Antidepressant Effect of Heracleum moellendorffii Extract on Behavioral Changes in Astrocyte Ablation Mouse Model of Depression by Modulating Neuroinflammation through the Inhibition of Lipocalin-2.

Astrocyte dysfunction and inflammation play a pivotal role in depression. In this study, we evaluated the antidepressant properties of Heracleum moellendorffii root extract (HME), which is traditionally used for inflammation-related diseases, in a mouse model with astrocyte depletion that resembles the prefrontal cortex pathology of depressive patients. Mice were divided into four groups, with 10 mice per group. To induce astrocyte ablation in the mice's prefrontal cortex (PFC), we used astrocytic toxin L-alpha-aminoadipic acid (L-AAA) and administered HME orally at 200 and 500 mg/kg for 22 days. We utilized the tail suspension test (TST) to assess depression-like behaviors and the open field test (OFT) to evaluate anxiety-like activities. Additionally, astrocytic and inflammatory markers in the PFC were evaluated using immunohistochemistry and ELISA. The results showed that infusion of L-AAA significantly decreased the expression of astrocytic glial fibrillary acidic protein (GFAP), which was accompanied by increased depression and anxiety-like behaviors. However, HME significantly reversed these effects by dose-dependently enhancing GFAP expression and modulating inflammatory markers, such as TNF-α, IL-6, and particularly lipocalin-2, a master proinflammatory mediator. These results imply that HME contributes to the alleviation of depression and anxiety-like behaviors by promoting astrocyte recovery and reducing neuroinflammation, especially through lipocalin-2 inhibition.

Mixture of Rhodiola rosea and Nelumbo nucifera Extracts Ameliorates Sleep Quality of Adults with Sleep Disturbance.

Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.

Feasibility of Emotional Freedom Techniques in Patients with Posttraumatic Stress Disorder: a pilot study.

Objectives: Posttraumatic stress disorder (PTSD) is a prevalent mental health condition, and techniques using sensory stimulation in processing traumatic memories have gained attention. The Emotional Freedom Techniques (EFT) is a psychotherapy that combines tapping on acupoints with exposure to cognitive reframing. This pilot study aimed to assess the feasibility of EFT as a treatment for PTSD by answering the following research questions 1) What is the compliance and completion rate of patients with PTSD with regard to EFT protocol? Is the dropout rate reasonable? 2) Is the effect size of EFT protocol for PTSD sufficient to justify a future trial? Methods: Thirty participants diagnosed with PTSD were recruited. They received weekly EFT sessions for five weeks, in which they repeated a statement acknowledging the problem and accepting themselves while tapping the SI3 acupoint on the side of their hand. PTSD symptoms were evaluated using the PTSD Checklist for DSM-5 (PCL-5) before and after the intervention. Results: Of the 30 PTSD patients (mean age 34.1 ± 9.1, 80% female), 96.7% showed over 80% compliance to the EFT sessions, and 86.7% completed the entire study process. The mean PCL-5 total score decreased significantly after the intervention, with a large effect size (change from baseline -14.33 [95% CI -19.79, -8.86], p < 0.0001, d = 1.06). Conclusion: The study suggests that EFT is a feasible treatment for PTSD, with high session compliance and low dropout rates. The effect size observed in this study supports the need for a larger trial in the future to further investigate EFT as a treatment for PTSD. However, the lack of a control group and the use of a self-rated questionnaire for PTSD symptoms are limitations of this study. The findings of this pilot study can be used to plan a future trial.

Spectrally Stable Deep-Blue Light-Emitting Diodes Based on Layer-Transferred Single-Crystalline Ruddlesden-Popper Halide Perovskites.

A novel approach to producing high-color-purity blue-light-emitting diodes based on single-crystalline Ruddlesden-Popper perovskites (RPPs) is reported. The utilization of a pure bromide composition eliminates any possibility of halide segregation, which can otherwise lead to undesired shifts in the emission wavelength or irreversible degradation of the spectral line width. Phase-pure PEA2MAPb2Br7 single crystals with a lateral size exceeding 1 cm2 can be synthesized using the inverse temperature crystallization method. To prepare RPP layers with a thickness of less than 50 nm, we employ a thinning process of the initially thick bulk crystals, followed by a dry-transfer process to place them onto a hole transport layer and an indium-tin-oxide-coated glass substrate. By utilizing polydimethylsiloxane as a handling layer, deformations of the bulk RPP crystal and exfoliated RPP layer, as well as the formation of defects such as pinholes, can be effectively suppressed. Subsequent depositions of an electron transport layer and a metal contact complete the fabrication of electroluminescence (EL) devices. The EL devices utilizing the single-crystalline RPP demonstrate excellent spectral stability across a broad range of the applied bias voltage spanning from 4.5 to 10 V, exhibiting a significantly narrow line width of 14 nm at an emission wavelength of 440 nm that can potentially cover 99.3% of the Rec. 2020 color gamut. The sharp EL emission spectrum can be effectively preserved, avoiding any broadening of the line width, by suppressing Joule heating throughout the device operation, in addition to the intrinsic stability of single-crystalline RPPs.

Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis.

BACKGROUND: The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy. METHODS: We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events. RESULTS: Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant. CONCLUSIONS: Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Emotional freedom technique versus written exposure therapy versus waiting list for post-traumatic stress disorder: protocol for a randomised clinical MRI study.

INTRODUCTION: The emotional freedom technique (EFT) is an acupuncture-based psychotherapy that combines tapping on acupoints with cognitive reframing. EFT has been previously shown to have potential for treating post-traumatic stress disorder (PTSD). However, further clinical evidence and underlying mechanisms of EFT are yet to be fully explored. This proposed clinical trial aims to examine the effect of EFT on patients with PTSD compared with the waitlist (WL) and active controls. METHODS AND ANALYSIS: This study was designed as a randomised, assessor-blinded, three-arm clinical MRI study. A total of 120 eligible patients with PTSD will be recruited and randomised into EFT, written exposure therapy (WET) or WL groups. EFT and WET will be applied once a week for 5 weeks. For patients in the WL group, EFT will be performed after 12 weeks. PTSD symptoms, depression, anxiety, somatic symptoms and quality of life will be evaluated. Assessments will be conducted at baseline (week 0), post-treatment (week 6) and follow-up (week 12). Structural and functional brain images and recording videos of facial expressions to emotional stimuli will be obtained before and after treatment. Sixty participants without lifetime traumatic experiences will be enrolled as healthy controls. The primary objective of the study is to compare the change from baseline in the Clinician-Administered PTSD Scale after treatment (week 6) between EFT and WL groups and between EFT and WET groups. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be shared at national and international conferences and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical Research Information Service KCT0007360 https://cris.nih.go.kr/cris/search/detailSearch.do/21974.

Bangpungtongsung-san for patients with major depressive disorder: study protocol for a randomized controlled phase II clinical trial.

BACKGROUND: Bangpungtongsung-san (BTS) is a representative herbal medicine that has been widely used for patients with obesity in east Asian countries. Various preclinical studies have demonstrated the anti-depressive effect of BTS granules in various animal models of depression. This phase II trial aimed to explore the efficacy and safety of BTS in human patients with depression. METHODS: A total of 126 patients diagnosed with major depressive disorder and who are not underweight (body mass index ≥ 18.5 kg/m2) will be enrolled in this study. Eligible participants will be randomly allocated into three groups: the high-dose BTS, low-dose BTS, and placebo groups in a 1:1:1 ratio. BTS or placebo granules will be orally administered twice a day for 8 weeks. The BTS and placebo granules will be made to have identical color, scent, and shape, and participants and investigators will be blinded to the allocation. The primary efficacy endpoint is the change from baseline of the 17-item Hamilton Depression Rating Scale total score at 8 weeks. The superiority of the high- and low-dose BTS granules to the placebo granules will be tested. DISCUSSION: The results of this clinical trial will provide evidence on the efficacy and safety of BTS for patients with major depressive disorder. This study will be conducted in accordance with ethical and regulatory guidelines, and the results will be submitted and published in international peer-reviewed journals. TRIAL REGISTRATION: CRIS registration Number: KCT0007571; registered on 2022/07/26 ( https://cris.nih.go.kr/cris/search/detailSearch.do/23192 ).

Effectiveness of the Shugan Jieyu Capsule against Psychiatric Symptoms in Epilepsy: a protocol for systematic review and meta-analysis.

