Taewon Han

Chlorogenic Acid from Hawthorn Berry (Crataegus pinnatifida Fruit) Prevents Stress Hormone‐Induced Depressive Behavior, through Monoamine Oxidase B‐Reactive Oxygen Species Signaling in Hippocampal Astrocytes of Mice

SCOPE Oxidative stress has been implicated in mental disorders, including depression. Chlorogenic acid (CGA), one of the abundant phenolic compounds in herbs and fruits, has the properties of a natural antioxidant and free-radical scavenger. Therfore, we investigated the antidepressant-like effects and active mechanisms of CGA from the extract of Crataegus pinnatifida (CP) fruit. METHODS AND RESULTS Depression-like phenotypes were induced in mice by daily injection of stress hormone for 1-2 weeks. The brains of these animals exhibited reduced brain-derived neurotrophic factor expression and increased astrocytic hypertrophy, which are typical markers of depression in animal models. Stress hormone injection 1) upregulated monoamine oxidase B (MAOB) expression and 2) reduced spine numbers along neuronal dendrites, which indicates synaptic depression. The oral administration of CGA (30 mg kg-1 ) or CP (300 mg kg-1 ) prevented MAOB activation following reactive oxygen species (ROS) production and had an ameliorative effect on depressive behavioral tests (e.g., tail suspension and forced swim tests). In vitro assays performed on cultured C8-D1A cells revealed that CGA and CP inhibited MAOB activity and ROS production. CONCLUSION Our study indicates that CGA and CP extracts prevented depressive behavior and thereby have potential as natural antidepressants.

Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M 2 and M 3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.