Osteoporosis Associated with Breast Cancer Treatments Based on Types of Hormonal Therapy: A Cross-Sectional Study Using Korean National Sample Data.

Background and Objectives: This study aimed to investigate osteoporosis-related treatments and the overall anticancer drug treatment tendencies, with a focus on selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), in Korean patients with breast cancer from 2010 to 2019. Materials and Methods: Data were obtained from the Health Insurance Review and Assessment Service. Patients with breast cancer (International Classification of Diseases, 10th Revision code: C50) as a principal diagnosis at least once from 2010 to 2019 were included. Those with osteoporosis (M80, M81, or M82) as a principal or sub-diagnosis or those who received osteoporosis treatment at least once were categorized as the osteoporosis-related treatment group, and others as the non-osteoporosis-related treatment group. The trends of drug prescriptions and treatment costs in patient groups were evaluated using descriptive statistics. Results: Among all included patients, those aged 45-54 years (40.20%) without osteoporosis treatment and those aged 55-64 years (34.11%) with osteoporosis treatment were the most common. SERM was the most commonly prescribed anticancer drug (29.20%) in the entire patient group, followed by AIs (20.83%). Patients without osteoporosis treatment had the highest prescription rate of SERM (31.48%), and those with osteoporosis treatment had a higher prescription rate of AIs (34.28%). Additionally, SERM and AIs were prescribed most frequently before and after the age of 55 years, respectively, regardless of the presence of treatment. Conclusions: This study found that osteoporosis-related treatment and patient age were associated with anticancer drug prescriptions. The present findings would help clinicians and researchers in the clinical diagnosis and treatment of breast cancer.

Analysis of Healthcare Utilization for Primary Dysmenorrhea in Korea: A Retrospective, Cross-Sectional Study.

Purpose: This study is a retrospective, cross-sectional study aiming to present basic data on the treatment modalities and cost of care for primary dysmenorrhea (PD) by analyzing healthcare utilization and patient distributions using the 2010 to 2018 Health Insurance Review and Assessment Service (HIRA) data. Patients and Methods: We used the HIRA-National Patient Sample (NPS) data to analyze medical service utilization for PD (ICD-10 code: N94.4, N94.6) in Western medicine (WM) or Korean medicine (KM) care between January 2010 and December 2018. Results: There were 41,139 patients diagnosed with PD who utilized Western medicine (WM) or Korean medicine (KM) care at least once during the study period. The number of claims and patients steadily rose over the years from 7430 claims for 3989 patients in 2010 to 11,523 claims for 6226 patients in 2018. The predominant age group was 15 to 24 years. Regarding the frequency of service categories for PD in the claims, consultation was the most common and costly service category in WM (72,120 cases, 47.89%; 631,912 USD, 69.74%), while injection and analogous treatments was the most common and costly service category in KM (97,157 cases, 72.41%; 314,696 USD, 55.86%). Regarding the drug prescriptions, nonsteroidal anti-inflammatory drugs (NSAIDs) (26,617 cases, 40.47%) were the most frequently prescribed drug for PD in pharmacies and hospitals. Conclusion: The result shows an annual increase in healthcare utilization for PD with the fastest rate in individuals aged 15 to 24 years. This study provides data on the current utilization of WM and KM care for PD for policymakers. Furthermore, we analyzed the frequency and cost of common treatment modalities in WM and KM, which would be useful data for clinicians and researchers.

Therapeutic Effect of Melittin-dKLA Targeting Tumor-Associated Macrophages in Melanoma.

Melanoma is an immunogenic tumor and a serious type of skin cancer. Tumor-associated macrophages (TAMs) express an M2-like phenotype and are involved in all stages of melanomagenesis; it is hence a promising target for cancer immunotherapy. We herein investigated whether melittin-dKLA inhibits the growth of melanoma by inducing apoptosis of M2-like macrophages. For the in vitro study, a conditioned medium of macrophages was prepared from M0, M1, or M2-differentiated THP-1 cells with and without melittin-dKLA. The affinity of melittin for M2 macrophages was studied with FITC (fluorescein isothiocyanate)-conjugated melittin. For the in vivo study, murine melanoma cells were inoculated subcutaneously in the right flank of mice, melittin-dKLA was intraperitoneally injected at 200 nmol/kg every three days, and flow cytometry analysis of TAMs was performed. Since melittin binds preferentially to M2-like macrophages, melittin-dKLA induced more caspase 3 expression and cell death in M2 macrophages compared with M0 and M1 macrophages and melanoma cells. Melittin-dKLA significantly inhibited the proliferation and migration of M2 macrophages, resulting in a decrease in melanoma tumor growth in vivo. The CD206+ M2-like TAMs were reduced, while the CD86+ M1-like TAMs were not affected. Melittin-dKLA is therapeutically effective against melanoma by inducing the apoptosis of M2-like TAMs.

