The aim of this study was to investigate the anti-inflammatory properties of each fraction of Hericium erinaceus (HE). The ethanol extract from HE was partitioned with different solvents in the order of increasing polarity. The treatment with 10-100μg/mL of each fraction did not reduce RAW 264.7 cell viability except ethyl acetate fraction. Among the various extracts, the chloroform fraction showed the most potent activity against nitric oxide (NO), prostaglandin E(2) (PGE(2)) and reactive oxygen species (ROS). The western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that chloroform fraction from HE (CHE) significantly reduced the protein level of iNOS and cyclooxygenase-2 (COX-2) or mRNA levels of iNOS in lipopolysaccharide-induced macrophages. Furthermore, CHE inhibited the translocation of nuclear factor (NF)-κB p65 subunit, phsophorylation of I-κB, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. Furthermore, the activation of both activator protein-1 (AP-1) and NF κB in the nucleus were abrogated by CHE with luciferase assay. In conclusion, these results indicate that CHE may provide an anti-inflammatory effect by attenuating the generation of excessive NO, PGE(2), and ROS and by suppressing the expression of pro-inflammatory genes through the inhibition of NF-κB and JNK activity.

Chronic pain is one of the most common clinical presentations in the primary care settings. In the US, Fibromyalgia (FM) affects about 1-3% of adults and commonly occurs in adults between the ages of 40-50 years. FM causes widespread muscular pain and tenderness with hyperalgesia and allodynia and may be associated with other somatic complaints. Hyperbaric oxygen therapy (HBOT) has been utilized and has recently shown promising effects in the management of FM and other chronic pain disorders. In HBOT, the intermittent breathing of 100% oxygen in a pressurized chamber where the pressure is higher than 1 atmosphere absolute (ATA) has been utilized. HBOT exhibits a significant anti-inflammatory effect through reducing production of glial cells and inflammatory mediators which results in pain alleviation in different chronic pain conditions. HBOT can also influence neuroplasticity and affects the mitochondrial mechanisms resulting in functional brain changes. In addition to that, HBOT stimulates nitric oxide (NO) synthesis which helps in alleviating hyperalgesia and NO-dependent release of endogenous opioids which seemed to be the primary HBOT mechanism of antinociception. Moreover, aerobic exercise and meditative movement therapies (MMT) have gained attention for their role in pain alleviation through different anti-inflammatory and antioxidant mechanisms. In this review, we aim to elucidate the different mechanisms of HBOT and aerobic exercise in attenuating pain as adjuvant therapy in the multidisciplinary treatment strategy of chronic pain, and more particularly fibromyalgia.

BACKGROUND:Loss of endothelium-derived nitric oxide (EDNO) contributes to the clinical expression of coronary artery disease (CAD). Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis, and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function.

METHODS AND RESULTS:In a randomized, double-blind, placebo-controlled study, we examined the effects of single-dose (2 g PO) and long-term (500 mg/d) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD. Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline, 2 hours after the single dose, and 30 days after long-term treatment in 46 patients with CAD. Flow-mediated dilation improved from 6.6+/-3.5% to 10.1+/-5.2% after single-dose treatment, and the effect was sustained after long-term treatment (9. 0+/-3.7%), whereas flow-mediated dilation was 8.6+/-4.7% at baseline and remained unchanged after single-dose (7.8+/-4.4%) and long-term (7.9+/-4.5%) treatment with placebo (P=0.005 by repeated-measures ANOVA). Plasma ascorbic acid concentrations increased from 41.4+/-12. 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95. 0+/-36.1 micromol/L after long-term treatment (P<0.001).

CONCLUSIONS:In patients with CAD, long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action. Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events, this study indicates that ascorbic acid treatment may benefit patients with CAD.

We have investigated D-fraction (MDF) extracted from Grifola frondosa (Maitake mushroom) on the inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production in RAW264.7 (RAW) cells, a murine monocyte/macrophage cell line, with special reference to antitumor activity of MDF against human hepatoma-derived huH-1 cells. MDF could induce iNOS mRNA expression in RAW cells in a dose range of more than 30 microg/ml, but the effect of 10 microg/ml of MDF was negligible. The iNOS mRNA expression induced by 100 microg/ml of MDF was 6 hrs later, but lasted for a longer time than that of lipopolysaccharide (LPS), a representative iNOS inducer. Although iNOS mRNA levels in MDF-stimulated cells were almost equal to LPS-stimulated cells at the peak time, the cumulative amount of nitrite was only about 50% compared with that of LPS-treated cells. When huH-I cells were cultured in MDF containing media in a 24-well plate with inserted porous bottom in the presence or absence of RAW cells, the viability of huH-1 cells decreased significantly only in the presence of RAW cells in MDF dose-dependent manner. This antitumor activity of RAW cells in the presence of MDF was abolished or attenuated by the addition of L-NAME, a NOS inhibitor, confirming that this phenomenon is due to iNOS-mediated NO production by RAW cells, but not direct cytotoxic activity of MDF against huH-1 cells. These data suggest that MDF is a novel inducer for iNOS which contributes at least in part to antitumor activity of MDF.