Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.

Loganin ameliorates depression-like behaviors of mice via modulation of serotoninergic system.

RATIONALE: Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression. OBJECTIVE: To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process. METHODS: We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively. RESULTS: Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST. CONCLUSION: Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

Connexins in oligodendrocytes and astrocytes: Possible factors for demyelination in multiple sclerosis.

Increasing evidences support that glial connexins are involved in the demyelination pathology of multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. Here, we review the data from patients with MS and animal models of MS that implicate connexins in demyelination. Connexins expressed in oligodendrocytes and astrocytes show diverse changes at the different phases of MS. Loss of oligodendrocyte or astrocyte connexins contributes to demyelination and exaggerates the pathology of MS. Channel-dependent and -independent connexins are involved in the pathology of demyelination, which is related with myelin integrity, metabolic homeostasis, the brain-blood barrier, the immune cell infiltration, and the inflammatory response. A comprehensive understanding of connexin function in demyelination may provide new therapeutic targets for MS.