Acupuncture as an adjuvant therapy for management of treatment-related symptoms in breast cancer patients: Systematic review and meta-analysis (PRISMA-compliant).

BACKGROUND: Although randomized controlled trials have revealed the considerable effectiveness of acupuncture in breast cancer patients, there have been no studies exploring current acupuncture research trends for treatment induced various symptoms in breast cancer patients. This review evaluated the effectiveness of acupuncture for treatment-induced symptoms in breast cancer patients. METHODS: We performed a systematic review and meta-analysis of the literature regarding acupuncture to treat symptoms associated with breast cancer therapies. The following databases were searched for relevant RCTs published before June 2018: MEDLINE, EMBASE, the Cochrane Library, AMED, CINAHL, OASIS, CNKI, and CiNii. RESULTS: Among the 19,483 records identified, 835 articles remained after screening titles and abstracts. A total of 19 RCTs were included in this qualitative synthesis. Among the studies, 8 explored climacteric symptoms, 4 explored pain, 2 explored lymphedemas, 2 explored nausea and vomiting and 3 investigated miscellaneous symptoms.explored miscellaneous symptoms due to cancer treatments. Most of the studies reported that acupuncture can alleviate various symptoms of breast cancer treatment. However, there is a lack of evidence as to whether accupuncture can alleviate chemotherapy associated side effects CONCLUSIONS:: Acupuncture may alleviate the treatment-related symptoms of breast cancer; however, further studies are necessary to obtain conclusive evidence of the effectiveness of acupuncture in treating breast cancer. REGISTRATION NUMBER: CRD42018087813.

Relationship of breastfeeding duration with joint pain and knee osteoarthritis in middle-aged Korean women: a cross-sectional study using the Korea National Health and Nutrition Examination Survey.

BACKGROUND: The effect of joint health on the quality of life of middle-aged and older women is becoming more widely recognized with the aging of the world's population. However, the association of long-term breastfeeding with joint pain and knee osteoarthritis has not been fully examined. The aim of this study was to determine the association of prior breastfeeding duration with current joint pain and knee osteoarthritis in middle-aged Korean women. METHODS: This cross-sectional study was conducted among 3454 women aged ≥50 years who underwent knee radiography and answered a questionnaire on breastfeeding and joint pain for the 5th Korea National Health and Nutrition Examination Survey (2010-2011). After adjusting for confounding sociodemographic, medical history, and obstetric and gynecologic variables, logistic regression analysis was conducted to analyze the prevalence of joint pain and knee osteoarthritis according to breastfeeding and its duration. RESULTS: Among the 3454 participants, 298 had not breastfed and 1042, 815, and 1299 had breastfed for 1-24, 25-48, and ≥ 49 months, respectively. Of all participants, 1731 had joint pain and 739 were diagnosed with knee osteoarthritis after radiography. Using the non-breastfeeding group as a reference, the odds ratio (OR) for joint pain among women who breastfed ≥1 month was 1.49 (95% confidence interval [CI] 1.01-2.21). As the breastfeeding duration increased, the OR of joint pain prevalence also increased (p for trend; p = 0.002). For knee osteoarthritis, the OR was 2.30 in the 25-48 months group (95% CI 1.09-4.86). The OR of knee osteoarthritis in the ≥49 months group was 2.17 (95% CI 1.01-4.64). Sensitivity analysis after selecting only participants aged ≥60 years showed that the prevalence of joint pain and knee osteoarthritis was more positively correlated with extended breastfeeding duration (joint pain, p for trend; p = 0.005) (knee osteoarthritis, p for trend; p = 0.012). CONCLUSIONS: Long-term feeding for more than 25 months was associated with an increased prevalence of joint pain and degenerative arthritis in Korean women aged ≥50 years.

