Isosinensetin Stimulates Glucagon-like Peptide-1 Secretion via Activation of hTAS2R50 and the Gßγ-Mediated Signaling Pathway.

Bitter taste receptors (TAS2Rs) are G protein-coupled receptors localized in the taste buds of the tongue. They may also be present in non-lingual organs, including the brain, lung, kidney, and gastrointestinal (GI) tract. Recent studies on bitter taste receptor functions have suggested TAS2Rs as potential therapeutic targets. The human bitter taste receptor subtype hTAS2R50 responds to its agonist isosinensetin (ISS). Here, we demonstrated that, unlike other TAS2R agonists, isosinensetin activated hTAS2R50 as well as increased Glucagon-like peptide 1 (GLP-1) secretion through the Gßγ-mediated pathway in NCI-H716 cells. To confirm this mechanism, we showed that ISS increased intracellular Ca2+ and was suppressed by the IP3R inhibitor 2-APB as well as the PLC inhibitor U73122, suggesting that TAS2Rs alters the physiological state of enteroendocrine L cells in a PLC-dependent manner. Furthermore, we demonstrated that ISS upregulated proglucagon mRNA and stimulated GLP-1 secretion. ISS-mediated GLP-1 secretion was suppressed in response to small interfering RNA-mediated silencing of Gα-gust and hTAS2R50 as well as 2-APB and U73122. Our findings improved the understanding of how ISS modulates GLP-1 secretion and indicates the possibility of using ISS as a therapeutic agent in the treatment of diabetes mellitus.

Anti-Obesity Effect of Polygalin C Isolated from Polygala japonica Houtt. via Suppression of the Adipogenic and Lipogenic Factors in 3T3-L1 Adipocytes.

Obesity is a risk factor for metabolic diseases including type 2 diabetes, nonalcoholic steatohepatitis (NASH), heart diseases, and cancer. This study aimed to investigate the anti-obesity effect of Polygalin C (PC) isolated from Polygala japonica Houtt. in 3T3-L1 adipocytes. Based on Oil Red O assay results, PC significantly decreased lipid accumulation compared to the control. We found that PC suppressed adipogenesis transcription factors including peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer-binding protein (C/EBP) α, and lipogenic factors such as sterol regulatory element-binding protein 1c (SREBP 1c) and fatty acid synthase (FAS), in 3T3-L1 adipocytes using Western blotting and real-time polymerase chain reaction (PCR). Moreover, PC inhibited the differentiation of 3T3-L1 cells by regulating the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase/protein kinase B (MAPK/Akt) signaling pathways. Additionally, we confirmed that PC inhibited early adipogenesis factors C/EBP ß and C/EBP δ. Therefore, PC inhibited adipogenesis and lipogenesis in vitro. Thus, PC appears to exert potential therapeutic effects on obesity by suppressing lipid metabolism.

The Use of Acupuncture in the Management of Patients With Humeral Fractures: A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis of the effects of acupuncture on humeral fractures. METHODS: Randomized controlled trials were searched systematically from inception to January 2020 using the Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and 7 Korean databases. Pain scale and Japanese Orthopaedic Association scores were the primary and secondary measurements. A risk-of-bias assessment and meta-analysis were conducted. RESULTS: Seven randomized controlled trials were included in the systematic review; the quality of the studies was ambiguous. The meta-analysis showed that acupuncture improved the pain severity score compared with conventional therapies (standard mean difference = -4.55, 95% confidence interval, -7.48 to -1.61, I2 = 98%, P < .00001) but did not improve the Japanese Orthopaedic Association score (standard mean difference = 4.99, 95% confidence interval, -0.31 to 10.30, I2 = 99%, P < .00001). CONCLUSION: Our meta-analysis shows that acupuncture reduced pain after proximal humeral fracture, in addition to common rehabilitative modalities. However, the conclusion of this review should be cautiously applied in clinical practice owing to the low quality of the included studies.

Ophiopogonin D ameliorates DNCB-induced atopic dermatitis-like lesions in BALB/c mice and TNF-α- inflamed HaCaT cell.

Atopic dermatitis (AD) can occur in both children and adults, and the symptoms include itching and eczema, which in turn cause patients to suffer. Ophiopogonin D (OP-D) is a steroidal glycoside from Radix Ophiopogon japonicus, which is well known as an effective anti-inflammatory herbal medicine in many Asian countries. In this study, we aimed to investigate the anti-inflammatory effects of OP-D, using an AD mouse model and inflamed HaCaT cells. Through a histopathological analysis, we were able to confirm the suppressive effects of OP-D on skin thickening and the mast cell activation in AD-like mouse back skin tissues stimulated by DNCB. In addition, we detected significant decreases in cytokine expression levels through multiplex assessment assays of the OP-D-treated mice blood. We observed the anti-inflammatory effect of OP-D in the spleen, causing weight loss in the spleen and in the mRNA expression levels related to diverse cytokines. In human keratinocytes inflamed by TNF-α, OP-D inhibited p38 and ERK protein activation and showed a reduction of NF-κB nuclear translocation. Furthermore, OP-D attenuated pro-inflammatory cytokine mRNA expressions in TNF-α-inflamed HaCaT cells. Accordingly, we came to the conclusion that OP-D is a potential natural drug which can be used in order to treat inflammatory skin diseases, such as AD.

Anti-Cancer Potential of Oxialis obtriangulata in Pancreatic Cancer Cell through Regulation of the ERK/Src/STAT3-Mediated Pathway.

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.

3-Formylchromone inhibits proliferation and induces apoptosis of multiple myeloma cells by abrogating STAT3 signaling through the induction of PIAS3.

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently observed and closely linked with proliferation, survival, metastasis and angiogenesis of various cancer cells, and thus its inhibition can be considered a potential therapeutic strategy. We found that 3-formylchromone (3FC) inhibited both constitutive and inducible STAT3 activation in multiple myeloma (MM) cells. Besides the inhibition of STAT3 phosphorylation, 3FC also abrogated constitutive activity and nuclear translocation of STAT3. This suppression was mediated through the inhibition of phosphorylation of Janus-activated kinase (JAK) 1/2 and Src. Furthermore, 3FC induced the expression of the protein inhibitors of activated STAT3 (PIAS3), and gene silencing of the PIAS3 by small interfering RNA abolished the ability of 3FC to inhibit STAT3 activation, suggesting a critical role for PIAS3 in the action of 3FC. 3FC also downregulated the expression of STAT3-regulated gene products such as Bcl-2, Bcl-xl, Mcl-1, Survivin, inhibitor of apoptosis protein-1 (IAP-1), Cyclin D1, cyclooxygenase-2 (COX-2), and matrix metalloproteinases-9 (MMP-9) in MM cells. This correlated with induction of substantial apoptosis as indicated by an increase in the sub-G1 cell population and caspase-3 induced poly ADP ribose polymerase (PARP) cleavage. Overall, these results suggest that 3FC is a novel blocker of STAT3 activation pathway thus may have a potential in therapy of MM and other cancers.

Effect of modified fasting therapy on body weight, fat and muscle mass, and blood chemistry in patients with obesity.

OBJECTIVE: The aim of this study was to investigate the effects and safety of modified fasting therapy using fermented medicinal herbs and exercise on body weight, fat and muscle mass, and blood chemistry in obese subjects. METHODS: Twenty-six patients participated in a 14-day fast, during which they ingested a supplement made from fermented medicinal herbs and carbohydrates (intake: 400-600 kcal/d). The schedule included 7 prefasting relief days and 14 days of stepwise reintroduction of food. The patients also took part in an exercise program that incorporated Qigong, weight training, and walking exercises. The efficacy of treatments was observed by assessing body fat mass and muscle mass, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides in each study period. Specific symptoms or side effects were reported. RESULTS: Body weight and body fat mass both decreased significantly by (5.16 ± 0.95) and (3.89 ± 0.79) kg (both P < 0.05), while muscle mass decreased by an average of (0.26 ± 0.22) kg, without statistical significance. ALT levels were significantly decreased (P < 0.05), while AST levels decreased without statistical significance (P = 0.052). The levels of total cholesterol and triglycerides were also significantly decreased (both P < 0.05). There were few adverse events except for mild dizziness, which did not affect everyday living. CONCLUSION: These results suggest that modified fasting therapy using fermented medicinal herbs and exercise could be effective and safe on obese patients.

