Bee Venom Acupuncture for Shoulder Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Our review aimed to summarize and evaluate evidence on the effectiveness of bee venom acupuncture (BVA) in the treatment of shoulder pain. METHODS: Randomized controlled trials (RCTs) evaluating the effectiveness of BVA on shoulder pain were searched up to October 2019 in 11 electronic databases (Medline, Embase, CENTRAL, CiNii, CNKI, VIP, Wanfang, Kmbase, NDSL, RISS, OASIS). The methodological quality of the included RCTs were evaluated using Cochrane Risk of Bias tool and a meta-analysis was performed. RESULTS: Seven studies were included in the review, and four studies were included in the meta-analysis. Comparing BVA plus conventional therapy (CT) with saline injection plus CT, it showed an effect in favor of BVA plus CT in visual analog scale (VAS) and pain rating scale (PRS) (p = 0.02, p = 0.009, respectively). Comparing BVA plus physiotherapy (PT) with saline injection plus PT, it showed that there was no significant difference in VAS and verbal rating scale (VRS) between the two groups. CONCLUSION: This systematic review and meta-analysis suggest that BVA could be beneficial as an adjuvant treatment for shoulder pain.

Araliasaponin II isolated from leaves of Acanthopanax henryi (Oliv.) Harms inhibits inflammation by modulating the expression of inflammatory markers in murine macrophages.

Araliasaponin II (AS II) is a bioactive compound isolated from Acanthopanax henryi (Oliv.) Harms, a plant widely used in traditional oriental medicine. The present study investigated the anti­inflammatory effects of AS II using murine macrophages. The effects of AS II on inflammatory mediator and cytokine production in lipopolysaccharide (LPS)­stimulated RAW 264.7 cells was evaluated. Nitric oxide (NO) and cytokine production were determined using the Griess reagent and an ELISA kit. The expression levels of cytokines, inducible NO synthase (iNOS) and cyclooxygenase­2 (COX­2) mRNA were examined by reverse transcription­quantitative polymerase chain reaction. The expression levels of iNOS, COX­2 and toll­like receptor (TLR)­4 protein were examined by western blotting. Translocation of nuclear factor­κB (NF­κB) and TLR­4 expression were visualized by immunofluorescence staining. AS II markedly inhibited the production of NO and prostaglandin E2, and reduced iNOS and COX­2 expression at the transcriptional and translational levels. AS II downregulated the expression of interleukin­6 and tumor necrosis factor­α at the protein and mRNA levels. Furthermore, pre­treatment with AS II significantly suppressed the TLR­4­NF­κB signaling pathway; this effect may be cause by AS II competing with LPS for binding to TLR­4 and subsequently inhibiting translocation of the NF­κB/p65 protein to the nucleus. The results suggested that the anti­inflammatory properties of AS II may result from inhibiting pro­inflammatory mediators by suppressing the initiation of the inflammatory response and inhibiting TLR-4-NF-κB signaling pathways.

Acupuncture for functional recovery after stroke: a systematic review of sham-controlled randomized clinical trials.

BACKGROUND: Acupuncture is frequently advocated as an adjunct treatment during stroke rehabilitation. The aim of this review was to assess its effectiveness in this setting. METHODS: We searched 25 databases and 12 major Korean traditional medicine journals from their inception to October 2009. We included randomized controlled trials, with no language restrictions, that compared the effects of acupuncture (with or without electrical stimulation) with sham acupuncture. We assessed the methodologic quality of the trials using the Cochrane risk-of-bias criteria and the PEDro (Physiotherapy Evidence Database) scale. RESULTS: Ten of 664 potentially relevant studies met our inclusion criteria. For acute and subacute stages after stroke, we included seven trials. A meta-analysis of the five studies that assessed functionality did not show a significant difference in favour of acupuncture, with high heterogeneity. A post-hoc sensitivity analysis of three trials with low risk of bias did not show beneficial effects of acupuncture on activities of daily living at the end of the intervention period (n = 244; standard mean difference 0.07, 95% confidence interval [CI] -0.18 to 0.32; I(2) = 0%) or after follow-up (n = 244; standard mean difference 0.10, 95% CI -0.15 to 0.35; I(2) = 0%). For the chronic stage after stroke, three trials tested effects of acupuncture on function according to the Modified Ashworth Scale; all failed to show favourable effects. INTERPRETATION: Our meta-analyses of data from rigorous randomized sham-controlled trials did not show a positive effect of acupuncture as a treatment for functional recovery after stroke.

