1,2-Bis[(3-Methoxyphenyl)Methyl]Ethane-1,2-Dicarboxylic Acid Reduces UVB-Induced Photodamage In Vitro and In Vivo.

This study investigated the effects and mechanisms of 1,2-bis[(3-methoxyphenyl)methyl]ethane-1,2-dicarboxylic acid (S4), a sesamin derivative, on anti-inflammation and antiphotoaging in vitro and in vivo. Human skin fibroblasts were treated with S4 and did not show cytotoxicity under concentrations of 5-50 µM. In addition, S4 also reduced ultraviolet (UV)B-induced intracellular reactive oxygen species (ROS) production. Additionally, S4 inhibited UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases, activator protein-1 (AP-1), and matrix metalloproteinases (MMPs) overexpression. Furthermore, S4 also inhibited UVB-induced Smad7 protein expression and elevated total collagen content in human dermal fibroblasts. For anti-inflammatory activity, S4 inhibited UVB-induced nitric oxide synthase (i-NOS) and cyclooxygenase (COX)-2 protein expression and inhibited nuclear factor-kappaB (NF-ĸB) translocation into the nucleus. S4 ameliorated UVB-induced erythema and wrinkle formation in hairless mice. On histological observation, S4 also ameliorated UVB-induced epidermal hyperplasia and collagen degradation. S4 reduced UVB-induced MMP-1, interleukin (IL)-6, and NF-ĸB expression in the mouse skin. The results indicated that S4 had antiphotoaging and anti-inflammatory activities, protecting skin from premature aging.

Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo.

Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.

Sesamol Inhibited Ultraviolet Radiation-Induced Hyperpigmentation and Damage in C57BL/6 Mouse Skin.

Melanin is synthesized through a series of oxidative reactions initiated with tyrosine and catalyzed by melanogenesis-related proteins such as tyrosinase, tyrosinase-related protein-1 (TRP-1), dopachrome tautomerase (TRP-2), and microphthalmia-associated transcription factor (MITF). Our previous study demonstrated that sesamol inhibited melanin synthesis through the inhibition of the melanocortin 1 receptor (MC1R)/MITF/tyrosinase pathway in B16F10 cells. In this study, sesamol was applied to C57BL/6 mouse skin to understand its activity with respect to skin pigmentation. The results indicated that ultraviolet (UV) B-induced hyperpigmentation in the C57BL/6 mouse skin was significantly reduced by topical application of sesamol for 4 weeks. Sesamol reduced the melanin index and melanin content of the skin. In addition, sesamol elevated the brightness (L* value) of the skin. Sesamol also reduced UVB-induced hyperplasia of epidermis and collagen degradation in dermis. In immunohistochemical staining, topical application of sesamol reduced UVB-induced tyrosinase, TRP-1, TRP-2, and MITF expression in the epidermis of the skin. These results demonstrated that sesamol is a potent depigmenting agent in the animal model.

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells.

Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation. Previous studies have revealed that sesamol is a strong antioxidant and a free radical scavenger. In this study, we investigated the effects of sesamol on the regulation of melanogenesis and related mechanisms in B16F10 cells. The results indicated that sesamol inhibited tyrosinase activity and melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells. Sesamol decreased the protein level of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1 by downregulating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathways that had been activated by α-MSH. Sesamol increased glycogen synthase kinase 3 beta (GSK3ß), protein kinase B (AKT), and extracellular signal-related kinase (ERK) phosphorylation, thus inhibiting the transcription of MITF. Sesamol also inhibited melanin synthesis and tyrosinase expression by modulating ERK, phosphoinositide 3-kinase (PI3K)/AKT, p38, and c-Jun amino-terminal kinase (JNK) signalling pathways. These results indicate that sesamol acted as a potent depigmenting agent.

Amelioration of carbon tetrachloride-induced hepatic injury by emulsified Antrodia extract.