6-Shogaol exerts anti-proliferative and pro-apoptotic effects through the modulation of STAT3 and MAPKs signaling pathways.

6-shogaol (6SG), one of active ingredients in ginger (Zingiber officinale), is known to exhibit anti-proliferative, anti-metastatic, and pro-apoptotic activities through a mechanism that is not fully elucidated. Because the aberrant activation of STAT3 and MAPKs have been associated with regulation of proliferation, invasion, and metastasis of tumors, we hypothesized that 6SG modulates the activation of STAT3 and MAPKs activation in tumor cells. We found that 6SG strongly inhibited constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK2 and c-Src kinases and nuclear translocation of STAT3 on both MDA-MB231 and DU145 cells. Also, 6SG caused the activation of JNK, p38 MAPK, and ERK. Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented 6SG-induced apoptosis. 6SG induced apoptosis as characterized by cleavage of PARP, accumulation of cells in subG1 phase, positive Annexin V binding, down-regulation of STAT3-regulated proteins, and activation of caspase-8, -9, -3 in both MDA-MB231 cells. Compared with other analogues of 6SG, such as 6-gingerol (6G), 8-gingerol (8G), and 10-gingerol (10G), 6SG was found to be the most potent blocker of STAT3 activation. We observed that the administration of 6SG alone significantly suppressed the growth of the tumor. As compared to the vehicle control, 6SG also suppressed the expression of STAT3-regulated gene products such as Bcl-2, Bcl-xL, and Survivin in tumor tissues. Overall, these findings suggest that 6SG can interfere with multiple signaling cascades involved in tumorigenesis and can be used as a potential therapeutic candidate for both the prevention and treatment of cancer.

The hydrolysed products of iridoid glycosides can enhance imatinib mesylate-induced apoptosis in human myeloid leukaemia cells.

Several studies have demonstrated that deregulated activation of signal transducer and activator of transcription 3 (STAT3) has been associated with survival, proliferation, chemoresistance and angiogenesis of tumour cells. Thus, inhibition of STAT3 expression could be a potent therapeutic approach for cancer treatment. Using several leukaemia cell lines, the effect of the hydrolysed-catalpol (H-catalpol) and hydrolysed-aucubin (H-aucubin) products on the STAT3 signalling pathway, inhibition of BCR-ABL activation, cellular proliferation and potentiation of imatinib mesylate-induced apoptosis was investigated. We found that iridoid glycosides (catalpol and aucubin) did not exert any cytotoxicity in the tumour cells, whereas both H-catalpol and H-aucubin exhibited significant cytotoxic effects on K562 human myeloid leukaemia cells. Indeed, H-catalpol and H-aucubin down-regulated BCR-ABL phosphorylation and inhibited constitutive STAT3 activation through abrogating upstream JAK2 and c-Src and constitutive STAT5 activation leading to apoptosis through caspase-3 activation. Hydrolysed-catalpol enhanced the apoptosis induced by imatinib mesylate and this correlated with down-regulation of gene products that mediate cell proliferation (cyclin D1), and cell survival (Bcl-2, Bcl-xL and survivin); all known to be regulated by the STAT3. Overall, our results provide novel insight into the role of hydrolysed iridoids in potentially treating leukaemia through the modulation of STAT3 signalling pathway.

Transcriptomic Analysis Reveals Wound Healing of Morus alba Root Extract by Up-Regulating Keratin Filament and CXCL12/CXCR4 Signaling.

Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA-mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real-time cell analysis and real-time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose-dependent manner on Kera-308 cell line, and up-regulated keratin expression including wound-induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up-regulated mRNA associated keratin filaments and toward a more up-regulated mRNA level of C-X-C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway.