Objectives: Psychiatric symptoms in epilepsy are very common, and the most common symptoms are depression, insomnia, and anxiety. These symptoms not only lower the quality of life of epilepsy patients, but also elevate the risk of epileptic seizures. There are no specific criteria for the available antiepileptic drugs to ameliorate these symptoms in patients with epilepsy, and there is a lack of evidence to support the efficacy and safety of existing drugs. The Shugan Jieyu capsule (SJC) is a traditional herbal medicine composed of Acanthopanax senticosus and Hypericum perforatum and is reported to be effective in relieving psychiatric symptoms. The purpose of this study was to assess the efficacy of SJC as a treatment for psychiatric symptoms in epilepsy patients. Methods: Electronic databases will be investigated for publications in English, Korean, Japanese, and Chinese. The participants of the study are epilepsy patients with psychiatric symptoms diagnosed using any validated criteria. All types of controls will be compared-placebo, conventional treatments, and no treatment-to groups treated with SJC or modified SJC. We will measure the degree of improvement in psychiatric symptoms and check epileptic symptoms, such as the frequency of seizures. The study selection and data extraction will be performed by two independent reviewers, who will also assess methodological quality using the risk-of-bias tool by Cochrane. We will use Review Manager software (RevMan) to carry out all statistical analyses. Results: This systematic review and meta-analysis will be performed in accordance with the PRISMA-P statement. Conclusion: This systematic review is the first study to assess the efficacy and safety of SJC for the treatment of psychiatric symptoms in epilepsy. We expect that this study will provide clinically applicable evidence for patients with epilepsy when selecting drug treatments.

Efficacy and safety of Gyejibokryeong-hwan (GBH) in major depressive disorder: study protocol for multicentre randomised controlled trial.

BACKGROUND: Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial. METHODS: This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed. DISCUSSION: This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder. TRIAL REGISTRATION: Clinical Research Information Service KCT0004417 . Registered on November 1, 2019 (prospective registration).

Efficacy of Yukmijihwang-tang on symptoms of Alzheimer disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia, which may lead to severe memory loss and other cognitive disorders. Yukmijihwang-tang (YMJ), a type of Korean traditional herbal medicine, has been shown to be effective against neurodegenerative diseases. Although a meta-analysis on the efficacy of YMJ on AD exists, the study had some limitations, and there have been several newly published studies assessing the effect of YMJ. Therefore, the purpose of this study is to evaluate the efficacy and safety of YMJ as a treatment for AD through a meta-analysis. METHODS: A systematic search of the following electronic databases will be conducted to identify eligible studies: MEDLINE (PubMed), Elsevier (EMBASE), The Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Korean Medical Database (KMBASE), Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Traditional Knowledge Portal, Citation Information by NII (CiNii), China National Knowledge Infrastructure (CNKI). All randomized controlled trials assessing the efficacy and safety of YMJ on the symptoms of AD will be included. Two independent reviewers will perform article retrieval, deduplication, data screening, data extraction, quality evaluation, and data analyses using RevMan version 5.4. The Cochrane risk of bias tool will be used to assess the quality of the trials. RESULTS: This study will provide synthesis of the cognitive function measured with neuropsychological tests, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADL) measured using validated scales. The clinical effective rate and adverse events will also be analyzed to assess the efficacy and safety of YMJ for treating AD. CONCLUSION: This systematic review will provide evidence for the efficacy and safety of YMJ in AD. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data will not be included in this study. The study findings will be disseminated through conference presentations.

The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis.

BACKGROUND: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. METHODS: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. RESULTS: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. CONCLUSION: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

Lindera glauca Blume ameliorates amyloid-ß1-42-induced memory impairment in mice with neuroprotection and activation of the CREB-BDNF pathway.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder presenting cognitive decline accompanied by deposits of amyloid-ß (Aß) and tau hyperphosphorylation. Without current treatment to AD, many studies suggested diverse approaches, one of which was herbal medicine and its active compounds. Very few studies have examined the effect of Lindera glauca Blume (L. glauca) in models of degenerative disease despite the attention that it received as a novel potential treatment source. We examined the efficacy of L. glauca in a mouse model of AD, which was induced by intrahippocampal injection of Aß1-42. METHODS: Mice were intrahippocampally infused with Aß1-42 and were orally administered ethanolic extract of L.glauca before and after infusion for 21 days. Y-maze test and Morris water maze was conducted to assess memory impairment. Immunohistochemistry and western blot analysis were performed to assess the effect of L. glauca administration on pathological changes in mice. RESULTS: L. glauca exhibited beneficial effects in spatial and reference learning as shown in increased time spent in the target quadrant in Morris water maze and increased spontaneous alternation in Y-maze. At the same time, decline of Aß burden and phosphorylated tau were observed in the hippocampus of L. glauca-treated mouse under intrahippocampal injection of Aß1-42. The results corresponded with amelioration of the decreased neuronal marker, neuronal-specific nuclear protein (NeuN) and attenuation of the increased reactive astrocyte marker, glial fibrillary acidic protein (GFAP) levels in hippocampus. Additionally, 21-day treatment with L. glauca inhibited downregulation of phosphorylated cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) levels. CONCLUSION: L. glauca improves behavioral deficits induced by Aß1-42 and inhibits both Aß- and tau-related pathological changes, stimulating neuroprotection mediated by CREB activation. L. glauca can be suggested as a new candidate for treatment of AD.

Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex.

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients' brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

Effect of herbal medicine (Huanglian-jie-du granule) for somatic symptoms and insomnia in patients with Hwa-byung: A randomized controlled trial.

BACKGROUND: Huanglian-jie-du (HJD) granule, which is composed of representative "heat-clearing" herbs has been used for Hwa-byung. Hwa-byung is a culture-bound syndrome in Korea, characterized by distinct somatic symptoms such as chest congestion and heat sensation resulting from suppressed anger. We investigated the effect of HJD in patients with Hwa-byung. METHODS: Forty-four patients with Hwa-byung were recruited, and HJD or placebo granules were administered orally three times daily for seven days. The two primary outcomes were somatic symptoms, which were measured by Patient Health Questionnaire of physical symptoms (PHQ-15), and insomnia, which was measured by Insomnia Severity Index (ISI) at post-treatment. RESULTS: Between July 10 and October 31, 2017, 44 patients with Hwa-byung (mean age 36.68 years; and 38 female) were randomly assigned to HJD (n = 22) or placebo (n = 22) group. After administration of HJD or placebo granule for seven days, ISI score was lower in the HJD group compared to placebo group at post-treatment (adjusted mean difference -2.56 [95% CI -4.72 to -0.39], p = 0.0208). Meanwhile, there was no difference in PHQ-15 score between HJD group and placebo group at post-treatment (adjusted mean difference -0.50 [95% CI: -3.02-4.02], p = 0.7812). CONCLUSIONS: Our results suggest that the administration of HJD granule has a potential to improve insomnia in Hwa-byung patients. Effect of HJD granule for general somatic symptoms in Hwa-byung patients is unclear, and further researches are needed. TRIAL REGISTRATION: Clinical Research Information Service, KCT0002379.

Efficacy and safety of Hominis placenta pharmacopuncture on mild cognitive impairment: Randomized, double blind, placebo-controlled, multi-center trial.

INTRODUCTION: Mild cognitive impairment (MCI) is cognitive decline which can be observed in a wide range of cognitive domains. It is considered as a prodromal stage of dementia; therefore, strategies for treatment are necessary, but current evidence is limited. Combining the memory enhancing effect of Hominis placenta (H placenta) and acupuncture elucidated separately in previous studies, efficacy of H placenta pharmacopuncture for treating MCI is anticipated. METHODS: Thirty participants will be recruited. Male and female adults aged 50 to 80 who voluntarily participate in the trial, are diagnosed with MCI according to diagnostic and statistical manual of mental disorders-5 criteria, and have a Clinical Dementia Rating score 0.5 will be enrolled. Participants who meet the criteria will be randomly allocated to either pharmacopuncture group or control group. Participants will undergo H placenta pharmacopuncture or saline pharmacopuncture in GV20, ST36, and CV12 twice weekly for 8 weeks and will be evaluated a month after the last treatment. Primary outcome will be difference in mean change of Korean version of Montreal Cognitive Assessment scores between intervention group and control group. Cognition, mood, sleep quality and quality of life will be also assessed using other neuropsychological tests and questionnaires regarding depression, anxiety, sleep and quality of life. DISCUSSION: Evaluating the efficacy and safety data obtained by assessing diverse aspects of patients with MCI will broaden the scope of MCI management and prevention of dementia progression. TRIAL REGISTRATION: Clinical Research Information Service (KCT0005368), Registered 02 Sep 2020, https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=16425.

Antidepressant effects of ginsenoside Rf on behavioral change in the glial degeneration model of depression by reversing glial loss.

BACKGROUND: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alpha-aminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. METHODS: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. RESULTS: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. CONCLUSION: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

