Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons

Abstract

Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20–50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons.

Schisandrin B exerts hypnotic effects in PCPA‑treated rats by increasing hypothalamic 5‑HT and γ‑aminobutyric acid levels

“…5-HIAA is associated with analgesia and sleep. Previous studies have revealed that in animal models of insomnia or sleep deprivation, 5-HIAA levels decrease with those of 5-HT (27,28). The HTR1A gene encodes the 5-HT1A receptor, the latter of which binds to the free form of 5-HT in the synaptic space, thus mediating 5-HT function, increasing its nervous system activity and promoting sleep (29).…”

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer’s Disease

“…Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting neuron apoptosis and MMP2/9 expression (Zeng et al, 2018). Loganin exerts sedative and hypnotic effects via modulation of the serotonergic system and GABAergic neurons (Shi et al, 2019). Cornuside attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons (Jiang et al, 2009; Jiang et al, 2014).…”

Cornusglucosides A and B, Two New Iridoid Glucosides from the Fruit of Cornus officinalis

“…The IR spectrum showed absorption bands for hydroxy (3401 cm À 1 ) and carbonyl (1687 and 1639 cm À 1 ) functionalities, respectively. Its 1 H-NMR 1 [3] and the extra carbons signals (δ(C) 38.1 (CH 2 ), 41.1 (CH 2 ), 52.9 (MeO), 71.6 (CH), 75.2 (CH), 76.6 (CH), 76.7 (C) and 175.8 (C=O)), which was closely similar to those of methyl quinate. [8 -10] confirmed that the C-1' of methyl quinate groups was connected to C-7 by an ether linkage.…”

“…is a well‐known traditional Chinese medicine used for nourishing the liver and kidney in China, which has been used for thousands of years. The chemical and pharmacological studies on the fruit of C. officinalis have been lasting for many years in our group . Recently, further chemical investigation on the title plant led two new iridoid glucosides, cornusglucoside A ( 1 ) and cornusglucoside B ( 2 ) ( Figure ).…”

“…The chemical and pharmacological studies on the fruit of C. officinalis have been lasting for many years in our group. [1][2][3][4][5][6][7] Recently, further chemical investigation on the title plant led two new iridoid glucosides, cornusglucoside A (1) and cornusglucoside B (2) (Figure 1). Herein, the isolation, structural determination, and biological activity of 1 and 2 were discussed in this article.…”