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.

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.

Benefit of Adjuvant Traditional Herbal Medicine With Chemotherapy for Resectable Gastric Cancer.

INTRODUCTION: Stomach cancer, historically, has a low survival rate advances in curative resection procedures. OBJECTIVES: To assess the potential benefits of traditional herbal medicines in conjunction with chemotherapy in postoperative gastric cancer patients in terms of overall survival and disease-free survival. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, a Chinese database (CNKI), a Korean database, a Japanese database, AMED, and CINAHL up to September 2016. We summarized survival data from all RCTs. STUDY SELECTION: All RCTs of oral traditional medicines for resectable gastric cancer compared with chemotherapy alone were eligible. DATA EXTRACTION: Thirteen eligible trials with survival data (1075 patients) were deemed eligible for inclusion. RESULTS: There were 217 documented deaths of the 574 patients assigned to adjuvant traditional medicines groups and 319 documented deaths of the 501 patients assigned to the chemotherapy-only groups. Adjuvant traditional medicines were associated with a statistically significant benefit in terms of overall survival rate (hazard ratio = 0.56; 95% confidence interval = 0.47-0.66; P < .00001) and disease-free survival (hazard ratio = 0.54; 95% confidence interval = 0.43-0.66; P < .00001). CONCLUSION: Among the RCTs included, the inclusion of postoperative adjuvant traditional medicines was associated with reduced risk of death in gastric cancer patients, when survival rates were compared with the group of patients who received chemotherapy alone. However, most of the included studies utilized are thought to be of low quality, so it would certainly appear that more trials are both advisable and necessary to arrive at correct and convincing conclusions.

Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review.

OBJECTIVES: To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs). METHODS: Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. RESULTS: Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of quality of life (QOL) compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed. CONCLUSION: THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QOL and in decreasing the number of hot flashes per day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues.

Traditional herbal medicine for cancer pain: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of traditional herbal medicine (THM) as an adjunctive therapy for cancer pain is unclear. OBJECTIVE: To assess the effectiveness of THM as an adjunctive therapy for cancer pain using randomized controlled trials (RCTs). METHODS: Five electronic databases, including those from the UK and China, were systematically searched for the period before September 2013. All RCTs involving the use of THM in combination with conventional cancer therapy for cancer pain were included. RESULTS: Twenty-four RCTs involving 4889 patients with cancer pain were systematically reviewed. Among them, nine studies of 952 patients reported a significant decrease in the number of patients with cancer pain in the treatment group. Four studies of 1696 patients reported a significant decrease in the degree of pain in the treatment group. CONCLUSION: The results of these studies suggest that THM combined with conventional therapy is efficacious as an adjunctive therapy for patients with cancer pain. However, more research, including well-designed, rigorous, and larger clinical trials, are necessary to address these issues.

Traditional herbal medicine as adjunctive therapy for nasopharyngeal cancer: a systematic review and meta-analysis.

The effectiveness of traditional herbal medicine (THM) as treatment for nasopharyngeal cancer (NPC) has not been clearly demonstrated. The aim of this study is to assess the effectiveness of THM as adjunctive therapies for NPC using the results of randomized controlled trials (RCTs). Five electronic databases, including English and Chinese databases, were systematically searched up to February 2014. All RCTs involving traditional herbal medicine in combination with conventional cancer therapy for NPC were included. Twenty-two RCTs involving 2,298 NPC patients were systematically reviewed. Of these 22 studies, 15 on 1482 patients reported a significant increase in the number surviving patients with survivals of more than 1, 3, or 5 years. Seven studies on 595 patients reported a significant increase in immediate tumor response, and three studies on 505 patients reported a significant decrease in distant metastasis. This meta-analysis of 22 studies suggests that THM combined with conventional therapy can provide an effective adjunctive therapy for NPC. More research and well-designed, rigorous, large clinical trials are required to address these issues.

Pharmacopuncture for cancer care: a systematic review.

Background. Pharmacopuncture, injection to acupoints with pharmacological medication or herbal medicine, is a new acupuncture therapy widely available in Korea and China for cancer-related symptoms. However, the evidence is yet to be clear. Objective. To determine pharmacopuncture's effectiveness on cancer-related symptoms. Methods. Eleven databases were searched for randomized controlled trials of pharmacopuncture in cancer patients. The Cochrane risk of bias (ROB) assessment tool was used for quality assessment. Results. Twenty-two studies involving 2,459 patients were included. Five trials of chemotherapy-induced nausea and vomiting (CINV) underwent meta-analysis. Pharmacopuncture significantly relieved severity of CINV compared with control group (3 trials, risk ratio (RR) 1.28, 95% confidence interval (CI) = 1.14-1.44). The frequency of CINV was also significantly reduced with pharmacopuncture (2 trials, RR 2.47, 95% CI = 2.12-2.89). Seventeen trials studied various symptoms, and in most studies, pharmacopuncture significantly relieved pain, ileus, hiccup, fever, and gastrointestinal symptoms and improved quality of life in various cancer patients. ROB was generally high. Conclusion. It may be suggested with caution that pharmacopuncture may help various symptom relief in cancer patients, but it is hard to draw a firm conclusion due to clinical heterogeneity and high ROB of the included studies, hence warranting further investigation.

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.

Cellular imaging assay for early evaluation of an apoptosis inducer.

The objective of this study was to propose a feasibility of a cellular imaging assay as an alternative to the conventional cytotoxicity assay, such as MTS assay, for apoptosis monitoring. As an apoptosis monitoring parameter, affinity interaction between phosphatidylserine (PS) and annexin V was chosen. First, the specific binding affinity between annexin V and PS in phospholipid bilayers consisting of various molar (0-15%) composition of PS was measured using a surface plasmon resonance biosensor. As PS composition increased, the binding level of annexin V increased proportionally. Second, various concentrations (0.1-10 µM) of staurosporine were used as to induce apoptosis and introduced to MCF-7 breast carcinoma cells. The cellular fluorescence images from annexin V-FITC conjugate were obtained by confocal microscopy, and their fluorescence intensities were quantified by image scanning. Dose-apoptosis (or cell death) relationships were very similar to those from MTS and FACS assays. In summary, our cellular imaging method could serve as a quicker and simpler alternative to MTS (end point assay) and FACS (flow cytometry) to screen potential apoptosis inducers.

Protective effects of Chunghyuldan against ROS-mediated neuronal cell death in models of Parkinson's disease.

Previous reports have suggested that the herbal medicine Chunghyuldan (CHD, Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) has wide-ranging biological effects, including anti-hyperlipidaemic, anti-ischaemic, anti-inflammatory and antioxidant activities. Reactive oxygen species (ROS)-mediated mitochondrial dysfunction is thought to be one of the major pathological mechanisms responsible for Parkinson's disease (PD) and may underlie the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that is a hallmark of this disease. In this study, we examined the neuroprotective effects of CHD in PD models produced by treatment with neurotoxins that act via ROS-mediated mitochondrial dysfunction. In an in vitro PD model using 6-hydroxydopamine, CHD applied at concentrations of 10 and 100 µg/ml exhibited significant protective effects in PC12 cells by inhibiting intracellular ROS generation. CHD applied at 10 and 100 µg/ml also prevented 6-hydroxydopamine-induced mitochondrial depolarization and elevation of caspase-3 activity. At the same doses, CHD showed regulatory effects on the haem oxygenase-1 and gp91 phagocytic oxidase which have critical roles in generating ROS. In addition, CHD protected dopaminergic neurons in a primary mesencephalic culture against MPP+ neurotoxicity. In an in vivo PD model produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (20 mg/kg, 4 times, i.p.), co-administration of CHD (50 mg/kg, 5 days, p.o.) ameliorated PD-like behavioural symptoms (bradykinesia) and reduced dopaminergic neuronal damage in the SNpc and striatum as measured by immunocytochemistry. These results demonstrate the neuroprotective effects of CHD in PD models that are mediated through inhibition of ROS generation and associated mitochondrial dysfunction.

Preparation of targeting proteoliposome by postinsertion of a linker molecule conjugated with recombinant human epidermal growth factor.

To develop a sterically stable, targeting proteoliposome, a postinsertion method was employed to biofunctionalize the liposome surface with a biocompatible anchor molecule (BAM) linker conjugated with epidermal growth factor (EGF) as a homing molecule. In this method, EGF was first conjugated with BAM that consisted of a hydrophilic reactive group at one end and oleic acid chains at the other end. The EGF-BAM complex was then inserted into the liposomal phospholipid bilayer through lipophilic interaction. When compared with the traditional surface modification method by amine coupling, the modification efficiency with BAM at 25 degrees C was about 2.5-fold higher, and the 24 h stability of the inserted BAM at 25 degrees C was also about 2.5-fold higher. The insertion affinity and stability of the BAM to the liposomal bilayer was not influenced by an increase in cholesterol concentration, a component in liposome preparation. Confocal microscopy studies showed that the proteoliposomes biofunctionalized with the BAM-EGF complex encapsulating Cy5 fluorescent dye were selectively bound to the surface of MDA-MB-231 cells overexpressing EGFR (epidermal growth factor receptor), but not to MCF-7 cells, which did not express EGFR. The same proteolipome encapsulating doxorubicin was selectively targeted to MDA-MB-231 cells and killed them. In sum, BAM could be used as a suitable postinsertion linker for biofunctionalization of liposome surface with high modification efficiency and stability. Furthermore, the protein used as a homing molecule maintained its bioactivity after the biofunctionalization.

Protective effects of standardized Thuja orientalis leaves against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells.

Although the etiology of Parkinson's disease (PD) remains unknown, recent studies have suggested that oxidative stress (OS) and apoptosis, as a result of mitochondrial defects, may play important roles in its pathogenesis. 6-Hydroxydopamine (6-OHDA), a neurotoxin commonly used in models of PD, induces selective catecholaminergic cell death, mediated by reactive oxygen species (ROS) and mitochondrial defects. This study investigated the protective effect of Thuja orientalis leaves (TOFE), a well-known oriental traditional medicine, on 6-OHDA-induced neurotoxicity in SH-SY5Y cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst staining showed that TOFE attenuated the cell damage caused by 6-OHDA stress. TOFE showed strong radical scavenging effects in 2,2-diphenyl-2-picrylhydrazyl and 2,2-azinobis-(3-ethyl-benzthiazoline-6-sulphonic acid) assays, and it reduced the intracellular ROS and extracellular nitric oxide production induced by 6-OHDA. Additionally, TOFE blocked the reduction in the mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase-3. Moreover, TOFE decreased the phosphorylation of extracellular signal-regulated kinase (pERK), which has pro-apoptotic functions. Taken together, TOFE might protect SH-SY5Y cells from 6-OHDA through the downregulation of OS and mitochondrial-mediated apoptosis, and regulation of pERK.