Perioperative Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome Aggravated by Hepatopulmonary Syndrome in Deceased Donor Liver Transplantation: A Case Report.

Background: Extracorporeal membrane oxygenation (ECMO) is an accommodation of the cardiopulmonary bypass technique that can support gas exchange and hemodynamic stability. It is used as a salvage maneuver in patients with life-threatening respiratory or cardiac failure that does not respond to conventional treatment. There are few case reports of successful perioperative use of ECMO, especially preoperatively, in liver transplantation (LT). Here, we report an experience of successful anesthetic management in deceased donor liver transplantation (DDLT) by applying perioperative veno-venous (VV) ECMO support in the setting of acute respiratory distress syndrome (ARDS) aggravated by hepatopulmonary syndrome (HPS). Case: A 25-year-old female (156.0 cm, 65.0 kg), without any underlying disease, was referred to our emergency department for decreased mentality. Based on imaging and laboratory tests, she was diagnosed with acute liver failure of unknown cause combined with severe ARDS aggravated by HPS. Since the patient faced life-threatening hypoxemia with a failure of conventional ventilation maneuvers, preoperative VV ECMO was initiated and maintained during the operation. The patient remained hemodynamically stable throughout DDLT, and ARDS showed gradual improvement after the administration of VV ECMO. As ARDS improved, the patient's condition alleviated, and VV ECMO was weaned on postoperative day 6. Conclusions: This case demonstrates that VV ECMO may be a useful therapeutic option not only during the intraoperative and postoperative periods but also in the preoperative period for patients with liver failure combined with reversible respiratory failure.

Comparison of Postoperative Nausea and Vomiting Incidence between Remimazolam and Sevoflurane in Tympanoplasty with Mastoidectomy: A Single-Center, Double-Blind, Randomized Controlled Trial.

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common adverse effect of general anesthesia, especially in middle ear surgery. Remimazolam is a newer benzodiazepine recently approved for use in general anesthesia. This study aimed to compare the incidence rate of PONV after tympanoplasty with mastoidectomy between using remimazolam and sevoflurane. Materials and Methods: This study included 80 patients undergoing elective tympanoplasty with mastoidectomy. The patients were randomly assigned to either the remimazolam or sevoflurane group. The primary outcome was the incidence rate of PONV 12 h after surgery. The secondary outcomes were the incidence rate of PONV 12-24 and 24-48 h after surgery, severity of PONV, incidence rate of vomiting, administration of rescue antiemetics, hemodynamic stability, and recovery profiles. Results: The incidence rate of PONV 0-12 h after tympanoplasty with mastoidectomy was significantly lower in the remimazolam group compared with that in the sevoflurane group (28.9 vs. 57.9%; p = 0.011). However, the incidence rate of delayed PONV did not differ between the two groups. PONV severity in the early periods after the surgery was significantly lower in the remimazolam group than in the sevoflurane group. The incidence rate of adverse hemodynamic events was lower in the remimazolam group than in the sevoflurane group, but there was no difference in the overall trends of hemodynamic data between the two groups. There was no difference in recovery profiles between the two groups. Conclusions: Remimazolam can significantly reduce the incidence rate of early PONV after tympanoplasty with mastoidectomy under general anesthesia.

Comparison of remimazolam-remifentanil and propofol-remifentanil during laparoscopic cholecystectomy.

BACKGROUND: Remimazolam is a novel benzodiazepine with fast onset and short half-life. We compared the effects of remimazolam and propofol on recovery profiles for general anesthesia in patients undergoing laparoscopic cholecystectomy. METHODS: We randomly assigned 108 patients to either a remimazolam (n=54) or propofol (n=54) group. Remimazolam and propofol were used for induction and maintanance of anesthesia. Following anesthesia, we recorded the time until an Aldrete score of 9 was achieved as the primary surrogate marker of complete recovery. The time to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 2 and the time from the end of anesthesia to eye opening time, recovery time of orientation, time to spontaneous breathing, extubation time, and the time required for analgesics were measured. Heart rate, blood pressure, and bispectral index were assessed before, during, and after pneumoperitoneum. RESULTS: We included 101 patients in the analysis. In the remimazolam group, it took longer to reach an Aldrete score of 9 after the drug infusion ended (P = 0.031). There was no difference in the time to reach MOAA/S 2 between the two groups. The time to eye opening, recovery time of orientation, and time required for analgesics were longer and heart rate was higher in the remimazolam group. Neither blood pressure, nor extubation time differed between groups. CONCLUSIONS: Remimazolam and propofol provided safe induction and maintenance of anesthesia in patients undergoing laparoscopic cholecystectomy. The recovery time from anesthesia was longer than that with propofol. Fewer hemodynamic changes were observed with remimazolam, but further studies are needed.

