Fermentation improves anti-inflammatory effect of sipjeondaebotang on LPS-stimulated RAW 264.7 cells.

Oh, You-Chang,Cho, Won-Kyung,Jeong, Yun Hee,Im, Ga Young,Yang, Min Cheol,Ma, Jin Yeul Institute for Advanced Research in Asian Science a 2012 The American journal of Chinese medicine Vol.40 No.4

<P>Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E(2) and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE(2), NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.</P>

Anti-inflammatory effect of resveratrol by inhibition of IL-8 production in LPS-induced THP-1 cells.

Oh, You-Chang,Kang, Ok-Hwa,Choi, Jang-Gi,Chae, Hee-Sung,Lee, Young-Seob,Brice, Obiang-Obounou,Jung, Hyun Ju,Hong, Seung-Heon,Lee, Young-Mi,Kwon, Dong-Yeul Institute for Advanced Research in Asian Science a 2009 The American journal of Chinese medicine Vol.37 No.6

<P>Resveratrol is a polyphenol compound and prominent anti-inflammatory agent found in plants, including the fruits of Morus alba. However, the therapeutic mechanisms of resveratrol remain largely unclear. To gain insight into the biological effects of resveratrol, we examined its influence on LPS-induced IL-8 production in the human monocytic cell line, THP-1. In inflammatory diseases, IL-8 plays a central role in the initiation and maintenance of inflammatory response. In the present study, IL-8 production was measured by ELISA and RT-PCR, while MAPK activation, IkappaBalpha degradation, nuclear factor (NF)-kappaB activation and cyclooxygenase (COX)-2 expression were determined by Western blot analysis. Resveratrol inhibited LPS-induced IL-8 production in a dose-dependent manner. Furthermore, resveratrol inhibited extracellular signal-regulated kinase (ERK) and p38 MAPK phosphorylation, IkappaBalpha degradation, NF-kappaB activation and cyclooxygenase (COX)-2 expression, which suggest that resveratrol inhibits IL-8 secretion by blocking MAPK phosphorylation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism by which resveratrol modulates THP-1 cell activation under inflammatory conditions.</P>

Protective effect of Rehmannia glutinosa on the UV-induced apoptosis in U937 cells.

Shin, Seoung Woo,Park, Chan Ik,Yang, Chae Ha,Park, Jeen-Woo Institute for Advanced Research in Asian Science a 2008 The American journal of Chinese medicine Vol.36 No.6

<P>Ultraviolet (UV) radiation has been shown to generate reactive oxygen species (ROS), such as singlet oxygen, superoxide radicals, hydroxyl radicals and hydrogen peroxide in a variety of cells. These ROS have the potential to damage critical cellular components such as DNA, proteins, and lipids and eventually result in physical and chemical damage to tissues that may lead to cell death. The steamed root of Rehmannia glutinosa (Saeng Jihuang, SJH) is reported to have an antioxidant activity. We investigated the effect of SJH on UV-induced apoptosis in U937 cells. Upon exposure to UV, there was a distinct difference between untreated cells and cells pre-treated with 0.5-2 mg/ml SJH for 12 hours in regard to cellular redox status and morphological change to cells. SJH pre-treated cells showed significant suppression of apoptotic features such as DNA fragmentation, damage to mitochondrial function, and modulation of apoptotic marker proteins upon exposure to UV. This study indicates that SJH may play an important role in regulating the apoptosis induced by UV presumably through scavenging of reactive oxygen species.</P>

Purified extract from Clematis mandshurica prevents adenoviral-TRAIL induced apoptosis on rat articular chondrocytes.

Lee, Sung Won,Lee, Hye Jeong,Moon, Jeong Bon,Choi, Sun Mee,Kim, Duk Kyu,Kim, In Ryoung,Choi, Won Chul,Park, Bong Soo Institute for Advanced Research in Asian Science a 2008 The American journal of Chinese medicine Vol.36 No.2

<P>Since TNF-related apoptosis inducing ligand (TRAIL) is one of several apoptotic stimuli on articular chondrocytes, the modulation of the mechanism mediated by TRAIL could be considered as a novel strategy for the treatment of osteoarthritis (OA). Previous studies demonstrated that Clematis mandshurica prevents staurosporin-induced apoptosis in articular chondrocytes. This study was undertaken to examine whether Clematis mandshurica could prevent TRAIL-induced apoptosis in articular chondrocytes. Our data show that Clematis mandshurica prevents adenoviral TRAIL (Ad-TRAIL)-induced apoptosis in primary cultured articular chondrocytes. Clematis mandshurica prevents Ad-TRAIL-induced down-regulation of 14-3-3 and phosphorylated Akt. In addition, Clematis mandshurica treatment prevents the Ad-TRAIL-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and phospho-ser136-Bad, and BcL-xL with phospho-ser155-Bad. A better understanding of the mechanism underlying inhibition of apoptosis in OA chondrocytes by Clematis mandshurica might lead to the development of a new therapeutic strategy for OA.</P>

Bee venom inhibits hepatic fibrosis through suppression of pro-fibrogenic cytokine expression.

Kim, Soo-Jung,Park, Ji-Hyun,Kim, Kyung-Hyun,Lee, Woo-Ram,Chang, Young-Chae,Park, Kwan-Kyu,Lee, Kwang-Gill,Han, Sang-Mi,Yeo, Joo-Hong,Pak, Sok Cheon Institute for Advanced Research in Asian Science a 2010 The American journal of Chinese medicine Vol.38 No.5

<P>Bee venom (BV) has a long tradition of use for the control of pain and inflammation in various chronic diseases. Carbon tetrachloride (CCl(4)) is known to induce hepatotoxicity after being metabolized to the highly reactive trichloromethyl free radical and its peroxy radical. The purpose of the current study was to examine whether BV regulates the pro-inflammation and fibrosis related genes against a mouse model of hepatic fibrosis induced by CCl(4) and ethanol-treated hepatocytes (ETH). Test mice were administered with CCl(4) (2 ml/mg) and hepatocytes were treated with 25 mM ethanol. BV was added to the final concentration of 0.05-0.5 mg/kg and 1-100 ng/ml for in vivo and in vitro testing, respectively. Fibrotic livers and ETH were used for the measurement of hepatocyte necrosis, pro-inflammatory cytokines and fibrogenic genes. BV suppressed CCl(4)-induced hepatocyte necrosis markers of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Moreover, BV inhibited CCl(4)-induced expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (SMA) and fibronectin. Similarly, ETH exhibited significant suppression of IL-1beta, TNF-alpha, TGF-beta1 and fibronectin when cultured with BV. These results suggest that BV possesses anti-fibrogenic properties that are mediated by the suppression of pro-inflammatory cytokines and fibrogenic gene expression. BV has substantial therapeutic potential for the treatment of fibrotic diseases.</P>

Transgenic Panax ginseng inhibits the production of TNF-alpha, IL-6, and IL-8 as well as COX-2 expression in human mast cells.

Kim, Su-Jin,Jeong, Hyun-Ja,Yi, Byoung-Jae,Kang, Tae-Hee,An, Nyeon-Hyung,Lee, Eun-Hyub,Yang, Deok-Chun,Kim, Hyung-Min,Hong, Seung-Heon,Um, Jae-Young Institute for Advanced Research in Asian Science a 2007 The American journal of Chinese medicine Vol.35 No.2

<P>The most well-known medicinal plant, Panax ginseng (P. ginseng), contains various phytosterols and bioactive triterpene saponins (ginsenosides). Squalene synthase is a key regulatory enzyme for triterpene biosynthesis and overexpression of the squalene synthase confers the hyper-production of triterpene saponins to form transgenic ginseng. In this study, we have investigated whether and how transgenic P. ginseng modulates an inflammatory reaction in a stimulated human mast cell line, HMC-1. It was found that transgenic P. ginseng inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and the expression of cyclooxygenase-2 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMACI)-stimulated HMC-1. Additionally, we have shown that transgenic P. ginseng suppressed the intracellular calcium level induced by PMACI. These results provide new insights into the pharmacological actions of transgenic P. ginseng as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.</P>

Anti-atherogenic effects of the aqueous extract of rhubarb in rats fed an atherogenic diet.

Moon, Mi Kyoung,Kang, Dae Gill,Lee, An Sook,Yeom, Ki Bok,Kim, Jin Sook,Lee, Ho Sub Institute for Advanced Research in Asian Science a 2008 The American journal of Chinese medicine Vol.36 No.3

<P>The present study was designed to investigate whether the aqueous extract of rhubarb (AR) could prevent the development of atherosclerosis through regulating vascular inflammatory processes in rats fed with an atherogenic diet. AR significantly reduced plasma low-density lipoprotein-cholesterol, and increased plasma high-density lipoprotein-cholesterol in rats fed with an atherogenic diet. AR inhibited vascular expressions of endothelin-1 (ET-1) and endothelin-converting enzyme (ECE) induced in rats with an atherogenic diet. On the other hand, AR augmented the vascular expression of endothelial nitric oxide synthase (ecNOS) and restored vascular nitric oxide (NO) production. Furthermore, AR suppressed the elevated expression of vascular nuclear factor-kappaB (NF-kappaB) p65 as well as adhesion molecules, including intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in rats fed with an atherogenic diet. Also, AR decreased endothelial expression of ICAM-1 and ET-1 in aorta. These results suggest that AR suppresses the development of atherosclerosis in the atherogenic-diet rat model through inhibiting vascular expressions of proinflammatory and adhesion molecules via the regulation of nitric oxide and endothelin system.</P>

The cardiovascular depression caused by bee venom in Sprague-Dawley rats associated with a decrease of developed pressure in the left ventricular and the ratio of ionized calcium/ionized magnesium.