OBJECTIVES: Antrodia cinnamomea (AC) is found with anti-inflammatory and immunomodulatory biological activities. In this study, we investigated the anti-hepatitis effect of the emulsified AC extract from RO water or supercritical fluid CO2 with ethanol co-solvent extract methods of AC preparations. MATERIALS AND METHODS: Five groups of eight to ten weeks male rats with a count of ten for each group were studied to evaluate the protection of two kinds of AC extract from hepatic injury. Acute liver injury of rats was induced by injecting 40% carbon tetrachloride (CCl4) 1 mg/kg intraperitoneally. Positive and negative control groups rats were perfused with CCl4 or isotonic saline, respectively. Experimental groups received oral administration once/day of AC preparations before CCl4 treatment: water AC extract (WAE group), or emulsified AC extract from supercritical fluid extraction (EAE group) for 5 days, and sacrificed on the 6th day and the blood and liver samples were collected under chloral hydrate anesthesia. The anti-inflammatory, antioxidant markers, and relevant signaling pathways were measured (AST, ALT, ROS, IL-1, IL-6, NO, and COX-2, MAPKs, and caspase-3). RESULTS: EAE at 50 mg/kg significantly decreased the serum AST, ALT, IL-1, IL-6, NO, and ROS levels. Both extracts reduced the activation of p-ERK in the liver samples, but EAE inhibited COX-2 and caspase-3 protein expression better than WAE. The EAE ameliorated CCl4-induced hepatic injury significantly; as compared with WAE and the positive control. CONCLUSION: The hepatoprotection of EAE could be attributed to the antioxidant and anti-inflammatory effects of Antrodia.

Neuroprotection of a sesamin derivative, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) against ischemic and hypoxic neuronal injury.

OBJECTIVES: Stroke may cause severe neuronal damage. The sesamin have been demonstrated to possess neuroprotection by its antioxidant and anti-inflammatory properties. One sesamin derivative was artificially composited, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) had been developed to study its antioxidative activity and neuroprotection. MATERIALS AND METHODS: The infaction of Sprague Dawley (SD) rats and hypoxia models of BV-2 microglia or PC12 cells were investigated for in vivo and in vitro test respectively. Lipid peroxidation and reactive oxygen species (ROS), prostaglandin E2 (PGE2) and related signaling pathways from hypoxic cells were analyzed by ELISA or Western blot assay, respectively. RESULTS: MMEDA showed a protective effect when given 90 min after the focal cerebral ischemia. The neuroprotection of MMEDA was further confirmed by attenuating ROS and PGE2 release from hypoxic BV-2 or PC12 cells. MMEDA significantly reduced hypoxia-induced JNK and caspase-3 (survival and apoptotic pathways) in PC12 cells. CONCLUSION: The neuroprotective effect of MMEDA on ischemia/hypoxia models was involved with its antioxidative activity and anti-inflammatory effects. These results suggest that MMEDA exert effective neuroprotection against ischemia/hypoxia injury.

Anti-inflammatory effect of longan seed extract in carrageenan stimulated Sprague-Dawley rats.

OBJECTIVES: Longan seeds have been used as a folk medicine in China. Longan seed extract (LSE) is known for antioxidative, antiproliferative, hypoglycemic, and hypouremic effects. However, its anti-inflammatory effect has not been shown. MATERIALS AND METHODS: In this study, Sprague-Dawley (SD) rats were given LSE orally (vehicle, 10, and 30 mg/kg) for 3 days to its test anti-inflammatory effect by injecting λ-carrageenan (CARR) in the right hind paw or lipopolysaccharide (LPS), IP. For the positive control, animals were given aspirin (20 mg/kg) orally and treated likewise. Serum or tissue samples from treated rats were collected after 3 hr of stimulation. Regarding the in vitro study, BV2 microglial cells were stimulated with LPS in the presence of LSE or normal saline for 10 min or 24 hr for Western blot and ELISA assay, respectively. RESULTS: LSE reduced CARR-induced edema in the experimental animals. LSE also reduced LPS/CARR-induced nitric oxide (NO), interleukin-1ß (IL1ß), IL6, and COX2 productions. These inflammatory factors were also reduced dose dependently by LSE in LPS-stimulated BV2 cells. Furthermore, Western blot analysis revealed that LSE inhibited LPS activated c-Jun NH2-terminal protein kinase (JNK), extracellular signal-regulated kinases (ERKs), and p38 MAP kinases signaling pathways, caspase-3, inducible NO synthase, and COX2 expressions. CONCLUSION: LSE pretreatment suppressed CARR- and LPS-induced inflammations and these effects might be through the inhibition of MAP kinases signaling pathways and inflammatory factors.

Ferulic acid protects PC12 neurons against hypoxia by inhibiting the p-MAPKs and COX-2 pathways.

OBJECTIVES: Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. Here, the protective effects of ferulic acid (FA) on hypoxia-induced neurotoxicity in PC12 cells were evaluated. MATERIALS AND METHODS: We investigated the effect of FA on PC12 cells subjected to hypoxia stress, in vitro. RESULTS: FA increased cell viability, prevented membrane damage (LDH release), scavenged free radicals, increased superoxide dismutase (SOD) activity, and attenuated the elevation of intracellular free Ca(2+), lipid peroxidation, apoptosis (evaluated by TUNEL staining) and PGE2 production in hypoxia-stressed PC12 cells. MAPKs were activated during hypoxia. FA reduced p-p38 MAPK, caspase-3, and COX-2 activation which correlated well with diminished LDH release in PC12 cells under hypoxia. Furthermore, FA reduced lipid peroxidation in PC12 cells subjected to hypoxia. CONCLUSION: Taken together, these results indicate that FA antioxidant effects could partly be involved in inhibition of p38 MAPK pathway and apoptosis through scavenging ROS in hypoxia-stressed PC12 cells.

Gardenia jasminoides extracts and gallic acid inhibit lipopolysaccharide-induced inflammation by suppression of JNK2/1 signaling pathways in BV-2 cells.

OBJECTIVES: Gardenia jasminoides Ellis (GJ, Cape Jasmine Fruit, Zhi Zi) has been traditionally used for the treatment of infectious hepatitis, aphthous ulcer, and trauma; however, the direct evidence is lacking. MATERIALS AND METHODS: We investigated the effect of the GJ extract (GJ) and gallic acid (GA) on lipopolysaccharide (LPS) induced inflammation of BV-2 microglial cells and acute liver injury in Sprague-Dawley (SD) rats. RESULTS: Our results showed that the GJ extract and GA reduced LPS-induced nitric oxide (NO), interleukin (IL)-1, IL-6, reactive oxygen species (ROS), and prostaglandin (PGE2) production in BV-2 cells. The GJ extract and GA 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 the GJ dose-dependently inhibited LPS-induced JNK2/1 and slightly p38 mitogen-activated protein kinases (MAPK), and cyclooxygenase-2 (COX-2) expression in BV-2 cells. CONCLUSION: Taken together, these results indicate that the protective mechanism of the GJ extract involves an antioxidant effect and inhibition of JNK2/1 MAP kinase and COX-2 expressions in LPS-induced inflammation of BV-2 cells.

Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7 cells.

Dietary prevention has been known to reduce breast cancer risk. Sesamin is one of the major components in sesame seeds and has been widely studied and proven to have anti-proliferation and anti-angiogenic effects on cancer cells. In this study, the influence of sesamin was tested in the human breast cancer MCF-7 cell line for cell viability (MTT assay) and cell cycling (flow cytometry). Results showed that sesamin dose-dependently (1, 10 and 50 µM) reduced the cell viability and increased LDH release and apoptosis (TUNEL assay). In addition, there was a significant increase of sub-G1 phase arrest in the cell cycle after sesamin treatment. Furthermore, sesamin increased the expression of apoptotic markers of Bax, caspase-3, and cell cycle control proteins, p53 and checkpoint kinase 2. Taken together, these results suggested that sesamin might be used as a dietary supplement for prevention of breast cancer by modulating apoptotic signal pathways and inhibiting tumor cell growth.

Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on Aß-stressed PC12 cells.

Amyloid beta-protein (Aß) is involved in the pathogenesis of Alzheimer's disease (AD). Aß induces free radical production in neuronal cells, leading to oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK), extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown to have protection to several models of neurodegenerative diseases by its antioxidant and anti-inflammatory properties. In the present study, we examined the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) on Aß1-42 induced cytotoxicity of PC12 cells. Aß1-42 induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells. The effect of BBD on these harmful factors and the related signaling pathways were examined by biochemical and western blot assays. The result showed that BBD protected PC12 cells from Aß1-42 induced cytotoxicity with the increased cell viability and acetylcholine release, and the decreased lactate dehydrogenase, malondialdehyde and calcium release. BBD significantly reduced Aß-induced JNK, ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the neuroprotective effect of BBD on Aß-induced cytotoxicity was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of AD.

Sesamin reduces acute hepatic injury induced by lead coupled with lipopolysaccharide.

BACKGROUND: In this study, we investigated the potential anti-inflammatory and antioxidative effects of sesamin on acute liver injury. Lead (Pb) causes oxidative damage and enhances the effects of low-dose lipopolysaccharide (LPS), inducing acute hepatic injury in rats. METHODS: Male Sprague-Dawley rats were given intraperitoneal injections of Pb acetate (5 mg/kg) and LPS (50 µg/kg) to induce liver injury, and we tested the effects of oral administration of sesamin (10 mg/kg) on liver damage. To assess the extent of acute hepatic injury in the rats, we measured the anti-inflammatory and antioxidant markers and relevant signaling pathways: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, nitric oxide (NO), and cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) levels, mitogen-activated protein kinases (MAPKs), c-Fos, and GADD45ß. RESULTS: Sesamin significantly decreased the serum AST, ALT, and CRP levels in the rat model. In the Pb and LPS-stressed rats, sesamin administration reduced the serum levels of TNF-α, IL-1, IL-6, NO, and ROS generation, and liver tissue expressions of c-Jun N-terminal kinase (JNK), p38 MAPK, GADD45ß, COX-2, and iNOS. CONCLUSION: Collectively, these results demonstrate that sesamin is associated with antioxidant and anti-inflammatory activity. The observed effect of scavenging of ROS and NO and inhibiting the production of proinflammatory cytokines may be achieved through the suppression of COX-2, iNOS, and MAPK pathways in the acute hepatic injury rats.

Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury.

BACKGROUND: Stroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood-brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect. METHODS: The focal cerebral ischemia of Sprague-Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively. RESULTS: BBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells. CONCLUSIONS: The neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.

Longan seed extract reduces hyperuricemia via modulating urate transporters and suppressing xanthine oxidase activity.

Hyperuricemia causes gouty arthritis, kidney disease, heart disease, and other diseases. Xanthine oxidase (XOD) and urate transporters play important roles in urate homeostasis. Numerous plants have been identified as XOD inhibitors. Longan seeds are known to contain high levels of polyphenols such as corilagin, gallic acid and ellagic acid. We examined the effect of longan seed extract on XOD inhibition and urate transporters GLUT1 and GLUT9 using both in vitro and in vivo assays. The results showed that dried longan seed extract (LSE) and its active components inhibited XOD dose-dependently in vitro. LSE inhibited uric acid production and XOD activity in normal liver cells (clone-9 cells) and was not cytotoxic under the concentration of 200 µg/ml. For the in vivo study, Sprague-Dawley (SD) rats were given intraperitoneally for thirty minutes with or without allopurinol (a XOD inhibitor, 3.5 mg/kg) or LSE (80 mg/kg) and then injected intraperitioneally with 250 mg/kg of oxonic acid and 300 mg/kg of hypoxanthine intragastrically. LSE was able to reduce serum uric acid level and XOD activity in hyperuricemic rats. However, LSE or allopurinol did not inhibit the liver XOD activities. On the other hand, GLUT1 protein was suppressed in kidney and GLUT9 was induced in liver from experimental rats and LSE or allopurinol decreased GLUT9 but increased GLUT1 protein level in the liver and kidney, respectively. These results confirmed the claimed effect of longan seeds on gout and other complications and suggested that its urate reducing effect might be due to modulation of urate transporters and inhibition of circulating xanthine oxidase.

Neuroprotective effects of carnosic acid on neuronal cells under ischemic and hypoxic stress.

Ischemia/hypoxia induces oxidative stress which is associated with neurodegenerative diseases. The present study investigated protective mechanism of carnosic acid (CA) on ischemia/reperfusion and hypoxia-induced neuronal cell injury. The results showed that CA reduced 52% of the infarct volume from brains under ischemia/reperfusion in vivo and protected the PC12 cells from hypoxic injury in vitro. CA (1.0 µM) enhanced cell viability, prevented lactic dehydrogenase (LDH) release, scavenged reactive oxygen species (ROS), increased superoxide dismutase activity, and attenuated Ca(2+) release, lipid peroxidation, and prostaglandin E2 production in hypoxic PC12 cells. In addition, CA also reduced nitric oxide (NO) and interleukine (IL)-1 and IL-6 production from activated BV-2 microglia. Furthermore, its effect on hypoxia-induced mitogen-activated protein kinases (MAPKs) signaling pathway and caspase-3 was examined. Extracellular signal-regulated protein kinases, c-jun NH2-terminal kinase, and p38 MAPK were activated during hypoxia. CA inhibited MAPKs, caspase-3, and COX-2 activation and correlated well with the diminished LDH release and apoptosis (TUNEL) in PC12 cells under hypoxia. Taken together, CA protected neuronal cells under ischemia/hypoxia through scavenging or reducing of ROS and NO, inhibiting COX-2 and MAPK pathways by anti-inflammatory and anti-oxidative properties.

Fresh green tea and gallic acid ameliorate oxidative stress in kainic acid-induced status epilepticus.

Green tea is one of the most-consumed beverages due to its taste and antioxidative polyphenols. However, the protective effects of green tea and its constituent, gallic acid (GA), against kainic acid (KA)-induced seizure have not been studied. We investigated the effect of fresh green tea leaf (GTL) and GA on KA-induced neuronal injury in vivo and in vitro. The results showed that GTL and GA reduced the maximal seizure classes, predominant behavioral seizure patterns, and lipid peroxidation in male FVB mice with status epilepticus (SE). GTL extract and GA provided effective protection against KA-stressed PC12 cells in a dose-dependent manner. In the protective mechanism study, GTL and GA decreased Ca(2+) release, ROS, and lipid peroxidation from KA-stressed PC12 cells. Western blot results revealed that mitogen-activated protein kinases (MAPKs), RhoA, and COX-2 expression were increased in PC12 cells under KA stress, and expression of COX-2 and p38 MAPK, but not RhoA, was significantly reduced by GTL and GA. Furthermore, GTL and GA were able to reduce PGE(2) production from KA-stressed PC12 cells. Taken together, the results showed that GTL and GA provided neuroprotective effects against excitotoxins and may have a clinical application in epilepsy.

Pu-Erh tea and GABA attenuates oxidative stress in kainic acid-induced status epilepticus.

BACKGROUND: Pu-Erh tea is one of the most-consumed beverages due to its taste and the anti-anxiety-producing effect of the gamma-aminobutyric acid (GABA) if contains. However the protective effects of Pu-Erh tea and its constituent, GABA to kainic acid (KA)-induced seizure have not been fully investigated. METHODS: We analyzed the effect of Pu-Erh tea leaf (PETL) and GABA on KA-induced neuronal injury in vivo and in vitro. RESULTS: PETL and GABA reduced the maximal seizure classes, predominant behavioral seizure patterns, and lipid peroxidation in male FVB mice with status epilepticus. PETL extracts and GABA were effective in protecting KA-treated PC12 cells in a dose-dependent manner and they decreased Ca(2+) release, ROS production and lipid peroxidation from KA-stressed PC12 cells. Western blot results revealed that mitogen-activated protein kinases (MAPKs), RhoA and cyclo-oxygenase-2 (COX-2) expression were increased in PC12 cells under KA stress, and PETL and GABA significantly reduced COX-2 and p38 MAPK expression, but not that of RhoA. Furthermore, PETL and GABA reduced PGE(2) production from KA-induced PC12 cells. CONCLUSIONS: Taken together, PETL and GABA have neuroprotective effects against excitotoxins that may have clinical applications in epilepsy.

Elephantopus scaber inhibits lipopolysaccharide-induced liver injury by suppression of signaling pathways in rats.

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 (PGE(2)) 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.

Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation.

BACKGROUND: Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHODS: Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. RESULTS: Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. CONCLUSIONS: Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.