The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut–brain axis.

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Four anthraquinones isolated for the first time from the aerial parts of Rumex acetosa (Polygonaceae), a Korean and a Japanese medicinal plant, and two synthetic derivatives were examined for their cytotoxicities against five cultured human tumor cell lines, i.e. A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCY15 (colon), using the Sulfrhodamine-B method in vitro and antimutagenic activities by Ames test with Salmonella typhimurium TA98 and TA100 and SOS chromotest with E. coli PQ37. Among the tested compounds, emodin strongly inhibited the proliferation of each examined tumor cell line with IC 50 values ranged from 2.94 to 3.64 m mg/ml and showed potent antimutagenic activities with 71.5% and 53.3% at the concentration of 0.1 mg/plate against the mutagens, NPD and sodium azide, respectively. Its antigenotoxic activity was also very effective at the final concentration of 10 m mg/reaction tube against the mutagens, MNNG and NQO by SOS chromotest, reducing the induction factors by 19.6% and 43.5%, respectively. The structure-activity correlation study suggests that an additional OH group at C-6 position in the anthraquinone nucleus may play an important role for their cytotoxicities and an introduction of OH-or OCH 3 group at C-6 position is necessary for their antimutagenicities.

The present study was designed to evaluate central inhibitory effects of the essential oil from Acori graminei Rhizoma (AGR), the dry rhizomes of Acorus gramineus SOLANDER (Araceae) upon fragrance inhalation (aroma therapy). Preinhalation of the oil markedly delayed the appearance of pentylenetetrazole-induced convulsion. Furthermore, inhalation impressively inhibited the activity of gamma-aminobutyric acid (GABA) transaminase, a degrading enzyme for GABA as the inhalation period was lengthened. The GABA level was significantly increased and glutamate content was significantly decreased in mouse brain by preinhalation of the essential oil. The above results suggest that the anticonvulsive effect of this AGR oil is originated by the enhancement of GABA level in the mouse brain, because convulsion depends partially on GABA concentration which can be properly preserved by inhibiting GABA transaminase. Moreover, fragrance inhalation progressively prolonged the pentobarbital-induced sleeping time as inhalation time was lengthened. Ten hour inhalation corresponded almost to the effect (145% increase) of oral administration (60 mg/kg). This sedative effect after inhalation or oral administration of AGR essential oil suggests that this oil may act on the CNS via the GABAergic system. The inhibitory activity of preinhalation of the essential oil on lipid peroxidation, to which the anticonvulsive action is attributed, also supported the above results, confirming and amplifying our previous reports on the CNS inhibitory effects of AGR.

Forest bathing is suggested to have beneficial effects on various aspects of human health. Terpenes, isoprene based-phytochemicals emitted from trees, are largely responsible for these beneficial effects of forest bathing. Although the therapeutic effects of terpenes on various diseases have been revealed, their effects on neuronal health have not yet been studied in detail. Here, we screened 16 terpenes that are the main components of Korean forests using Drosophila Alzheimer's disease (AD) models to identify which terpenes have neuroprotective effects. Six out of the 16 terpenes, ρ-cymene, limonene (), limonene (), linalool, α-pinene (), and β-pinene (), partially suppressed the beta amyloid 42 (Aβ42)-induced rough eye phenotype when fed to Aβ42-expressing flies. Among them, limonene () restored the decreased survival of flies expressing Aβ42 in neurons during development. Limonene () treatment did not affect Aβ42 accumulation and aggregation, but did cause to decrease cell death, reactive oxygen species levels, extracellular signal-regulated kinase phosphorylation, and inflammation in the brains or the eye imaginal discs of Aβ42-expressing flies. This neuroprotective effect of limonene () was not associated with autophagic activity. Our results suggest that limonene () has a neuroprotective function against the neurotoxicity of Aβ42 and, thus, is a possible therapeutic reagent for AD.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive neuronal loss with amyloid β-peptide (Aβ) plaques. Despite several drugs currently used to treat AD, their beneficial effects on AD progress remains under debate. Here, we established a rapid in vivo screening system using Drosophila AD models to assess the neuroprotective activities of medicinal plants that have been used in traditional Chinese medicine. Among 23 medicinal plants tested, the extracts from five plants, Coriandrum sativum, Nardostachys jatamansi, Polygonum multiflorum (P. multiflorum), Rehmannia glutinosa, and Sorbus commixta (S. commixta), showed protective effects against the Aβ42 neurotoxicity. We further characterized the neuroprotective activity of ethanol extracts from P. multiflorum and S. commixta. Aβ42-expressing flies that we used showed AD neurological phenotypes, such as decreased survival and motility and increased cell death and reactive oxygen species level. However, feeding these flies extracts from P. multiflorum or S. commixta showed strong suppression of such phenotypes. Similar results were observed in human cells, so that the treatment of P. multiflorum and S. commixta extracts increased the viability of Aβ-treated SH-SY5Y cells. Moreover, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, one of the main constituents of P. multiflorum, also showed similar protective activity against Aβ42 cytotoxicity in both Drosophila and human cells. Taken together, our results suggest that both P. multiflorum and S. commixta have therapeutic potential for the treatment of neurodegenerative diseases, such as AD.Key words amyloid β-peptide 42 (Aβ42); Alzheimer's disease; Drosophila; Polygonum multiflorum; reactive oxygen species (ROS); Sorbus commixta Alzheimer's disease (AD) is a common neurodegenerative disease that is characterized by progressive neural loss caused by amyloid β-peptide (Aβ) plaques and cognitive deficits. 1,2) During disease progression, neurotoxic forms of Aβ cause neuronal damages via various cellular abnormalities such as increased oxidative damage, impaired energy metabolism, disrupted cellular calcium homeostasis, and increased inflammatory response.2,3) Several drugs have been approved to treat AD, given the dysfunction of cholinergic and glutamatergic neurotransmission; they function as acetylcholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. 4,5) However, the beneficial effects of these drugs during the progression of AD are still in question. 6) Due to its complex etiology, a combination therapy including the use of medicinal plants with effective components has been proposed as an alternative choice for treatment of AD. 7,8) Chinese traditional medicine has employed a variety of herbs to treat dementia, and a number of neuroprotective agents were isolated from these herbs. 7,8) For example, Polygonum multiflorum (P. multiflorum; syn. Reynoutria multiflora) has been known as a tonic and antiaging agent in many remedies for centuries, and...

