Magnolia kobus Extract Inhibits Periodontitis-Inducing Mediators in Porphyromonas gingivalis Lipopolysaccharide-Activated RAW 264.7 Cells.

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis, a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression (n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1ß, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE.

Magnolia kobus Extract Suppresses Porphyromonas gingivalis LPS-Induced Proinflammatory Cytokine and MMP Expression in HGF-1 Cells and Regulates Osteoclastogenesis in RANKL-Stimulated RAW264.7 Cells.

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.

Cyclin D1 promotes radioresistance through regulation of RAD51 in melanoma.

Melanoma is a notoriously radioresistant type of skin cancer. Elucidation of the specific mechanisms underlying radioresistance is necessary to improve the clinical efficacy of radiation therapy. To identify the key factors contributing to radioresistance, five melanoma cell lines were selected for study and genes that were upregulated in relatively radioresistant melanomas compared with radiosensitive melanoma cells determined via RNA sequencing technology. In particular, we focused on cyclin D1 (CCND1), a well known cell cycle regulatory molecule. In radiosensitive melanoma, overexpression of cyclin D1 reduced apoptosis. In radioresistant melanoma cell lines, suppression of cyclin D1 with a specific inhibitor or siRNA increased apoptosis and decreased cell proliferation in 2D and 3D spheroid cultures. In addition, we observed increased expression of γ-H2AX, a molecular marker of DNA damage, even at a later time after γ-irradiation, under conditions of inhibition of cyclin D1, with a response pattern similar to that of radiosensitive SK-Mel5. In the same context, expression and nuclear foci formation of RAD51, a key enzyme for homologous recombination (HR), were reduced upon inhibition of cyclin D1. Downregulation of RAD51 also reduced cell survival to irradiation. Overall, suppression of cyclin D1 expression or function led to reduced radiation-induced DNA damage response (DDR) and triggered cell death. Our collective findings indicate that the presence of increased cyclin D1 potentially contributes to the development of radioresistance through effects on RAD51 in melanoma and could therefore serve as a therapeutic target for improving the efficacy of radiation therapy.

Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications.

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Impact of intraoperative zero-balance fluid therapy on the occurrence of acute kidney injury in patients who had undergone colorectal cancer resection within an enhanced recovery after surgery protocol: a propensity score matching analysis.

PURPOSE: An enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection encourages perioperative euvolemic status, and zero-balance fluid therapy is recommended for low-risk patients. Recently, several studies have reported concerns of increased acute kidney injury (AKI) in patients within an ERAS protocol. In the present study, we investigated the impact of intraoperative zero-balance fluid therapy within an ERAS protocol on postoperative AKI. METHODS: Patients who underwent elective surgery for primary colorectal cancer were divided into zero-balance and non-zero-balance fluid therapy groups according to intraoperative fluid amount and balance. After propensity score (PS) matching, 210 patients from each group were selected. Incidences of AKI were compared between the two groups according to the Kidney Disease Improving Global Outcomes criteria. Postoperative kidney functions and surgical outcomes were also compared. RESULTS: AKI was significantly higher in the zero-balance fluid therapy group compared to the non-zero-balance fluid therapy group (21.4% vs. 13.8%, p = 0.040) in PS-matched patients. The decrease in the estimated glomerular filtration rate on the day of surgery was significantly higher in the zero-balance fluid therapy group (- 5.9 mL/min/1.73 m2 vs. - 1.4 mL/min/1.73 m2, p = 0.005). There were no differences in general morbidity or mortality rate, although surgery-related complications were more common in the zero-balance group. CONCLUSIONS: Despite the proven benefits of zero-balance fluid therapy in colorectal ERAS protocols, care should be taken to monitor for postoperative AKI. Further studies regarding the clinical significance of postoperative AKI occurrence and optimised intraoperative fluid therapy are needed in a colorectal ERAS setting.

Anti-Allodynic Effects of Polydeoxyribonucleotide in an Animal Model of Neuropathic Pain and Complex Regional Pain Syndrome.

BACKGROUND: Spinal nerve ligation (SNL) model is one of the representative models of the neuropathic pain model. Neuropathic pain in a chronic post-ischemic pain (CPIP) mimics the symptoms of complex regional pain syndrome (CRPS). The administration of polydeoxyribonucleotide (PDRN), which has regenerative and anti-inflammatory effects, has been studied and is used in clinical practice treating various diseases. However, the analgesic effect of PDRN in a neuropathic pain or CRPS model remains unknown. METHODS: PDRN (3.3, 10, and 20 mg/kg) was administered into the subcutaneous (SC) layer of the hind paws of SNL and CPIP models. Mechanical anti-allodynic effects were then investigated using the von Frey test. In the immunohistochemical examination, dorsal root ganglia (DRG) and the spinal cord were harvested and examined for the expression of glial fibrillary acidic protein (GFAP) after the 20 mg PDRN injection. RESULTS: Mechanical allodynia was significantly alleviated by administration of PDRN in SNL and CPIP mice at all of the time point. As the dose of PDRN increased, the effect was greater. The 20 mg PDRN injection was found to have the most effective anti-allodynic effect. The increased expression of GFAP in DRG and the spinal cord of SNL and CPIP model decreased following the administration of PDRN than vehicle. CONCLUSION: SC administration of PDRN results in the attenuation of allodynia and activation of astrocytes in neuropathic pain or CRPS models. We propose that PDRN can have significant potential advantages in neuropathic pain treatment.

Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1ß level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats.

Anti-osteoarthritic Effects of an Herbal Composition LI73014F2 on Interleukin-1ß-induced Primary Human Articular Chondrocytes.

Osteoarthritis (OA) is one of the most well-characterized joint diseases and is associated with chondrocyte inflammation, metalloproteinase upregulation and apoptosis. LI73014F2 is a novel composition prepared from aqueous extract of Terminalia chebula fruit, alcohol extract of Curcuma longa rhizome, and Boswellia serrata extract at 2:1:2 ratio. Earlier studies have shown that LI73014F2 inhibits cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) activities, and attenuates clinical symptoms in OA subjects. In the present study, we evaluated the protective anti-inflammatory and anti-apoptotic effects, as well as the underlying mechanisms, of LI73014F2 in interleukin (IL)-1ß-induced inflammation in human primary chondrocytes. Human chondrocytes were treated with LI73014F2 (0, 12.5, 25 and 50 µg/mL) in IL-1ß (10 ng/mL)-containing chondrocyte growth medium for 24 h. Cell viability was assessed using an MTT assay. The pro-inflammatory mediator, inflammatory cytokines, MMPs, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways protein expression levels were detected by western blot analysis. The results demonstrated that LI73014F2 normalized the expressions of COX-2, mPGES-1, PGE2, 5-LOX, LTB4, IL-1ß, TNFα, IL-6, MMP-2, MMP-3, MMP-9, MMP-13, Bax/Bcl-2, cleaved caspase-9 and -3, cleaved PARP, phospho-NF-κB p65 and phospho-p38 MAPK proteins in IL-1ß-induced primary human chondrocytes. Moreover, the data suggested that LI73014F2 reduced IL-1ß-induced inflammation and apoptosis, at least partially via the inhibition of the NF-κB/MAPK signaling pathway. In conclusion, the present findings provide the molecular basis of the anti-OA efficacy of LI73014F2.

Preventive Effect of Citrus aurantium Peel Extract on High-Fat Diet-Induced Non-alcoholic Fatty Liver in Mice.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation, which is the most common form of chronic liver disease. Multiple clinical studies using natural compounds such as flavonoids have been conducted to treat NAFLD. In the present study, the pharmacological effect of Citrus aurantium L. (Rutaceae) peel extract (CAE), which contains over 27% of polymethoxyflavone nobiletin, on NAFLD was evaluated using a high-fat diet (HFD) animal model susceptible to developing NAFLD. C57BL/6 mice were fed an HFD (60% kcal of energy derived from fat) for 8 weeks to induce obesity. Obese mice were randomly allocated to four groups of eight mice each (HFD alone, HFD with silymarin, HFD with 50 mg/kg CAE, and HFD with 100 mg/kg CAE). After 8 weeks of treatment, all mice were euthanized, and plasma and liver tissues were analyzed biochemically and histopathologically. The results indicate that CAE treatment significantly reduced HFD-induced NAFLD, as shown by decreased serum lipid index and prevented liver histopathology. The expression of genes involved in lipid synthesis including free fatty acid (FFA), peroxisome-proliferator-activated receptor γ (PPAR-γ), sterol receptor element binding protein 1c (SREBP-1c), and fatty acid synthesis enzyme was suppressed by CAE treatment. Moreover, compared to untreated mice, CAE-treated HFD mice showed decreased pro-inflammatory cytokine expression. These results demonstrated that CAE prevented HFD-induced NAFLD by reducing plasma levels of triglyceride and cholesterol and de novo lipid synthesis.

Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy.

The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel "atopic march animal model"), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy.

Topical acidic cream prevents the development of atopic dermatitis- and asthma-like lesions in murine model.

Long-standing or repeated skin barrier damage followed by atopic dermatitis (AD) is the initial step of the atopic march that eventually progresses to respiratory allergies. Maintenance of an acidic pH in the stratum corneum (SC) is an important factor for normal skin barrier function. We performed this study to determine whether an oxazolone (Ox)-induced AD murine model can develop airway inflammation by topical application and nasal inhalation of a house dust mite, Dermatofagoides pteronyssinus (Dp), which is a novel 'atopic march animal model', and whether an acidic SC environment, made by repeated application of acidic cream, can interrupt this atopic march. During repeated treatment with Ox and Dp to make an atopic march murine model, acidic cream (pH 2.8) and neutral cream (pH 7.4) adjusted by citric acid and sodium hydroxide mixed with vehicle were applied twice daily. Repeated treatment with Ox and Dp to hairless mice induced AD-like skin lesions followed by respiratory allergy, defining it as an atopic march model. Acidic cream inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. These results indicate that a novel atopic march animal model can be developed by repeated topical and nasal treatments with house dust mite on Ox-induced AD mice and that the acidification of SC could be a novel intervention method to block the atopic march.

Comparison of cellular responses to ionizing radiation in keratinocytes isolated from healthy donors and type II diabetes patients.

PURPOSE: Due to the expanding repertoire of treatment devices that use radiation, the possibility of exposure to both low-dose and high-dose radiation continues to increase. Skin is the outermost part of the body and thus directly exposed to radiation-induced damage. In particular, the skin of diabetes patients is fragile and easily damaged by external stimuli, such as radiation. However, damage and cellular responses induced by ionizing irradiation in diabetic skin have not been explored in detail. In this study, we investigated the effects of several irradiation dose on normal keratinocytes and those from type II diabetes patients, with particular focus on DNA damage. MATERIALS AND METHODS: Cellular responses to low-dose radiation (0.1 Gy) and high-dose radiation (0.5 and 2 Gy) were evaluated. Cell cycle analysis was conducted via flow cytometry and cell viability analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Proteins related to the DNA damage response (DDR) and repair signaling pathways and apoptosis were detected via immunoblot analysis. Apoptosis and cell differentiation were additionally examined in 3D skin organoids using immunohistochemistry. RESULTS: Compared to respective control groups, no significant changes were observed in cell cycle, DDR and repair mechanisms, cell survival, and differentiation in response to 0.1 Gy irradiation in both normal and diabetes type II keratinocytes. On the other hand, the cell cycle showed an increase in the G2/M phase in both cell types following exposure to 2 Gy irradiation. At radiation doses 2 Gy, activation of the DDR and repair signaling pathways, apoptosis, and cell differentiation were increased and viability was decreased in both cell types. Notably, these differences were more pronounced in normal than diabetes type II keratinocytes. CONCLUSIONS: Normal keratinocytes respond more strongly to radiation-induced damage and recovery than diabetes type II keratinocytes.

Association of NAFLD with FGF21 Polygenic Hazard Score, and Its Interaction with Protein Intake Level in Korean Adults.

Fibroblast growth factor 21 (FGF21) is a hormone that participates in the regulation of energy homeostasis and is induced by dietary protein restriction. Preclinical studies have suggested that FGF21 induction exerts a protective effect against non-alcoholic fatty liver disease (NAFLD), while human studies have revealed elevated levels of and potential resistance to FGF21 in patients with NAFLD. However, whether the FGF21 pathway also contributes to NAFLD risk at the genetic level remains uncertain. A few attempts to investigate the impact of individual genetic variants at the loci encoding FGF21 and its receptors on NAFLD risk have failed to establish a clear association due to a limited effect size. Therefore, this study aimed to (1) develop a polygenic hazard score (PHS) for FGF21-related loci that are associated with NAFLD risk and (2) investigate the effect of its interaction with protein intake level on NAFLD risk. Data on 3501 participants of the Korean Genome Epidemiology Study (Ansan-Ansung) were analyzed. Eight single-nucleotide polymorphisms of fibroblast growth factor receptors and beta-klotho were selected for PHS determination using forward stepwise analysis. The association between the PHS and NAFLD was validated (p-trend: 0.0171 for men and <0.0001 for women). Moreover, the association was significantly modulated by the protein intake level in all participants as well as women (p-interaction = 0.0189 and 0.0131, respectively) but not in men. In particular, the women with the lowest PHS values and a protein intake lower than the recommended nutrient intake (RNI) exhibited a greater NAFLD risk (HR = 2.021, p-trend = 0.0016) than those with an intake equal to or greater than the RNI; however, those with higher PHS values had a high risk, regardless of protein intake level. These findings demonstrate the contribution of FGF21-related genetic variants and restricted protein intake to NAFLD incidence.

Microbiological survey of Korean mouse facilities from 2014 to 2019.

We surveyed mouse microbiological contamination rates by testing rates for common contaminants using serological, culture, and parasitological methods. A total of 21,292 experimentally housed mice from 206 animal facilities, including hospitals, universities, companies, and research institutes, were tested over a 6-year period from 2014 to 2019. The most commonly found contaminants were various species of nonpathogenic protozoa (47.2%). The most common pathogenic bacteria were Staphylococcus aureus (21.2%), Pasteurella pneumotropica (12.5%), and Pseudomonas aeruginosa (5.8%). Mouse hepatitis virus (6.1%) was detected, but no other viral or bacterial pathogens were found. These results establish that the main pathogens that currently contaminate mouse facilities in Korea are opportunistic pathogens and that contamination with important pathogens, such as those in Categories B or C, has decreased.

Deciphering the key factors determining spatio-temporal heterogeneity of cyanobacterial bloom dynamics in the Nakdong River with consecutive large weirs.

Following the construction of eight large weirs in a 200-km section of the Nakdong River, which is a major water source for the region, harmful cyanobacterial blooms have been occurring annually, causing severe problems with water quality. The present study investigated the community structure of harmful cyanobacteria and identified temporal and spatial patterns in harmful cyanobacterial blooms and their dynamic relationships with physicochemical, hydrological, and meteorological variables in the eight weir sections for 6 years from 2013 to 2018. The dominant harmful cyanobacteria in the eight weir sections were Aphanizomenon and Microcystis spp. There was a successional phenomenon wherein Aphanizomenon spp. first bloomed in spring, and then Microcystis spp. bloomed as water temperatures increased. Additionally, the initiation and duration of the blooms of both genera were affected by the timing and volume of heavy rainfall that caused flushing of cyanobacterial biomass, resulting in direct reduction of cyanobacterial growth in all sections. The harmful cyanobacteria of upstream weirs did not affect the biomass of downstream weirs in terms of either growth initiation or time taken to reach peak biomass, despite being physically connected. Owing to the long retention time during the dry season, similar to what occurs in separate reservoirs, the water quality of each weir section, particularly regarding nutrient characteristics and retention time, were the major factors determining the harmful cyanobacterial abundance, resulting in heterogeneous spatial distribution of harmful cyanobacterial blooms in the Nakdong River.

A built-up-type deformable phantom for target motion control to mimic human lung respiration.

Existing human lung-mimicking requirements in various radiology application fields have led to the development of many different phantoms. However, most are static apparatus designed for equipment calibration. Although there are a few dynamic phantoms that generate predefined motions, they have complicated mechanisms that hamper even simple modifications for various lung illness simulations. As a result, existing dynamic phantoms in which a target can be embedded normally generate rectilinear target motions with limited displacement. Nevertheless, volume changes in the human lungs during normal respiration are significant, and targets inside the lungs move along various random paths depending on their location, stiffness, and the properties of the surrounding tissues. In the present work, a novel phantom design is introduced and tested. The phantom mimics the human lung motion and its deformation is initiated by a diaphragm movement. The phantom provides a fairly large deformation and the capability to adjust target motion paths. The presented device has a simple mechanism that can be easily modified to generate various pulmonary diseases. To produce a large deformation by diaphragm compressive motion, polyurethane cubic blocks constitute the deformable part of the lung phantom and a tumor made with silicone is inserted in the structure. The assembled lung part is housed within an acrylic case that is filled with water. The phantom system consists of acrylic, plastic, and low-density polyurethane to minimize artifacts when it undergoes computed tomography (CT) scans. The lung part is organized with various density polyurethane blocks, making it possible to produce nonlinear motion paths of the tumor. The lung part is deformed by a silicon film that is driven by external hydraulic pressure. A finite element method simulation and two-dimensional target motion tests were performed to verify phantom performance. The functionality of the proposed phantom system was confirmed in a series of CT images.

The effects of Ginkgo biloba extract EGb 761 on mechanical and cold allodynia in a rat model of neuropathic pain.

BACKGROUND: Neuropathic pain is chronic pain that is caused by an injury to the peripheral or central nervous system. The symptoms of neuropathic pain are continuing pain, hyperalgesia, and allodynia. Ginkgo biloba extract is an oriental herbal medicine that has various pharmacological actions. We examined the effect of Ginkgo biloba extract, EGb 761, on the mechanical and cold allodynia in a rat model of neuropathic pain. METHODS: Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves. All the rats developed mechanical and cold allodynia 7 days after surgery. Fifty neuropathic rats were assigned into five groups for the intraperitoneal administration of drugs. The study was double-blind and the order of the treatments was randomized. Normal saline and EGb 761 (50, 100, 150, and 200 mg/kg) were administered, respectively, to the individual groups. We examined mechanical and cold allodynia at preadministration and at 15, 30, 60, 90, 120, 150, and 180 min after intraperitoneal drug administration. Mechanical allodynia was quantified by measuring the paw withdrawal threshold to stimuli with von Frey filaments of 1.0, 1.4, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 15.0, and 26.0 g. Cold allodynia was quantified by measuring the frequency of foot lift with applying 100% acetone. We measured the locomotor function of the neuropathic rats by using the rotarod test to reveal if EGb 761 has side effects, such as sedation or reduced motor coordination. RESULTS: The control group showed no differences for mechanical and cold allodynia. For the EGb 761 groups, the paw withdrawal thresholds to mechanical stimuli and withdrawal frequencies to cold stimuli were significantly reduced versus the preadministration values and versus the control group. The duration of antiallodynic effects increased in a dose-dependent fashion, and these were maintained for 120 min at the highest dose (P < 0.05). Only at the highest dose (200 mg/kg) did EGb 761 reduce the rotarod performance time. CONCLUSION: We conclude that Ginkgo biloba extract, EGb 761, attenuates mechanical and cold allodynia in a rat model of neuropathic pain, and it may be useful for the management of neuropathic pain.

Antiperiodontitis Effects of Magnolia biondii Extract on Ligature-Induced Periodontitis in Rats.

Over the past decades, periodontitis has become a rising health problem and caused various diseases. In the many studies shows that some extracts and compound to the prevention and treatment of periodontitis. This study focuses on the effects of inhibition of gingival damage and alveolar bone loss. The aim of this study was to evaluate the protective effects of Magnolia biondii extract (MBE) against ligature-induced periodontitis in rats. A ligature was placed around the molar teeth for 8 weeks, and MBE was administered for 8 weeks. Gingival tissue damage and alveolar bone loss were measured by microcomputed tomography (CT) analysis and histopathological examination. Serum Interluekin-1 ß (IL-1ß), tumor necrosis factor-α (TNF-α), cyclooxygenases-2 (COX-2), and receptor activator of nuclear factor-κB ligand (RANKL) levels were investigated using commercial kits to confirm the antiperiodontitis effects of MBE. We confirmed that ligature-induced periodontitis resulted in gingival tissue damage and alveolar bone loss. However, treatment for 8 weeks with MBE protected from periodontal tissue damage and downregulated serum inflammatory cytokine factors and RANKL levels. These results suggest that MBE exerts antiperiodontitis effects by inhibiting gingival tissue destruction and alveolar bone loss through regulation of anti-inflammatory cytokines in periodontitis-induced rats.

Ameliorating effect of Citrus aurantium extracts and nobiletin on ß­amyloid (1­42)­induced memory impairment in mice.

The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid ß 1­42 (Aß 1­42)­induced spatial learning and memory impairment in mice. After injecting Aß 1­42 (5 µl/2.5 min, intracerebroventricular injection), amnesic mice were orally administered CAE and nobiletin for 28 days. Memory, spatial and cognitive ability were measured using passive avoidance and a Morris water maze task. Acetylcholinesterase (AchE) activity was investigated in the hippocampus and cortex using commercial kits and the analysis of Bax, Bcl­2, and cleaved caspase­3 protein expression by western blot assays was used to confirm the anti­apoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Aß­induced neurodegenerative mice with increased AchE activity in the brain. However, the daily administration of CAE and nobiletin reduced the spatial learning deficits and increased the AchE activity in the cortex and hippocampus. Furthermore, CAE and nobiletin significantly downregulated the Bax and cleaved caspase­3 protein expression and upregulated the Bcl­2 and Bcl­2/Bax expression in the cortex and hippocampus of Aß­treated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating anti­apoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.