A newly developed PLD1 inhibitor ameliorates rheumatoid arthritis by regulating pathogenic T and B cells and inhibiting osteoclast differentiation.

Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline, plays multiple roles in inflammation. We investigated the therapeutic effects of the newly developed PLD1 inhibitors A2998, A3000, and A3773 in vitro and in vivo rheumatoid arthritis (RA) model. A3373 reduced the levels of LPS-induced TNF-α, IL-6, and IgG in murine splenocytes in vitro. A3373 also decreased the levels of IFN-γ and IL-17 and the frequencies of Th1, Th17 cells and germinal-center B cells, in splenocytes in vitro. A3373 ameliorated the severity of collagen-induced arthritis (CIA) and suppressed infiltration of inflammatory cells into the joint tissues of mice with CIA compared with vehicle-treated mice. Moreover, A3373 prevented systemic bone demineralization in mice with CIA and suppressed osteoclast differentiation and the mRNA levels of osteoclastogenesis markers in vitro. These results suggest that A3373 has therapeutic potential for RA.

Effects of Medicinal Herb Extracts on In vitro Ruminal Methanogenesis, Microbe Diversity and Fermentation System.

This study was aimed to evaluate the in vitro effects of medicinal herb extracts (MHEs) on ruminal fermentation characteristics and the inhibition of protozoa to reduce methane production in the rumen. A fistulated Hanwoo was used as a donor of rumen fluid. The MHEs (T1, Veratrum patulum; T2, Iris ensata var. spontanea; T3, Arisaema ringens; T4, Carduus crispus; T5, Pueraria thunbergiana) were added to the in vitro fermentation bottles containing the rumen fluid and medium. Total volatile fatty acid (tVFA), total gas production, gas profiles, and the ruminal microbe communities were measured. The tVFA concentration was increased or decreased as compared to the control, and there was a significant (p<0.05) difference after 24 h incubation. pH and ruminal disappearance of dry matter did not show significant difference. As the in vitro ruminal fermentation progressed, total gas production in added MHEs was increased, while the methane production was decreased compared to the control. In particular, Arisaema ringens extract led to decrease methane production by more than 43%. In addition, the result of real-time polymerase chain reaction indicted that the protozoa population in all added MHEs decreased more than that of the control. In conclusion, the results of this study indicated that MHEs could have properties that decrease ruminal methanogenesis by inhibiting protozoa species and might be promising feed additives for ruminants.

Therapeutic efficacy of biochanin A against arsenic-induced renal and cardiac damage in rats.

The present study was investigated the effects of biochanin A (BCA) on arsenic toxicity in rats. For this purpose, rats were orally treated with arsenic in the form of sodium meta-arsenite alone (10mg/kg body weight (bw)/day) and co-administered selenium (10mg/kgbw/day) and BCA at different doses (10, 20 and 40mg/kgbw/day) for 6 weeks. Arsenic altered the oxidative stress indices in both renal and cardiac tissues. There was an increase in plasma renal markers, triglyceride, lipoproteins with no alterations in cholesterol levels were noted in arsenic-intoxicated rats. Non-significant changes of phospholipids and free fatty acids levels in the tissues of arsenic-exposed rats. The biochemical disturbances were well correlated with the histological findings in the kidney, but not in the heart. The administration of BCA and selenium significantly reversed the alterations in the above-mentioned parameters in arsenic-intoxicated rats. Our findings revealed the beneficial effects of BCA against arsenic toxicity.

Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons.

Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 µM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 µg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.

Protective effect of Ilex latifolia, a major component of "kudingcha", against transient focal ischemia-induced neuronal damage in rats.

AIMS OF THE STUDY: Ilex latifolia (Aquifoliaceae), a primary component of "kudingcha", has been used in Chinese folk medicine to treat various kinds of diseases including headaches, inflammatory diseases, and cardiac ischemic injury. The present study investigated the protective effect of the ethanol extract of Ilex latifolia against transient, focal, ischemia-induced neuronal damage. MATERIALS AND METHODS: Transient focal ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, brain infarction and neuronal death were measured by triphenyltetrazolium chloride and hematoxylin and eosin staining, respectively. Glutathione concentration and lipid peroxidation rate were measured. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), cyclooxygenase 2 (COX-2), and anti-apoptotic and pro-apoptotic proteins were detected by Western blot. RESULTS: Ilex latifolia (50-200 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of Ilex latifolia. The increase of phosphorylated MAPKs, COX-2, and proapoptotic proteins and the decrease of antiapoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with Ilex latifolia. CONCLUSION: Ilex latifolia ameliorated ischemic injury induced by MCAO/reperfusion in rats, and this neuroprotective effect might be associated with its anti-apoptotic effect, resulting from anti-oxidative and anti-inflammatory actions.

Leaf and stem of Vitis amurensis and its active components protect against amyloid ß protein (25-35)-induced neurotoxicity.

This study investigated a methanol extract from the leaf and stem of Vitis amurensis (Vitaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid ß protein (Aß) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10 µM Aß (25-35) for 36 h induced neuronal apoptotic death. At concentrations of 1-10 µg/mL, V. amurensis inhibited neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)) and the generation of reactive oxygen species (ROS), all of which were induced by Aß (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 16 nmol Aß (25-35) was inhibited by chronic treatment with V. amurensis extract (50 and 100 mg/kg, p.o. for 7 days), as measured by a passive avoidance test. Amurensin G, r-2-viniferin and trans-ɛ-viniferin isolated from V. amurensis also inhibited neuronal death, the elevation of [Ca(2+)](i) and the generation of ROS induced by Aß (25-35) in cultured rat cortical neurons. These results suggest that the neuroprotective effect of V. amurensis may be partially attributable to these compounds. These results suggest that the antidementia effect of V. amurensis is due to its neuroprotective effect against Aß (25-35)-induced neurotoxicity and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing the progression of Alzheimer's disease.

Aralia cordata protects against amyloid beta protein (25-35)-induced neurotoxicity in cultured neurons and has antidementia activities in mice.

The present study investigated an ethanol extract of the aerial part of Aralia cordata Thunb. (Araliaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid beta (Abeta) protein (25 - 35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to 10 muM Abeta(25 - 35) for 36 h induced neuronal apoptotic death. At 1 - 10 mug/ml, A. cordata inhibited neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), glutamate release into the medium, and generation of reactive oxygen species (ROS) induced by Abeta(25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Abeta(25-35) was inhibited by chronic treatment with A. cordata (50 and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test, and corresponding reductions were observed in brain cholinesterase activity and neuronal death measured histologically in the hippocampal region. Oleanolic acid isolated from A. cordata also inhibited neuronal death, elevation of [Ca(2+)](i), glutamate release, and generation of ROS induced by Abeta(25-35) in cultured rat cortical neurons, suggesting that the neuroprotective effect of A. cordata may be, at least in part, attributable to this compound. From these results, we suggest that the antidementia effect of A. cordata is due to its neuroprotective effect against Abeta(25-35)-induced neurotoxicity and that A. cordata may have a therapeutic role in preventing the progression of Alzheimer's disease.