Narrow Results

The present study was intended to examine the analgesic effect of the 70% methanol extract of Torenia concolor Lindley var. formosana Yamazaki (TC_MeOH) and betulin using models of acetic acid-induced writhing response and formalin test. In addition, we investigated the anti-inflammatory effect of TC_MeOH and betulin using model of λ-carrageenan-induced paw edema. We observed the activities of antioxidant enzymes (SOD, GPx and GR) in the liver and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the edema paw. The results showed that TC_MeOH (1.0 and 2.0 g/kg) and betulin (30 and 90 mg/kg), significantly inhibited the acetic acid-induced writhing response. TC_MeOH (2.0 g/kg) and betulin (30 and 90 mg/kg) significantly inhibited formalin-induced licking time during both the early and late phases. TC_MeOH (0.5, 1.0 and 2.0 g/kg) and betulin (30 and 90 mg/kg) also significantly decreased the paw edema at the 4th hour after λ-carrageenan injection. Furthermore, TC_MeOH and betulin treatment also significantly increased the activities of SOD, GR and GPx in the liver while decreasing the level of MDA in the edema paw. Finally, betulin (30 and 90 mg/kg) also caused considerable reduction of NO level in the edema paw. Taken together, the present results indicated that TC_MeOH and betulin possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of TC_MeOH and betulin may be related to decreasing the levels of MDA and NO in the edema paw by increasing the activities of antioxidant enzymes in the liver.

The brown seaweed Undaria pinnatifida (Harvey) Suringar is used in traditional medicine to treat fever, urination problems, lumps and swelling, and as a dietary supplement for post-childbirth women. We examined the anti-inflammatory activities of the seaweed. The methanol extract of the seaweed was active against mouse ear edema induced by phorbol myristate acetate (PMA), with an IC₅₀ of 10.3 mg/ml. The extract reduced the edema to a half-maximal level when applied at the concentration of 40 mg/ml within 3 hours before or 2 hours after application of PMA. Extract taken from the blade section of the seaweed demonstrated the highest activity. The Northern form of U. pinnatifida was more active than the Southern form. In the analgesic test, the methanol extract suppressed the acetic acid-induced writhing response, with an IC₅₀ of 0.48 g/kg body weight. The extract also demonstrated antipyretic activity in yeast-induced hyperthermic mice. Activity-related constituents were arachidonic, eicosapentaenoic, and stearidonic acids.

In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by λ-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (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, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after λ-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after λ-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1β, tumor necrosis factor-α, NO and MDA which were induced by λ-carrageenan. The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1β production and the level of TNF-α in the inflamed tissues.

Paeoniflorin, a component in Paeonia lactiflora Pall, inhibits nuclear factor-κB expression in chronic hypoperfusion rat and has anti-inflammatory properties. Therefore, the aim of the present study was to investigate the effect of paeoniflorin on cerebral infarct, and the involvement of anti-inflammation. We established an animal model of cerebral infarct by occluding both the common carotid arteries and the right middle cerebral artery for 90 min, followed by reperfusion of 24 hours. The ratios of cerebral infarction area to total brain area, and neuro-deficit score were used as an index to observe the effects of paeoniflorin on cerebral infarct. ED1 (mouse anti rat CD68), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), intercellular adhesion molecular-1 (ICAM-1), myeloperoxidase (MPO) immunostaining and apoptotic cells in the cerebral infarction region also were studied. The results indicated that both pre-treatment and post-treatment with paeoniflorin reduced the ratio of cerebral infarction area; pre-treatment with paeoniflorin also reduced the neurological deficit score. The counts of ED1, IL-1β, TNF-α, ICAM-1 of microvessels and MPO immunoreactive cells and apoptotic cells were increased in the cerebral infarction region; however, these increases were reduced by Paeoniflorin pre-treatment.

In conclusion, Paeoniflorin reduced cerebral infarct and neurological deficit in ischemia-reperfusion injured rats, suggesting that paeoniflorin may have a similar effect in humans and might be a suitable treatment for stroke. Paeoniflorin reduced cerebral infarct, at least in part, involves the anti-inflammatory properties.