Alpinae Oxyphyllae Fructus (Alpinia oxyphylla MIQ) (Korean name Ik-Jj-In) is a medicinal plant used in Korea for the treatment of various symptoms accompanying hypertension and cerebrovascular disorders. The present study was performed to investigate the effects of Alpinae Oxyphyllae Fructus water-extracts (AOF) on a cultured primary neuron cell system, cell cytotoxicity and lipid peroxidation in Abeta treatment conditions. Cell killing was significantly enhanced by addition of increasing concentrations of Abeta. Pretreatment of AOF attenuated in cell killing enhanced by increasing concentrations of Abeta. Abeta-induced cell death was protected by the application of water extract of AOF in a dose-dependent manner, and concentrations of 50 to 100 micro g/ml had a significant effect compared to exposure of Abeta only. AOF has been shown to protect primary cultured neurons from N-methyl-D-aspartate (NMDA) receptor-mediated glutamate toxicity. The evidence indicated that AOF protects neurons against ischemia-induced cell death. Oral administration of AOF into mice prevented ischemia-induced learning disability and rescued hippocampal CA1 neurons from lethal ischemic damage. The neuroprotective action of exogenous AOF was also confirmed by counting synapses in the hippocampal CA1 region. The presence of AOF in neuron cultures did not repress a NMDA receptor-mediated increase in intracellular Ca(2+), but rescued the neurons from NO-induced death. AOF may exert its neuroprotective effect by reducing the NO-mediated formation of free radicals or antagonizing their toxicity.

SuHeXiang Wan (SHXW), a Chinese traditional medicine, has been used to treat infantile convulsions, seizures and strokes. Previously, we reported that modified SHXW, called KSOP1009, suppressed the hyperactivation of c-Jun N-terminal kinase (JNK) and Alzheimer's disease (AD)-like phenotypes in amyloid-β42 (Aβ42)-expressing Drosophila AD models. In the present study, we, further, investigated the detailed mechanism by which KSOP1009 suppresses the AD-like phenotypes of the model flies. As seen in the brains of AD patients, pan-neuronal expression of Aβ42 in Drosophila increased activation of extracellular signal-regulated kinase (ERK), which was monitored by its phosphorylation level, and the number of glial cells in the brain. Suppression of caspase activity did not affect these phenomena, suggesting that Aβ42 induces ERK activation and glial cell proliferation independently of apoptotic processes. KSOP1009 intake significantly reduced the level of ERK activation and the number of glial cells. Moreover, KSOP1009 intake also effectively decreased the defects in the wing vein formation induced by Epidermal growth factor receptor (Egfr) overexpression in fly wings, suggesting that it may contain an inhibitory substance that inhibits the EGFR/ERK signaling pathway. In addition, the Aβ42-induced locomotive defect was partially rescued by inhibition of the elevated ERK activity through its antagonistic drug treatment. Taken together, these results suggest that KSOP1009 exerts its therapeutic effect by inhibiting the EGFR/ERK pathway and glial cell proliferation and by suppressing the JNK pathway and apoptosis.