Acteoside Counteracts Interleukin-1ß-Induced Catabolic Processes through the Modulation of Mitogen-Activated Protein Kinases and the NFκB Cellular Signaling Pathway.

Osteoarthritis (OA) is the most common degenerative joint disease with chronic joint pain caused by progressive degeneration of articular cartilage at synovial joints. Acteoside, a caffeoylphenylethanoid glycoside, has various biological activities such as antimicrobial, anti-inflammatory, anticancer, antioxidative, cytoprotective, and neuroprotective effect. Further, oral administration of acteoside at high dosage does not cause genotoxicity. Therefore, the aim of present study is to verify the anticatabolic effects of acteoside against osteoarthritis and its anticatabolic signaling pathway. Acteoside did not decrease the viabilities of mouse fibroblast L929 cells used as normal cells and primary rat chondrocytes. Acteoside counteracted the IL-1ß-induced proteoglycan loss in the chondrocytes and articular cartilage through suppressing the expression and activation of cartilage-degrading enzyme such as matrix metalloproteinase- (MMP-) 13, MMP-1, and MMP-3. Furthermore, acteoside suppressed the expression of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in the primary rat chondrocytes treated with IL-1ß. Subsequently, the expression of proinflammatory cytokines was decreased by acteoside in the primary rat chondrocytes treated with IL-1ß. Moreover, acteoside suppressed not only the phosphorylation of mitogen-activated protein kinases in primary rat chondrocytes treated with IL-1ß but also the translocation of NFκB from the cytosol to the nucleus through suppression of its phosphorylation. Oral administration of 5 and 10 mg/kg acteoside attenuated the progressive degeneration of articular cartilage in the osteoarthritic mouse model generated by destabilization of the medial meniscus. Our findings indicate that acteoside is a promising potential anticatabolic agent or supplement to attenuate or prevent progressive degeneration of articular cartilage.

Efficacy and safety of Sihogayonggolmoryeo-tang (Saikokaryukotsuboreito, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) for post-stroke depression: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to analyze the efficacy and safety of Sihogayonggolmoryeo-tang (SGYMT), a classical herbal medicine consisting of 11 herbs, for treatment of post-stroke depression (PSD). Thirteen databases were comprehensively searched from their inception dates until July 2019. Only randomized controlled trials (RCTs) using SGYMT as a monotherapy or adjunctive therapy for PSD patients were included. Where appropriate data were available, meta-analysis was performed and presented as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). We assessed the quality of RCTs using the Cochrane risk of bias tool and the Jadad scale. The quality of evidence for each main outcome was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Twenty-one RCTs with 1,644 participants were included. In the comparison between the SGYMT and antidepressants groups, the SGYMT group scored significantly lower on both the Hamilton Depression Scale (HAMD) (8 studies; MD -2.08, 95% CI -2.62 to -1.53, I2 = 34%) and the National Institutes of Health Stroke Scale (NIHSS) (2 studies; MD -0.84, 95% CI -1.40 to -0.29, I2 = 19%), and significantly higher on the Barthel index (3 studies; MD 4.30, 95% CI 2.04 to 6.57, I2 = 66%). Moreover, the SGYMT group was associated with significantly fewer adverse events (6 studies; RR 0.13, 95% CI 0.05 to 0.37, I2 = 0%) than the antidepressants group. In the subgroup analysis, SGYMT treatment consistently reduced HAMD scores within the first 8 weeks of treatment, but thereafter this difference between groups disappeared. Comparisons between SGYMT combined with antidepressants, and antidepressants alone, showed significantly lower scores in the combination group for both HAMD (7 studies; MD = -6.72, 95% CI = -11.42 to -2.01, I2 = 98%) and NIHSS scores (4 studies; MD -3.03, 95% CI -3.60 to -2.45, I2 = 87%). In the subgroup analysis, the reductions of HAMD scores in the SGYMT combined with antidepressants group were consistent within 4 weeks of treatment, but disappeared thereafter. The quality of RCTs was generally low and the quality of evidence evaluated by the GRADE approach was rated mostly "Very low" to "Moderate." The main causes of low quality ratings were the high risk of bias and imprecision of results. Current evidence suggests that SGYMT, used either as a monotherapy or an adjuvant therapy to antidepressants, might have potential benefits for the treatment of PSD, including short-term reduction of depressive symptoms, improvement of neurological symptoms, and few adverse events. However, since the methodological quality of the included studies was generally low and there were no large placebo trials to ensure reliability, it remains difficult to draw definitive conclusions on this topic. Further well-designed RCTs addressing these shortcomings are needed to confirm our results.

Herbal medicine for acute management and rehabilitation of traumatic brain injury: A protocol for a systematic review.

BACKGROUND: This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of herbal medicine in treating traumatic brain injury. METHODS AND ANALYSIS: The following electronic databases will be searched up to December 2018 without language or publication status restrictions: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature. We will also search Korean, Chinese, and Japanese databases. Any randomized controlled trials related to herbal medicine for traumatic brain injury will be included. The functional outcome, consciousness state, morbidity, and mortality will be assessed as primary outcomes. The quality of life, adverse events, and total effective rate will be evaluated as secondary outcomes. Two researchers will independently perform the study selection, data extraction, assessment of study quality, and evaluation of the quality of evidence for the main findings. Data synthesis and analysis will be performed using RevMan version 5.3. The results will be expressed as a risk ratio for the binary outcome and as the mean difference or standardized mean difference for a continuous outcome. We will synthesize the data by either fixed effects or random effects model according to a heterogeneity test or the number of studies included in the meta-analysis. The methodological quality of the included studies will be evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each main outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018116559.

Herbal medicine Sihogayonggolmoryeo-tang or Chai-Hu-Jia-Long-Gu-Mu-Li-Tang for the treatment of post-stroke depression: A protocol for a systematic review and meta-analysis.

INTRODUCTION: This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of herbal medicine Sihogayonggolmoryeo-tang (SGYMT) or Chai-Hu-Jia-Long-Gu-Mu-Li-Tang for the treatment of post-stroke depression. METHODS AND ANALYSIS: The following electronic databases will be searched up to July 2018 without language or publication status restrictions: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), Cumulative Index to Nursing, and Allied Health Literature (CINAHL), and PsycARTICLES. We will also search Korean and Chinese databases. Any clinical randomized controlled trials related to SGYMT treatment for post-stroke depression will be included. Changes in the degree of depression and adverse events will be assessed as primary outcomes. The total effective rate and changes in neurological function, activities of daily living, and quality of life will be evaluated as secondary outcomes. Study selection, data extraction, assessment of study quality, and evaluation of the quality of evidence for the main findings will be performed independently by 2 researchers. The data synthesis and analysis will be performed using RevMan version 5.3. The results will be expressed as a risk ratio for dichotomous data and as the mean difference or standardized mean difference for continuous data. Data will be synthesized by either a fixed-effects or random-effects model according to a heterogeneity test or the number of studies included in the meta-analysis. The methodological quality of the included studies will be evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each main outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018102939.

Types of household humidifier disinfectant and associated risk of lung injury (HDLI) in South Korea.

From 2002 through 2015, hundreds of people died of fatal lung injuries associated with the use of humidifier disinfectants (HDs) in Korea. Several chemical disinfectants used for household humidifiers were later clinically confirmed to cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the registered lung disease cases and to compare the distribution of HDLI patients, including deaths, by HD use characteristics including types of HD and HD brands categorized by age group. A total of 530 registered were clinically examined through two rounds of investigations conducted from July 2013 until April 2015. Information on HD use was obtained from a structured questionnaire and home investigations. Approximately one-half of the patients (n=221) were clinically confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and pre-school children≤6years old (n=128, 58%) accounted for most of the HD-associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI patients developed HDLI after less than one year of HD use. HD products containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2-ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%). Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients (n=85, 38.5%) was found to use only Oxy Saksak® products containing PHMG. The development of HDLI was clinically found to be associated with the use of several HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.

Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.

RATIONALE: Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011. OBJECTIVES: A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships. METHODS: By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant. MEASUREMENTS AND MAIN RESULTS: Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 µg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration. CONCLUSIONS: Dose-response analysis indicated that development of humidifier disinfectant lung injury and death were associated strongly with recurrent, intense, acute exposure without sufficient recovery time between exposures, more so than long-term cumulative exposure. These findings may explain some reversible or clinically unapparent cases among coexposed family members.

Relationship between Exposure to Household Humidifier Disinfectants and Risk of Lung Injury: A Family-Based Study.

BACKGROUND: In South Korea, a cluster of acute lung disease patients included lung injury disease suspected of being caused by the use of humidifier disinfectants. We examined the relationship between humidifier disinfectant exposure and clinically diagnosed humidifier disinfectant-associated lung injury (HDLI) in a family-based study. METHODS: This case-control study included 169 clinically confirmed HDLI cases and 303 family controls who lived with the HDLI patients. A range of information on exposure to humidifier disinfectants was obtained using a structured questionnaire and field investigations. Odds ratios (ORs) and confidence intervals (CIs) were estimated using unconditional logistic regression models that were adjusted for age, sex, presence of a factory within 1 km of residence, and the number of household chemical products used. RESULTS: HDLI risk increased approximately two-fold or more among the highest quartile compared with the lowest quartile in terms of the hours sleeping in a room with an operating humidifier treated with disinfectant (adjusted OR = 2.0, 95 % CI = 1.1-3.7), average hours of disinfectant-treated humidifier use per day (adjusted OR = 2.1, 95 % CI = 1.0-4.5), airborne disinfectant intensity (adjusted OR = 2.6, 95% CI = 1.2-5.3), and cumulative disinfectant inhalation level (adjusted OR = 2.0, 95% CI = 1.0-4.1). HDLI risk increased as the distance of the bed from humidifier gets shorter; compared with longer distance (> 1 m), the odds ratio was 2.7 for 0.5 to 1 m (95 % CI = 1.5-5.1) and 13.2 for <0.5 m (95 % CI = 2.4-73.0). CONCLUSIONS: The use of household humidifier disinfectants was associated with HDLI risk in a dose-response manner.