Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo.

The aim of this study was to identify the active compound responsible for the pharmacological activities of Manchurian spikenard (Aralia continentalis Kitag.). Interleukin (IL)-1ß-stimulated human chondrocytes and monoiodoacetate (MIA)-induced osteoarthritic rats were treated with the 50% ethanolic extract of spikenard or its major components, such as continentalic acid (ent-pimara-8(14),15-diene-19-oic acid) and kaurenoic acid (ent-kaura-16-en-19-oic acid). The spikenard extract significantly inhibited IL-1ß-stimulated production of IL-6, IL-8, metalloproteinase (MMP)-1, MMP-13, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and prostaglandin(PG)E2 in a dose-dependent manner but not MMP-3 production. The extract also inhibited the IL-1ß-induced translocation of NF-κB/p65 into the nucleus and dose-dependent phosphorylation levels of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase. Continentalic acid exhibited significant anti-arthritic activity corresponding exactly to that of the extract containing an equivalent amount of continentalic acid. On the other hand, kaurenoic acid exhibited a compatible activity at about a 10-times higher molar concentration than that of continentalic acid. In vitro anti-arthritic activities of the spikenard extract and continentalic acid were also confirmed in MIA-induced osteoarthritic rats. The 50% ethanolic extract of Manchurian spikenard exhibited promising anti-arthritic activities in the in vitro and in vivo osteoarthritis models, and continentalic acid, not kaurenoic acid, was most probably responsible for those activities.

Electroacupuncture ameliorates poloxamer 407-induced hyperlipidemia through suppressing hepatic SREBP-2 expression in rats.

AIMS: Acupuncture, particularly electroacupuncture (EA) has been shown to have the lipid-lowering effects, but not completely investigated. The present study was aimed to examine whether EA could attenuate poloxamer-407 (P-407)-induced hyperlipidemia in the rats and to investigate its potential mechanisms. MAIN METHODS: Rats received P-407 (0.4 g/kg, i.p.) to induce hyperlipidemia. EA was performed at ST36 and ST40 acupoints a total of three times with 12 h-interval starting 1 h before the P-407 injection at 0.6 mA intensity and 2 Hz frequency for 10 min. KEY FINDINGS: In P-407-induced hyperlipidemic rats, EA stimulation at ST36 and ST40 acupoints significantly lowered the serum levels of triglycerides, total cholesterol, LDL-cholesterol and atherogenic index, while markedly increasing the serum HDL-cholesterol levels. Meanwhile, hyperlipidemic rats had significantly higher expression of sterol regulatory element-binding protein (SREBP)-2, without any difference in SREBP-1 expression in the liver, as compared with normal ones. EA significantly attenuated the expression of SREBP-2 with a subsequent decrease in 3-hydroxy-3-methylglutaryl coenzyme A reductase and an increase in low-density lipoprotein receptor at both mRNA and protein levels in the liver of hyperlipidemic rats. These changes did not occur after electrical stimulation at a non-acupoint. SIGNIFICANCE: Taken together, our findings indicate that EA stimulation to P-407-induced hyperlipidemic rats improves the lipid abnormalities, which may be associated with regulation of the expression of key enzymes of cholesterol synthesis in the liver through modulation of SREBP-2.

An herbal formula consisting of Schisandra chinensis (Turcz.) Baill, Lycium chinense Mill and Eucommia ulmoides Oliv alleviates disuse muscle atrophy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (SC), Lycium chinense Mill (LC) and Eucommia ulmoides Oliv (EU) are representative tonic herbal medicines that help to strengthen body muscles and bones making them stronger according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: To evaluate effects of an herbal formula consisting of SC, LC and EU on muscle atrophy in C2C12 myotubes and in a rat model of immobilization-induced muscle atrophy. MATERIALS AND METHODS: Muscle atrophy was developed by cast immobilization of unilateral hindlimb on rats for 3 weeks. Treatments were administered orally 14 times over 3 weeks. After treatments, we compared the change of body weight, muscle weight, grip strength, muscle fiber size, muscle fiber type shift by Grip strength meter, H&E stain and ATPase stain. And western blot was used for evaluating molecular mechanism in muscle atrophy on C2C12 cells. RESULTS: When taken individually, SC was the most effective of the three in inhibiting tumor necrosis factor alpha (TNF-α)-induced degeneration of C2C12 myogenesis. The formulation with a mass ratio of 2:1:1 SC: LC: EU (SSLE) was more effective against TNF-α-induced muscle atrophy than was a 1:1:1 SC: LC: EU (SLE) formula or any of the single herbal extracts. In a rat model of disuse muscle atrophy, the SSLE formula significantly inhibited reductions in muscle weight, grip strength and muscle fiber size induced by hindlimb immobilization, in a dose-dependent manner. The formula also inhibited immobilization-induced shifting of the muscle fiber type in soleus muscle. Treatment with SSLE inhibited TNF-α-induced expression of the atrogenes atrogin-1 and muscle RING-finger protein 1 in C2C12 cells. The SSLE formula also increased myoblast differentiation markers (myoD and myogenin) and activation of the Akt and mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSION: These findings suggest that the SSLE formula prevents muscle atrophy through inhibition of the ubiquitin-proteasome system as well as upregulation of myoblast differentiation and muscle protein synthesis in C2C12 cells. Taken together, we conclude that the SSLE formula is invaluable for the development of therapeutic medicines to prevent disuse muscle atrophy and its accompanying muscle weakness.

Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway.

Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1), 10 µM substance P (SP) and 200 nM corticotrophin-releasing factor (CRF) were sequentially added with 48 h-interval. PTW extract (500 µg/mL) was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE) levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF)-α and interleukin (IL)-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA) activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK) phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.

The Seoul Metropolitan Lifestyle Intervention Program and Metabolic Syndrome Risk: A Retrospective Database Study.

Since 2011, the Seoul Metabolic Syndrome Management (SMESY) program has been employed as a community-wide, lifestyle modification intervention in Seoul, Korea. We aimed to determine if the SMESY intervention would be significantly associated with improvements in metabolic syndrome (MetS) risk factors. This retrospective database study included data from 25,449 participants aged 30-64 years between 1 January 2013 and 30 June 2013. In the SMESY program, 3 risk-stratified groups by the number of MetS factors were followed for 12 months with different intensity and timeframe of intervention. Among the high-(n = 7116) and moderate-risk groups (n = 14,762), all MetS factors (except triglycerides among the moderate-risk group) as well as MetS z-scores significantly improved over 12 months (all p < 0.05). Among the low-risk group (n = 3571), all factors aggravated significantly over 12 months (all p < 0.05). We observed temporal associations between the implementation of the SMESY program and improvements in MetS risk factors. However, such improvements differed by risk-stratified group, being most robust for the high-risk group, modest for the moderate-risk group, and aggravated for the low-risk group. Thus, more intensive interventions targeting different risk-stratified groups are needed, given a better understanding of the increase in risk factors observed in the low-risk group.

Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice.

BACKGROUND: Bee venom acupuncture (BVA), a novel type of acupuncture therapy in which purified bee venom is injected into the specific acupuncture point on the diseased part of the body, is used primarily for relieving pain and other musculoskeletal symptoms. In the present study, therapeutic potential of BVA to improve atopic dermatitis, a representative allergic dysfunction, was evaluated in the mouse model of trimellitic anhydride (TMA)-induced skin impairment. METHODS: Mice were treated with 5% TMA on the dorsal flank for sensitization and subsequently treated with 2% TMA on the dorsum of both ears for an additional 12 days after a 3-day interval. From the 7(th) day of 2% TMA treatment, bilateral subcutaneous injection of BV (BV, 0.3 mg/kg) was performed daily at BL40 acupuncture points (located behind the knee) 1 h before 2% TMA treatment for 5 days. RESULTS: BVA treatment markedly inhibited the expression levels of both T helper cell type 1 (Th1) and Th2 cytokines in ear skin and lymph nodes of TMA-treated mice. Clinical features of AD-like symptoms such as ear skin symptom severity and thickness, inflammation, and lymph node weight were significantly alleviated by BV treatment. BV treatment also inhibited the proliferation and infiltration of T cells, the production of Th1 and Th2 cytokines, and the synthesis of interleukin (IL)-4 and immunoglobulin E (IgE)-typical allergic Th2 responses in blood. The inhibitory effect of BVA was more pronounced at BL40 acupoint than non-acupuncture point located at the base of the tail. CONCLUSIONS: These results indicate that BV injection at specific acupuncture points effectively alleviates AD-like skin lesions by inhibiting inflammatory and allergic responses in a TMA-induced contact hypersensitivity mouse model.

Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review.

OBJECTIVES: To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs). METHODS: Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. RESULTS: Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of quality of life (QOL) compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed. CONCLUSION: THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QOL and in decreasing the number of hot flashes per day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues.

Acupuncture for chronic low back pain: a multicenter, randomized, patient-assessor blind, sham-controlled clinical trial.

STUDY DESIGN: Multicenter, randomized, patient-assessor blind, sham-controlled clinical trial. OBJECTIVE: To investigate the efficacy of acupuncture treatment with individualized setting for reduction of bothersomeness in participants with chronic low back pain (cLBP). SUMMARY OF BACKGROUND DATA: Low back pain is one of the main reasons of disability among adults of working age. Acupuncture is known as an effective treatment of cLBP, but it remains unclear whether acupuncture is superior to placebo. METHODS: One hundred thirty adults aged 18 to 65 years with nonspecific LBP lasting for at least last 3 months prior to the trial participated in the study from 3 Korean medical hospitals. Participants received individualized real acupuncture treatments or sham acupuncture treatments for more than 6 weeks (twice a week) from Korean Medicine doctors. Primary outcome was change of visual analogue scale (VAS) score for bothersomeness of cLBP. Secondary outcomes included VAS score for pain intensity and questionnaires including Oswestry Disability Index, general health status (Short Form-36), and Beck Depression Inventory (BDI). RESULTS: There were no baseline differences observed between the 2 groups, except in the Oswestry Disability Index. One hundred sixteen participants finished the treatments and 3- and 6-month follow-ups, with 14 subjects dropping out. Significant difference in VAS score for bothersomeness and pain intensity score of cLBP has been found between the 2 groups (P < 0.05) at the primary end point (8 wk). In addition, those 2 scores improved continuously until 3-month follow-up (P = 0.011, P = 0.005, respectively). Oswestry Disability Index, the Beck Depression Inventory, and Short Form-36 scores were also improved in both groups without group difference. CONCLUSION: This randomized sham-controlled trial suggests that acupuncture treatment shows better effect on the reduction of the bothersomeness and pain intensity than sham control in participants with cLBP.

In vitro and in vivo activities of LCB01-0371, a new oxazolidinone.

LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.

A solvent extraction approach to recover acetic acid from mixed waste acids produced during semiconductor wafer process.

Recovery of acetic acid (HAc) from the waste etching solution discharged from silicon wafer manufacturing process has been attempted by using solvent extraction process. For this purpose 2-ethylhexyl alcohol (EHA) was used as organic solvent. In the pre-treatment stage >99% silicon and hydrofluoric acid was removed from the solution by precipitation. The synthesized product, Na(2)SiF(6) having 98.2% purity was considered of commercial grade having good market value. The waste solution containing 279 g/L acetic acid, 513 g/L nitric acid, 0.9 g/L hydrofluoric acid and 0.030 g/L silicon was used for solvent extraction study. From the batch test results equilibrium conditions for HAc recovery were optimized and found to be 4 stages of extraction at an organic:aqueous (O:A) ratio of 3, 4 stages of scrubbing and 4 stages of stripping at an O:A ratio of 1. Deionized water (DW) was used as stripping agent to elute HAc from organic phase. In the whole batch process 96.3% acetic acid recovery was achieved. Continuous operations were successfully conducted for 100 h using a mixer-settler to examine the feasibility of the extraction system for its possible commercial application. Finally, a complete process flowsheet with material balance for the separation and recovery of HAc has been proposed.