Herbal medicine (Taohong Siwu Tang) for the treatment of primary dysmenorrhea: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the efficacy and safety of Tao-Hong Siwu Tang (TST) for the treatment of primary dysmenorrhea. METHODS: We searched four English databases (MEDLINE, EMBASE, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials [CENTRAL, Cochrane Library]), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical Database), two Korean databases (Oriental Medicine Advanced Searching Integrated System and Korean traditional Knowledge Portal), and one Japanese database (Citation Information by NII). All randomized controlled trials (RCTs) using TST or modified TST (MTST) were included. Three independent reviewers extracted the data, assessed the risk of bias according to the Cochrane criteria, and performed a meta-analysis. RESULTS: A total of 85 possibly relevant articles were identified, and five trials met our inclusion criteria. The meta-analysis showed a favorable effect of MTST compared to non-steroidal anti-inflammatory drugs (NSAIDs) (n = 486, risk ratio [RR] = 1.53, 95% confidence interval [95% CI] = 1.37-1.72, I2 = 39%). Among the included trials, one RCT showed superior effects of MTST on primary dysmenorrhea recurrence rate compared to NSAIDs (n = 246, RR = 0.31, 95% CI = 0.15-0.63, P = 0.001). Another RCT revealed a beneficial impact of oral contraceptives (OCs) used in combination with TST compared to OCs alone (n = 60, RR = 1.35, 95% CI = 1.02-1.79, P = 0.04). CONCLUSION: This systematic review and meta-analysis provides moderate quality evidence for the superiority of MTST over NSAIDs as well as that of TST plus OCs over OCs in the treatment of primary dysmenorrhea.

Effectiveness, safety, and economic evaluation of adjuvant moxibustion therapy for aromatase inhibitor-induced arthralgia of postmenopausal breast cancer stage I to III patients: Study protocol for a prospective, randomized, assessor-blind, usual-care controlled, parallel-group, pilot clinical trial.

INTRODUCTION: This study is a prospective, assessor-blinded, parallel-group, randomized controlled pilot trial to explore the effectiveness of 12-week adjuvant moxibustion therapy for arthralgia in menopausal females at stage I to III breast cancer on aromatase inhibitor (AI) administration, compared with those receiving usual care. METHODS/DESIGN: Forty-six menopausal female patients with breast cancer who completed cancer therapy will be randomly allocated to either adjuvant moxibustion or usual care groups with a 1:1 allocation ratio. The intervention group will undergo 24 sessions of adjuvant moxibustion therapy with usual care for 12 weeks, whereas the control group will receive only usual care during the same period. The usual care consists of acetaminophen administration on demand and self-directed exercise education to manage AI-related joint pain. The primary outcome is the mean change of the worst pain level according to the Brief Pain Inventory-Short Form between the initial visit and the endpoint. The mean changes in depression, fatigue, and quality of life will also be compared between groups. Safety and pharmacoeconomic evaluations will also be included. DISCUSSION: Continuous variables will be compared by an independent t test or Wilcoxon rank-sum test between the adjuvant moxibustion and usual care groups. Adverse events will be analyzed using the chi-square or Fisher exact test. The statistical analysis will be performed by a 2-tailed test at a significance level of .05.

Prophylactic Effects of Bee Venom Phospholipase A2 in Lipopolysaccharide-Induced Pregnancy Loss.

Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-α and IFN-γ expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations.

[Complementary and Alternative Medicine for Breast Cancer Patients: An Overview of Systematic Reviews].

The application of systematic review (SR) has been increased rapidly in the field of cancer treatment. Complementary and alternative medicine (CAM) for cancer is no exception. The aim of this review is to evaluate and summarize systematic reviews on the CAM use in breast cancer patients. Search sources were Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR), and PubMed. In addition, we assessed the quality of SR with the Assessing the Methodological Quality of Systematic Reviews (AMSTAR). This review did not consider control groups and outcomes. Thirty-four SRs met a set of criteria. According to interventions, there were twenty SRs which included yoga, acupuncture, and herbal medicines. Meta-analysis of 19 out of 34 reviews showed the followings: (1) acupuncture had a beneficial effect on the frequency of hot flushes, (2) yoga had a beneficial effect on depression and health-related QOL, (3) mindfulness-based stress reduction (MBSR) had a beneficial effect on anxiety and depression, (4) combination of herbal medicine and chemotherapy synergistically improved clinical outcomes, (5) acupuncture did not show significant effect on the severity of hot flushes and cancer-related pain, (6) yoga was unable to be confirmed as having an effect on cancer-related pain and physical well-being. Given the results of AMSTAR, 9 out of 34 reviews were of high quality and 3 reviews were deemed to be of low quality. In conclusion, since most SRs were at moderate or high quality levels, CAM could be helpful for treating specific symptoms related to breast cancer.

