Effectiveness of lumbar motion style acupuncture treatment on inpatients with acute low back pain: A pragmatic, randomized controlled trial.

BACKGROUND AND PURPOSE: This parallel, single-center, pragmatic, randomized controlled study aimed to investigate the effectiveness and safety of motion style acupuncture treatment (MSAT; a combination of acupuncture and Doin therapy) to reduce pain and improve the functional disability of patients with acute low back pain (aLBP) due to road traffic accidents. MATERIALS AND METHODS: Ninety-six patients with aLBP admitted to the Haeundae Jaseng Hospital of Korean Medicine in South Korea due to traffic accidents were treated with integrative Korean medicine (IKM) with additional 3-day MSAT sessions during hospitalization (MSAT group, 48 patients) or without (control group, 48 patients), and followed up for 90 days. RESULTS: The mean numeric rating scale (NRS) scores of low back pain (LBP) of the MSAT and control groups were both 6.7 (95% confidence interval [CI]: 6.3, 7.1) at baseline. After completing the third round of all applicable treatment sessions (the primary endpoint in this study), the mean NRS scores of the MSAT and control groups were 3.76 (95% CI: 3.54, 3.99) and 5.32 (95% CI: 5.09, 5.55), respectively. The difference in the mean NRS score between the two groups was 1.56 (95% CI: 1.25, 1.87). CONCLUSION: IKM treatment combined with MSAT can reduce pain and improve the range of motion of patients with aLBP. TRIAL REGISTRATION: This trial is registered at ClinicalTrial.gov (NCT04956458).

Uncovering the colorectal cancer immunotherapeutic potential: Evening primrose (Oenothera biennis) root extract and its active compound oenothein B targeting the PD-1/PD-L1 blockade.

BACKGROUND: The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability. PURPOSE: As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components. METHODS: The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins. RESULTS: EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8+T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8+ TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions. CONCLUSION: This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs.

Effectiveness of motion style acupuncture treatment for patients with shoulder disorders: A prospective observational study.

CONTEXT: Shoulder disorders impair the ability to work. In most cases, the primary symptoms caused by shoulder disorders consist of pain and limitations in the range of motion. OBJECTIVES: This study aimed to investigate the efficacy of motion style acupuncture treatment (MSAT), a conservative treatment modality for shoulder disorders. DESIGN: prospective observational study SETTING: A Korean Medicine hospital PATIENTS: Eighty outpatients with shoulder disorders INTERVENTION: Either MSAT with integrative Korean medicine treatment (MSAT group; n = 40) or integrative Korean medicine treatment only (control group; n = 40). OUTCOME MEASURES: The primary outcome was the shoulder range of motion (ROM), and the secondary outcomes were the numeric rating scale (NRS), visual analog scale (VAS), shoulder pain and disability index (SPADI), and 5-level EuroQol 5-dimension (EQ-5D-5L) scores. RESULTS: At the primary endpoint (2 weeks from the start of the treatment), the MSAT group showed statistically significantly larger ROM for all motions, except adduction ROM, compared to the control group [Flexion ROM (165.10±4.14 vs. 150.49±4.06; P<0.001), extension ROM (43.24±1.55 vs. 40.56±1.51; P<0.05), abduction ROM (160.92±5.68 vs. 134.95±5.54; P<0.001), internal rotation ROM (73.38±2.96 vs. 65.00±2.89; P<0.001), and external rotation ROM (73.78±3.61 vs. 65.88±3.50; P<0.01)]. Additionally, the MSAT group showed significantly lower NRS, SPADI scores at week 2 than the control group; this trend was maintained until the 3-month follow-up.

The Effectiveness of Pharmacopuncture in Patients with Lumbar Spinal Stenosis: A Protocol for a Multi-Centered, Pragmatic, Randomized, Controlled, Parallel Group Study.

Purpose: Lumbar spinal stenosis (LSS) is a chronic degenerative disease. Non-surgical intervention is recommended, considering the risks and benefits for the affected age group, as well as the characteristics of the disease. However, to date, no studies have compared various non-surgical interventions to ascertain the appropriate first-line non-surgical treatment for LSS. Therefore, the objective of this study will be to assess the efficacy of pharmacopuncture as a non-surgical, conservative treatment for LSS. Patients and Methods: A multi-centered, pragmatic, parallel-group study will be conducted. In total, 98 patients will be recruited at seven institutes; recruitment began in May 2022. After two treatment sessions per week over a period of 12 weeks, follow-up assessments will be held at weeks 13, 25, and 53. Results: The efficacy of pharmacopuncture and conservative care will be pragmatically compared in patients radiologically diagnosed with LSS. Pain severity will be measured using the numeric rating scale and visual analog scale. Walking distance will also be evaluated. Patient-centered evaluations will include the Zurich Claudication Questionnaire, Short-Form 12 for Health-Related Quality of Life, EuroQoL 5 Dimension 5 Levels, and Patient Global Impression of Change. Conclusion: The results of this study will confirm the efficacy of pharmacopuncture in comparison to conventional non-surgical treatment and will thus facilitate the prioritization of patient-centered interventions for LSS. Trial registration: This study was registered at Clinicaltrials.gov (registration identifier: NCT05242497) and CRiS (registration identifier: KCT0007145).

Pain, disability, and MRI changes in lumbar disc herniation patients treated with integrative medicine: Ten-year results of an observational study.

BACKGROUND: To date, a 10-year follow-up study on complementary and alternative medical treatment of lumbar intervertebral disc herniation (LDH) has never been conducted. Therefore, we aimed to perform a prospective 10-year follow-up study on the integrated treatment of LDH in Korea. METHODS: One hundred and fifty patients from the baseline study, who initially met the LDH diagnostic criteria with a chief complaint of radiating pain and received integrated treatment, were recruited for this follow-up study. The 10-year follow-up was conducted from February 2018 to March 2018 on pain, disability, satisfaction, quality of life, and changes in herniated disc, muscles, and fat through magnetic resonance imaging. RESULTS: Sixty-five patients were included in this follow-up study. Visual analogue scale score for lower back pain and radiating leg pain were maintained at a significantly lower level than the baseline level. Significant improvements in Oswestry disability index and quality of life were consistently present. MRI confirmed that disc herniation size was reduced over the 10-year follow-up. In total, 95.38% of the patients were either "satisfied" or "extremely satisfied" with the treatment outcomes and 89.23% of the patients claimed their condition "improved" or "highly improved" at the 10-year follow-up. CONCLUSIONS: The reduced pain and improved disability was maintained over 10 years in patients with LDH who were treated with nonsurgical Korean medical treatment 10 years ago. Nonsurgical traditional Korean medical treatment for LDH produced beneficial long-term effects, but future large-scale randomized controlled trials for LDH are needed. STUDY REGISTRATION: ClinicalTrials.gov, NCT03426215.

Age-related digestibility of nutrients depending on the moisture content in aged dogs.

Digestibility of pet food can affect the health of dog, especially of aged animals. To maintain the health of dogs in an overall good status it is necessary to provide nutritionally balanced food. For example, the digestibility of dogs was known to be decreased along aging. In addition, losing teethes is an often event in aged dogs that could induce a problem to eat a large size dry pet food. Nonetheless, few detailed information is available on the most suited feeding for aged dogs. As part of the nutritional study of food for aged dogs, in this study, we tested whether food type impacts on digestibility on adult versus senior dogs. The methodology to measure the digestibility of nutrients was chosen the index method using chromium oxide. Dogs were fed the same commercial dry or wet diets, which were supplemented with 0.5% chromium oxide. The wet food was prepared by adding twice volume of water in the dry food prior to incubated overnight (14-16 hours) at room temperature. After five days, their feces were collected up to a total weight of > 200 g which was the amount to analyze undigested nutrients in feces as 3 repeats. In the apparent total tract digestibility analysis of the experimental breed, no difference in the digestibility of crude protein, crude fat, crude fiber, ash, and energy was observed regarding the moisture content of the food. Noteworthy, the digestibility of nitrogen free extract was significantly increased in senior dogs fed dry dog food compared with adult dogs fed the same diet, whereas no difference was observed between senior and adult dogs fed wet food. The small breed dogs showed similar results to the experimental breed dogs. However, the digestibility of crude fat was additionally affected by age and food type unlike the experimental breed dogs. This finding suggests that the food moisture content affects the digestibility of nutrients in dogs with aging. Hence, it may be helpful to determine the nutrient contents in foods for senior dogs depending on the food type.

Chuna Manual Therapy vs Usual Care for Patients With Nonspecific Chronic Neck Pain: A Randomized Clinical Trial.

