Antidepressant Effects of Ginsenoside Rc on L-Alpha-Aminoadipic Acid-Induced Astrocytic Ablation and Neuroinflammation in Mice.

Depression is a prevalent and debilitating mental disorder that affects millions worldwide. Current treatments, such as antidepressants targeting the serotonergic system, have limitations, including delayed onset of action and high rates of treatment resistance, necessitating novel therapeutic strategies. Ginsenoside Rc (G-Rc) has shown potential anti-inflammatory and neuroprotective effects, but its antidepressant properties remain unexplored. This study investigated the antidepressant effects of G-Rc in an L-alpha-aminoadipic acid (L-AAA)-induced mouse model of depression, which mimics the astrocytic pathology and neuroinflammation observed in major depressive disorder. Mice were administered G-Rc, vehicle, or imipramine orally after L-AAA injection into the prefrontal cortex. G-Rc significantly reduced the immobility time in forced swimming and tail suspension tests compared to vehicle treatment, with more pronounced effects than imipramine. It also attenuated the expression of pro-inflammatory cytokines (TNF-α, IL-6, TGF-ß, lipocalin-2) and alleviated astrocytic degeneration, as indicated by increased GFAP and decreased IBA-1 levels. Additionally, G-Rc modulated apoptosis-related proteins, decreasing caspase-3 and increasing Bcl-2 levels compared to the L-AAA-treated group. These findings suggest that G-Rc exerts antidepressant effects by regulating neuroinflammation, astrocyte-microglia crosstalk, and apoptotic pathways in the prefrontal cortex, highlighting its potential as a novel therapeutic agent for depression.

Protective Effects and Mechanism of Heracleum moellendorffii Hance on Alcohol-Induced Cognitive Decline in Mice.

Chronic and continuous alcohol consumption increases the risk of cognitive decline and may lead to alcohol-related dementia. We investigated the potential of Heracleum moellendorffii Hance root extract (HME) for treating alcohol-related cognitive impairment. Behavioral tests evaluated the effects of HME on cognitive function and depression. Changes in hippocampus and liver tissues were evaluated by Western blotting and H&E staining. The group treated with HME 200 mg/kg showed a significant increase in spontaneous alternation in Y-maze and a decrease in immobility in a forced swimming test (FST) compared to the vehicle-treated group. These results suggest that HME can restore memory deficits and reverse depressive symptoms caused by chronic alcohol consumption. The HME-treated group also upregulated brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated cAMP response element-binding protein (CREB) in the hippocampus. Additionally, it reduced lipid vacuolation in the liver and increased the expression of aldehyde dehydrogenase 1 (ADH1). The administration of HME improves cognitive impairment and reverses depressive symptoms due to alcohol consumption, restoring neural plasticity in the hippocampus and alcohol metabolism in the liver. These findings suggest that HME is a promising treatment for alcohol-related brain disorders. Molecular mechanisms underlying the therapeutic effects of HME and its active ingredients should be investigated further.

Standardized Lycium chinense fruit extract enhances attention and cognitive function in healthy young people by a double-blind, randomized, placebo-controlled, crossover trial.

BACKGROUND: Lycium chinense fruit (LCF) is widely distributed in East Asia that has been used traditionally for antiaging purposes. This study was performed to examine the effects of LCF on attention and cognitive function in healthy young people. MATERIALS AND METHODS: An 11-week, double-blind, randomized, placebo-controlled, crossover trial of 74 patients was conducted and its data were collected on Kyung-Hee University Korean Medical Hospital, Seoul, Korea. In crossover treatment, LCF or placebo was administered three times a day, total 3600 mg as two capsules of 600 mg once for 4 weeks with 3-week washout each. The computerized neurocognitive function test (CNT), the Korean version of the attention-deficit/hyperactivity disorder rating scale-IV, the clinical global impression rating scale, and the Frankfurt attention inventory (FAIR) for two groups were conducted 0 week before and 4 week, 11 week after the experiment, and significant mean changes of these tests for within group or two groups were measured by paired t-test or unpaired t-test. RESULTS: The administration of LCF or placebo crossover for 8 weeks in healthy young people presented significant improvement in the verbal learning test, digit span forward test, digit span backward test, auditory continuous performance task of CNT, and FAIR-performance value compared with the placebo group (each group n = 43, P < 0.05). CONCLUSION: Thus, the consumption of LCF might be beneficial to increase learning and memory through attention and cognitive enhancing effect in normal young people, at an average age of 18 years of age.

Diagnostic Value of Time-Constrained Naming Test in Mild Cognitive Impairment.

BACKGROUND: Naming difficulties have recently garnered more interest in elderly individuals with mild cognitive impairment (MCI). We anticipate that naming tests with the consideration of response time can provide more informative and distinct neuropsychological profiles of individuals with MCI. METHODS: Naming tests were administered to 76 elderly individuals with MCI and 149 healthy elderly (HE). We analyzed the impact of MCI on naming performance and occurrence of "delayed" response. We also validated the predictive power of naming tests with a time-constrained scoring system. RESULTS: MCI participants performed poorer on the noun naming test than HE participants (p = 0.014). MCI was significantly associated with the occurrence of "delayed" response on the noun (odds ratio [OR] = 3.57; 95% confidence interval [CI] = 1.78-7.17) and verb naming tests (OR = 4.66; 95% CI = 2.07-10.46). The time-constrained naming scores were significantly better able to distinguish the MCI from the HE group than the conventional spontaneous naming score on both the noun (p < 0.001) and verb (p = 0.002) naming tests. CONCLUSIONS: Our findings broaden the knowledge related to the naming ability in individuals with MCI, with respect to the response time. We also confirmed the validity of the naming tests by applying the "delayed" responses as supplementary assessments in the diagnosis of MCI.

Effect of ginseng and ginsenosides on attention deficit hyperactivity disorder: A systematic review.

Attention deficit hyperactivity disorder (ADHD) is a rapidly increasing neurodevelopmental disorder but currently available treatments are associated with abuse risk, side effects, and incomplete symptom relief. There is growing interest in exploring complementary options, and ginseng has gained attention for its therapeutic potential. This systematic review aimed to assess current evidence on the efficacy of ginseng and its active components, ginsenosides, for ADHD. Eligible studies were identified through searches of PubMed, Embase, Cochrane Library, and Web of Science, up to June 2023. The inclusion criteria included both human and animal studies that investigated the effects of ginseng or ginsenosides on ADHD. The risk of bias was assessed according to study type. Six human studies and three animal studies met the inclusion criteria. The results suggest that ginseng and ginsenosides may have beneficial effects on ADHD symptoms, particularly inattention, through dopaminergic/norepinephrinergicmodulation and BDNF/TrkB signaling. Ginseng and ginsenosides have promising potential for ADHD treatment. Due to limitations in evidence quality, such as the risk of bias and variability in study designs, larger controlled studies are essential. Integrating ginseng into ADHD management may have valuable implications for individuals seeking well-tolerated alternatives or adjunctive therapies.

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.

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.

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.

Effect of woohwangchungsimwon and donepezil co-treatment on cognitive function and serum metabolic profiles in a scopolamine-induced model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). AIM OF THE STUDY: The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. MATERIALS AND METHODS: Cell viability and reactive oxygen species (ROS) levels were measured in amyloid ß-peptide25-35 (Aß25-35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Co-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aß25-35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment. CONCLUSIONS: Co-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.

Acupuncture for gouty arthritis: a concise report of a systematic and meta-analysis approach.

OBJECTIVE: To assess the effectiveness of acupuncture as complementary therapy for gouty arthritis from randomized controlled trials (RCTs). METHODS: Five electronic databases, including English and Chinese, were systematically searched until August 2012. All RCTs involving acupuncture in combination with conventional therapy for gouty arthritis were included. RESULTS: Ten RCTs involving 852 gouty arthritis patients were systematically reviewed. Among them six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no significant decrease in uric acid in the treatment group compared with the control group. The remaining four studies of 380 patients reported a significant decrease in visual analogue scale score in the treatment group. CONCLUSION: The results of the studies included here suggest that acupuncture is efficacious as complementary therapy for gouty arthritis patients. More research and well-designed, rigorous and large clinical trials are necessary to address these issues.

The effects of Gamijinhae-tang on elastase/lipopolysaccharide-induced lung inflammation in an animal model of acute lung injury.

BACKGROUND: Gamijinhae-tang (GJHT) has long been used in Korea to treat respiratory diseases. The therapeutic effect of GJHT is likely associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of GJHT in a porcine pancreatic elastase (PPE) and lipopolysaccharide(LPS) induced animal model of acute lung injury (ALI). METHODS: In this study, mice were intranasally exposed to PPE and LPS for 4 weeks to induce chronic obstructive pulmonary disease (COPD)-like lung inflammation. Two hours prior to PPE and LPS administration, the treatment group was administered GJHT extracts via an oral injection. The numbers of neutrophils, lymphocytes, macrophages and total cells in the bronchoalveolar lavage (BAL) fluid were counted, and pro-inflammatory cytokines were also measured. For histologic analysis, hematoxylin and eosin (H&E) stains and periodic acid-Schiff (PAS) stains were evaluated. RESULTS: After inducing ALI by treating mice with PPE and LPS for 4 weeks, the numbers of neutrophils, lymphocytes and total cells were significantly lower in the GJHT group than in the ALI group. In addition, the IL-1ß and IL-6 levels were significantly decreased in the GJHT group. The histological results also demonstrated the attenuation effect of GJHT on PPE- and LPS-induced lung inflammation. CONCLUSIONS: The results of this study indicate that GJHT has significantly reduces PPE- and LPS-induced lung inflammation. The remarkable protective effects of GJHT suggest its therapeutic potential in COPD treatment.

Acupuncture for Attenuating Frontal Lobe α Band Asymmetry Induced by Anger: a pilot study.

Objectives: Previous studies have shown that anger can lead to frontal lobe α (8-13 Hz) band asymmetry (FAA) in electroencephalogram (EEG), in accordance with motivational direction. This pilot study aimed to investigate the impact of acupuncture on FAA elicited by anger. Methods: Thirty-four right-handed participants scoring above 75 points on the Novaco Anger Scale were included. Baseline EEG signals were recorded for eight minutes using a 32-channel cap under comfortable conditions. Anger was induced through a nine-minute sequence of Articulated Thoughts in Simulated Situations (ATSS) task. Following that, participants received acupuncture at GB20 and GB21 for 10 minutes. Fast Fourier transform was employed for frequency analysis, and repeated measure ANOVA was conducted for statistical analysis. Results: The results revealed that participants exhibited significantly higher FAA (p = 0.026), particularly in the left hemisphere, after the ATSS task sequence compared to the baseline. During acupuncture treatment, the greater left-sided FAA was significantly reduced (p = 0.027) and reversed. Upon the cessation of acupuncture, FAA returned to a value between the baseline and the anger-evoked stage (p = 0.046). Conclusion: The EEG results of this study revealed that anger stimulation induced an increase in left-sided FAA, which was effectively alleviated by acupuncture. This led to an immediate restoration of FAA asymmetry induced by anger. These findings suggest the potential of acupuncture as a treatment option for reducing FAA associated with anger.

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.

Corrigendum to "The Efficacy and Safety of Acupuncture for the Treatment of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis".

[This corrects the article DOI: 10.1155/2018/1057539.].

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 ).

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).

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.