Kang, Hyung-Sub,Kim, Shang-Jin,Lee, Mun-Young,Jeon, Seol-Hee,Kim, Sung-Zoo,Kim, Jin-Shang Institute for Advanced Research in Asian Science a 2008 The American journal of Chinese medicine Vol.36 No.3

<P>Bee venom (BV) has been used in Oriental medicine to treat inflammatory diseases, such as tendonitis, bursitis, and rheumatoid arthritis, despite the sensitivity of the victims and toxicity of the venom. This study examined the mechanisms for the effects of BV on the cardiovascular system in rats. The arterial pressure and heart rate (HR) were measured in anesthetized rats. In addition, the left ventricular development pressure (LVDP) and total magnesium efflux ([Mg]e) in isolated perfused hearts, the vascular tonic responses in the isolated aorta, and the blood ionic and biochemical changes were determined simultaneously. In the anesthetized rats, the mean arterial pressure, systolic pressure, and pulse pressure were reduced by BV in a dose-dependent manner, even though the HR was increased. BV had no effects on the relaxation of phenylephrine- or KCl-induced contraction of the aortic rings. In the isolated hearts, BV generated a reversible decrease in the LVDP and velocity with changes in pressure, which were accompanied by increases in the HR and [Mg]e. BV increased the plasma ionized and total magnesium concentrations, and decreased the total magnesium level in the red blood cells. The ratio of ionized calcium/ionized magnesium was also decreased by the BV treatment. BV caused a detectable increase in blood creatine kinase, glutamic oxaloacetic transaminase, and lactic dehydrogenase, as well as a decrease in the blood total protein albumin and globulin levels. These results suggest that BV induces cardiovascular depression by decreasing the cardiac pressure and increasing the ionized magnesium concentration in the blood.</P>

Selective cytotoxic effects on human cancer cell lines of phenolic-rich ethyl-acetate fraction from Rhus verniciflua Stokes.

Kim, Ji Hye,Jung, Chang Hwa,Jang, Bo-Hyoung,Go, Ho Yeon,Park, Jong-Hyeong,Choi, You-Kyung,Hong, Seong Il,Shin, Yong Cheol,Ko, Seong-Gyu Institute for Advanced Research in Asian Science a 2009 The American journal of Chinese medicine Vol.37 No.3

<P>Rhus verniciflua Stokes (RVS) is a plant with a long history of medicinal use in Eastern Asia. RVS has been widely used to treat gastritis, stomach cancer and atherosclerosis. The cytotoxic effects of different solvent fractions from an RVS ethanol extract were measured in 11 human cancer cell lines. The study showed that the ethyl-acetate (EtOAC) fraction was the most cytotoxic. This fraction contains a number of phenolic compounds, and this phenolic-rich EtOAC fraction was particularly effective against gastric and breast cancer cells. A purified phenolic-rich EtOAC fraction (PPEF) had a stronger apoptotic effect on these cells. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the PPEF contained gallic acid, protocatechuic acid, fisetin, sulfuretin, butein and 8 unknown compounds. There were only small amounts of flavonoids: fisetin, sulfuretin and butein. The results showed that PPEF induces apoptosis only in gastric and breast cancer cell lines, but not in lung, colon or liver cancer cell lines. Therefore, PPEF may have a significant potential as an organ-specific anti-cancer agent.</P>

Protective Effects of Natrii Sulfas on Cerebral Focal Ischemia Induced by MCAO in Rats.

Sohn, Youngjoo,Kang, Ho Chang,Kim, Kon Sik,Park, Sun-Min,Sohn, Nak-Won,Jung, Hyuk-Sang,Kim, Sung-Hoon Institute for Advanced Research in Asian Science a 2009 The American journal of Chinese medicine Vol.37 No.2

<P>This study examined the effect of Natrii sulfas, a treatment for stroke patients suffering constipation in Oriental medicine, on the physiological indices and brain edema of rats. Brain edema was induced by a middle cerebral artery occlusion (MCAO), Natrii sulfas was administered after the MCAO. At 3, 6, 15, 24, and 48 hours after reperfusion, the physiological indices such as the fecal weight, urine volume and water content in the stools were assessed. The edema index was measured 48 hours after reperfusion. At 48 hours, the expressions of iNOS, MMP9, VEGF, GFAP, Bax, Bcl-2, c-Fos, and HSP72 positive astrocytes were observed on the brain tissues by immunohistochemistry. Natrii sulfas significantly improved the decrease in fecal weight, urine volume and water content in the stool caused by the ischemic insult (p < 0.05) and attenuated the brain edema caused by the ischemia insult (p < 0.05). Natrii sulfas significantly down-regulated iNOS and MMP9 expressions and attenuated the astrocyte swelling due to brain edema in the penumbra of the cerebral cortex of MCAO rats. Natrii sulfas reduced the excess Bax and HSP72 expressions in ischemic brain, which was statistically significant in the penumbra of the cerebral cortex but not in the caudate putamen. These results suggest Natrii sulfas has a protective effect on ischemia-induced brain edema and improves the physiological symptoms.</P>