Extract of Aster koraiensis Nakai Leaf Ameliorates Memory Dysfunction via Anti-inflammatory Action.

Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-ß-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand-receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aß-overexpressing 5XFAD transgenic mice to investigate Aß accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-ß (Aß) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand-receptor interaction-related genes and inhibiting Aß accumulation. Therefore, AK extract could be a functional material improving cognition and memory.

Monitored anesthesia care with remimazolam for gynecological day surgeries: Case reports.

Remimazolam is a newly approved benzodiazepine characterized by rapid onset, predictable maintenance, fast recovery, and availability of a reversal agent. We describe four cases of patients who received monitored anesthesia care with remimazolam for gynecological day surgery.

Anesthetic Management of Upper Tracheal Cancer Resection and Reconstruction: A Case Report.

Tracheal tumor resection and reconstruction is the primary treatment for tracheal tumors. The trachea is the surgical site as well as an important channel to ensure ventilation and maintain oxygenation during surgery. In this report, we describe the successful management of an upper tracheal tumor in a 50-year-old patient. The tumor was situated approximately 2-3 cm below the vocal cords, occluding the tracheal lumen by 80%. Conventional orotracheal intubation was expected to be impossible, and the patient was managed with an I-Gel supraglottic airway for mechanical ventilation with the assistance of venovenous extracorporeal membrane oxygenation (VV ECMO). After securing tracheal intubation via the tracheostomy site, VV ECMO was weaned off, and mechanical ventilation was changed to tracheal intubation. Eventually, tracheal tumor resection and reconstruction were successfully performed under general anesthesia. No specific events occurred during anesthetic management. Careful preoperative planning and good teamwork made the procedure possible without complications.

Effects of Perilla frutescens var. acuta in amyloid ß toxicity and Alzheimer's disease-like pathology in 5XFAD mice.

Although accumulation of amyloid ß (Aß) plaque is a major hallmark of Alzheimer's disease (AD), various pathologies have been suggested therapeutic targets. Therefore, therapies-targeting multiple pathologies would be required for effective managements of AD. Accordingly, natural products, which has multiple active ingredients, have been receiving a lot of attention. In this study, we tested whether standardized ethanol extract of leaves of Perilla frutescens var. acuta (L.) Britt. (Lamiaceae) (ELPF) could modulate various pathologies in AD using 5XFAD mice. ELPF blocked Aß aggregation and disassembled pre-formed Aß aggregates. ELPF blocked Aß aggregates-induced LTP impairment and ELPF-disassembled Aß aggregates failed to impair hippocampal LTP. Systemic administration of ELPF blocked Aß aggregates-induced memory impairment in a passive avoidance test. ELPF-disassembled Aß aggregates failed to impair passive avoidance memory. Prolonged administration of ELPF ameliorated memory impairments in 5XFAD mice. In the hippocampus of 5XFAD mice, ELPF administration significantly reduced Aß deposits and neuroinflammation. These results demonstrate that ELPF could be a promising therapeutic candidate for AD.

Hydrangea macrophylla and Thunberginol C Attenuate Stress-Induced Anxiety in Mice.

