Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release

Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeonjoong; Hwang, Sung‐Hee; Lee, Myung Koo; Bae, Chun‐Sik; Kim, Hyoung‐Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

doi:10.1016/j.neulet.2015.12.026

Cited by 22 publications

(18 citation statements)

References 15 publications

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“…A Rotarod treadmill device was purchased from Ugo Basile (S.R.L., VA, Italy). One hour after the injection of GBT or EA stimulation, mice of all groups were placed on a rotating drum revolving at a constant speed of 20 revolutions per minute [ 40 ]. Before the test, animals were trained to adapt to the horizontal revolving rod.…”

Section: Methodsmentioning

confidence: 99%

The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain

Kim

Lee

Jang

et al. 2017

Korean J Physiol Pharmacol

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Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, 20 μg), or noradrenergic (idazoxan, 10 μg) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

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Section: Methodsmentioning

confidence: 99%

The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain

Kim

Lee

Jang

et al. 2017

Korean J Physiol Pharmacol

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“…35 The performance was determined via measuring the latency of mice to stay on a 3 cm diameter drum accelerated from 4 to 40 rpm. The latency to falling was recorded automatically.…”

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confidence: 99%

Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

Zhu

Wang

et al. 2016

IJN

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Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment.

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“…LPI and GPR55 are implicated as potential key modulators of stress responses, depression, motor functions, and memory in the central nervous system, since GPR55 is highly expressed in the cortex, hippocampus, striatum, and spinal cord [22][23][24]. In previous studies, we showed that gintonin attenuated depressive behaviors, enhanced motor function performance, and enhanced hippocampal-dependent cognitive functions [11,35,36]. Although we did not demonstrate that these gintonin-mediated effects on the central nervous system were directly achieved via GPR55, gintonin LPIs and LPAs might play important roles in various brain functions.…”

Section: Discussionmentioning

confidence: 93%

Ginseng Gintonin Contains Ligands for GPR40 and GPR55

et al. 2020

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Gintonin, a novel ginseng-derived glycolipoprotein complex, has an exogenous ligand for lysophosphatidic acid (LPA) receptors. However, recent lipid analysis of gintonin has shown that gintonin also contains other bioactive lipids besides LPAs, including linoleic acid and lysophosphatidylinositol (LPI). Linoleic acid, a free fatty acid, and LPI are known as ligands for the G-protein coupled receptors (GPCR), GPR40, and GPR55, respectively. We, herein, investigated whether gintonin could serve as a ligand for GPR40 and GPR55, using the insulin-secreting beta cell-derived cell line INS-1 and the human prostate cancer cell line PC-3, respectively. Gintonin dose-dependently enhanced insulin secretion from INS-1 cells. Gintonin-stimulated insulin secretion was partially inhibited by a GPR40 receptor antagonist but not an LPA1/3 receptor antagonist and was down-regulated by small interfering RNA (siRNA) against GPR40. Gintonin dose-dependently induced [Ca2+]i transients and Ca2+-dependent cell migration in PC-3 cells. Gintonin actions in PC-3 cells were attenuated by pretreatment with a GPR55 antagonist and an LPA1/3 receptor antagonist or by down-regulating GPR55 with siRNA. Taken together, these results demonstrated that gintonin-mediated insulin secretion by INS-1 cells and PC-3 cell migration were regulated by the respective activation of GPR40 and GPR55 receptors. These findings indicated that gintonin could function as a ligand for both receptors. Finally, we demonstrated that gintonin contained two more GPCR ligands, in addition to that for LPA receptors. Gintonin, with its multiple GPCR ligands, might provide the molecular basis for the multiple pharmacological actions of ginseng.

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Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release

Cited by 22 publications

References 15 publications

The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain

The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain

Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

Ginseng Gintonin Contains Ligands for GPR40 and GPR55

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