrophages was confirmed	[87]
Acute ischemic stroke		Permanent middle cerebral artery occlusion SD rat model	Increased the protein levels of IκBα, and blocked the translocation of NF-κB p65 from the cytosol to the nucleus, down-regulated NF-κB p65 downstream pro-apoptotic gene p53 and/or c-Myc, protected neurons and astrocytes via inhibition of NF-κB signaling pathway	[88]
Porcine circovirus associated diseases		Porcine alveolar macrophages (PAMs) cells model co-infected with PRRSV/PCV2	Down-regulated the expression of TLR3, TLR4 and TNF-α, and suppressed p-IκBα expression, ihibited antiviral activity against PRRSV/PCV2 co-infection in PAM cells by regulating TLR3, 4/NF-κB/TNF-α signaling pathway	[89]
Porcine reproductive and respiratory syndrome virus (PRRSV) disease		Inflammatory model of PAMs by transfecting PRRSV 5ʹUTR RNA and LPS	Inhibited the expression of IL-1β, IL-6, IL-8 and TNF-α, down-regulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC spots formation, suppressed IκBα phosphorylation, and interfered the translocation of NF-κB from the cytoplasm to the nucleus, inhibited inflammatory response through the MyD88/NF-κB pathway and NLRP3 inflammasome	[90]
Gastric mucosal injury		Gastric mucosal injury induced by N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in rats	Decreased the expression levels of VEGF-C, VEGFR3, BAX, caspase-3, Cyt-C, TLR4, MyD88 and NF-κB p65, and increased Bcl2 protein level, reduced gastric mucosal damage induced by MNNG in rats via the down-regulation of VEGF-C/VEGFR3 and NF-κB/TLR4 signaling pathway.	[91]
Asthma		BEAS-2B, MLE-12; allergic airway inflammation BALB/c mice model	Abrogated the level of IL-4 and IL-13 but enhanced IFN-γ expression, impeded TNF-α-induced expression of IL-6 and adhesion molecules, suppressed airway inflammation by downregulating SOCS3 expression via inhibiting NF-κB signaling	[92]
Rheumatoid arthritis		Rat model of rheumatoid arthritis (RA)	Modulated the imbalance of Th1 and Th2 cytokine responses in rats with RA by reducing the levels of Th1 cytokines (IFN-γ, TNF-α, IL-1β), but increasing Th2 cytokine (IL-4 and IL-10) through attenuating the NF-κB signaling in T cells	[93]
		Type II collagen-induced arthritis (CIA) in rats	Decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9, also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB, possessing the anti-arthritic effect in CIA rats via inhibiting the NF-κB pathway activation	[94]
	MASM	DBA/1 mice with collagen-induced arthritis (CIA) and fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLS)	Suppressed the expression of inflammatory mediators pro-inflammatory cytokines (TNF-α, IL-6, IL-8) and matrix metalloproteinases (MMP-1, MMP-3 and MMP-13) by inhibiting both the MAPK and NF-κB pathways and inducing apoptosis of RA-FLS	[95]
Osteoarthritis	Matrine	Human articular cartilage chondrocytes	Inhibited the IL-1β-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1, inhibited the p-p38, p-ERK, p- c-JNK and p-IκBα degradation in chondrocytes, thus exerted anti-inflammatory effects by suppressing the activation of MAPK and NF-κB signaling pathways	[96]
Endometritis		Bovine endometrial epithelial cells BEND cells; Staphylococcus aureus lipoteichoic acid (LTA)-induced endometritis in BALB/c mice	Reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β), suppressed TLR2 expression and its downstream nuclear factor (NF)-κB activation, alleviating LTA-induced endometritis through negative regulation of TLR2-mediated NF-κB pathway	[97]
Atherosclerosis		HASMCs	Inhibited the expression of VCAM 1 and ICAM 1 in TNF α stimulated HASMCs via the suppression of ROS production as well as NF κB and MAPK pathway activation	[98]