Complementary medicine use and costs in patients with breast cancer who experienced treatment-related side effects: A cross-sectional survey in Korea.

OBJECTIVES: Population-based information on the costs of complementary medicine for treatment-related side effects in patients with breast cancer is scarce. We aimed to investigate the prevalence and expenditure on complementary medicine in patients with breast cancer who experienced treatment-related side effects. DESIGN AND SETTING: Two datasets were analyzed: 1) a 2017 survey on direct and indirect costs for treatment-related side effects, which was completed by 100 patients with stage 0-IV breast cancer, and 2) a Korean representative cross-sectional survey (Patient Survey 2014) that examined the prevalence of integrative medicine in 41 patients with breast cancer. MAIN OUTCOME MEASURES: The direct and indirect costs for treatment-related side effects. RESULTS: In the first dataset, the mean total direct medical cost for complementary medicine was US$1,584 and the mean indirect cost was US$6,988 per patient per year. Some patients (6%) visited non-medical institutions to utilize complementary medicine and additionally spent US$460 per patient per year. Approximately one-third of participants reported a substantial-to-heavy financial burden for using complementary medicine. However, only 17% of patients got information about complementary medicine through their physician. In the second dataset, 49% of patients with breast cancer who were discharged from Korean Medicine hospitals in Patient Survey 2014 data indicated that integrative medicine had been used. CONCLUSIONS: Despite some complementary medicine could be reimbursed by National Health Insurance in Korea, a considerable number of patients reported an economic burden associated with their use of complementary medicine. Strategies for guiding patients to receive evidence-based and cost-effective complementary medicine are needed.

Effectiveness, safety, and economic evaluation of topical application of a herbal ointment, Jaungo, for radiation dermatitis after breast conserving surgery in patients with breast cancer (GREEN study): Study protocol for a randomized controlled trial.

INTRODUCTION: This is a prospective, open-label, parallel-group, randomized controlled trial that evaluates the effectiveness and safety of adjuvant application of Jaungo (JUG) for radiation-induced dermatitis (RD) in breast cancer patients undergoing radiation therapy, in comparison with general supportive care (GSC). METHODS/DESIGN: Eighty female patients, who have been diagnosed with unilateral breast cancer, will be allocated to either the JUG or GSC group with an allocation ratio of 1:1 after breast conservation surgery, in the Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. Both the groups will be subjected to GSC, but only the JUG group participants will apply adjuvant JUG ointment on the irradiated skin for 6 weeks, twice a day. The primary outcome of this study is the assessment of incidence rate of RD using the Radiation Therapy Oncology Group (RTOG) for toxicity gradation of 2 or more. Maximum pain level, quality of life, adverse reactions, and pharmacoeconomic evaluations will also be included. DISCUSSION: The primary outcome will be statistically compared using the logrank test after estimating the survival curve using the Kaplan-Meier method. Continuous variables will be tested using independent t test or Mann-Whitney U test. The adverse events will be evaluated with Chi-square or Fisher exact test. All the data will be analyzed at a significance level of 0.05 (two-sided) with R software (The R Foundation). TRIAL REGISTRATION: CRIS (Clinical Research Information Service), KCT0003506, 14 February 2019.

Apoptotic effect of Gyejibokryunghwan on uterine sarcoma cells (SK-UT-1B).