Stress is an important neurological input for successful life. However, chronic stress and stress hormones could be a cause of various neurological disorders including anxiety disorders. Therefore, there have been many efforts to find effective materials for curing stress-induced neurological disorders. In this study, we examined the effect of Hydrangea macrophylla (HM) on corticosterone-induced neurotoxicity, stress-induced anxiety in mice and suggested a possible active ingredient of HM. HM protected cortical neurons against neurotoxicity of corticosterone (CORT), a stress hormone. HM also blocked CORT-induced hippocampal synaptic deficit via regulating Akt signaling. Oral administration of HM improved chronic restraint stress-induced anxiety in Elevated Plus maze test along with reduction of plasma corticosterone and TNF-α levels. Moreover, HM reduced stress-induced neuroinflammation and oxidative stress. Thunberginol C, an active ingredient of HM, also prevented CORT-induced neuronal cell death and restraint stress-induced anxiety. Moreover, thunberginol C reduced plasma TNF-α level and neuroinflammation and oxidative stress. Collectively, HM could be a good candidate for preventing stress-induced neurological disorders and thunberginol C may be an active ingredient of HM for this purpose.

ß-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus.

Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. ß-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether ß-amyrin can prevent AD-like pathology. ß-Amyrin blocked amyloid ß (Aß)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, ß-amyrin improved Aß-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of ß-amyrin on Aß-induced LTP impairment. In in vivo experiments, we observed that ß-amyrin ameliorated object recognition memory deficit in Aß-injected AD mice model. Moreover, neurogenesis impairments induced by Aß was improved by ß-amyrin treatment. Taken together, ß-amyrin might be a good candidate of treatment or supplement for AD patients.

Hydrangeae Dulcis Folium Attenuates Physical Stress by Supressing ACTH-Induced Cortisol in Zebrafish.

OBJECTIVE: To determine the effects of Hydrangeae Dulcis Folium (EHDF) on physical stress, changes in the whole-body cortisol level and behaviour in zebrafish (Danio rerio). METHODS: One hundred and seventy-four fish were randomly divided into 4 [adrenocorticotropin hormone (ACTH) challenge test: 4 fish per group] or 6 groups (behavioural test: 10-12 fish per group, whole-body cortisol: 4 fish per group). Net handling stress (NHS) was used to induce physical stress. Fish were treated with vehicle or EHDF (5-20 mg/L) for 6 min before they were exposed to stress. And then, fish were sacrificed for collecting body fluid from whole-body or conducted behavioural tests, including novel tank test and open field test, and were evaluated to observe anxiety-like behaviours and locomotion. In addition, to elucidate the mode of action of the anti-stress effects of EHDF, ACTH (0.2 IU/g, i.p.) challenge test was performed. RESULTS: The increased anxiety-like behaviours in novel tank test and open field test under stress were prevented by treatment with EHDF at 5-20 mg/L (P <0.05). Moreover, compared with the unstressed group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS (P <0.05). Compared with the NHS-treated stressed control group, pre-treatment with EHDF at concentrations of 5-20 mg/L for 6 min significantly prevented the NHS-increased whole-body cortisol level (<0.05). In addition, ACTH challenge test showed that EHDF completely blocked the effects of ACTH on cortisol secretion (P <0.05). CONCLUSION: EHDF may be a good antistress candidate and its mechanism of action may be related to its positive effects on cortisol release.

The fruit of Crataegus pinnatifida ameliorates memory deficits in ß-amyloid protein-induced Alzheimer's disease mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Crataegus pinnatifida is a traditional medicine widely used as digestive drug in East Asia. Although Chinese herbal medicine used it for mental health, scientific evidence does not exist, yet. AIMS OF STUDY: The aim of this study is to show that the ethanol extract of the fruit of Crataegus pinnatifida (CPE) has neuroprotective effect on Alzheimer' disease model mice. MATERIALS AND METHODS: Intracerebroventricular injection of Aß was used to induce Alzheimer's disease-like pathology. Passive avoidance and Y-maze tasks were used to examine the effect of CPE on memory impairments by Aß. Immunohistochemistry was used to examine the effect of CPE on glial activation. ThT assay was used to observe the effect of CPE on Aß aggregation. MTT and LDH release assays were utilized to examine effects of CPE on Aß-induced cytotoxicity. RESULTS: CPE prevented memory deficit in Aß-induced memory impairment model. Moreover, CPE prevented glial activation in the hippocampus of Aß-injected model. In in vitro test, CPE inhibited Aß fibril formation in a concentration-dependent manner. CPE also caused disaggregation of Aß fibrils. Along with this, CPE blocked neuronal cell death induced by Aß. CONCLUSIONS: Collectively, these experimental findings demonstrated that CPE could be a candidate for development of AD therapy.

Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor.

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg-1) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.

Effects of Angelica gigas Nakai as an Anti-Inflammatory Agent in In Vitro and In Vivo Atopic Dermatitis Models.

We investigated the cellular and molecular mechanisms mediating the effects of Angelica gigas Nakai extract (AGNE) through the mitogen-activated protein kinases (MAPKs)/NF-κB pathway using in vitro and in vivo atopic dermatitis (AD) models. We examined the effects of AGNE on the expression of proinflammatory cytokines and chemokines in human mast cell line-1 (HMC-1) cells. Compound 48/80-induced pruritus and 2,4-dinitrochlorobenzene- (DNCB-) induced AD-like skin lesion mouse models were also used to investigate the antiallergic effects of AGNE. AGNE reduced histamine secretion, production of proinflammatory cytokines including interleukin- (IL-) 1ß, IL-4, IL-6, IL-8, and IL-10, and expression of cyclooxygenase- (COX-) 2 in HMC-1 cells. Scratching behavior and DNCB-induced AD-like skin lesions were also attenuated by AGNE administration through the reduction of serum IgE, histamine, tumor necrosis factor-α (TNF-α), IL-6 levels, and COX-2 expression in skin tissue from mouse models. Furthermore, these inhibitory effects were mediated by the blockade of the MAPKs and NF-κB pathway. The findings of this study proved that AGNE improves the scratching behavior and atopy symptoms and reduces the activity of various atopy-related mediators in HMC-1 cells and mice model. These results suggest the AGNE has a therapeutic potential in anti-AD.

The enhancing effect of Aubang Gahl Soo on the hippocampal synaptic plasticity and memory through enhancing cholinergic system in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aubang Gahl Soo (AGS) is a Korean traditional drink manufactured from medicinal plants and fruits using sugar or honey. Although traditional old book stated its effects on body, there is no scientific evidence yet. Therefore, in the present study, we tested AGS on brain functions. AIM OF THIS STUDY: In this study, we tried to uncover the effect of on brain functions. To do this we examined the action of AGS on the hippocampal synaptic function and memory in mice. MATERIALS AND METHODS: To examine the effect of AGS on synaptic plasticity, we observed input-output curves (I/O curve), paired-pulse facilitation (PPF), and long-term potentiation (LTP) using mouse hippocampal slices. Moreover, to investigate the functional relevance of the effect of AGS on synaptic plasticity, we conducted passive avoidance, Y-maze and Morris water maze tests. To examine relevant mechanism, acetylcholinesterase (AChE) activity and acetylcholine (ACh) level assay were also conducted. RESULTS: In the basal synaptic transmission study, we found that AGS did not affect I/O curves and PPF. However, AGS facilitated hippocampal LTP in a concentration-dependent manner. Moreover, AGS blocked AChE activity (IC50 = 485 µg/ml). Moreover, ACh level was increased by AGS (100 µg/ml) treatment. Along with this, facilitating effect of AGS on hippocampal LTP also blocked by scopolamine, a muscarinic acetylcholine receptor antagonist. Moreover, AGS also ameliorated memory impairments induced by scopolamine in passive avoidance, Y-maze, and Morris water maze tests. CONCLUSIONS: These results suggest that AGS facilitates hippocampal LTP through activating cholinergic system and ameliorates cholinergic dysfunction-induced memory deficit.

The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer's Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling.