Danggui-Shaoyao-San for dementia: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Although memory loss and other symptoms of dementia pose tremendous burdens on patients and societies, there is currently no cure for dementia. METHODS: We conducted a systematic review and meta-analysis of the anti-dementia effects of Danggui-Shaoyao-San (DSS), which is derived from natural resources. We searched for randomized controlled trials (RCTs) from inception to June 2019. We searched PubMed, Embase, Korean databases (Research Information Service System and Oriental Medicine Advanced Searching Integrated System), Chinese databases (China Knowledge Resource Integrated Database and Wanfang Database), and Japanese databases (CiNii and J-STAGE). Studies were included if they were a RCT, investigated the efficacy of DSS or its modified form, and included participants with dementia. Use of DSS with other treatment (eg, acupuncture, anti-dementia drugs, etc) was included. Items of each trial were evaluated by 2 independent reviewers. Data were pooled by using random-effect models. RESULTS: A total of 482 studies were identified, and 5 eligible studies for Alzheimer disease (AD) and 4 studies for vascular dementia (VD) were included in the final analysis, representing a total of 567 participants. As for AD, pooled results of the Mini-Mental State Examination (MMSE) (mean differences [MD] 4.60; 95% confidence interval [CI] 4.29, 4.91) and activities of daily living (MD 11.40; 95% CI 10.94, 11.86) favored DSS. DSS had synergistic effect with acupuncture over acupuncture alone in MMSE (MD 1.69; 95% CI 1.05, 2.34), Hasegawa Dementia Scale (MD.62; 95% CI -0.20, 1.44), and activities of daily living (MD 2.38; 95% CI 1.92, 2.85). In VD, pooled results showed a significant difference in the score of dementia scales such as MMSE and Hasegawa Dementia Scale compared with nootropic drugs. DSS significantly reduced symptoms (odds ratio 5.02, 95%, CI 2.76-9.11) in patients with VD. The respective size of each RCTs was small and some included studies were of low quality due to their limited description on methodological issues. CONCLUSION: These estimates suggest that DSS provides clinically important reductions in symptoms of AD and VD and can be a promising anti-dementia drug candidate.

Neurocircuitry of acupuncture effect on cognitive improvement in patients with mild cognitive impairment using magnetic resonance imaging: a study protocol for a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is defined as a decline in cognitive state with preservation of activities of daily living. Medications such as donepezil and rivastigmine have been commonly prescribed for MCI, but their use is controversial. Acupuncture has been widely used in Korea and has been shown to improve cognitive function. The aim of this study is to evaluate the efficacy of acupuncture for MCI and investigate the effect of acupuncture on structural and functional brain changes in patients with MCI. METHODS: This study is a randomized, assessor-blinded, sham-controlled trial. Fifty participants with MCI will be randomly assigned to the acupuncture group (n = 25) or sham acupuncture group (n = 25). The acupuncture group will receive acupuncture treatment at nine acupuncture points (GV20, EX-HN1, bilateral LI4, and ST36) twice a week for 12 weeks. The sham acupuncture group will receive sham acupuncture treatment at the same points with non-penetrating sham needles. Both groups will be restricted from all other treatments for the improvement of cognitive function. The primary outcome measure is the Digit Span Test (DST). The secondary outcome measures are the Digit Symbol Substitution Test (DSST), Korean version of Montreal Cognitive Assessment (MoCA-K), Seoul Neuropsychological Screening Battery-II (SNSB-II), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), working memory (WM) task performance score, and structural/functional brain changes. Outcomes will be assessed at screening, baseline, 4 and 8 weeks, and after the end of treatment. We will also observe adverse events. In the statistical analysis, a full analysis set and per-protocol analysis will be performed. DISCUSSION: This randomized clinical trial aims to examine the efficacy of acupuncture treatment for MCI. Neuropsychological tests, psychological inventories for measuring depression and anxiety, and magnetic resonance imaging will be performed to investigate the underlying neurological mechanisms and the association between cognition, emotion, and brain networks following acupuncture treatment. The results of the trial will provide evidence supporting the efficacy of acupuncture and also add to the neurobiological understanding of acupuncture treatment for MCI. TRIAL REGISTRATION: Clinical Research Information Service, KCT0002896 . Registered on 25 May 2018.

Treatment of Hominis placenta pharmacopuncture for a patient with mild neurocognitive disorder: Case report.

Hominis placenta pharmacopuncture, a treatment that injects Hominis placenta extract into acupoints, has been suggested in the literature and researches that it could be used for cognitive decline. We experienced a case of mild neurocognitive disorder treated with Hominis placenta pharmacopuncture. Hominis placenta pharmacopuncture could be a possible treatment modality producing substantial clinical result in cognitive function which is assessed with Mini-Mental State Examination-Dementia Screening (MMSE-DS), Korean Version of Montreal Cognitive Assessment (MoCA-K), and Korean-Dementia Rating Scale (K-DRS). A 84-year-old man with mild neurocognitive disorder received Hominis placenta pharmacopuncture on GV20, CV12, and bilateral ST36 for a month. The results of neuropsychological examination showed increase in scores after treatment of Hominis placenta pharmacopuncture. Before treatment, they were 15 points for MoCA-K, and 120 points for K-DRS (7.6%), but after treatment, they elevated by 21 points for MoCA-K and 137 points for K-DRS (100%). MMSE-DS score was 28 points, unchanged before and after treatment. It did not cause any side-effect. Hominis placenta pharmacopuncture could be a safe option for treating mild neurocognitive disorder.