Cinobufagin exerts anti-proliferative and pro-apoptotic effects through the modulation ROS-mediated MAPKs signaling pathway.

Cinobufagin (CBG) is a cardiotoxic bufanolide steroid secreted by the skin and parotid venom glands of the Asiatic toad Bufo bufo gargarizans (called Chan-Su). Although CBG is known to exhibit anti-cancer activities, very little is known about its potential mechanism(s) of action. In this study, we investigated whether CBG mediates its effect through the modulation of the mitogen-activated protein kinases (MAPKs) signaling pathway in human multiple myeloma (MM) U266 cells. We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells. CBG showed much higher cytotoxicity against U266 cells as compared to peripheral blood mononuclear cells (PBMC). Induction of CBG increased reactive oxygen species (ROS) generation from mitochondria, which is associated with the induction of apoptosis as characterized by increased sub-G1 DNA contents of cell cycle, positive Annexin V binding, activation of caspase-3 and cleavage of PARP. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis. CBG also down-regulated the expression of various downstream gene products that mediate cell proliferation, survival, angiogenesis and metastasis. Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells. Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.

ß-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products.

We have recently reported that ß-caryophyllene oxide (CPO) can induce apoptosis, suppress tumor growth, and inhibit metastasis through the suppression of signal transducer and activator of transcription 3, PI3K/AKT/mTOR/S6K1 signaling cascades and ROS-mediated MAPKs activation. In the present study, we found that CPO potentiated the apoptosis induced by tumor necrosis factor α (TNFα) and chemotherapeutic agents, suppressed TNFα-induced tumor cell invasion, all of which are known to require NF-κB activation. We found that TNFα stimulated the expression of gene products involved in anti-apoptosis (IAP1, IAP2, Bcl-2, Bcl-xL, and survivin), proliferation (COX-2, cyclin D1, and c-Myc), invasion (MMP 9 and ICAM-1), and angiogenesis (VEGF) and that CPO treatment suppressed their expression. Because these gene products are also regulated by proinflammatory transcription factor NF-κB, we postulated that CPO may mediate its effects by modulating the NF-κB pathway. We found that CPO blocked both inducible and constitutive NF-κB activation in a wide variety of tumor cells. CPO was also found to inhibit the TNFα-induced degradation of IκBα through the inhibition of activation of IκBα kinase and p65 nuclear translocation and phosphorylation. Interestingly, CPO failed to potentiate the apoptotic effect induced by TNFα in p65 (-/-) cells as compared to the wild-type. Thus, overall, our results indicate that the inhibition of NF-κB is one of major mechanisms by which CPO enhances TNFα-induced apoptosis and suppresses invasion.

Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIM: The efficacy of treatment with multispecies probiotics on irritable bowel syndrome (IBS) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated. METHODS: This randomized, double-blind, placebo-controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks. The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary end-points were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the 4 weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time polymerase chain reaction assays. RESULTS: The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) versus 37.5% (9/24) (P < 0.05). Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus, and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group. CONCLUSIONS: Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota.

Anti-metastatic effect of supercritical extracts from the Citrus hassaku pericarp via inhibition of C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase-9 (MMP-9).

The fruit of hassaku (Citrus hassaku Hort. ex Tanaka) is locally known as phalsak in Korea. Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB-induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA-MB-231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase-9 (MMP-9) expression and its enzymatic activity under non-cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF-κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12-stimulated invasion of MDA-MB-231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP-9 expressions through blockade of NF-κB activation and thus has the potential to suppress metastasis of breast cancer.

Effect of Moxibustion Combined with Other Interventions on Body Weight Reduction in the Treatment of Obesity: A Systematic Review and Meta-Analysis.

Background: Moxibustion has been used in the treatment and prevention of obesity. However, there has been no systematic review or meta-analysis conducted on the use of moxibustion on obesity treatment. This study aimed to evaluate the role of moxibustion in the treatment of obesity. Methods: The Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE/PubMed databases were searched to identify all randomized controlled trials (RCTs) that evaluated the effect of moxibustion on obesity. The primary outcome was body weight. The secondary outcomes were the body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). The risk of bias assessment and meta-analysis were conducted using the Cochrane Collaboration tool. Results: Eleven RCTs involving 761 participants were included in this systematic review and meta-analysis. Other interventions that were included in the analyses were manual acupuncture, electroacupuncture, embedding therapy, herbal medicine, and diet control. Moxibustion combined with other interventions resulted in a significant improvement in body weight reduction (mean difference [MD] -3.32, 95% confidence interval [CI: -4.25 to -2.38]; I2 = 17%), BMI (MD -1.51, 95% CI [-1.88 to -1.14]; I2 = 76%), and WC (MD -2.82, 95% CI [-3.50 to -2.13]; I2 = 75%), but did not improve HC (MD -2.05, 95% CI [-4.21 to 0.11]; I2 = 0%) or WHR (MD -0.01, 95% CI [-0.03 to 0.01]; I2 = 57%). Conclusions: Moxibustion can be used with other interventions to improve body weight, BMI, and WC in people with obesity. However, the conclusions of this review should be cautiously applied to clinical practice because most of the included studies had a high or unclear risk of bias.

Bibliometric analysis of auriculotherapy research trends over the past 20 years.

OBJECTIVES: Auriculotherapy has long been used to treat various diseases. We analyzed and visualized auriculotherapy's geographical distribution, key contributors, and thematic trends over the past 20 years to provide current trends in auriculotherapy field and to offer recommendations for future research directions. DESIGN/SETTING: We searched for relevant studies in the Web of Science between January 10, 2003, and December 31, 2022. A bibliometric analysis was performed using VOSviewer for annual publications, journals, countries, institutions, authors, and keywords. RESULTS: A total of 800 studies were included in the analysis, and the number of studies steadily increased over the 20 examined years. In 2018, there was a noteworthy rise in publications, nearly twice as many as the preceding year. Integrative & complementary medicine was the most researched area, with most articles published in Evidence-Based Complementary and Alternative Medicine. China was the country with the most published research, and the most active organization was Guangzhou University of Chinese Medicine in China, followed by Kyung Hee University in South Korea. The most prolific author was Yeh Mei-ling, who reported the effects of auriculotherapy on dysmenorrhea and smoking cessation. Keyword analysis revealed four clusters: pain, mental health, obesity, and smoking cessation. CONCLUSION: Auriculotherapy research primarily focused on clinical studies related to pain, obesity, smoking cessation, and depression. Future research should place greater emphasis on verifying the mechanisms of auriculotherapy for specific ailments and may require efforts to enhance the robustness of clinical trials. Through visual analysis, our study may serve as a foundational resource, offering valuable insights into the trajectory of auriculotherapy research.

Effects of electroacupuncture on obesity: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis evaluated the efficacy of electroacupuncture for the treatment of obesity. METHODS: We searched 8 electronic databases for articles published between 2005 and 2021, including only randomized controlled trials (RCTs) in the review. The intervention groups received either electroacupuncture alone or electroacupuncture with standard care, whereas the control groups received sham electroacupuncture, standard care, or no treatment. The primary outcome was the body mass index (BMI), and the secondary outcomes were the body weight (BW), waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat mass, body fat percentage, and adverse effects. Continuous outcome data are presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: This systematic review and meta-analysis included 13 RCTs involving 779 participants. Results revealed that the BMI (MD: -0.98; 95% CI: -1.35 to -0.61), BW (MD: -1.89; 95% CI: -2.97 to -0.80), WC (MD: -2.67; 95% CI: -4.52 to -0.82), and WHR (MD: -0.03; 95% CI: -0.06 to -0.01) were significantly improved in the intervention groups compared with those in the control groups. Adverse effects were reported in 5 studies. The most commonly used acupoint in the abdomen was ST25, whereas the most commonly used acupoints in other regions were ST36 and SP6 for the treatment of obesity. ST25 was the most commonly used acupoint connected by electroacupuncture. CONCLUSION: This systematic review and meta-analysis suggested that electroacupuncture is an effective and safe therapy for simple obesity. To increase the reliability of this study, further detailed, long-term studies should be conducted on the effects of electroacupuncture on obesity.