Dimethoxycurcumin, a synthetic curcumin analogue with higher metabolic stability, inhibits NO production, inducible NO synthase expression and NF-kappaB activation in RAW264.7 macrophages activated with LPS.

Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) in activated macrophages is linked to acute and chronic inflammation. Thus, it would be valuable to develop inhibitors of NO and/or iNOS for potential therapeutic use. We investigated whether dimethoxycurcumin (DiMC), a synthetic curcumin analogue with higher metabolic stability over curcumin, could inhibit NO production and iNOS expression in activated macrophages. RAW264.7 macrophages were activated with lipopolysaccharide (LPS) in the absence or presence of DiMC, which contains four methoxy groups at two aromatic rings, curcumin containing two, bis-demethoxycurcumin (BDMC) containing none, or tetrahydrocurcumin (THC) containing two but lacking conjugated double bonds in the central seven-carbon chain. NO production, iNOS expression and NF-kappaB activity were examined. DiMC, curcumin and BDMC inhibited NO production, iNOS expression and NF-kappaB activation, with DiMC being the most effective, followed by curcumin and BDMC. THC failed to inhibit NO production, iNOS expression and NF-kappaB activation. Our results suggest that DiMC inhibits NO production, iNOS expression and NF-kappaB activation in LPS-activated macrophages, which may be due not only to the conjugated double bonds but also the increased number of methoxy groups.

Effectiveness of combining manual therapy and acupuncture on temporomandibular joint dysfunction: a retrospective study.

This retrospective study investigated the effects of combining manual therapy and acupuncture on the pain and maximal mouth opening (MMO), which were associated with temporomandibular joint dysfunction (TMD). The 49 TMD patients (15 men, 34 women; mean age = 30.47 years, SD = 13.52 years) were treated with a combination of acupuncture and manual therapy two or three times a week at the hospital. The pain and maximal mouth opening were assessed before and after 1 and 4 weeks of treatment. The combination therapy produced significant changes in pain levels (p < 0.001) and mouth opening (p < 0.001). All pairwise non-parametric comparison showed a significant improvement in pain (p < 0.05 for all pairs) and MMO (p < 0.05 for all pairs). These findings suggest that combining manual therapy and acupuncture decreases the pain level and increases the MMO of TMD patients. However, future studies should further investigate the efficacy of combined treatment on TMD with more rigorous randomized clinical trials.

Interleukin-1 receptor antagonist gene polymorphism and traditional classification in obese women.

Cytokines appear to be the major regulators of adipose tissue metabolism. Interleukin- 1 receptor antagonist (IL-1ra) serum levels are increased in human obesity, and are under strong genetic control. The hypothesis was tested that the IL-1ra gene might be a candidate for obesity. Furthermore, the relationship was investigated between Sasang constitution and IL-1ra polymorphism. The frequency of a penta-allelic 86-bp tandem repeat (VNTR) in the intron 2 of IL-1ra gene in 67 lean (BMI<25 kg/m2), 133 overweight (BMI 25-29.9 kg/m2) and 61 obese (BMI>or=30 kg/m2) otherwise healthy Korean subjects was investigated. Total fat mass and percentage body fat were determined by dual-energy X-ray absorptiometry. Subjects were discriminated into four types by QSCC II program as well as clinical data (weight, height, blood pressure, etc.); Teaeumin, Taeyangin, Soyangin, and Soeumin. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of IL-1ra. The genotypic, or allelic distribution did not differ markedly between the three groups. The relative risk of being obese in comparison with lean was twofold increased in allele 2 carriers, although it was not statistically significant. Carriers of the allele 2 did not show a significant difference in physical and clinical characteristics. However, the relative risk of being obese in comparison with lean was increased in Taeumin subjects (p=.050), and so was in IL-1ra A2- carriers (p=.047). No relationship was found between the IL-1ra polymorphism and BMI in Korean women, but the authors first attempted to find an association among IL-1ra polymorphism, obesity, and Sasang constitution.

Cheongyeolsaseuptang inhibits production of TNF-alpha, IL-6 and IL-8 as well as NF-kappa B activation in human mast cells.

Traditional Korean medicine, Cheongyeolsaseuptang (CYSST) has been widely applied as a treatment of rheumatoid arthritis (RA) in Korea. However, its effect in experimental models remains unknown. Recent reports suggest that in patients with RA, synovial mast cells increase in number and show signs of activation and production of cytokines. In this study, we investigated the effect of CYSST on production of cytokines by activated human mast cell line, HMC-1. When CYSST (1mg/ml) was added, the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 was significantly inhibited about 37, 33.6, and 48%, respectively on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated HMC-1 cells. In addition, CYSST inhibited PMA plus A23187-induced activation of nuclear factor-kappaB. These findings may help understanding the mechanism of action of this medicine leading to control activated mast cells on inflammatory condition like RA.