Importance: The incidence rate of neck pain is increasing worldwide, and the disease is associated with a high social burden. Manual therapy has been widely applied in the treatment of neck pain, but a high-quality, pragmatic randomized clinical trial for this treatment has not been conducted to date. Objective: This study aimed to compare the effectiveness of Chuna manual therapy with that of usual care for patients with chronic neck pain. Design, Setting, and Participants: A multicenter, assessor-blinded, pragmatic, randomized clinical trial was conducted between October 18, 2017, and June 28, 2019. This intention-to-treat analysis included 108 patients with chronic neck pain persisting for at least 3 months; patients were recruited from 5 hospitals in Korea. Interventions: Ten sessions (2 sessions per week for 5 weeks) of Chuna manual therapy or usual care (electrotherapy and oral medication) were conducted. Main Outcomes and Measures: The main outcome was the difference in visual analog scale (VAS) score for chronic neck pain between baseline and 5 weeks after randomization. Results: This randomized clinical trial recruited 108 patients (mean [SD] age, 38.4 [9.3] years; 73 women [67.6%]). Fifty-four patients were allocated to the Chuna therapy group, and 54 received usual care. At 5 weeks after randomization, manual therapy showed statistically superior results compared with usual care in terms of pain (difference in chronic neck pain VAS, 16.8 mm; 95% CI, 10.1-23.5 mm), function (difference in Neck Disability Index, 8.6%; 95% CI, 4.2%-13.1%), and quality of life (difference in the European Quality of Life-5 Dimension 5 Levels (EQ-5D-5L) scores, -0.07 points; 95% CI, -0.11 to -0.02 points). Regarding the 1-year cumulative values measured using area under the curve analyses, superior outcomes were attained in the manual therapy group in terms of the numerical rating scale for chronic neck pain (1.3 points; 95% CI, 0.5-2.0 points), Neck Disability Index (6.7%; 95% CI, 2.5%-10.9%), Neck Pain Questionnaire (7.4%; 95% CI, 2.3%-12.6%), and EQ-5D-5L scores (-0.03 points; -0.07 to 0.00 points). Conclusions and Relevance: In this randomized clinical trial, for patients with chronic neck pain, Chuna manual therapy was more effective than usual care in terms of pain and functional recovery at 5 weeks and 1 year after randomization. These results support the need to consider recommending manual therapies as primary care treatments for chronic neck pain. Trial Registration: ClinicalTrials.gov identifier: NCT03294785.

Factors influencing clinical symptoms and treatment of patients with traffic accident injuries: A retrospective chart review with a questionnaire survey.

This study analyzed factors influencing clinical symptoms and treatment of patients with traffic accident injuries. It used a retrospective chart review and questionnaire survey obtained from 560 patients (266 men and 294 women). It also conducted follow-up observations of progress after car insurance settlements and investigated the usefulness of and patient satisfaction with integrative Korean medicine treatment for traffic accident injuries. Retrospective data of patients admitted for traffic accident injury were obtained. A questionnaire survey was conducted to collect data regarding the degree of traffic accident damage, severity of pain at settlement, any treatment after settlement and duration and cost of such treatment, and patient satisfaction with car insurance services and Korean medicine treatment for traffic accident injury. The results showed no significant association between pain and the degree of damage to the car at the time of traffic accident (P = 0.662), although the degree of damage to the car was more significantly associated with time to reach a car insurance settlement than severity of pain in the patient (P = 0.003). There was no significant association between the degree of damage to the car in a traffic accident and pain after a traffic accident. Greater severity of pain at the time of the car insurance settlement was associated with greater cost and longer time spent in treatment after the car insurance settlement.

Long-Term Follow-Up of Inpatients with Failed Back Surgery Syndrome Who Received Integrative Korean Medicine Treatment: A Retrospective Analysis and Questionnaire Survey Study.

INTRODUCTION: this study aimed to investigate the long-term clinical efficacy and satisfaction degree of integrative Korean medicine (KM) treatment for patients with failed back surgery syndrome (FBSS). METHODS: we performed a follow-up questionnaire survey and retrospective analysis of medical records for patients with FBSS who underwent inpatient treatment for ≥ 1 week. The primary evaluation indices were numeric rating scale (NRS) scores for low back pain (LBP) and leg pain at admission and discharge. Sub-evaluation indices included the Oswestry Disability Index (ODI) and EuroQol 5-dimension (EQ-5D) score. The follow-up questionnaire survey obtained information regarding previous surgeries; reasons for satisfaction/dissatisfaction with surgical and KM treatment; and current status. RESULTS: compared with at admission, there was a significant post-treatment decrease in the NRS scores for LBP and leg pain, as well as the ODI score. Further, there was a significant post-treatment increase in the EQ-5D score. Regarding the patients' global impression of change for KM treatment administered during admission and at the follow-up questionnaire survey, 101 (95.3%) patients selected "minimally improved" or better. CONCLUSION: integrative KM treatment could effectively reduce pain, as well as improve function and health-related quality of life, in patients with FBSS.