In this study, we evaluated the analgesic effect of the methanol extract of Kalanchoe gracilis (MKGS) stem in animal models by inducing writhing response with acetic acid and conducting formalin test. The anti-inflammatory effect of MKGS was also estimated on mice with λ-carrageenan induced paw edema model. In order to investigate the anti-inflammatory mechanism of MKGS, we analyzed the activities of glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver, and the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic tests, MKGS (0.5 and 1.0 g/kg) decreased both the acetic acid-induced writhing response and the licking time in the late phase of the formalin test. In the anti-inflammatory test, MKGS (0.1, 0.5 and 1.0 g/kg) decreased paw edema at the third, fourth, fifth and sixth hours after λ-carrageenan had been administrated. Furthermore, MKGS increased the activities of SOD and GRx in liver tissues and decreased MDA level in the edema paws three hours after λ-carrageenan was injected. MKGS also affected the levels of IL-1β, TNF-α and NO induced by λ-carrageenan. All these results suggested that MKGS possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MKGS might be related to the lowering of MDA level in the edema paw via increasing the activities of superoxide dismutase (SOD) and GRx in the liver, as well as the decreases in the levels of TNF-α and NO, and the production of IL-1β in inflamed tissues.

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 λ-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 λ-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 λ-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.

Eriobotryae folium (EF), the dried leaves of Eriobotrya japonica (Thunb.) Lindl. has been traditionally used to treat various diseases such as chronic bronchitis, cough, inflammation, skin diseases, and diabetes. In this study, we examined the effects of Eriobotryae folium extract (EFE) on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E₂(PGE₂) in RAW264 murine macrophage cells. EFE suppressed LPS-induced NO and PGE₂ production in a dose-dependent manner. Consistent with these observations, EFE reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both protein and mRNA levels. Furthermore, EFE significantly inhibited LPS-induced NF-κB binding activity, which was associated with the inhibition of IκB-α degradation. EFE also attenuated LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). These results suggest that the anti-inflammatory properties of EF might result from inhibition of iNOS and COX-2 expression through the downregulation of NF-κB activation and MAPK phosphorylation in LPS-stimulated RAW264 cells.

Elephantopus scaber (ES, Teng-Khia-U) has been traditionally used for the treatment of nephritis, pain, and fever; however, the direct evidence is lacking. We investigated the effect of ES on lipopolysaccharide (LPS) induced inflammation of BV-2 microglial cells and acute liver injury in Sprague-Dawley (SD) rats. Our results showed that ES reduced LPS-induced nitric oxide (NO), interleukin (IL)-1, IL-6, reactive oxygen species (ROS), and prostaglandin (PGE₂) production in BV-2 cells. ES significantly decreased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in LPS-treated rats. Furthermore, the water extract, but not the ethanol extract, of ES dose-dependently inhibited LPS-induced JNK, p38 mitogen-activated protein kinases (MAPK), and slightly inhibited cyclooxygenase (COX-2) in BV-2 cells but decreased p38 MAPK and COX-2 expressions in the liver of LPS-treated rats. Taken together, these results indicate that the protective mechanism of ES involves an antioxidant effect and inhibition of p38 MAP kinase and COX-2 expressions in LPS-stressed acute hepatic injury in SD rats.

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

Eucommiae cortex (EC) is used in various traditional Korean medicines in the form of tonics, analgesics, and sedatives. However, the underlying mechanism of its anti-inflammatory effect remains unclear. This study attempts to determine the effects of EC on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of the study show that EC inhibits the LPS-induced production of tumor necrosis factor-alpha and interleukin-6. Exposure to EC also reduces an inflammation-induced increase in the levels of cyclooxigenase-2 and the production of prostaglandin E₂ and nitric oxide in mouse peritoneal macrophages. Furthermore, EC suppresses the activation of nuclear factor-kappa B and caspase-1. These results provide novel insights into the pharmacological action of EC and indicate that EC has a potential in the treatment of inflammatory diseases.

Antioxidant fractions from Ophioglossum thermale were extracted with five different polar solvents using a Soxhlet type extractor. The total phenolic content of the extracts was determined by the Folin-Ciocalteu method. The ethyl acetate fraction of O. thermale was found to contain maximum phenolics. The dried fractions were screened for their antioxidant activity potential using in vitro model systems such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitroblue tetrazolium (NBT) and lipid-peroxidation reduction at different concentrations. Results revealed that the EtOAc fraction exhibited the best performance in the DPPH assay, NBT assay and lipid peroxidation. All fractions showed more potent antioxidant capacity than green tea extract, a well-known antioxidant. Furthermore, the EtOAc fraction has the highest total phenolic content (475.65 mg of EGCG/g). In addition, the EtOAc fraction at 0.005% and 0.01% (g/100 ml) also significantly inhibited UVB irradiation-induced ROS generation in human dermal fibroblasts (HDFs). In a carrageenan-induced edema model, the EtOAc fraction showed an inhibitory effect (21.5%, p < 0.05) at 200 mg/kg (p.o.) after 300 min administration. Consequently, 3-O-methylquercetin (3MQ) was also isolated from the antioxidative EtOAc fraction. The data obtained using the above in vitro and in vivo tests suggest that the antioxidant activity of O. thermale and its anti-inflammatory effect on carrageenan-induced acute inflammation can be attributed to its ameliorating effect on oxidative damage, and thus it has great potential as a source for natural health products. To the best of our knowledge, this is the first report on the antioxidant activity of different polar extracts from O. thermale.