Proteoglycan isolated from Phellinus linteus induces toll-like receptors 2- and 4-mediated maturation of murine dendritic cells via activation of ERK, p38, and NF-kappaB.

Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Phellinus linteus proteoglycan (PL) has been reported to have anti-tumor and immunomodulatory properties. However, the cellular and molecular mechanism underlying its therapeutic effect is poorly understood. In this study, we investigated whether PL induces the phenotypic and functional maturation of murine bone marrow-derived dendritic cells (DC) and the possibility that Toll-like receptors (TLRs), which are known to be involved in immune-related responses, may be the receptor(s) of PL. The expression of surface molecules, including major histocompatibility complex (MHC) class II and CD86, increased on DC that were stimulated in a dose-dependent manner with PL, in comparison with unstimulated DC. Furthermore, PL increases the production of IL-12 by DC, as well as the IL-2 secretion and proliferation of allogeneic T cells. In addition, the activities of PL on DC were significantly reduced by treating the cells with anti-TLR2 or anti-TLR4 antibody (Ab) prior to PL, suggesting that both of them are possible receptors of PL. Also, maturation of DC by PL was able to directly activate mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38, and the nuclear transcription factor NF-kappaB p65. Also, the pretreatment of DC with inhibitors of NF-kappaB p65, and ERK and p38 MAPK signal pathways inhibited PL-induced up-regulation of surface molecules, such as MHC class II and CD86, and IL-12 production. Our results demonstrated that PL stimulation could induce the phenotypic and functional maturation of DC via TLR2 and/or TLR4 mediated-NF-kappaB, ERK and p38 MAPK signal pathways.

Sophorae radix extract inhibits high glucose-induced vascular cell adhesion molecule-1 up-regulation on endothelial cell line.

BACKGROUND: Sophorae radix (SR) has been used for various diseases including atherosclerosis and arrhythmias. Atherosclerosis induced by hyperglycemia is an important factor in the promotion of diabetic complications. An early event in atherosclerosis is the adhesion of monocytes to endothelium via adhesion molecules. Among them, vascular cell adhesion molecule-1 (VCAM-1) expression mediates the binding of monocytes and lymphocytes to vascular endothelial cells. METHODS: The study was performed on vascular endothelial cells (ECV304 cells) that were pretreated with various concentrations of SR extract for 3 h before exposure with high glucose (55.5 mmol/l) for 48 h. The protein expression of VCAM-1 was measured by enzyme-linked immunosorbent assay (ELISA) and its mRNA expression was by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: SR extract significantly inhibited high glucose-induced expression of VCAM-1 in a dose-dependent manner and reduced the level of VCAM-1 mRNA through interfering with translocation of nuclear factor-kappaB (NF-kappaB). Decreased VCAM-1 expression by SR extract was associated reduction of adherence between high glucose-stimulated ECV304 cells and human monocyte-like HL-60 cells. CONCLUSIONS: These data suggest that SR extract inhibits high glucose-mediated monocytes-endothelial cells adhesions and expression of VCAM-1 via inhibition of NF-kappaB translocation.

Suppression of nuclear translocation of nuclear factor-kappaB and nuclear factor of activated T cells by Younggaechulgam-tang.

Younggaechulgam-tang (YGCGT) is known to suppress inflammatory and autoimmune responses, and it has clinically been used among Oriental medical doctors in South Korea. We investigated YGCGT-mediated changes in downstream T cell signal transduction. The expression levels of nuclear factor-kappaB (NFkappaB) subunit RelA and nuclear factor of activated T cells (NFATc1) in cytoplasm and nucleus were examined by western blot analysis. Interlukin-2 (IL-2) expression in MOLT-4 cells activated by phytohemagglutinin (PHA) was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. IL-2 secretion was measured by an enzyme-linked immunosorbent assay (ELISA). PHA-induced translocation of Rel A and NFATcl to the nucleus were markedly reduced by YGCGT treatment. Furthermore, IL-2 mRNA and protein levels and IL-2 secretion were significantly diminished by YGCGT treatment. In conclusion, YGCGT treatment of T cells inhibits selectively nuclear translocation of RelA and NFATc1, resulting in diminished production of IL-2. These results suggest that YGCGT may have potential as immunosuppressive drugs with improved efficacy and reduced side effects.

Inhibitory effect of inflammatory cytokines production from activated mast cells by Gamisopoonghwanghyul-tang.

