Salvianolic Acid B Suppresses Inflammatory Mediator Levels by Downregulating NF-κB in a Rat Model of Rheumatoid Arthritis

Abstract

BackgroundSalvianolic acid B (SB) is a major active phyto-component of the plant Radix Salvia miltiorrhiza, which is traditionally used to treat joint pain and arthritis. The present study examined the anti-rheumatoid arthritis efficacy of SB on collagen-induced rheumatoid arthritis (CIA) in a rat model.Material/MethodsForty-eight rats were divided into 4 groups: Control rats treated with saline (Group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type at the tail (Group II), and rats subjected to CIA and supplemented with either 20 or 40 mg/kg of SB for 28 days (group III or IV).ResultsPaw swelling, edema, arthritis score, thymus and spleen indexes, and neutrophil infiltration were significantly decreased (p<0.01) by treatment with 20 or 40 mg/kg of SB. The levels of inflammatory cytokines (interleukin-1β, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were markedly decreased (p<0.01), and those of antioxidant enzymes (SOD, CAT, and GSH) were significantly increased (p<0.01) in SB-treated rats. Administration with SB (20 or 40 mg/kg) resulted in lower phosphorylated IκB-α and NF-κB p65 protein levels and markedly downregulated IκB-α expression. Furthermore, CIA rats revealed the presence of highly diffused polymorphonuclear cells (PMNs) infiltration with eroded cartilage; however, these phenomena were considerably ameliorated by SB.ConclusionsSB alleviates oxidative stress and inflammation in CIA rats, thus verifying its anti-rheumatoid arthritis property.

Role of High-affinity Choline Transporter 1 in Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome

“…Firstly, Wang and Liu 37 reported that activation of NF-κB signaling contributed to the occurrence of inflammation-related IBS-diarrhea. In addition, recently, we detected that NF-κB signaling was also implicated in IBS-related hyperalgesia in an unpublished research, consistent with previous studies reporting that NF-κB signaling participated in the pain modulation in inflammatory diseases, 38 cancer, 39 and autoimmune diseases, 40 via the release of inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Moreover, our findings indicate that the excitatory effect of CHT1 in GI motility is closely associated with increased ACh release.…”

“…Colorectal distension (CRD) was then conducted after 20 minutes of adaptation. Each recording progression consisted of a 5-minute predistention baseline activity measurements, a 20-second CRD-evoked response (20,40,60, and 80 mmHg), and a 3-minute postdistention activity measurement, followed by a 3-minute rest between 2 CRD episodes. The EMG signals expressed by visceromotor response (VMR), the area under the curve in response to the CRD stimuli, were collected and analyzed using Lab Chart 7 software (AD instruments).…”

The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

“…It is currently used as one of the therapeutic agents for RA and has been reported to be effective [56]. Thus, targeting NF-κB is effective at maintaining bone mass during inflammation [13][14][15][34][35][36][37][49][50][51][52][53][54][55][56][58][59][60][61][62][63][64][65][66][67][68][69]85,[91][92][93][94], and there is a possibility for "killing two birds with one stone". However, embryonic lethality has been reported in mice where molecules involved in the NF-κB signaling have been knocked out [26][27][28][29][30][31], and it is necessary to consider the possibility of causing serious side effects simply by inhibiting NF-κB.…”

“…There are various stages of BMP/Smad signaling, but the classical NF-κB pathway does not affect the phosphorylation of Smad1/5 or the formation of the Smad1-Smad4 complex; however, the classical NF-κB pathway does interfere with the DNA binding complex. Furthermore, we found that the p65 subunit of the classical NF-κB pathway associates with Smad4 but not Smad1 [64]. Therefore, when the association sites of p65 and Smad4 were examined, the transactivation domain 2 (TA2) of p65 and the mad homology (MH) 1 region of Smad1 were directly associated.…”

“…It has been reported that not only these inhibitors but also components contained in plant extracts, such as turmeric supplements, Trachelospermi caulis, Moutan cortex radicis, or Saposhnikovia divaricata, can suppress the activation of the classical NF-κB pathway, which mediates excessive immune responses and inflammation followed by cartilage destruction in arthritis [58][59][60][61][62][63][64][65][66]. The dietary ω-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), originating from fish oils, also reduce pain and inflammation in RA by suppressing IL-1 or TNF-α production via NF-κB activation.…”