Ziziphus jujuba is a plant, which bears fruits and seeds that are used for medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in Chinese and Korean medicines. Recent findings have indicated that EZJ improves memory impairment, a common symptom of various neurological diseases. However, the effects of EZJ on amyloid ß (Aß) toxicity, which is a main cause of Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the effect of standardized EZJ on Aß-induced synaptic long-term potentiation (LTP) deficit in the hippocampal tissue. EZJ blocked Aß-induced LTP deficits in a concentration-dependent manner. Moreover, EZJ increased brain-derived neurotrophic factor (BDNF) level in naïve hippocampal slices. The finding that the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ ameliorates the Aß-induced LTP deficit through BDNF/topomyosin receptor kinase B (TrkB) signaling. However, transcription or translation inhibitors failed to block the effect of EZJ, suggesting that BDNF synthesis is not required for the action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In contrast, plasmin inhibitor blocked the effect of EZJ on the Aß-induced LTP deficit. Our findings indicate that EZJ ameliorates Aß-induced LTP deficits through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of EZJ on the post-translation modification of BDNF.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis.

OBJECTIVE: To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). METHODS: The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. RESULTS: Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. CONCLUSIONS: The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Echinocystic Acid Facilitates Neurite Outgrowth in Neuroblastoma Neuro2a Cells and Enhances Spatial Memory in Aged Mice.

Aging leads to functional changes in the brain and decreases ability of learning and memory. Neurite outgrowth is important in learning and memory, therefore regulation of neurite outgrowth might be a candidate for treating aged brain. Echinocystic acid (EA), a pentacyclic triterpene, has shown to exert various neurological effects. However, the effect of EA on neurite outgrowth has not been studied. In this study, we examined if EA is effective on neurite outgrowth and memory in aged mice. The effect of EA on neurite outgrowth was observed by examining neurite processes of Neuro2a cells treated with EA. Western blot analysis was conducted to examine possible mechanisms. Morris water maze test was used to examine the effect of EA on learning and memory in aged mice. Immunohistochemistry was conducted to observe the effect of EA on neurite outgrowth in the hippocampus. EA was shown to induce neurite outgrowth in a concentration dependent manner without affecting cell viability. Moreover, EA treatment increased phosphorylation of c-jun N-terminal kinase (JNK) and JNK inhibitor, SP600125, blocked the effect of EA on neurite outgrowth. These results demonstrated that EA treatment promotes neurite outgrowth through the JNK signaling pathway. In in vivo experiments, EA treatment increased neurite outgrowth in aged mouse hippocampus. Moreover, EA treatment enhanced spatial learning and memory in aged mice. These results suggest that EA can be developed as a new, naturally occurring drug to treat ageing-related neurological diseases.

Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS: DHP1401 (50µg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.

Osteoprotective Effects of Polysaccharide-Enriched Hizikia fusiforme Processing Byproduct In Vitro and In Vivo Models.

The traditional manufacturing method used to produce goods from Hizikia fusiforme, utilizes extraction steps with hot water. The byproduct (of hot water extraction) is rich in polysaccharide and is considered a waste. To evaluate the osteogenic effects of the byproduct of H. fusiforme (HFB), osteogenic cells and animal models were used to test it effects on osteogenesis. The HFB-treated mouse myoblast C2C12 cells exhibited significant dose dependently elevated alkaline phosphatase (ALP) activity and slightly increased bone morphogenetic protein-2 (BMP-2). HFB also suppressed the formation of tartrate-resistant acid phosphatase (TRAP) activity and TRAP staining in the bone marrow-derived macrophages (BMM) cells that had been stimulated with the receptor activator of the nuclear factor kB ligand/macrophage colony-stimulating factor kB ligand. In addition, HFB also increased the phosphorylation of extracellular signal-regulated protein kinase (p-ERK) level. Finally, osteogenic effects of HFB were clearly confirmed in the three in vivo models: zebrafish, ovariectomized mice, and mouse calvarial bones. HFB accelerated the rate of skeletal development in zebrafish and prevented much of the mouse femoral bone density loss of ovariectomized mice. Moreover, HFB enhanced woven bone formation over the periosteum of mouse calvarial bones. Our result showed that HFB functions as a bone resorption inhibitor as well as an activator of bone formation in vivo and in osteogenic in vitro cell systems.

Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission.

Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 µg/ml) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol.