Lactobacillus plantarum LMT1-48 exerts anti-obesity effect in high-fat diet-induced obese mice by regulating expression of lipogenic genes.

Obesity is a major health problem and is known to be closely associated with metabolic diseases. Abnormal hepatic accumulation of fat causes fatty liver or hepatic steatosis, and long-term consumption of a high-fat diet is known to be a key obesity-causing factor. Recent studies have demonstrated that probiotics such as Lactobacillus strains, exert an anti-obesity effect by regulating adipogenesis. However, it is still unknown how the consumption of probiotics can reduce abdominal fat volume by regulating the hepatic expression of lipogenic genes. Therefore, we evaluated the effect of long-term ingestion of L. plantarum LMT1-48 on the expression of lipogenic genes in high-fat diet (HFD)-fed mice. We observed that treatment of 3T3-L1 adipocytes with L. plantarum LMT1-48 extract inhibited their differentiation and lipid accumulation by downregulating lipogenic genes, namely, PPARγ, C/EBPα, FAS, and FABP4. Interestingly, administration of L. plantarum LMT1-48 reduced liver weight and liver triglycerides concurrently with the downregulation of the lipogenic genes PPARγ, HSL, SCD-1, and FAT/CD36 in the liver, resulting in the reduction of body weight and fat volume in HFD-fed obese mice. Notably, we also observed that the administration of at least 106 CFU of L. plantarum LMT1-48 significantly lowered body weight and abdominal fat volume in modified diet-fed mouse models. Collectively, these data suggest that L. plantarum LMT1-48 is a potential healthy food for obese people.

Antiobesity Effects of Lactobacillus plantarum LMT1-48 Accompanied by Inhibition of Enterobacter cloacae in the Intestine of Diet-Induced Obese Mice.

The gut microbiota is the most important environmental factor that plays a role in inducing obesity. The gram-negative bacteria, Enterobacter cloacae strains, recently identified in obese mice are considered to be pathogenic bacteria in the gut. Probiotics are important members of the gut microbiota and exert beneficial effects, including inhibiting the growth of potential pathogenic bacteria. Therefore, we isolated a total of 230 lactic acid bacteria from traditional, Korean fermented foods and fecal samples from newborn infants, including Lactobacillus plantarum LMT1-48, which exhibited maximal antimicrobial activity against E. cloacae. We next investigated the functional antiobesity effects of L. plantarum LMT1-48 in an E. cloacae-induced high-fat diet (HFD)-fed animal obesity model. To this end, the L. plantarum LMT1-48 showed antiobesity effects, including body weight loss and reduction of abdominal fat volume, which was accompanied by a decrease in leptin and total cholesterol levels in E. cloacae-induced HFD-fed mice. Notably, gut microbiota diversity also increased after long-term ingestion of L. plantarum LMT1-48, resulting in amelioration of obesity in E. cloacae-induced HFD-fed mice. Accordingly, results suggest that dietary intake of L. plantarum LMT1-48 protects against the onset of E. cloacae-induced obesity.

Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis.

Houttuyniae Herba Attenuates Kainic Acid-Induced Neurotoxicity via Calcium Response Modulation in the Mouse Hippocampus.

Epilepsy is a complex neurological disorder characterized by the repeated occurrence of electrical activity known as seizures. This activity induces increased intracellular calcium, which ultimately leads to neuronal damage. Houttuyniae Herba, the aerial part of Houttuynia cordata, has various pharmacological effects and is widely used as a traditional herb. In the present study, we evaluated the protective effects of Houttuyniae Herba water extract on kainic acid-induced neurotoxicity. Kainic acid directly acts on calcium release, resulting in seizure behavior, neuronal damage, and cognitive impairment. In a rat primary hippocampal culture system, Houttuyniae Herba water extract significantly protected neuronal cells from kainic acid toxicity. In a seizure model where mice received intracerebellar kainic acid injections, Houttuyniae Herba water extract treatment resulted in a lower seizure stage score, ameliorated cognitive impairment, protected neuronal cells against kainic acid-induced toxicity, and suppressed neuronal degeneration in the hippocampus. In addition, Houttuyniae Herba water extract regulated increases in the intracellular calcium level, its related downstream pathways (reactive oxygen species production and mitochondrial dysfunction), and calcium/calmodulin complex kinase type II immunoreactivity in the mouse hippocampus, which resulted from calcium influx stimulation induced by kainic acid. These results demonstrate the neuroprotective effects of Houttuyniae Herba water extract through inhibition of calcium generation in a kainic acid-induced epileptic model.

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3ß pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: A growing body of literature supports the concept that antiaging herbs may be potential candidates for use in treating age-related neurodegeneration, including Alzheimer׳s disease (AD). Mori Fructus is a well-known traditional herbal medicine, food, and dietary supplement. This study employed models of amyloid beta (Aß)-induced AD to investigate the protective effects of Mori Fructus ethanol extract (ME) against age-related disease and cognitive deficits. MATERIALS AND METHODS: To examine the protective effect of ME, we measured cell viability, cytotoxicity, and survival in rat primary hippocampal cultures. We performed behavioral tests and histological analysis in mouse models of AD induced by Aß(25-35) toxicity. To investigate the mechanism underlying the protective effect, we performed western blotting using antibodies against apoptotic markers as well as the nonphosphorylated and phosphorylated forms of Akt, glycogen synthase kinase-3ß (GSK-3ß), and tau. We also measured apoptotic marker fluorescence intensity. RESULTS: ME significantly attenuated Aß-induced cell damage, enhanced Akt and GSK-3ß phosphorylation, and reduced tau phosphorylation. ME reduced apoptotic markers that were activated by GSK-3ß, and reduced reactive oxygen species production. Further, ME decreased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X expression ratio, mitochondria depolarization, cytochrome c release from mitochondria, and caspase-3 activation. We confirmed that ME treatment improved cognitive impairment and neuronal cell death induced by Aß(25-35) toxicity in the mouse hippocampus via its antiapoptotic activity. CONCLUSIONS: These results indicate that ME protects cognition and neurons in AD-like models induced by Aß via reduction of tau phosphorylation and apoptosis through GSK-3ß inactivation.

Mori folium and mori fructus mixture attenuates high-fat diet-induced cognitive deficits in mice.

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities.

Cistanches Herba enhances learning and memory by inducing nerve growth factor.

Nerve growth factor (NGF) has potent biological activities such as preventing neuronal death, promoting neurite outgrowth, supporting synapse formation, and enhancing memory function. NGF and NGF-like molecules can potentially be used to treat neurodegenerative disorders, such as dementia. This study investigated the effects of Cistanches Herba, a widely used medicinal herb, on NGF regulation and its neuronal actions, including neurite outgrowth, synapse formation, and learning and memory enhancement. Cistanches Herba extract (CHE; 250 µg/ml) increased NGF induction in C6 cells and led to neurite extension in PC12 cells. It also stimulated NGF secretion in the cortex and hippocampus of the mouse brain at 5 and 20mg/kg/day (3 days, p.o.). Furthermore, CHE increased neuronal cell differentiation, neurite length, and synapse formation in the mouse hippocampus. CHE significantly enhanced learning and memory, as demonstrated by passive avoidance test and novel object recognition test. These results suggest that CHE is useful for improving memory function via its action in upregulating NGF.