An Aqueous Extract of Herbal Medicine ALWPs Enhances Cognitive Performance and Inhibits LPS-Induced Neuroinflammation via FAK/NF-κB Signaling Pathways.

Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In the present study, we developed ALWPs, a mixture of Antler and LWPs, and investigated whether ALWPs can affect neuroinflammatory responses. We found that ALWPs (500 mg/ml) inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine IL-1ß mRNA levels in BV2 microglial cells but not primary astrocytes. ALWPs significantly reduced LPS-induced cell-surface levels of TLR4 to alter neuroinflammation. An examination of the molecular mechanisms by which ALWPs regulate the LPS-induced proinflammatory response revealed that ALWPs significantly downregulated LPS-induced levels of FAK phosphorylation, suggesting that ALWPs modulate FAK signaling to alter LPS-induced IL-1ß levels. In addition, treatment with ALWPs followed by LPS resulted in decreased levels of the transcription factor NF-κB in the nucleus compared with LPS alone. Moreover, ALWPs significantly suppressed LPS-induced BV2 microglial cell migration. To examine whether ALWPs modulate learning and memory in vivo, wild-type C57BL/6J mice were orally administered ALWPs (200 mg/kg) or PBS daily for 3 days, intraperitoneally injected (i.p.) with LPS (250 µg/kg) or PBS, and assessed in Y maze and NOR tests. We observed that oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly rescued short- and long-term memory. More importantly, oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly reduced microglial activation in the hippocampus and cortex. Taken together, our results suggest that ALWPs can suppress neuroinflammation-associated cognitive deficits and that ALWPs have potential as a drug for neuroinflammation/neurodegeneration-related diseases, including Alzheimer's disease (AD).

Neuroprotective Effect and Molecular Mechanism of [6]-Gingerol against Scopolamine-Induced Amnesia in C57BL/6 Mice.

We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day). To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF). The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB) signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.

Toralactone glycoside in Cassia obtusifolia mediates hepatoprotection via an Nrf2-dependent anti-oxidative mechanism.

Cassia obtusifolia L. (Leguminosae) seeds are a well-known medicinal food in East Asia and are used to clear liver heat, sharpen vision, lubricate the intestines, and promote bowel movement. The aims of the present study were to identify the hepatoprotective components of C. obtusifolia seeds by bioactivity-guided isolation and to elucidate their mechanisms of action. Ten phenolic glycosides were isolated from the most active ethyl acetate fraction, and their chemical structures were elucidated by spectroscopic analyses. Among the isolated compounds, toralactone 9-O-gentiobioside (5) had the highest hepatoprotective efficacy against tert-butylhydroperoxide-induced cell death in HepG2 cells. Immunoblotting and real-time polymerase chain reaction analyses revealed that the hepatoprotective effects were exerted through nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent antioxidative signaling. Together, these results provide insights into the effects of this medicinal plant as well as a basis for developing hepatoprotective agents as pharmaceuticals and/or nutraceuticals.

Evaluation of Samjunghwan, a traditional medicine, for neuroprotection against damage by amyloid-beta in rat cortical neurons.

AIM OF THE STUDY: Samjunghwan (SJH) is a multi-herbal traditional medicine composed of Mori Fructus, Lycii Radicis Cortex, and Atractylodis Rhizoma Alba and it is clinically applied as an anti-aging agent in neurodegenerative disorders, to promote longevity. In the present study, we evaluated the neuroprotective effect of SJH in Alzheimer's disease induced by amyloid-beta (Abeta) and examined the related pathways. MATERIALS AND METHODS: To evaluate the protective effect of SJH, we conducted thiazolyl blue tetrazolium bromide, lactate dehydrogenase, and MAP-2 staining assays of primary cultured rat cortical neurons stressed by Abeta(25-35). To investigate the possible mechanism of action, we examined the Bcl-2/Bax expression ratio, mitochondrial membrane potential (Deltapsi(M)), cytochrome C release, and caspase-3 activation, focusing on the mitochondria-mediated apoptotic pathways. RESULTS: SJH at concentrations of 10 and 100 microg/ml provided significant protection of rat cortical neurons from Abeta(25-35) neurotoxicity. At the maximum effective dose of 100 microg/ml, SJH significantly increased the anti-apoptotic protein (Bcl-2)/pro-apoptotic protein (Bax) ratio and inhibited Deltapsi(M) depolarization, cytosolic cytochrome C release, and caspase-3 activation. CONCLUSION: SJH appears to provide neuroprotection against mitochondria-mediated apoptotic pathways in this Abeta(25-35)-induced Alzheimer's disease model.