Preventive Action of Kai Xin San Aqueous Extract on Depressive-Like Symptoms and Cognition Deficit Induced by Chronic Mild Stress

Abstract

Kai Xin San (KXS), a traditional Chinese herbal medicine, has been used clinically for the treatment of depressive disorders and cognitive impairment for centuries. However, the effects of KXS on cognitive dysfunction induced by depression have not been evaluated scientifically. The present study aimed to explore the antidepressant-like and nootropic effects of an aqueous extract of KXS (at doses of 0.3, 0.9, and 2.7 g/kg/day) using chronic mild stress (CMS) as a model of depression. Depressive symptoms were analyzed using the sucrose-preference and novelty-induced inhibition of feeding tests. Cognitive function was evaluated using a two-way active avoidance task. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels, acetylcholinesterase (AChE) protein expression in the hippocampus, and monoamine neurotransmitter concentrations in the prefrontal cortex and hippocampus were also determined to elucidate the neurochemical mechanisms. Experimental results showed that KXS aqueous extract significantly ameliorated the CMS-induced depressive symptoms, including the reduced preference index and prolonged latency to novelty-suppressed feeding. Simultaneously, KXS significantly reversed the CMS-induced decrease in the numbers of active avoidance and active movement distances and increase in the numbers of the passive avoidance and passive movement distances, thereby producing nootropic effects in the two-way active avoidance test. KXS also inhibited the increased AChE expression in the hippocampus, up-regulated the decreased monoamine neurotransmitter concentrations of both brain areas and reduced the elevated ACTH concentrations in the serum induced by CMS. Taken together, these results indicate that KXS exerts its antidepressant-like and nootropic effects in the CMS model by modulating the HPA axis, monoamine neurotransmitter and cholinergic systems.

Quality assessment of a formulated Chinese herbal decoction, Kaixinsan, by using rapid resolution liquid chromatography coupled with mass spectrometry: A chemical evaluation of different historical formulae

“…The herbal preparation in the form of powder is used only when the patient has to take the drug for a prolonged period of time. In the extraction of KXS, water was selected as the solvent for two reasons: (i) water is the common solvent in TCM preparation and frequently used for the KXS preparation, and (ii) the water extract of KXS was reported to exert anti-depressant-like effects on the chronic mild stress animal model [7]. The extracts were dried and stored at À201C.…”

“…Indeed, KXS has been reported to enhance the memory [6] and to relieve the symptoms of depressive disorder, as revealed in animal studies [7]. The first description of KXS is in Beiji Qianjin Yaofang oThousand Formulae for Emergency4 written by Sun Si-miao of Tang Dynasty in 652 A.D.…”

Characterization of multiple constituents in Kai-Xin-San prescription and rat plasma after oral administration by liquid chromatography with quadrupole time-of-flight tandem mass spectrometry

“…It eventually damages the ability to implement simplest tasks [1][2][3][4]. AD has been officially listed as the fifth-leading cause of death for individuals age 65 and older.…”

Antidepressant and Neuroprotective Effect of the Chinese Herb Kaixinsan against Lentiviral shRNA Knockdown Brain-Derived Neurotrophic Factor-Induced Injury in vitro and in vivo

“…In addition, previous studies have also demonstrated that KXS ameliorates learning and memory deficit in amygdala-lesioned and thymectomy-, ethanol- and scopolamine-induced injury in mice, even in senescence-accelerated mice, by the step-down or MWM test [13,18,20]. Further studies demonstrated that part of the KXS mechanism is antidepressant-like by modulating the HPA axis and the monoamine neurotransmitters [30] and increasing the levels of phosphorylated CREB in CA1, CA3 and DG in the hippocampus of rats suffering from chronic stress [29]. The effects of stress on body weight are still controversial.…”