We investigated possible mechanisms of analgesic and anti-inflammatory activities of the methanol extract from the leaf of Elaeagnus oldhamii Maxim. (EO_MeOH). EO_MeOH was evaluated for its analgesic activity in acetic acid-induced writhing response and formalin test, and anti-inflammatory effect was examined by λ-carrageenan-induced paw edema assay. We detected the activities of GPx, GRd and SOD in the liver, and the levels of inflammatory mediators including IL-1β, IL-6, TNF-α, COX-2, MDA and NO in the edema paw to investigate the mechanism of action against inflammation. Total polyphenol, flavonoid and flavanol contents of EO_MeOH were detected to explore its antioxidant activities. Results showed that, in the analgesic test, EO_MeOH decreased acetic acid-induced writhing response and the licking time in the late phase of formalin test. In the anti-inflammatory test, EO_MeOH decreased paw edema at the 2nd, 3rd, 4th and 5th h after λ-carrageenan had been injected. EO_MeOH increased the activities of SOD and GPx in liver tissue and decreased MDA, NO, IL-1β, IL-6, TNF-α and COX-2 levels in paw edema tissue at the 3rd h after λ-carrageenan-induced inflammatory reaction. EO_MeOH exhibited abundant polyphenol, flavonoid and flavanol contents. In HPLC fingerprint test of EO_MeOH, two index ingredients, ursolic acid and pomolic acid, were isolated from EO_MeOH and were exhibited in HPLC chromatographic analysis. The results demonstrated analgesic and anti-inflammatory effects of EO_MeOH. It was indicated that the anti-inflammatory mechanism of EO_MeOH may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx and GRd in the liver. Additionally, EO_MeOH decreased IL-1β, IL-6, TNF-α and COX-2 levels in the edema paw. The results suggested its value in future development of herbal medicine for the treatment of inflammatory diseases.

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti-pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan. This study aims to determine the mechanism of anti-inflammatory activities of ethyl acetate fraction of ACE (EA-ACE) using a model of λ-carrageenan (Carr)-induced paw edema in mouse model. In HPLC analysis, chemical characterization of EA-ACE was established. In order to investigate the anti-inflammatory mechanism of EA-ACE, we have detected the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were evaluated. Chemical characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw edema after Carr administration, increased the activities of CAT, SOD, and GPx and decreased the MDA level in the edema paw at the 5th hr after Carr injection. EA-ACE affects the serum NO, TNF-α, and IL-1β levels at the 5th hr after Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia callosa var. ephippioides have the potential to provide a therapeutic approach to inflammation-associated disorders.

Sargassum fulvellum (Turner) C. Agardh has been used to treat various inflammatory diseases, including lump, dropsy, swollen and painful scrotum, and urination problems for several centuries with no side effects. This study aims to investigate the anti-inflammatory effect of the hexane fraction of S. fulvellum (HFS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and phorbol 12-myristate 13-acetate (PMA)-induced mouse-ear edema. The anti-inflammatory activity of HFS in LPS-stimulated RAW 264.7 cells was investigated by assessing the inhibition of nitric oxide (NO) and pro-inflammatory cytokine production during Griess reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The molecular mechanisms that underlie the anti-inflammatory action of HFS were investigated by analyzing the activation of transcription factor and its upstream signaling proteins. Additionally, an in vivo study of the anti-inflammatory effect of HFS was carried out using PMA-induced mouse-ear edema. HFS inhibited LPS-induced NO production in a dose-dependent manner and suppressed the expression of inducible NO synthase (iNOS) in the RAW 264.7 cells. Further, HFS reduced the production of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. HFS significantly inhibited LPS-induced nuclear factor kappa B (NF-κB) transcriptional activity and NF-κB translocation into the nucleus by preventing degradation of inhibitor κB-α. Moreover, HFS inhibited the activation of Akt and mitogen-activated protein kinases (MAPKs) in the LPS-stimulated RAW 264.7 cells. Furthermore, HFS suppressed PMA-induced mouse-ear edema. The above data indicate that the anti-inflammatory effects of HFS on LPS-stimulated cells are associated with the suppression of NF-κB through the inhibition of MAPKs and Akt phosphorylation.

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis(CC_MeOH) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20–500 mg/kg of CC_MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC_MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC_MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC_MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC_MeOHin vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

Inflammation is a serious health issue worldwide that induces many diseases, such as inflammatory bowel disease (IBD), sepsis, acute pancreatitis and lung injury. Thus, there is a great deal of interest in new methods of limiting inflammation. In this study, we investigated the leaves of Nelumbo nucifera Gaertn, an aquatic perennial plant cultivated in eastern Asia and India, in anti-inflammatory pharmacological effects in the murine macrophage cell line RAW264.7. Results showed that lipopolysaccharide (LPS) increased the protein expression of inducible nitric oxide synthase (iNOS) and COX-2, as well as the mRNA expression and level of IL-6 and TNF-α, while NNE significantly reduced these effects of LPS. LPS also induced phospho-JNK protein expression. The JNK-specific inhibitor SP600125 decreased the proteins expression of phospho-JNK, iNOS, COX-2, and the mRNAs expression and levels of IL-6 and TNF-α. Further, NNE reduced the protein expression of phospho-JNK. LPS was also found to promote the translocation of NF-κB from the cytosol to the nucleus and to decrease the expression of cytosolic IκB. NNE and SP600125 treatment recovered the LPS-induced expression of NF-κB and IκB. While phospho-ERK and phospho-p38 induced by LPS, could not be reversed by NNE. To further investigate the major components of NNE in anti-inflammatory effects, we determined the quercetin and catechin in inflammatory signals. Results showed that quercetin and catechin significantly decreased the proteins expression of iNOS, COX-2 and phospho-JNK. Besides, the mRNAs and levels of IL-6 and TNF-α also decreased by quercetin and catechin treatment in LPS-induced RAW264.7 cells. These results showed that NNE and its major components quercetin and catechin exhibit anti-inflammatory activities by inhibiting the JNK- and NF-κB-regulated pathways and could therefore be an useful anti-inflammatory agent.

The present study was designed to investigate the in vitro and in vivo anti-inflammatory activity of flavonoids isolated from Millettia pachycarpa Benth. The seeds of M. pachycarpa Benth were extracted with ethanol and subjected to chromatographic separation for the isolation of bioactive compounds. Their structures were elucidated by spectroscopic methods. The anti-inflammatory activity of the compounds was investigated by evaluating the inhibition ability of NO production, iNOS activity and iNOS protein expression induced by LPS-stimulated RAW264.7 macrophages in vitro and the carrageenan-induced hind paw edema model in vivo. Molecular docking simulation was also employed to obtain the binding parameters in the binding pocket of iNOS. Thirteen compounds (1–13) were isolated from Chinese herbal medicine M. pachycarpa Benth. Among them, 4-hydroxylonchocarpin (6) and deguelin (7) exhibited remarkable inhibitory rates of 66.5% and 57.7%, respectively, compared with that of 52.5% of indomethacin in LPS-induced macrophages cells. 4-hydroxylonchocarpin (6) with low toxicity (IC₅₀ > 100 μm) exhibited better inhibitory effects to positive control of 1400W on iNOS activity at the concentration of 10 μm. Western blot assay revealed that 4-hydroxylonchocarpin (6) inhibited iNOS protein expression in RAW264.7 cells and molecular docking simulation showed that 4-hydroxylonchocarpin (6) fit well into the binding pocket of iNOS. In the carrageenan-induced paw edema model, our data revealed that the anti-inflammatory potential of 4-hydroxylonchocarpin (6) at 10 mg/kg showed comparable inhibitory ability to indomethacin at 5 h while a higher concentration of 4-hydroxylonchocarpin (6) at 50 mg/kg showed higher inhibitory activity than indomethacin, which was further confirmed by plasma levels of nitrite. The overall results suggest that 4-hydroxylonchocarpin (6) might be used as a potential therapeutic agent for inflammation-associated disorders.

In this study, we have investigated the anti-inflammatory effects of trilinolein (TL) using a lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with different concentrations of TL together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1 (IL-1β), and IL-6 production was detected. Western blotting revealed that TL blocked the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), IκBα, and mitogen-activated protein kinases (MAPKs). In the anti-inflammatory test, TL decreased the paw edema at the 5th h after λ-Carr administration in paw edema. We also demonstrated TL significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. TL decreased the NO and TNF-α levels on the serum level at the 5th h after Carr injection. Western blotting revealed that TL decreased Carr-induced iNOS and COX-2 expressions at the 5th h in the edema paw. The anti-inflammatory mechanisms of TL might be related to the decrease in the level of iNOS, COX-2, IκBα, and MAPK pathway through the suppression of TNF-α, IL-1β, and IL-6.

Forsythiae Fructus, the fruits of Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, we investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-$\alpha$ and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE.