Geng-Xin Liu

Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia.

Microglial-mediated neuroinflammation is now considered to be central to the pathogenesis of various neurodegenerative processes, including Alzheimers disease and Parkinsons disease. Therefore, rational modulation of microglia function to obtain neuroprotective effects is important for the development of safe and effective anti-inflammatory and neuroprotective agents. Here, we investigated the anti-inflammatory and neuroprotective effects, and potential molecular mechanism of action of Schisandrin B (Sch B); which is isolated from the Schizandra fruit (Schisandra chinesnesis). Sch B exerted significant neuroprotective effects against microglial-mediated inflammatory injury in microglia-neuron co-cultures. In addition, Sch B significantly downregulated pro-inflammatory cytokines, including nitrite oxide (NO), tumor necrosis factor (TNF)-α, prostaglandin E(2) (PGE(2)), interleukin (IL)-1β and IL-6. Additionally, Sch B inhibited the interaction of Toll-like receptor 4 with the Toll adapter proteins MyD88, IRAK-1 and TRAF-6 resulting in an inhibition of the IKK/nuclear transcription factor (NF)-κB inflammatory signaling pathway. Furthermore, Sch B inhibited the production of reactive oxygen species (ROS) and NADPH oxidase activity in microglia. In summary, Sch B may exert neuroprotective activity by attenuating the microglial-mediated neuroinflammatory response by inhibiting the TLR4-dependent MyD88/IKK/NF-κB signaling pathway.

Aluminum maltolate induces primary rat astrocyte apoptosis via overactivation of the class III PI3K/Beclin 1-dependent autophagy signal

Aluminum-induced neuronal cell apoptosis has been implicated in various neurodegenerative disorders. However, whether autophagy, a vital lysosomal degradation pathway, is involved in this pathogenesis still remains unknown. Our present findings demonstrated that aluminum significantly increased rat astrocyte apoptosis and autophagy levels in a dose-dependent manner. Examination of the associated mechanisms revealed that aluminum at low levels (400μM) did not increase apoptosis protein expressions (cleaved caspase-3 and cleaved PARP), but markedly up-regulated autophagy-related protein Beclin 1 expression. This indicates that the autophagy process occurs earlier than neuronal apoptosis. Moreover, aluminum at high levels (1600μM) significantly induced autophagy-related protein (Beclin 1 and LC3II) and apoptosis-related protein expressions, showing that both autophagy and apoptosis processes are activated under high levels of aluminum exposure. We used 3-methyladenine, an inhibitor of class III phosphatidylinositol-3 kinase, to treat astrocytes and found that the apoptosis rate in the 3-MA/aluminum co-treated group was markedly down-regulated compared with aluminum alone-treated astrocytes. The apoptosis protein and autophagy-related protein expressions were also decreased. These observations showed that the mild autophagy process may precede apoptosis in low dose aluminum-insulted astrocytes, and high dose aluminum-induced serious autophagy may result in cell apoptosis via the Beclin 1-dependent autophagy signal pathway.

A randomized double-blind placebo-controlled study of Pu’er tea (普洱茶) extract on the regulation of metabolic syndrome

ObjectiveTo explore the regulative efficacy of Pu’er tea (普洱茶) extract on metabolic syndrome.MethodsNinety patients with metabolic syndrome were randomly divided into two groups, the intervention group administered with Pu’er tea extract, and the placebo group with placebo capsules. After 3 months’ treatment, body mass index, waist hip ratio, blood lipids, blood sugar, immune and inflammatory index, and oxidation index of the patients with metabolic syndrome were tested and analyzed.ResultsIn the intervention group, the body mass index, waist-hip ratio, fasting and 2 h postprandial blood glucose, serum total cholesterol, triglycerides, low density lipoprotein and apolipoprotein B-100 all decreased in the patients with metabolic syndrome, and also the high-density lipoprotein level increased and apolipoprotein A-1 showed the tendency to increase. Serum C-reactive protein, tumor necrosis factor-α, and interleukin-6 were decreased in the intervention group. Interleukin-10 level was increased, MDA was decreased and superoxide dismutase was increased. Compared with before treatment and the placebo group, there were significant differences (P<0.05, P<0.01).ConclusionsPu’er tea demonstrated excellent potential in improving central obesity, adjusting blood lipid, lowering blood sugar, regulating immunity and resisting oxidation. It can adjust the metabolic syndrome of different clinical phenotypes to different degrees, and is ideally fit for early prevention of metabolic syndrome.

Effect of modified Wuzi Yanzong Granule (加味五子衍宗颗粒) on patients with mild cognitive impairment from oxidative damage aspect

ObjectiveTo observe the effects of modified Wuzi Yanzong Granule (加味五子衍宗颗粒, WYG) on memory function and the activity of serum superoxide dismutase (SOD), malondialdehyde (MDA) levels, leukocyte mitochondrial DNA (mtDNA) deletion rate and β-amyloid protein1–28 (A β1–28) in patients with mild cognitive impairment (MCI).MethodsThirty-six patients with MCI were selected based on the internationally recognized Petersen’s criteria, and equally and randomly assigned to two groups. The treated group was treated with WYG and the control group was treated with placebo for 3 months. In addition, 20 healthy subjects were included in the study as the normal control group. Changes of memory function, SOD activity, MDA content, leukocyte mtDNA deletion rate and A β1–28 content were observed before and after treatment.ResultsCompared with the normal control group, the memory quotient and SOD activity in patients with MCI decreased significantly (P < 0.01), while MDA, A β1–28 levels and the leukocyte mtDNA deletion rate increased significantly (P < 0.01). After treatment, levels of memory quotient and serum SOD activity increased while the serum MDA level, leukocyte mtDNA deletion rate and A β1–28 level decreased in the treated group compared with those before treatment (P<0.01, P<0.05). Meanwhile, leukocyte mtDNA deletion rate and A β1–28 content in the treated group were all lower than those in the control group (P<0.05).ConclusionWYG could improve memory function in patients with MCI and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase, the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage. WYG shows clinical significance in delaying the progression of MCI.

Modified Wu-Zi-Yan-Zong prescription, a traditional Chinese polyherbal formula, suppresses lipopolysaccharide-induced neuroinflammatory processes in rat astrocytes via NF-κB and JNK/p38 MAPK signaling pathways.

Neuroinflammation plays an important role in several neurodegenerative diseases. In this study, we investigated the anti-inflammatory properties of modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese polyherbal formula, in primary cultured rat astrocytes treated with lipopolysaccharide (LPS). The results showed that MWP significantly inhibited release of nitric oxide (NO) and prostaglandin E (PGE), as well as expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in LPS-induced rat astrocytes. Mechanism study indicated that MWP significantly inhibited nuclear factor-kappa B (NF-κB) inflammatory signaling pathway through attenuating inhibitor of nuclear factor-κB (IκB) degradation and down-regulating IκB kinases (IKKs) phosphorylation level. Moreover, MWP also decreased c-Jun NH(2)-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which play an important role in the induction of proinflammatory gene expressions. At last, MWP protected neurons from LPS-activated astrocytes in neuron-astrocyte co-culture system. Taken together, our results suggest that MWP may act to suppress neuroinflammatory response in LPS-stimulated rat astrocytes via NF-κB and JNK/p38 MAPK signaling cascades, and MWP may be a useful agent for prevention and treatment of neuroinflammatory disease.

Relationship between tissue distributions of modified Wuzi Yanzong prescription (加味五子衍宗方) in rats and meridian tropism theory

ObjectiveTo investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription (加味五子衍宗方, MWP) in rats and meridian tropism theory.MethodsA high-performance liquid chromatography with Fourier transform-mass spectrometry (HPLC-FT) method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature.ResultsNineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine.ConclusionThe tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.