The relationship between anti-C-reactive protein and disease activity in patients with systemic lupus erythematosus.

Background/Aims: Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. METHODS: This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. RESULTS: The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions: These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system.

BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo). METHODS: Chronic BCCAo was induced in adult male Wistar rats to reflect the CCH conditions. On day 21 after BCCAo, the animals were treated orally with saline or GBE (5, 10, 20, and 40mg/kg) daily for 42 days. After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs). RESULTS: BCCAo increased glial proliferation in the hippocampus and white matter, whereas proliferation was significantly attenuated by GBE treatment. GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). Furthermore, GBE treatment restored the ChAT expression in the basal forebrain following BCCAo. CONCLUSIONS: These findings suggest that GBE has specific neuroprotective effects that may be useful for the treatment of CCH. The pharmacological mechanism of GBE partly involves the modulation of inflammatory mediators and the cholinergic system.

Fructus mume Ethanol Extract Prevents Inflammation and Normalizes the Septohippocampal Cholinergic System in a Rat Model of Chronic Cerebral Hypoperfusion.

Fructus mume (F. mume), the unripe fruit of Prunus mume, has long been used in Asian countries to treat cough and chronic diarrhea. We previously reported that F. mume exerts anti-inflammatory effects in a model of chronic cerebral hypoperfusion (CCH), a key etiological factor of vascular dementia (VaD). The present study was performed to investigate the protective effects of an ethanolic extract of F. mume on the inflammatory response and cholinergic dysfunction in a model of CCH induced by bilateral common carotid artery occlusion (BCCAo) in Wistar rats. Rats were assigned to three treatment groups: sham plus vehicle, BCCAo plus vehicle, and BCCAo plus F. mume extract (200 mg/kg). F. mume was administered by oral gavage from days 21 to 42 following BCCAo. Glial cell numbers were measured in the white matter and hippocampus. The hippocampal expressions of proinflammatory cytokines, angiotensin-II (Ang-II), receptor for advanced glycation end products (RAGE), and mitogen-activated protein kinase (MAPKs) were also evaluated. Choline acetyltransferase (ChAT) levels in the hippocampus and basal forebrain were examined. Rats with BCCAo showed an increase in the number of glial cells and levels of proinflammatory cytokines, Ang-II, RAGE, and MAPKs, all of which were significantly attenuated by F. mume treatment. F. mume administration also restored ChAT expression in the basal forebrain and hippocampus following chronic BCCAo. These results suggest that F. mume is a potentially valuable drug or nutraceutical for the treatment of VaD.

Salvia miltiorrhiza extract protects white matter and the hippocampus from damage induced by chronic cerebral hypoperfusion in rats.

BACKGROUND: Salvia miltiorrhiza (SM), an herbal plant, is traditionally used in the treatment of cardiovascular and cerebrovascular diseases in Asian countries. SM has multiple biological effects including anti-inflammatory activity. The present study is aimed at investigating the effects of SM extract in rats with chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). The rats were divided into 3 groups: sham-control, BCCAo treated with vehicle, and BCCAo treated with SM extract. Vehicle or SM extract (200 mg/kg) were administered daily by oral gavage beginning on day 21 after BCCAo and continuing to day 42. Immunohistochemical analyses were used to measure Iba-1-positive microglia and myelin basic protein (MBP) in white matter and hippocampal tissue. In addition, the expression levels of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, and the toll-like receptor (TLR) pathway in the hippocampus, were analyzed by western blot. RESULTS: Administration of SM extract attenuated the activation of microglial cells in the white matter and hippocampus after BCCAo. SM extract also prevented neuroinflammation after BCCAo by reducing hippocampal levels of TNF-α, IL-1ß, and IL-6, and increasing the reduced levels of MBP in the white matter and hippocampus. Further, the administration of SM extract alleviated the up-regulation of hippocampal TLR4 and myeloid differentiation primary response gene 88 (MyD88) in rats with chronic BCCAo. CONCLUSIONS: Our findings suggest that SM may be a promising therapeutic candidate in vascular dementia because of its protective effects against damage to the white matter and hippocampus after BCCAo.

Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat.

BACKGROUND: The cardiotonic pill (CP) is a herbal medicine composed of Salvia miltiorrhiza (SM), Panax notoginseng (PN), and Dryobalanops aromatica Gaertner (DAG) that is widely used to treat cardiovascular diseases. The present experiment was conducted to examine the effects of CP on white matter and hippocampal damage induced by chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). Daily oral administration of CP (200 mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of microglial activation and myelin basic protein (MBP) were measured in the white matter and hippocampus of rats with chronic BCCAo, and the expression levels of mitogen-activated protein kinases (MAPKs) and inflammatory markers such as cyclooxygenase-2, interleukin-1ß, and interleukin-6 were examined. RESULTS: MBP expression was reduced in the white matter and hippocampal regions of rats that received BCCAo. In contrast, reduced levels of MBP were not observed in BCCAo rats given CP treatments. The administration of CP alleviated microglial activation, the alteration of ERK and p38 MAPK signaling, and inflammatory mediator expression in rats with chronic BCCAo. CONCLUSION: These results suggest that CP may have protective effects against chronic BCCAo-induced white matter and hippocampal damage by inhibiting inflammatory processes including microglial activation and proinflammatory mediator expression, and downreguating the hyperphosphorylation of ERK and p38 MAPK signaling.

Carbamylated albumin stimulates microRNA-146, which is increased in human renal cell carcinoma.

Carbamylation is a post-translational modification, the pathophysiological consequences of which remain poorly understood. MicroRNAs (miRNAs) are endogenous non-coding small ribonucleic acids that have emerged as one of the central players in gene expression regulation. This study was designed to determine the effect of carbamylated albumin (cAlb) on the expression of miRNAs. Albumin was carbamylated, and the extent of carbamylation was monitored using trinitrobenzenesulphonic acid. Albumin or cAlb were added to rat mesangial cells (RMCs), and RNA was extracted. miRNA microarray analysis was performed. The expression of microRNA-146a (miR-146a) and microRNA-146b (miR-146b) was analyzed by real-time RT-PCR. Of 365 miRNAs analyzed, the expression of miR-146a/b was found to be markedly induced by cAlb (miR-146a, 12.75-fold increase; miR-146b, 5.88-fold increase). Real-time RT-PCR analysis confirmed the increased levels of miR-146a/b by cAlb (p<0.05). It was also found that expression levels of miR-146a/b were increased in renal cell carcinoma tumor tissues compared to corresponding non-tumor tissues (p<0.05). Our data suggest that cAlb stimulates miR-146a/b in RMCs, the levels of which are increased in renal cell carcinoma. Further studies on the function of cAlb may provide new insights into the pathophysiology of renal cell carcinoma.