The complete chloroplast genome of Bupleurum euphorbioides, a traditional medicinal plant.

Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic tree indicated that B. euphorbioides was most closely related to B. latissimum.

The complete chloroplast genome of Bupleurum euphorbioides, a traditional medicinal plant.

Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree indicated that B. euphorbioides was the most closely related to B. latissimum.

Association Between Acupuncture and Knee Surgery for Osteoarthritis: A Korean, Nationwide, Matched, Retrospective Cohort Study.

Objectives: The present study was undertaken to investigate the relationship between acupuncture therapy and surgery rate. Design: Matched, retrospective cohort study. Materials and Methods: From nationwide health insurance data (2002-2013 cohort data published by the National Health Insurance Service of Korea), patients with new cases of knee osteoarthritis that occurred between January 1, 2004 and December 31, 2010 were analyzed. Patients were divided into an acupuncture group (AG) and a control group (CG), based on records of acupuncture therapy. Propensity scores were calculated by using gender, age, income level, and Charlson comorbidity index (CCI), with the groups matched at a ratio of 1:3 (AG:CG). The final analysis period was 2 years after the first acupuncture therapy for AG and 2 years after initial diagnosis for CG; surgery rates were compared between the two groups. Stratified analyses were performed based on age, gender, and income level; sensitivity analyses were performed based on the frequency and duration of acupuncture therapy. Results: Propensity score-matched AG and CG included 8,605 and 25,815 subjects, respectively. Post-matching surgery rates were 0.26 and 0.93% in AG and CG, respectively. For all age groups, AG showed a lower surgery rate than CG. In the analysis based on gender, the female group showed a significantly lower hazard ratio of 0.225. In analysis based on income level, the results of the entire group were significant, with the lower income group showing the lowest hazard ratio. In sensitivity analyses, AG tended to show a lower surgery rate than CG. Conclusions: The present study demonstrated that acupuncture therapy is associated with a low rate of surgery for knee osteoarthritis. Additional studies are needed to support this conclusion.

The effectiveness and cost-effectiveness of motion style acupuncture treatment (MSAT) for acute neck pain: A multi-center randomized controlled trial.

BACKGROUND: Neck pain is a common complaint in the general population. Despite the consistent ongoing pain and the resulting economic burden on affected individuals, there have only been a few studies investigating the treatment of acute neck pain. This study aims to evaluate the effectiveness, safety, and cost-effectiveness of the motion style acupuncture treatment (MSAT) and acupuncture treatment for acute neck pain. METHODS: This 2-armed, parallel, multi-centered randomized controlled trial will be conducted at 4 community-based hospitals in Korea. A total of 128 subjects will be randomly assigned, at a 1:1 ratio, to the MSAT and the acupuncture treatment groups. Treatment will be administered 2 to 3 times a week for 2 weeks. The primary outcome will be the visual analog scale of neck pain on movement. The secondary outcomes will be the numeric rating scale of the neck, neck disability index, Northwick Park questionnaire, patient global impression of change, range of motion of the neck, 5-level EuroQol-5 dimension, 12-item Short-Form Health Survey, and EuroQol visual analogue scale. This protocol has been registered at the Clinicaltrials.gov (NCT04539184). DISCUSSION: To our knowledge, this study is the first well-designed multi-centered randomized controlled trial to evaluate the effectiveness, safety, and cost-effectiveness of MSAT on acute neck pain. The results of this study will be useful for clinicians in primary medical institutions that frequently treat acute neck pain patients and for policymakers working with national health insurance.

Observational study on effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation.

We developed a protocol for a prospective registry to prove the effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation. We plan on recruiting 1000 inpatients receiving integrative Korean medicine treatment for lumbar intervertebral disc herniation at four spine specialized Korean medical hospitals. Patients enrolled in the registry will be evaluated at the time of hospitalization, 2 weeks after hospitalization, at discharge, and 6 months after hospitalization on predefined outcome variables such as intensity of back and leg pain, Oswestry Disability Index, quality of life, Patient Global Impression of Change, and adverse effects. The protocol of this study was registered in CRIS (KCT0003709) and Clinical trial gov (NCT03750591). This study is significant in that it cannot only be a basis for safety-related evidence of complementary alternative medicine, which has been lacking, but it also gives clear evidence on the effectiveness and validity of treatment effects such as accompaniment of stenosis, sex, age, and type of disc herniation.

A 13-week repeated oral dose toxicity evaluation and a 4-week recovery evaluation of the Sam So Eum (SSE) in male and female rats.

ETHNOPHAMACOLOGICAL RELEVANCE: Sam So Eum (SSE), used in traditional Korean medicine, has been prescribed for the treatment of various ailments including emesis, and fever for centuries. SSE is known by several different names (Shen Su Yin in traditional Chinese medicine; Jin So In traditional Japanese Kampo medicine). It is a mixture of medicinal plants including Panax ginseng C. A. Mey., Perilla frutescens (L.) Britton, and Peucedanum praeruptorum Dunn. Studies have revealed that SSE has many pharmacological effects including anti-inflammatory, anti-cancer, and anti-allergic properties, but its toxic effects have not been evaluated in vivo. Recently, the use of traditional medicinal herbs to treat various diseases has increased, owing to increased number of studies supporting their efficacy. However, safety evaluations for toxicity and other adverse effects have not been extensive. It is commonly considered that natural products extracted from traditional medicinal herbs are safer than synthetic drugs, but this lacks a scientific basis. Thus, in this study, we evaluated the toxicity of SSE in male and female rats. AIM OF THE STUDY: To evaluated the safety of SSE in male and female rats. MATERIALS AND METHODS: SSE was administered orally for 13 weeks at 1000, 2000, and 4000 mg kg-1·day-1, and then the rats were maintained for 4 weeks without SSE administration (recovery evaluation). RESULTS: We observed the animals for changes in clinical signs, including hematological parameters, and food consumption; serum chemistry profiling and urinalysis were also carried out. Creatinine levels in the serum were significantly increased following oral administration of SSE at 2000 and 4000 mg kg-1·day-1 in male and female rats, but returned to the normal levels during the recovery period. In addition, SSE administration does not cause kidney and liver toxicity. Thus, we determined that the no-observed-adverse-effect level of SSE is 4000 mg kg-1·day-1. The no-observed-effect level of SSE was determined to be 1000 mg kg-1·day-1, because serum creatinine was increased by oral administration of SSE at 2000 and 4000 mg kg-1·day-1 in male and female rats. CONCLUSIONS: SSE administration does not cause toxicity at 4000 mg kg-1·day-1 in male and female rats.

Characterization of the complete chloroplast genome of Liriope platyphylla (Asparagaceae: Nolinoideae) isolated in Korea.

Liriope platyphylla is used as an important medicinal plant for fatigue, cough, and inflammation in South Korea. Here, we report the complete chloroplast genome of L. platyphylla. The total genome size of the chloroplast is 157,076 bp with a large single-copy region (LSC: 85,374 bp), a small single-copy region (SSC: 18,748 bp), and inverted repeat regions (IRa and IRb: 26,477 bp). The GC content of the L. platyphylla chloroplast was 37.6%. The cp genome encoded a set of 129 genes, including 83 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic tree analysis indicated that L. platyphylla is closely related to L. spicata.

Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance.

Orexin A (OXA) is a neuropeptide associated with plasma insulin and leptin levels involved in body weight and appetite regulation. However, little is known about the effect of OXA on leptin secretion in adipocytes and its physiological roles. Leptin secretion and expression were analysed in 3T3-L1 adipocytes. Plasma leptin, adiponectin and insulin levels were measured by ELISA assay. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) levels in the hypothalamus were evaluated by western blotting. OXA dose-dependently suppressed leptin secretion from 3T3-L1 adipocytes by inhibiting its gene expression while facilitating adiponectin secretion. The leptin inhibition by OXA was mediated via orexin receptors (OXR1 and OXR2). In addition to the pathway via extracellular signal-regulated kinases, OXA triggered adenylyl cyclase-induced cAMP elevation, which results in protein kinase A-mediated activation of cAMP response element-binding proteins (CREB). Accordingly, CREB inhibition restored the OXA-induced downregulation of leptin gene expression and secretion. Exogenous OXA for 4 weeks decreased fasting plasma leptin levels and increased hypothalamic pSTAT3 levels in high-fat diet-fed mice, regardless of increase in body weight and food intake. These results suggest that high dose of OXA directly inhibits leptin mRNA expression and thus secretion in adipocytes, which may be a peripheral mechanism of OXA for its role in appetite drive during fasting. It may be also critical for lowering basal plasma leptin levels and thus maintaining postprandial hypothalamic leptin sensitivity.

Subchronic toxicity evaluation of ethanol extract of Cassia tora L. seeds in rats.

Cassia tora Linn. is an annual or perennial plant of the Fabaceae/Leguminosae family. It is used in traditional medicine for various biological activities including anti-constipation, anti-inflammatory, visual acuity, and hepato-protective activities. The present study was carried out to investigate the potential toxicity of C. tora L. seed ethanol extract (CTSEE) following a 13-week repeated oral administration to Sprague-Dawley rats. CTSEE was administered orally to male and female rats for 13 weeks at 0 (control), 500, 1000, and 2000 mg/kg/day (n = 10, for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 4-week recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples collected. There were no treatment-related adverse effects in clinical signs, body weight, food consumption, estrous cycle, sperm parameters, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any doses tested. Under the present experimental conditions, the no-observed-adverse-effect level of the CTSEE was >2000 mg/kg/day in both genders, and no target organs were identified.

Nelumbo nucifera Receptaculum Extract Suppresses Angiotensin II-Induced Cardiomyocyte Hypertrophy.

Nelumbo nucifera Gaertn. (lotus) is an important medicinal plant, and many parts of the plant have been investigated for their therapeutic effects. However, the therapeutic effect of receptacles of lotuses on pathological cardiomyocyte hypertrophy has not been investigated yet. Therefore, the current study aimed to determine the protective effect of lotus against angiotensin II (Ang II)-induced cardiomyocyte hypertrophy in vitro. Ang II was used to induce hypertrophy of H9c2 cells. The lotus receptacle powder (MeOH extract of receptaculum Nelumbinis; MRN) used in the experiments was prepared by MeOH extraction and subsequent evaporation. To evaluate the effect of MRN on cardiomyocyte hypertrophy, cell size, protein synthesis, and hypertrophic marker expressions were examined. The antioxidant ability of MRN was determined by using CM-H2DCFDA, a general oxidative stress indicator. Ang II-induced cardiomyocyte hypertrophy was significantly attenuated by 5 µg/mL of MRN, as confirmed by the reductions in cell size, protein synthesis, and hypertrophic marker expression. MRN also attenuated Ang II-induced excessive intracellular reactive oxygen species (ROS) production through the suppression of protein kinase C (PKC), extracellular-signal-regulated kinase (ERK), and NF-κB activation and subsequent type I angiotensin receptor (AT1R), receptor for advanced glycation end products (RAGE), and NADPH oxidase (NOX) expression. MRN exerted a significant protective effect against Ang II-induced cardiomyocyte hypertrophy through suppression of PKC-ERK signaling, and this subsequently led to attenuation of intracellular ROS production.

Antioxidant and Antimelanogenic Activities of Compounds Isolated from the Aerial Parts of Achillea alpina L.

Achillea alpina is widely distributed in Korea and is often used as a folk medicine for stomach disorders. Although a previous study isolated antioxidant compounds (flavonoid O-glucoside, sesquiterpene) from this plant, no systematic study of its chemical constituents had been reported. The present study aimed to identify the phytochemicals present in a methanol extract of A. alpina, assess their potential antioxidant activities in vitro, and determine their effects on melanogenesis in B16F10 melanoma cells. Column chromatographic separation of aqueous fractions of A. alpina led to the isolation of 17 compounds. The chemical structures of these compounds were determined using spectroscopic data from electrospray ionization-mass spectrometry and nuclear magnetic resonance. To the best of our knowledge, the present study is the first to identify compounds 2-10 and 12-17 in A. alpina. Furthermore, compound 6 possessed powerful antioxidant activity, while compound 15 suppressed intracellular tyrosinase activity and thus reduced melanogenesis in B16F10 cells. Therefore, our research suggested that these naturally occurring compounds have the potential to reduce oxidative stress and promote skin whitening. Further investigations will be required to elucidate the mechanisms underlying the antioxidant and antityrosinase activities of these compounds.