Hoon Jeon

Anti-inflammatory and antinociceptive properties of the leaves of Eriobotrya japonica.

AIM OF THE STUDY The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including coughs and asthma. The present study was designed to validate the anti-inflammatory and antinociceptive properties of the n-BuOH fraction of E. japonica (LEJ) leaves. MATERIALS AND METHODS The anti-inflammatory properties of LEJ were studied using IFN-γ/LPS activated murine peritoneal macrophage model. The antinociceptive effects of LEJ were assessed using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test, and chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. To examine the possible connection of the opioid receptor to the antinociceptive activity of LEJ, we performed a combination test with naloxone, a nonselective opioid receptor antagonist. RESULTS In the IFN-γ and LPS-activated murine peritoneal macrophage model, LEJ suppressed NO production and iNOS expression via down-regulation of NF-κB activation. It also attenuated the expression of COX-2 and the secretion of pro-inflammatory cytokines like TNF-α and IL-6. Moreover, LEJ also demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. In a combination test using naloxone, diminished analgesic activities of LEJ were observed, indicating that the antinociceptive activity of LEJ is connected with the opioid receptor. CONCLUSIONS The results indicate that LEJ had potent inhibitory effects on the inflammatory mediators including nitric oxide, iNOS, COX-2, TNF-α and IL-6 via the attenuation of NF-κB translocation to the nucleus. LEJ also showed excellent antinociceptive activity in both central and peripheral mechanism as a weak opioid agonist. Based on these results, LEJ may possibly be used as an anti-inflammatory and an analgesic agent for the treatment of pains and inflammatory diseases.

Apoptosis-inducing effect of Akebia saponin D from the roots of Dipsacus asper Wall in U937 cells

Methanol extracts of the root of Dipsacus asper Wall (Dipsacaceae) were found to exhibit apoptosis-inducing activities in U937 (human monocyte-like histiocytic) cells. Investigation of the active n-BuOH fraction led to the isolation of akebia saponin D (ASD). Structure was established by spectroscopic methods. Treatment of U937 cells with ASD induced apoptosis in a dose dependent manner. ASD exerted strong cytotoxicity against human and murine leukemia cells. It is significantly increased the subG1 cell population and expression of p53 and Bax gene. And also ASD enhanced NO production from RAW264.7 macrophage cells. Taken together, these results strongly indicate that ASD may exert apoptosis-inducing activity via induction of apoptosis through activation chiefly via the nitric oxide and apoptosis-related p53 and Bax gene expression. These data provide scientific evidence that Dipsacus asper Wall can be useful as a chemopreventive agent.

Cytotoxic isoquinoline alkaloids from the aerial parts ofCorydalis incisa

Three known isoquinoline alkaloids were isolated from the chloroform-soluble fraction of the methanolic extract of the aerial parts ofCorydalis incisa (Papaveraceae) through repeated column chromatography. Their chemical structures were elucidated as corynoline (1), corynoloxine (2) and 6-oxocorynoline (3) using spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2 and HCT15 tumor cells.

Anti-inflammatory activity of Motherwort (Leonurus sibiricus L.).

Motherwort (MW), a Korean folk medicine, has been applied to treat inflammatory disease. However, its effect on inflammatory cytokine release from mast cells is not well known. We investigated the anti- inflammatory effect of MW on the secretion of inflammatory cytokine such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-8 in human mast cell line (HMC-1). MW was treated in vitro before activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. MW had no cytotoxic effects on HMC-1 cell viability. MW (1 mg/ml) inhibited PMA plus A23187-stimulated gene expression and production of TNF-α, IL-6, and IL-8. Stimulation with PMA plus A23187 induced NF-κB activation in HMC-1 cells, which was inhibited by MW (1 mg/ml). MW inhibited secretion of TNF-α, IL-6, and IL-8 possibly by inhibiting NF-κB activation. These results indicate that MW may be helpful in regulating inflammatory diseases.

Antinociceptive and hypnotic properties of Celastrus orbiculatus.

ETHNOPHARMACOLOGICAL RELEVANCE Celastrus orbiculatus, a woody vine of the Celastraceae family, has been widely used as a traditional medicine for the treatment of many diseases, including rheumatoid arthritis and odontalgia. In this study, we assessed the sedative and antinociceptive activities of the methanolic extract of Celastrus orbiculatus (MCO). MATERIALS AND METHODS The antinociceptive effect of MCO was evaluated using several experimental pain models, including thermal nociception methods, such as the tail immersion and the hotplate tests, as well as chemical nociception induced by intraperitoneal acetic acid and subplantar formalin administration in mice. To verify the possible connection of the opioid receptor to the antinociceptive activity of MCO, we performed a combination test with naloxone, a nonselective opioid receptor antagonist. The sedative effect of MCO was studied using the pentobarbital-induced sleeping model. RESULTS MCO demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. The combination test using naloxone revealed that the antinociceptive activity of MCO is associated with activation of the opioid receptor. MCO also caused decreased sleep latency and increased sleeping time in the pentobarbital-induced sleeping model; however, MCO alone did not induce sleep. CONCLUSIONS In the present study, MCO showed potent antinociceptive and sedative activities. Based on these results, MCO may be considered a valuable anti-nociceptive and hypnotic agent for the treatment of various diseases.

Anti-allergic effects of Teucrium japonicum on mast cell-mediated allergy model

The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Teucrium japonicum Houttuyn (Labiatae) (AXTJ) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXTJ inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXTJ decreased immunoglobulin E-mediated passive cutaneous anaphylaxis reaction. AXTJ reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. In addition, AXTJ attenuated activation of nuclear factor (NF)-kappaB, and downstream tumor necrosis factor (TNF)-alpha expression in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXTJ inhibits mast cell-derived allergic reactions and involvement of intracellular calcium, TNF-alpha, and NF-kappaB in these effects.

Memory-Enhancing Effect of a Supercritical Carbon Dioxide Fluid Extract of the Needles of Abies koreana on Scopolamine-Induced Amnesia in Mice

Abies koreana Wilson (A. koreana) is a shrub or broadly pyramidal evergreen tree endemic in the mountainous regions of South Korea. We obtained the essential oil (EO) from alpine needle leaves of A. koreana by the supercritical fluid extraction (SFE) method. EO was analyzed by gas chromatography–mass spectrometry (GC–MS), and 68 compounds were identified constituting 95.66% of the oil. The major components were elemol (11.17%), terpinen-4-ol (9.77%), sabinene (8.86%), 10(15)-cadien-4-ol (7.16%), α-terpineol (6.13%), α-pinene (6.07%) and γ-terpinene (4.71%). To investigate the memory-enhancing effects, we conducted a passive avoidance test using a scopolamine (1 mg/kg, ip)-induced amnesia mouse model. A peritoneal injection of EO from A. koreana (100 mg/kg) showed a memory enhancing effect of 72.7% compared with the control. These results suggest that EO of A. koreana may be a useful therapeutic agent against such amnesia-inducing diseases as Alzheimer and vascular dementia.

Regulation of cytokine production by exogenous nitric oxide in murine splenocyte and peritoneal macrophage.

Nitric oxide (NO), products of activated macrophages, have a great impact on the regulation of cytokine production. The role of NO in non-specific host cells is commonly accepted. On the contrary, its role as an immuno-regulatory molecule is still controversial. In this study, we have investigated the effect of NO on the production of cytokines from murine splenocytes and macrophages. S-nitroso-L-glutathione inhibited the release of both interferone-γ and interleukin-2 produced by Th1 cells and tumor necrosis factor-α and interleukin-1β produced by macrophages, but did not affect the release of interleukin-4 and interleukin-10 produced by Th2 cells. These results suggest that NO exerts a down-regulatory effect on the secretion of cytokines from Th1 cells and macrophages which are implicated in immune response. Thus, NO may have an important role as an immuno-modulatory as well as effector molecule in the immune system.

Anti-metastatic properties of the leaves of Eriobotrya japonica

The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including gastroenteric disorders, diabetes mellitus, chronic bronchitis and asthma. In the present study, the anti-metastatic action of the EtOAc fraction of the leaves of E. japonica (LEJ) was investigated. LEJ showed potent inhibitory effects on MMP-2 and MMP-9 activities and expressions via down-regulation of NF-κB translocation to the nucleus in B16F10 cells. In addition, the cell migration and invasion were down-regulated by LEJ. LEJ also significantly suppressed lung metastasis in vivo. Moreover, we isolated the compounds ursolic acid and 2α-hydroxyursolic acid from LEJ and both compounds also significantly suppressed MMP-2 and MMP-9 activities, indicating that they are the active components of LEJ. The present results demonstrate that LEJ may be used as valuable antimetastatic agent for the treatment of cancer metastasis.

Anti-inflammatory and anti-nociceptive properties of Prunus padus.

ETHNOPHARMACOLOGICAL RELEVANCE Prunus padus Linne has been widely used as a traditional medicine, with beneficial effects in numerous diseases, including stroke, neuralgia and hepatitis. In this study, we demonstrated anti-inflammatory and anti-nociceptive activities of the methylene chloride fraction of P. padus (MPP). MATERIALS AND METHODS In vitro studies, the anti-inflammatory effects of MPP were examined using IFN-γ/LPS-activated murine peritoneal macrophage model. To confirm the anti-inflammatory effects of MPP in vivo, trypsin-induced paw edema test was also conducted. The anti-nociceptive activities of MPP were measured using various experimental pain models including thermal nociception methods such as the tail immersion test and the hot plate test as well as chemical nociception methods like acetic acid-induced writhing test and formalin test. To determine whether analgesic activity of MPP is connected with the opioid receptor, we carried out combination test with naloxone, a nonselective opioid receptor antagonist. RESULTS In the current study, MPP showed potent inhibitory effect on IFN-γ/LPS-induced NO production. MPP also suppressed not only iNOS enzyme activity but also iNOS expression. Moreover, MPP inhibited COX-2 expression dose dependently. IFN-γ/LPS stimulation induced the translocation of NF-κB to nucleus but it was attenuated in the presence of MPP. In vivo study revealed that MPP could reduce paw volume after subplantar injection of trypsin. In addition, MPP showed potent analgesic activities both thermal and chemical nociception compared to tramadol and indomethacin. Furthermore, pre-treatment of naloxone slightly suppress the analgesic activity of MPP indicating that MPP acts as a partial opioid receptor agonist. CONCLUSIONS In the present study, MPP showed potent anti-inflammatory properties through not only by suppressing various inflammatory mediators in vitro, but reducing the inflammatory edema in vivo. MPP also exhibited strong anti-nociceptive activities via both central and peripheral mechanism by acting as a partial opioid agonist. Based on these results we suggest that P. padus has the potential to provide a therapeutic approach to inflammation-mediated chronic diseases as an effective anti-inflammatory agent and painkiller.