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.

Morinda citrifolia Leaf Extract Enhances Osteogenic Differentiation Through Activation of Wnt/ß-Catenin Signaling.

Morinda citrifolia (Noni) leaf is an herbal medicine with application in the domestic treatment of a broad range of conditions, including bone fracture and luxation. However, the basic mechanism underlying the stimulation of osteogenic differentiation by Noni leaf extract remains poorly understood. This study aimed to examine the effect of this extract on osteogenic differentiation and the mechanism by which Noni leaf extract enhances osteogenic differentiation. Aqueous extract of Noni leaves was prepared, and rutin and kaempferol-3-O-rutinoside were identified to be two of its major components. C2C12 and human periodontal ligament (hPDL) cells were used to study the effect of Noni. Noni did not show cytotoxicity at a concentration range of 0.015%-1.0% (w/v%) and significantly enhanced the activity of alkaline phosphatase (ALP) and expression levels of osteoblast differentiation markers, including Runx2, ALP, osterix, and osteocalcin, bone morphogenetic protein 2, Wnt3a, and ß-catenin. In addition, Noni enhanced the matrix mineralization of hPDL cells. In the signaling pathways, Noni increased the phosphorylation levels of Akt and GSK3ß and nuclear translocation and transcriptional activity of ß-catenin, which were attenuated by the addition of Dkk-1, a Wnt inhibitor, or LY294002, a PI3K inhibitor. These results suggest that Noni leaf extract enhances osteogenic differentiation through the PI3K/Akt-dependent activation of Wnt/ß-catenin signaling. Noni leaf extract might be a novel alternative medicine for bone and periodontal regeneration in patients with periodontal diseases.

Comparison of the efficacy and safety of 2% lidocaine HCl with different epinephrine concentration for local anesthesia in participants undergoing surgical extraction of impacted mandibular third molars: A multicenter, randomized, double-blind, crossover, phase IV trial.

BACKGROUND: The most commonly impacted tooth is the third molar. An impacted third molar can ultimately cause acute pain, infection, tumors, cysts, caries, periodontal disease, and loss of adjacent teeth. Local anesthesia is employed for removing the third molar. This study aimed to evaluate the efficacy and safety of 2% lidocaine with 1:80,000 or 1:200,000 epinephrine for surgical extraction of bilateral impacted mandibular third molars. METHODS: Sixty-five healthy participants underwent surgical extraction of bilateral impacted mandibular third molars in 2 separate visits while under local anesthesia with 2% lidocaine with different epinephrine concentration (1:80,000 or 1:200,000) in a double-blind, randomized, crossover trial. Visual analog scale pain scores obtained immediately after surgical extraction were primarily evaluated for the 2 groups receiving different epinephrine concentrations. Visual analog scale pain scores were obtained 2, 4, and 6 hours after administering an anesthetic. Onset and duration of analgesia, onset of pain, intraoperative bleeding, operator's and participant's overall satisfaction, drug dosage, and hemodynamic parameters were evaluated for the 2 groups. RESULTS: There were no statistically significant differences between the 2 groups in any measurements except hemodynamic factors (P >.05). Changes in systolic blood pressure and heart rate following anesthetic administration were significantly greater in the group receiving 1:80,000 epinephrine than in that receiving 1:200,000 epinephrine (P ≤.01). CONCLUSION: The difference in epinephrine concentration between 1:80,000 and 1:200,000 in 2% lidocaine liquid does not affect the medical efficacy of the anesthetic. Furthermore, 2% lidocaine with 1:200,000 epinephrine has better safety with regard to hemodynamic parameters than 2% lidocaine with 1:80,000 epinephrine. Therefore, we suggest using 2% lidocaine with 1:200,000 epinephrine rather than 2% lidocaine with 1:80,000 epinephrine for surgical extraction of impacted mandibular third molars in hemodynamically unstable patients.

Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats.

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors.

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey's test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4- L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

An ethanolic extract of Lindera obtusiloba stems, YJP-14, improves endothelial dysfunction, metabolic parameters and physical performance in diabetic db/db mice.

Lindera obtusiloba is a medicinal herb traditionally used in Asia for improvement of blood circulation, treatment of inflammation, and prevention of liver damage. A previous study has shown that an ethanolic extract of Lindera obtusiloba stems (LOE) has vasoprotective and antihypertensive effects. The possibility that Lindera obtusiloba improves endothelial function and metabolic parameters in type 2 diabetes mellitus (T2DM) remains to be examined. Therefore, the aim of the present study was to determine the potential of LOE to prevent the development of an endothelial dysfunction, and improve metabolic parameters including hyperglycemia, albuminuria and physical exercise capacity in db/db mice, an experimental model of T2DM. The effect of LOE (100 mg/kg/day by gavage for 8 weeks) on these parameters was compared to that of an oral antidiabetic drug, pioglitazone (30 mg/kg/day by gavage). Reduced blood glucose level, body weight and albumin-creatinine ratio were observed in the group receiving LOE compared to the control db/db group. The LOE treatment improved endothelium-dependent relaxations, abolished endothelium-dependent contractions to acetylcholine in the aorta, and normalized the increased vascular oxidative stress and expression of NADPH oxidase, cyclooxygenases, angiotensin II, angiotensin type 1 receptors and peroxynitrite and the decreased expression of endothelial NO synthase in db/db mice. The angiotensin-converting enzyme (ACE) activity was reduced in the LOE group compared to that in the control db/db group. LOE also inhibited the activity of purified ACE, COX-1 and COX-2 in a dose-dependent manner. In addition, LOE improved physical exercise capacity. Thus, the present findings indicate that LOE has a beneficial effect on the vascular system in db/db mice by improving endothelium-dependent relaxations and vascular oxidative stress most likely by normalizing the angiotensin system, and also on metabolic parameters, and these effects are associated with an enhanced physical exercise capacity.

Anti-diabetic effect of standardized herbal formula PM021 consisting of Mori Folium and Aurantii Fructus on type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

PM021, which consists of two herbal components, Mori Folium and Aurantii Fructus, is routinely used to treat diabetes in Korea. In this study, the anti-diabetic effect of PM021 on an animal model of developing type 2 diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated. Eight weeks of age male OLETF rats were treated daily with PM021 or vehicle for five months. Specifically, changes in body weight, blood glucose, urine volume, food intake and oral glucose tolerance were measured in rats for five months. The rats in this study were divided into four groups: a Long-Evans Tokushima Otsuka (LETO) rat group, which is a genetic control group for OLETF, that received no treatment; a PM021 treatment group of LETO rats; OLETF rats that received no treatment; and OLETF rats that received PM021 treatment. The results showed that PM021 significantly prevented increases in body weight, blood glucose, and urine and food intake that resulted from the induction of obesity and diabetes. PM021 also improved glucose tolerance in OLETO rats. However, PM021 had no effect on LETO rats, a control group of OLETF rats. Taken together, these findings indicate that PM021 has distinct anti-diabetic effects without any adverse effects or toxicities.

The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China. AIM OF THE STUDY: This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis. MATERIALS AND METHODS: Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model. RESULTS: WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods. CONCLUSION: When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis.

Evidence from limited proteolysis of a ristocetin-induced conformational change in human von Willebrand factor that promotes its binding to platelet glycoprotein Ib-IX-V.

von Willebrand factor (VWF) does not normally interact with platelets in the bloodstream. Binding to exposed vascular subendothelium, however, enables VWF to interact with the platelet glycoprotein Ib-IX-V complex (GP Ib-IX-V). This change in function may reflect a change in its conformation. Ristocetin also promotes interaction of VWF with GP Ib-IX-V; it thus provides a model for changes in VWF conformation and function that may occur in vivo. The fluid-phase conformation of VWF was evaluated from its susceptibility to proteolytic digestion. Ristocetin markedly altered the pattern of VWF digestion by trypsin, increasing the prevalence of two major proteolytic fragments (109 and 160 kDa), and decreasing that of four fragments (130, 145, 181 and 199 kDa). Vancomycin, a structurally related antibiotic, did not affect the digestion pattern. However, it partially reversed the ristocetin-induced change in digestion. Changes in prevalence of five of the tryptic fragments of VWF with ristocetin and vancomycin correlated closely with changes in VWF binding to GP Ib-IX-V. Heparin also partially inhibited the ristocetin-induced changes in tryptic digestion of VWF. These observations suggest that ristocetin may modulate VWF conformation in such a way as to expose its GP Ib-binding domain and enable it to interact with the platelet. Such modulation also exposes a cryptic site (or sites) for proteolytic cleavage by trypsin.

Naturally occurring tyrosinase inhibitors: mechanism and applications in skin health, cosmetics and agriculture industries.

Tyrosinase is a copper-containing enzyme, which is widely distributed in microorganisms, animals and plants and is a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. In addition, unfavorable enzymatic browning of plant-derived foods by tyrosinase causes a decrease in nutritional quality and economic loss of food products. The inadequacy of current conventional methods to prevent tyrosinase action encourages researchers to seek new potent tyrosinase inhibitors for food and cosmetics. This article presents a study on the importance of tyrosinase, biochemical characteristics, type of inhibitions, activators from various natural sources with its clinical and industrial importance in recent prospects is discussed in this paper.

Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages.

Moutan cortex (MC) is one of the most widely used Oriental herbal medicines for treating inflammatory diseases. In this study, the effect of MC on lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN-gamma)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined using mouse peritoneal macrophages. MC inhibited the LPS/rIFN-gamma-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha release. To clarify the mechanism involved, the effect of MC on the activation of nuclear factor (NF)-kappaB was examined. The LPS/rIFN-gamma-induced activation of NF-kappaB was almost completely blocked by MC at 0.5 mg/ml. These findings demonstrate that the inhibition of the LPS/rIFN-gamma-induced production of NO and TNF-alpha by MC is due to the inhibition of NF-kappaB activation.

Anti-ischemic effect of Aurantii Fructus on contractile dysfunction of ischemic and reperfused rat heart.

Aurantii Fructus (AF) is one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in Korea. The anti-ischemic effects of AF on ischemia-induced isolated rat heart were investigated through analyses of changes in perfusion pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group with AF treatment. There were no significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for 10 min to induce ischemia in isolated rat hearts, and AF was administered during ischemia induction. AF treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions (p < 0.01). These results suggest that AF has distinct anti-ischemic effects through recovery of contractile dysfunction in ischemic heart.

Effects of Nelumbinis Semen on contractile dysfunction in ischemic and reperfused rat heart.

Nelumbinis Semen (NS), or lotus seed, is one of the most well-known traditional herbal medicines and is frequently used to treat cardiovascular symptoms in Korea. The anti-ischemic effects of NS on ischemia-induced isolated rat heart were investigated through analyses of changes in blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: a control, untreated ischemia-induced group, and an ischemia-induced group treated with NS. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between the groups before ischemia was induced. The supply of oxygen and buffer was stopped for ten minutes to induce ischemia in isolated rat hearts, and NS was administered during ischemia induction. NS treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow and cardiac output under ischemic conditions (p < 0.01). In addition, the mechanism of the anti-ischemic effects of NS was also examined through quantitation of intracellular calcium content in rat neonatal cardiomyocytes. NS significantly prevented intracellular calcium increases induced by isoproterenol (p < 0.01). These results suggest that NS has distinct anti-ischemic effects through calcium antagonism.

Effects of Yukmijihwang-tang derivatives (YMJd) on ibotenic acid-induced amnesia in the rat.

The present study investigates the effects of Yukmijihwang-tang Derivatives (YMJd) on learning and memory through the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position for 6 d and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed the impaired performance in the Morris water maze test and severe cell losses in the MS, as indicated by decreased choline acetyltransferase-immunoreactivity in the medial septum. Daily administrations of YMJd (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of choline acetyltransferase (ChAT) immunoreactivity in the MS induced by ibotenic acid. These results suggest that impairments of spatial learning and memory might be attributable to the degeneration of septohippocampal cholinergic (SHC) neurons and that YMJd treatment ameliorated learning and memory deficits partly due through neuroprotective effects on the central acetylcholine system. Our studies suggest that YMJd might be useful in the treatment of Alzheimer's disease.

Survey and mechanism of skin depigmenting and lightening agents.

The type and amount of melanin synthesized by the melanocyte, and its distribution pattern in the surrounding keratinocytes, determines the actual color of the skin. Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Tyrosinase catalyses three different reactions in the biosynthetic pathway of melanin in melanocytes: the hydroxylation of tyrosine to l-DOPA and the oxidation of l-DOPA to dopaquinone; furthermore, in humans, dopaquinone is converted by a series of complex reactions to melanin. Among the skin-lightening and depigmenting agents, magnesium-l-ascorbyl-2-phosphate (MAP), hydroxyanisole, N-acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-beta-d-glucopyranoside) and hydroquinone (HQ) are the most widely prescribed worldwide. However, with reports of potential mutagenicity and epidemics of ochronosis, there has been an increasing impetus to find alternative herbal and pharmaceutical depigmenting agents. A review of the literature reveals that numerous other depigmenting or skin-lightening agents are either in use or in investigational stages. Some of these, such as kojic, glycolic and azelaic acids, are well known to most dermatologists. Others have been discovered and reported in the literature more recently. Several depigmentation and lightening agents are discussed, including their historical background, biochemical characteristics, type of inhibition and activators from various sources. In addition, the clinical importance of mushroom tyrosinase as a recent prospect is discussed in this paper.

Effect of Acori graminei Rhizoma on contractile dysfunction of ischemic and reperfused rat heart.

Acori graminei Rhizoma is one of the best-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in Asian countries. The anti-ischemic effect of Acori graminei Rhizoma on ischemia-induced isolated rat heart was investigated through analysis of changes in perfusion pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups, an ischemia-induced group without any treatment (I), and an ischemia-induced group with Acori graminei Rhizoma treatment (I+AGR). There were no significant differences in perfusion pressure, aortic flow, coronary flow, or cardiac output between the two groups before ischemia was induced. The supply of oxygen and buffer was stopped for 10 min to induce ischemia in isolated rat hearts, and Acori graminei Rhizoma was administered while inducing ischemia. The data showed that Acori graminei Rhizoma treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under an ischemic condition. In addition, hemodynamics (except heart rate) of the AGR-treated group was significantly recovered 60 min after reperfusion compared to the control group, (systolic aortic pressure: 85.5% vs. 62.5%, aortic flow volume: 68.1% vs. 49.4%, coronary flow volume: 86.8% vs. 60.1%, and cardiac output: 73.1% vs. 54.1%, p<0.01). These results suggest that Acori graminei Rhizoma has distinct anti-ischemic effects.

Inhibition of lipopolysaccharide and interferon-gamma-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by Lithospermi radix in mouse peritoneal macrophages.

Lithospermi radix (LR, root of Lithospermum erythrorhizon Siebold. et Zuccarinii) has been used to treat various conditions, such as septic shock, eczema and burns. In this study, the effect of LR on lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN-gamma)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined using mouse peritoneal macrophages. At 0.01-1 mg/ml, LR inhibited the LPS/rIFN-gamma-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha release. To clarify the mechanism involved, the effect of LR on the activation of nuclear factor (NF)-kappaB was examined. The LPS/rIFN-gamma-induced activation of NF-kappaB was almost completely blocked by LR at 1mg/ml without cytotoxicity. These findings demonstrate that the inhibition of the LPS/rIFN-gamma-induced production of NO and TNF-alpha by LR involves the inhibition of NF-kappaB activation.

The anti-depressant effect of Nelumbinis semen on rats under chronic mild stress induced depression-like symptoms.

Nelumbinis Semen is a well-known traditional herbal medicine frequently used in treatment of depression in many Asian countries. In this study, its anti-depression effects in rats were investigated by comparing the test results of those treated with Nelumbinis Semen to those treated with other herbal anti-depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus, Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like symptoms, the animals were placed under chronic mild stress in the form of overnight illumination for 2 consecutive days. They were treated with the respective herbal extract and forced swimming tests were conducted afterwards. The anti-depression effects of each extract were then evaluated based on a measured index, which consisted of struggling time, first latency and first rest duration. These test results show that Nelumbinis Semen provides greater anti-depression effects than the other herbal extracts. Specifically, only the rats treated with Nelumbinis Semen showed significant increases in struggling time (43.9%, p < 0.005, p = 0.0037) and in first latency time (90.2%, p < 0.05, p = 0.0116). However, the first rest duration for Nelumbinis Semen treated rats was not significantly different from the other rats. It appears that Nelumbinis Semen provides even greater anti-depression effects than Hypericum Perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural antidepressant today). The anti-depression effects of Nelumbinis Semen might be due to the modulation of the amount of neurotransmitters involved in depression.

Nelumbinis Semen reverses a decrease in hippocampal 5-HT release induced by chronic mild stress in rats.

Depression is associated with a dysfunctional serotonin system. Recently, several lines of evidence have suggested that a very important evoking factor in depression may be a serotonin deficit in the hippocampus. This study assessed the antidepression effects of Nelumbinis Semen (NS) through increasing serotonin concentrations under normal conditions and reversing a decrease in serotonin concentrations in rat hippo-campus with depression-like symptoms induced by chronic mild stress (CMS). Using an in-vivo microdialysis technique, the serotonin-enhancing effect of NS on rat hippocampus was investigated and its effects compared with those of two well-known antidepressants, Hypericum perforatum (St John's wort) and fluoxetine (Prozac). Rats were divided into five groups: saline-treated normal, without CMS; saline-treated stress control; NS-, St John's wort- and fluoxetine-treated rats under CMS for 8 weeks or no stress treatment. NS and fluoxetine significantly increased serotonin in normal conditions and reversed a CMS-induced decrease in serotonin release in the hippocampus (P<0.05 compared with normal group or control group under CMS). These results suggest that NS increases the serotonin levels normally decreased in depression, resulting in an enhancement of central serotonergic transmission and possible therapeutic action in depression. It is suggested that NS may present an antidepressant effect through enhancement of serotonin.

Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of Moutan Cortex Radicis in oxidative stressed PC12 cells.

Moutan Cortex Radicis (MCR) is one of the most widely used Oriental medicines. In this study, we assessed the reducing effect of ethanol extract of MCR on hydrogen peroxide-induced reactive oxygen production, the main cause of cell damage or death in PC12 cells. The viability of cells treated with 1 mg/ml of MCR was significantly restored from that of oxidative-stressed PC12 cells. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H(2)DCFDA assay. MCR at 1-0.01 mg/ml concentration inhibited ROS production in oxidative-stressed cells. To identify candidate genes responsible for the anti-oxidative effects of MCR on PC12 cells, an oligonucleotide microarray analysis was performed. The result of gene expression profiles showed that 10 genes were up-regulated and 7 were down-regulated in MCR plus hydrogen peroxide treated cells compared with hydrogen peroxide treated cells. Among them, heme oxygenase (HO) and cathechol-O-methyltransferase (COMT) are related to regulation of ROS generation and the others are known to regulate cell survival and progression. Subsequently, we performed real-time RT-PCR to quantify the ROS related gene. MCR treatment increased the expression of HO by 370% and COMT by 280% at the concentration of 1 mg/ml. These findings suggest that MCR inhibits the production of ROS and cytotoxicity by oxidative-stressed PC12 cells through over-expression of HO and COMT.