Recovery of nitric acid from waste etching solution using solvent extraction.

A process was developed to recover nitric acid from the waste stream of wafer industry using solvent extraction technique. Tributyl phosphate (TBP) was selected among several extractants because of its better selectivity towards HNO(3), overall superiority in operation, favorable physical properties and economics. The waste solution containing 260 g/L CH(3)COOH, 460 g/L HNO(3), 113 g/L HF and 19.6g/L Si was used as feed solution for process optimization. In the pre-treatment stage >99% silicon and hydrofluoric acid was precipitated out as Na(2)SiF(6). Equilibrium conditions for HNO(3) recovery were optimized from the batch test results as: four stages of extraction at an organic:aqueous (O:A) ratio of 3, four stages of scrubbing at O:A ratio of 5 and five stages of stripping at an O:A ratio of 1.5. The extraction of HNO(3) was suppressed by the presence of acetic acid (HAc) in the feed solution. To examine the feasibility of the extraction system a continuous operation was carried out for 200 h using a multistage mixer-settler. The concentration of pure HNO(3) recovered was 235 g/L with a purity of 99.8%.

Korean acupuncture: the individualized and practical acupuncture.

BACKGROUND: Acupuncture has long been a central part of medicine in East Asia. Recently its therapeutic effects are world-widely recognized with scientific bases being established by means of basic research and clinical studies in the biomedical sciences. Even though Korean acupuncture (KA) shares its origins with traditional Chinese medicine (TCM), it has developed into its own unique system. METHODS: We assessed the unique characteristics of KA and discussed the potential contributions of KA to modern medicine. RESULTS: Individualized approach by KA is based on constitutional energy traits which are considered as a main element in Saam, Taegeuk and eight constitution acupunctures. New practical and integrated forms of therapeutic modalities, such as herbal acupuncture or pharmacopuncture, have also been developed by KA. CONCLUSION: Given its individualized and practical characteristics, KA is expected to make significant contributions to the understanding and the treatment of neurological disorders through basic research and clinical trials.

Efficacy of combined treatment by scalp and penetration acupunctures with TKM medication (tang) on stroke patients.

BACKGROUND: Traditional Korean medicine (TKM) therapy of scalp and penetration acupuncture has been used for the treatment of stroke in Korea. This study investigated the efficacy of scalp and penetration acupuncture in combination with TKM medication. METHODS: Twenty-four stroke patients were enrolled in the program. Control group (n = 12) received herbal medicines (Baepungtang, Sopungtang or Sosokmyeongtang) and conventional body acupuncture. Treatment group (n = 12) received scalp and penetration acupuncture in addition to herbal medicines and conventional body acupuncture. Improvements in the motor functions were scored by the modified Barthel index (MBI). RESULTS: After 4 weeks of treatment, statistical analysis showed significant improvement in the MBI scores for both groups. Significant difference in the MBI scores between two groups, however, was not observed. CONCLUSION: The supportive effect of scalp and penetration acupuncture in the treatment of stroke needs further investigation.

A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis.

Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.

Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, and it has been suggested that treatments promoting survival and functional recovery of affected dopaminergic neurons could have a significant and long-term therapeutic value. In the present study, we investigated the neuroprotective effects of acupuncture on the nigrostriatal system in rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA, 4 microg/microl, intrastriatal injection) using tyrosine hydroxylase (TH) and receptor for brain-derived neurotrophic factor, trkB, immunohistochemistries. Two weeks after the lesions were made, rats presented with asymmetry in rotational behavior (118.3 +/- 17.5 turns/h) following injection with apomorphine, a dopamine receptor agonist (0.5 mg/kg, sc). In contrast, acupunctural treatment at acupoints GB34 and LI3 was shown to significantly reduce this motor deficit (14.6 +/- 13.4 turns/h). Analysis via TH immunohistochemistry revealed a substantial loss of cell bodies in the substantia nigra (SN) (45.7% loss) and their terminals in the dorsolateral striatum ipsilateral to the 6-OHDA-induced lesion. However, acupunctural treatment resulted in the enhanced survival of dopaminergic neurons in the SN (21.4% loss) and their terminals in the dorsolateral striatum. Acupuncture also increased the expression of trkB significantly (35.6% increase) in the ipsilateral SN. In conclusion, we observed that only acupuncturing without the use of any drug has the neuroprotective effects against neuronal death in the rat PD model and these protective properties of acupuncture could be mediated by trkB.

Decrease of the electroacupuncture-induced analgesic effects in nuclear factor-kappa B1 knockout mice.

To investigate the involvement of nuclear factor kappa B1 (NF-kappaB1; p50/p105) in electroacupuncture (EA)-induced analgesia, 2 and 100 Hz EA stimulations were applied at acupoint ST36 (Zusanli) in NF-kappaB1 knockout mice. EA was performed for 30 min and tail-flick latencies (TFLs) were evaluated every 15 min for 1 h. Wild-type mice displayed a 63.3% increase in TFLs compared to baseline after 2 Hz EA, whereas NF-kappaB1+/- mice exhibited a 41.8% increase and NF-kappaB1-/- mice showed only a 3.9% increase of TFLs. The TFLs of 100 Hz EA showed similar trends: a 72.6% increase of TFLs in wild-type, a 38.6% increase in NF-kappaB1+/- and a 9.3% increase in NF-kappaB1-/- mice. The present findings suggest that NF-kappaB1 may play a crucial role in both low and high frequency EA-induced analgesic effects.

Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats.

Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo-2'-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the significant increase in the number of BrdU-positive cells in DG. However, acupuncture at acupoint ST36, near the knee joint, produced no increase in the number of BrdU-positive cells. These findings indicate that acupuncture at acupoint HT7 appears to stimulate cell proliferation, and we suggested that acupuncture may be useful in the treatment of diseases related to maternal separation.

Evaluation of a Apo-1/Fas promoter polymorphism in Korean stroke patients.

Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases such as stroke and Alzheimer's disease. Apo-1/Fas gene is one of the mediators of apoptosis in stroke. Mval polymorphism is the first polymorphic marker identified in the Apo-1/Fas gene promoter, which was typed by PCR and followed by Mval digestion and gel electrophoresis. DNA isolated from peripheral blood collected from 91 stroke patients and 103 healthy blood donors was used for genotypes of GG, GA and AA by sequence specific primer PCR. Mval polymorphism was examined based on Fas gene promotor region by restriction fragment length polymorphism (RFLP). The Fas-GG genotype was the least frequent in patients with stroke and healthy controls (P = 0.57). In normal Korean controls the Mval polymorphism GA, AA and GG were 48.6%, 34.9% and 16.5%. In stroke patients were 56.2%, 29.6% and 14.2% respectively. And the allelic frequencies of Mval*2 (G) allele were less frequent than Mval*1 (A) allele in patients with stroke and healthy controls (P = 0.76). In normal Korean controls Mval*1 (A) and Mval*2 (G) alleles were 59.2% and 40.8%. In stroke patients were 57.6% and 42.4%, respectively. Our results, pending confirmation in a larger study, indicate that the Fas genotype may not appear to be a risk factor for stroke in Korean stroke patients.