Capillarisin inhibits iNOS, COX-2 expression, and proinflammatory cytokines in LPS-induced RAW 264.7 macrophages via the suppression of ERK, JNK, and NF-κB activation.

The aerial parts of Artemisia capillaris (Compositae) have been used in traditional Korean medicine as a cholagogic, antipyretic, anti-inflammatory, and diuretic purposes. In our previous study, ethanolic extracts of the plant demonstrated a marked anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (J. Korean Soc. Appl. Biol. Chem., 2010, 53, 275-282). In the present study, capillarisin (CPS), a flavone, main constituent of A. capillaris, was examined for its anti-inflammatory activity in the cells. We found that CPS highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells. CPS inhibited the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and their mRNA in a dose-dependent manner. Also, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, and prostaglandin E(2) (PGE(2)) secretion were decreased by CPS in LPS-stimulated macrophages. As a result, CPS inhibited proinflammatory cytokines, iNOS, and COX-2, which is attributed to the suppression of LPS-induced ERK, JNK, and nuclear factor-κB (NF-κB) activation. Therefore, we demonstrate here that CPS potentially inhibits the biomarkers related to inflammation through the abrogation of ERK, JNK, and NF-κB p65 activation, and it may be a potential therapeutic candidate for the treatment of inflammatory diseases.

8ß-hydroxy-3-oxopimar-15-ene exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway.

The flying squirrel's droppings (Pteropus pselaphon) have been used for improving the blood circulation, arresting bleeding to treat hematological disorders, and reducing pain. Here, 8ß-hydroxy-3-oxopimar-15-ene (OXO), one of main constituents of P. pselaphon, was examined for its anti-inflammatory activity in murine macrophages. We found that OXO significantly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells. OXO inhibited the expression of LPS-induced iNOS and COX-2 protein and their mRNA in a dose-dependent manner. Also, TNF-α, IL-6, and PGE2 secretion was decreased by OXO in LPS-stimulated macrophages. These inflammatory biomarkers were attributed to the suppression of LPS-induced activation of p38 MAPK and subsequent activation of two components of AP-1 (c-Jun and c-Fos), but not of ERK, JNK, NF-κB. Moreover, OXO inhibited LPS-induced intracellular reactive oxygen species (ROS) production and co-incubation of OXO and hydrogen peroxide (H2O2) suppressed the phosphorylation of p38 in a concentration-dependent manner. In addition, OXO completely disrupted the formation of TRAF6-ASK complex in the cells. Therefore, we demonstrate here that OXO can potentially inhibit several biomarkers related to inflammation through inhibition of ROS-mediated activation of TRAF6-ASK1-p38 pathway.

Traditional Chinese medicine for foot pain in a patient with complex regional pain syndrome: A case report.

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by pain as well as sensory, motor, and sudomotor disorders. Generally, it is classified into two types CRPS-I and CRPS-II. There is no single diagnostic test or treatment approach for CRPS, and a multidisciplinary approach is gaining attention to improve patients' symptoms and their quality of life. CASE SUMMARY: A 35-year-old woman with an unremarkable medical history sought treatment for CRPS at a hospital of Korean medicine. During her first visit, she was wheelchair-bound due to severe pain in her left lower extremity. She had edema and discoloration of the left foot. She was treated with a combination of traditional Chinese medicine (TCM) approaches, including acupuncture, moxibustion, pharmacopuncture, and herbal decoction, for approximately 20 sessions. The foot and ankle outcome score (FAOS) and visual analog scale (VAS) score for pain were evaluated, along with general signs and functions. Her symptoms, signs, FAOS, and VAS scores improved after treatment, with a significant 7-degree decrease in the VAS score and a 62-point increase in the FAOS score. Additionally, the foot swelling and discoloration gradually resolved. During the phone follow-up, 5 mo after the last visit, additional improvements in outcomes were observed. CONCLUSION: Combined TCM treatment may be a reasonable and safe option for alleviating symptoms and improving function in patients with CRPS.