BACKGROUND: Diagnosis of uterine sarcomais is a challenging task for clinicians because its position is not easily accessible by current conventional techniques. In addition, standardized treatment for uterine sarcoma has not yet been established due to its rarity and heterogeneity. HYPOTHESIS/PURPOSE: We investigated the apoptotic cell death of uterine sarcoma cells (SK-UT-1B) induced by Gyejibokryunghwan (GBH). GBH, an herbal medicine, has been widely used for gynecological diseases in Koean medicine. METHODS: SK-UT-1B cells were treated with GBH of varying concentrations from 0 to 500 µg/ml. The mechanism of cell death was investigated through multiple analysis methods, including flow cytometry, cell cycle, and western blotting. RESULTS: Flow cytometric analysis revealed that the number of apoptotic cells increased in a GBH dose-dependent manner. The cell populations of sub-G1 and G0/G1 phases were increased by GBH treatment, indicating apoptosisand cell arrest, while the population of S and G2/M phases decreased. With GBH, the expression levels of cleaved caspase-3, -6, and -9 were upregulated, while the expression levels of pro-caspase-3, -6, and -9 were down-regulated in SK-UT-1B cells. CONCLUSION: These results are the first observation of uterine sarcoma cell death induced by GBH and confirmation of the mechanism of cell death, which occurred through the intrinsic apoptotic pathway. Clinically, uterine sarcoma has a poor prognosis with no appropriate treatment. GBH may become a new treatment modality for uterine sarcoma.

Is cupping therapy effective in patients with neck pain? A systematic review and meta-analysis.

OBJECTIVES: Neck pain is a significant condition that is second only to depression as a cause of years lived with disability worldwide. Thus, identifying and understanding effective treatment modalities for neck pain is of heightened importance. This systematic review aimed to investigate the effects of cupping on neck pain from the current literature. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). SETTING: Nine databases, including Chinese, Korean and Japanese databases, were searched for data up to January 2018 with no restrictions on publication language. PARTICIPANTS: Patients with neck pain. INTERVENTIONS: Cupping therapy as the sole or add-on intervention compared with no treatment or active controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Pain severity, functional disability and quality of life. RESULTS: Eighteen RCTs were selected. Compared with the no intervention group, the cupping group exhibited significant reduction in pain (mean difference (MD) -2.42(95% CI -3.98 to -0.86)) and improvement in function (MD -4.34(95% CI -6.77 to -1.19)). Compared with the active control, the cupping group reported significant reduction in pain (p=0.0009) and significantly improved quality of life (p=0.001). The group that received control treatment with cupping therapy (add-on group) displayed significant pain reduction compared with the active control group (p=0.001). Of the 18 studies, only 8 reported occurrence of adverse events, which were mostly mild and temporary. CONCLUSIONS: Cupping was found to reduce neck pain in patients compared with no intervention or active control groups, or as an add-on treatment. Depending on the type of control group, cupping was also associated with significant improvement in terms of function and quality of life; however, due to the low quality of evidence of the included studies, definitive conclusions could not be drawn from this review. Future well-designed studies are needed to substantiate the effectiveness of cupping on neck pain. PROSPERO REGISTRATION NUMBER: CRD42016047218.

Characteristics of heart rate variability in women with polycystic ovary syndrome: A retrospective cross-sectional study.

We aimed to compare the modulation of the autonomic nervous system (ANS) in women with polycystic ovary syndrome (PCOS) with that in healthy ovulatory women on the basis of heart rate variability (HRV), and to analyze the characteristics of the ANS in PCOS.In a retrospective chart review, HRV, body mass index, and physical examination data in women with PCOS and those with regular menstrual cycles were collected. Approval from the institutional review board (IRB) was obtained (IRB No. 2017-05-007-001) for this study. The mean outcomes were the values of HRV in the time [standard deviation of all normal R-R intervals (SDNN), the square root of the sum of the squares of the differences between the adjacent normal R-R intervals (rMSSD), and the mean heart rate turbulence (mean HRT)] and frequency [total power (TP), very-low-frequency power (VLF), low-frequency power (LF), normalized low-frequency power (LF norm), high-frequency power (HF), normalized high-frequency power (HF norm), and LF/HF ratio] domains. Differences between the 2 groups were analyzed by Mann-Whitney U test, using SPSS for Windows (version 22.0).There was no significant difference in the values of the time domain (SDNN, rMSSD, and mean HRT) between the groups. In the frequency domain, women with PCOS showed significantly higher LF (598.63 ±â€Š94.38 vs 459.13 ±â€Š163.64, P = .028), LF norm (48.64 ±â€Š3.39 vs 36.49 ±â€Š2.82, P = .009), and LF/HF ratio (1.49 ±â€Š0.31 vs 0.73 ±â€Š0.13, P = .009) than the control group. HF norm was significantly lower in the women with PCOS than in the controls (51.38 ±â€Š3.39 vs 63.51 ±â€Š2.82, P = .009). The TP, VLF, and HF showed no significant difference between the groups.The results of the present study indicated that PCOS is related to increased sympathetic modulation in HRV.

