Analgesic and Antiinflammatory Activities of the Aqueous Extract from Plectranthus amboinicus (Lour.) Spreng. Both In Vitro and In Vivo.

Plectranthus amboinicus (Lour.) Spreng. is a native Labiatae plant of Taiwan. The plants are commonly used in Chinese folk medicine for the treatment of cough, fever, sore throats, mumps, and mosquito bite. The aim of this study was to investigate the analgesic and antiinflammatory properties of the aqueous extract from Plectranthus amboinicus (PA) in vivo and in vitro. PA inhibited pain induced by acetic acid and formalin, and inflammation induced by carrageenan. The anti-inflammatory effect of PA was related to modulating antioxidant enzymes' activities in the liver and decreasing the Malondialdehyde (MDA) level and the production of tumor necrosis factor alpha (TNF-α), and cyclooxygenase2 (COX-2) in edema-paw tissue in mice. In vitro studies show that PA inhibited the proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). PA blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit. Finally, the amount of carvacrol in the aqueous extract of PA was 1.88 mg/g extract. Our findings suggest that PA has analgesic and anti-inflammatory activities. These effects were mediated by inhibiting the proinflammatory mediators through blocking NF-κB activation. Meanwhile, the effects observed in this study provide evidence for folkloric uses of Plectranthus amboinicus (Lour.) Spreng. in relieving pain and inflammation.

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin.

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine.

Analgesic effects and the mechanisms of anti-inflammation of hispolon in mice.

Hispolon, an active ingredient in the fungi Phellinus linteus was evaluated with analgesic and anti-inflammatory effects. Treatment of male ICR mice with hispolon (10 and 20 mg/kg) significantly inhibited the numbers of acetic acid-induced writhing response. Also, our result showed that hispolon (20 mg/kg) significantly inhibited the formalin-induced pain in the later phase (P<.01). In the anti-inflammatory test, hispolon (20 mg/kg) decreased the paw edema at the fourth and fifth hour after λ-carrageenin (Carr) administration, and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver tissue. We also demonstrated that hispolon significantly attenuated the malondialdehyde (MDA) level in the edema paw at the fifth hour after Carr injection. Hispolon (10 and 20 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at the fifth hour after Carr injection. Also, hispolon (10 and 20 mg/kg) diminished the serum TNF-α at the fifth hour after Carr injection. The anti-inflammatory mechanisms of hispolon might be related to the decrease in the level of MDA in the edema paw by increasing the activities of SOD, GPx and GRx in the liver. It probably exerts anti-inflammatory effects through the suppression of TNF-α and NO.

Analgesic and anti-inflammatory activities of aqueous extract from Glycine tomentella root in mice.

In the present study, we have investigated the analgesic effect of the aqueous extract of the root of Glycine tomentella (AGT) using models of acetic acid-induced writhing response and formalin test, the anti-inflammatory effect of AGT using model of lambda-carrageenan-induced paw edema. In order to investigate the anti-inflammatory mechanism of AGT, we have detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver and the levels of malondialdehyde (MDA) and NO in the edema paw. In the analgesic test, AGT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, AGT (0.5 and 1.0 g/kg) decreased the paw edema at the third, fourth, fifth and sixth hour after lambda-carrageenan administration, and increased the activities of SOD, GPx and GRx in the liver tissue and decreased the MDA level in the edema paw at the third hour after lambda-carrageenan injection. However, AGT could not affect the NO level which induced by lambda-carrageenan. These results suggested that AGT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of AGT might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, GPx and GRx in the liver.

Immunogenicity studies of bivalent inactivated virions of EV71/CVA16 formulated with submicron emulsion systems.

We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 µg) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.

Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV.

Combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. Here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (H5N1/H1N1), enterovirus 71 (EV71), and/or Japanese encephalitis virus (JEV) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. We demonstrated that the antigenic competition happens between H5N1/H1N1 or H5N1/EV71 inactivated virions when the vaccine combinations either formulated with Alum suspensions or without adjuvant. In the presence of PELC emulsified particles, EV71-specific immune responses before and after incorporating H5N1 virus into EV71 vaccine were detected of no significant difference; in addition, H5N1- and EV71-specific immune responses were found at the same level when H5N1/EV71/JEV consolidating into combination vaccine. Emulsified vaccine formulation was represented as a potential tool that is found to reduce the number of injections required to prevent multiple infectious strains causing the same disease (H5N1/H1N1) and/or that protect against different diseases (H5N1/EV71). Combination vaccines can also include a third component to protect against H5N1/EV71/JEV at the same time.

Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

Analgesic and anti-inflammatory activities of the aqueous extracts from three Flemingia species.

I-Tiao-Gung has long been used in the Kinmen area of Taiwan as an anti-inflammatory agent for the treatment of rheumatic illness. The roots of Flemingia lineata (FL), Flemingia macrophylla (FM) and Flemingia prostrata (FP) are also used as I-Tiao-Gung in the Taiwan markets. In the present study, we investigated the analgesic effect of aqueous extracts of Flemingia lineata (FL), Flemingia macrophylla (FM), and Flemingia prostrata (FP) by acetic acid-induced writhing response, formalin test, and the anti-inflammatory effect of FM, FL and FP by lambda-carrageenan-induced paw edema in mice. We also detected the changes in the activities of superoxide dismutase (SOD), glutathione reductase (GRx) and glutathione peroxidase (GPx) of liver in the lambda-carrageenan-induced paw edema in mice to investigate the anti-inflammatory mechanism of FL and FM. The results showed that FL and FM significantly inhibited the acetic acid-induced writhing response and formalin-induced licking time during the late phase (p < 0.001). FL and FM also significantly decreased the lambda-carrageenan-induced paw edema (p < 0.001). FL and FM significantly increased the GRx and GPx activities in the liver and decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) in the edema paw (p < 0.001). These results indicated that FL and FM possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of FL and FM might be related to the decrease in the level of MDA in the edema paw via increasing the activities of GPx and GRx in the liver and decreasing the NO level in the edema paw.

Analgesic and anti-inflammatory activities of ethanol root extract of Mahonia oiwakensis in mice.

AIMS OF THE STUDY: This study investigated the anti-inflammatory and analgesic activities, and protoberberine alkaloid contents of ethanol extract of MO roots (MOR(EtOH)). MATERIALS AND METHODS: The analgesic activity of MOR(EtOH) was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity of MOR(EtOH) was determined using the lambda-carrageenan-induced paw oedema model. The protoberberine alkaloid contents of MOR(EtOH) were identified by high-performance liquid chromatography (HPLC). RESULTS: MOR(EtOH) (100 and 500 mg/kg) decreased the acetic acid-induced writhing responses and licking times of the second phase in the formalin test. Moreover, carrageenan-induced paw oedema was significantly reduced in a dose-dependent manner by administering MOR(EtOH) (100 and 500 mg/kg) at 3, 4, and 5h after the carrageenan injection. The serum levels of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) of MOR(EtOH)-treated mice were significantly reduced compared with those in the serum of animals administered carrageenan. Notably, MOR(EtOH) attenuated the expression of cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) and neutrophil infiltration in paw tissues injected with carrageenan. The anti-inflammatory mechanisms of MOR(EtOH) appear to be related to the inhibition of neutrophil infiltration, iNOS and COX-2 protein expression, NO release, and the decreasing TNF-alpha level in serum. The analytical results showed that the contents of berberine, palmatine and jatrorrhizine were 191.45 mg/g extract, 100.15 mg/g extract and 66.45 mg/g extract, respectively. CONCLUSION: These experimental results suggest that MOR(EtOH) produced both analgesic and anti-inflammatory effects in mice and may be a candidate for the development of pharmacological agents used in the treatment of inflammatory disorders.

Schizandrin protects primary cultures of rat cortical cells from glutamate-induced excitotoxicity.

The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 microM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 microM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 microM. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.