Antagonism for NPY signaling reverses cognitive behavior defects induced by activity-based anorexia in mice.

Patients with AN often express psychological symptoms such as body image distortion, cognitive biases, abnormal facial recognition, and deficits in working memory. However, the molecular mechanisms underlying the impairment of cognitive behaviors in AN remain unknown. In the present study, we measured cognitive behavior using novel object recognition (NOR) tasks and mRNA expressions in hypothalamic neuropeptides in female C57BL/6J mice with activity-based anorexia (ABA). Additionally, we evaluated the effects of antagonists with intracerebroventricular (icv) administration on the impairment of cognitive behavior in NOR tasks. Our results showed that NOR indices were lowered, subsequently increasing mRNA levels of agouti-related peptide (AgRP) and neuropeptide Y (NPY), and c-Fos- and AgRP- or NPY-positive cells in the hypothalamic arcuate nucleus in ABA mice. We also observed that icv administration of anti-NPY antiserum (2 µl), anti-AgRP antibody (0.1 µg), and Y5 receptor antagonist CPG71683 (15 nmol) significantly reversed the decreased NOR indices. Therefore, our results suggest that increased NPY and AgRP signaling in the brain might contribute to the impairment of cognitive behavior in AN.

Good Rehabilitation Outcomes and Improved Nutritional Status After Treatment With the Japanese Herbal Medicine Ninjin'yoeito in an Elderly Patient With Hip Fracture and Sarcopenia: A Case Report.

We report a case involving a 92-year-old man who successfully received treatment with ninjin'yoeito, a Japanese herbal medicine, during the rehabilitation phase after hip fracture surgery. The patient was diagnosed with a left femoral neck fracture and underwent surgery. Two weeks after surgery, he was admitted to a rehabilitation hospital. At that time, his height, weight, body fat percentage, muscle mass, and Functional Independence Measure (FIM) score were 167 cm, 61 kg, 34.1%, 38.2 kg, and 49, respectively. For 1 month after surgery (i.e., 2 weeks after admission to the rehabilitation facility), he received rikkunshito, a traditional Japanese herbal medicine also known as Kampo medicine, for appetite loss and underwent rehabilitation. However, his appetite loss showed no improvement, and rikkunshito (7.5 g/d) was replaced with ninjin'yoeito (7.5 g/d). Two months later, although the patient's body weight and body fat percentage decreased to 56.5 kg and 21.1%, respectively, his muscle mass increased to 38.9 kg. Nutritional status evaluation indicated an improvement in the level of proteins such as transferrin, prealbumin, and retinol-binding protein, which reflected an increase in food intake. The FIM score improved from 49 to 105. No side effects were observed. The findings from this case suggest that ninjin'yoeito, which includes Astragalus root and Schisandra fruit, may be an effective treatment option for sarcopenia or frailty with appetite loss and impaired activities of daily living in aged patients.

Rubiscolin-6 activates opioid receptors to enhance glucose uptake in skeletal muscle.

Rubiscolin-6 is an opioid peptide derived from plant ribulose bisphosphate carboxylase/oxygenase (Rubisco). It has been demonstrated that opioid receptors could control glucose homeostasis in skeletal muscle independent of insulin action. Therefore, Rubiscolin-6 may be involved in the control of glucose metabolism. In the present study, we investigated the effect of rubiscolin-6 on glucose uptake in skeletal muscle. Rubiscolin-6-induced glucose uptake was measured using the fluorescent indicator 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose (2-NBDG) in L6 and C2C12 cell lines. The protein expressions of glucose transporter 4 (GLUT4) and AMP-activated protein kinase (AMPK) in L6 cells were observed by Western blotting. The in vivo effects of rubiscolin-6 were characterized in streptozotocin (STZ)-induced diabetic rats. Rubiscolin-6 induced a concentration-dependent increase in glucose uptake levels. The increase of phospho-AMPK (pAMPK) and GLUT4 expressions were also observed in L6 and C2C12 cells. Effects of rubiscolin-6 were blocked by opioid receptor antagonists and/or associated signals inhibitors. Moreover, Rubiscolin-6 produced a dose-dependent reduction of blood glucose and increased GLUT4 expression in STZ-induced diabetic rats. In conclusion, rubiscolin-6 increases glucose uptake, potentially via an activation of AMPK to enhance GLUT4 translocation after binding to opioid receptors in skeletal muscle.

The Role of Ghrelin and Ghrelin Signaling in Aging.

With our aging society, more people hope for a long and healthy life. In recent years, researchers have focused on healthy longevity factors. In particular, calorie restriction delays aging, reduces mortality, and extends life. Ghrelin, which is secreted during fasting, is well known as an orexigenic peptide. Because ghrelin is increased by caloric restriction, ghrelin may play an important role in the mechanism of longevity mediated by calorie restriction. In this review, we will discuss the role of orexigenic peptides with a particular focus on ghrelin. We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may play an important role in the anti-aging mechanism.

A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders.

Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.