Effects of Rhei Undulati Rhizoma on lipopolysaccharide-induced neuroinflammation in vitro and in vivo.

Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders. In this study, we investigated whether RUR modulates inflammatory processes in lipopolysaccharide (LPS)-stimulated BV2 microglia cells and the mouse brain. RUR exerted anti-neuroinflammatory effects by inhibiting the production of nitric oxide and reactive oxygen species induced by LPS via the downregulation of transcription factors such as inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) without causing cytotoxicity. RUR also regulated mitogen-activated protein kinase pathway by inhibiting phosphorylation of p38 and c-Jun N-terminal kinases and translocation of nuclear factor kappa B. Moreover, RUR attenuated LPS-induced glial activation and COX-2 expression in the substantia nigra and hippocampus of the mouse brain. These results indicate that RUR is a potential candidate to treat neurodegenerative diseases by regulating neuroinflammation.

Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by upregulating hippocampal estrogen synthesis.

BACKGROUND: Dangguijakyak-san (DJS) is an herbal formulation that has been clinically applicable for treating postmenopausal symptoms and neurological disorders. It is reported that hippocampal estrogen attenuates memory impairment via neuroprotection and synaptogenesis. However, the effect of DJS on hippocampal estrogen synthesis remains unknown. In this study, we explored the effect of DJS and its neuroprotective mechanism against memory impairment in ovariectomized (OVX) mice, with respect to hippocampal estrogen stimulation. METHODS: Cell cultures were prepared from the hippocampi of 18-day-old embryos from timed pregnant Sprague-Dawley rats. The hippocampi were dissected, collected, dissociated, and plated in 60-mm dishes. The cells were treated with DJS for 48 h and the supernatant was collected to determine estrogen levels. Female ICR mice (8-weeks-old) were housed for 1 week and ovariectomy was performed to remove the influence of ovary-synthesized estrogens. Following a 2-week post-surgical recovery period, the mice were administrated with DJS (50 and 100 mg/kg/day, p.o.) or 17ß-estradiol (200 µg/kg/day, i.p.) once daily for 21 days. Hippocampal and serum estrogen levels were determined using enzyme-linked immunosorbent assay kit. Memory behavioral tests, western blot, and immunohistochemical analyses were performed to evaluate the neuroprotective effects of DJS in this model. RESULTS: DJS treatment promoted estrogen synthesis in primary hippocampal cells and the hippocampus of OVX mice, resulting in the amelioration of OVX-induced memory impairment. Hippocampal estrogen stimulated by DJS treatment contributed to the activation of cAMP response element-binding protein and synaptic protein in OVX mice. CONCLUSION: DJS may attenuate memory deficits in postmenopausal women via hippocampal estrogen synthesis.

Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice.

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa ß, tumor necrosis factor-α, and interleukin-1ß (IL-1ß) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology.

Schisandrae Fructus Reduces Symptoms of 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure in Mice.

Menopause is associated with a decrease in the level of sex hormones such as ovarian estradiol and progesterone and can cause various symptoms such as depression, hot flash, fatigue, heart palpitations, and headache. Furthermore, there is a risk of developing complications such as osteoporosis, cardiovascular diseases, Alzheimer's disease, and ovarian cancer. Schisandrae Fructus (SF) is widely used in Korean medicine as a cure for such complications. This study was conducted to evaluate the therapeutic effects of SF against menopause symptoms associated with follicle depletion caused by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in mice. VCD directly targets the preantral follicles. Mice were injected with VCD (160 mg/kg intraperitoneally) daily for 15 days and then with SF dosage 3 times/week for six weeks. To evaluate the effects of SF, body weight, tail skin temperature, uterine weight, lipid profile, and osteocalcin levels were measured. A decrease in body weight and tail skin temperature and an increase in uterine weight were observed upon SF treatment. Moreover, SF treatment significantly decreased total cholesterol, triglyceride, osteocalcin, and low-density lipoprotein levels and low-density/high-density lipoprotein ratio. These results suggest the potential use of SF in the treatment of menopausal symptoms in women.