Rheumatoid arthritis (RA) is a chronic inflammatory disease and its exact cause and pathophysiological process remain unclear. Because the mast cell contains potent mediators, including multifunctional cytokines, its potential contributions to the processes of inflammation and matrix degradation have recently become evident. Gamisopoonghwanghyul-tang (GSPHHT) has been used as a traditional Korean medicine for the treatment of RA. In this study, we investigated the effect of Gamisopoonghwanghyul-tang (GSPHHT) on the production of inflammatory cytokines by activated human mast cell line HMC-1 cells. When GSPHHT (1 mg/ mL) was added, the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10 was inhibited by 36.3%, 36.3%, 30.8%, 48.7% respectively in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 cells. However, the production of IL-4 was significantly increased at 0.01 mg/mL. GSPHHT had no effect on TNF-alpha mRNA expression. These results suggest that GSPHHT regulates production of inflammatory cytokines from activated mast cells.

Polymorphism of angiotensin-converting enzyme gene and BMI in obese Korean women.

BACKGROUND: The renin-angiotensin system (RAS) plays a role in the pathogenesis of metabolic diseases. This system was recently found to be completely expressed in human adipose tissue. Especially angiotensin II, the active component of RAS, may affect adipogenesis and adipocyte metabolism. We examined whether obese and non-obese subjects differ from angiotensin-converting enzyme (ACE) genotype distribution, and whether the ACE genotypes affect the anthropometric parameters or the degrees of body mass index (BMI). METHODS: The study included 155 obese healthy women (BMI > or = 25 kg/m(2), range 25-54.7, age range 15-40 years), 82 non-obese women (BMI < 25 kg/m(2), range 15-40 years), and 613 random controls. Total fat mass and percent body fat (PBF) were determined by dual-energy X-ray absorptiometry (DEXA). Genomic DNA was extracted and used for polymerase chain reaction (PCR)-based genotyping of ACE. RESULTS: Age, percent body fat, waist-to-hip ratio (WHR), body mass index, and cholesterol concentrations did not differ from ACE genotype. No differences were observed for allelic and genotype frequencies between obese women (BMI > or = 25) and 82 non-obese women or 613 random controls. In addition, no association of ACE polymorphism was observed with BMI for genotype in obese women. CONCLUSIONS: ACE polymorphism is not a significant factor for BMI and does not contribute to the odds of obesity in obese healthy women from Korea.

Anti-inflammatory activity of Korean folk medicine purple bamboo salt.

Purple bamboo salt is a specially processed salt according to the traditional recipe using normal salt and bamboo. It has been used for the purpose of prevention and treatment of various diseases in Korea. We investigated the anti-inflammatory activity of purple bamboo salt by using human mast cell line (HMC-1). Purple bamboo salt (1 mg/mL) inhibited phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 secretion, by 67.04% +/- 0.08%, 68.01% +/- 1.85%, and 69.48% +/- 0.54%, respectively. In addition, the expression of TNF-alpha mRNA in HMC-1 cells was inhibited by purple bamboo salt under the same condition. When NaCl (1 mg/mL) was added, the secretion of TNF-alpha and IL-6 was also inhibited but the effect was markedly lower than purple bamboo salt. Our results suggest that purple bamboo salt importantly contributes to the prevention or treatment of inflammatory diseases.

CancerB increases production of nitric oxide and tumor necrosis factor-alpha in peritoneal macrophages.

BACKGROUND: CancerB (CCB, IMSF-5), herbal combination, may be able to stimulate potential toxic mediators such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in isolated mouse peritoneal macrophages. METHODS: NO production was determined by Griess method, and TNF-alpha production by enzyme-linked immunosorbent assay. Amounts of proteins were observed by Western blotting. RESULTS: CCB had no effect on NO production by itself, but CCB alone did stimulate the production of TNF-alpha. When CCB was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production, TNF-alpha production and NF-kappa B activation. The increase in NO synthesis was reflected as an increased amount of inducible NO synthase protein. The increased production of NO from rIFN-gamma plus CCB-stimulated peritoneal macrophages was decreased by the treatment with N(G)-monomethyl-L-arginine or N(alpha)-Tosyl-Phe Chloromethyl Ketone. Nuclear factor-kappa B (NF-kappa B) inhibitor, pyrrolidine dithiocarbamate was able to completely inhibit the production of NO and TNF-alpha. CONCLUSIONS: These findings demonstrate that CCB increases the production of NO and TNF-alpha by rIFN-gamma-primed peritoneal macrophages and suggest that NF-kappa B plays a critical role in mediating these effects of CCB.