• The Korean Journal of Pain
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• 제37권3호
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• pp.218-232
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• 2024

Background: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). Methods: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine H₁-receptor antagonist, 20 mg/kg), cimetidine (histamine H₂-receptor antagonist, 12.5 mg/kg), flumazenil (GABA_A/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systems implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Results: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS remained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC₅₀) of HECS was 161.32 ± 0.03 ㎍/mL. Conclusions: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 1999년도 춘계학술발표논문집 논문집
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• pp.243-248
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• 1999

There is substantial evidence that anatomical connections and functional interactions exist between vestibular and autonomic systems. Heart rate variability (HRV) including mean, standard deviation, coefficient of variation (CV), power spectrum was analyzed for evaluation of the physiological role of the vestibular system on control of heart rate in rabbits. In anesthetized rabbits, electrical stimulation of the vagus nerve decreased heart rate and decreased LF/HF by increasing HF. On the cervical sympathetic nerve increased heart rate and increased LF/HF by increasing LF. Atropine, cholinergic blocker, increased heart rate and increased LF/HF by reducing HF, and propranolol, ${\beta}$-adrenergic blocker, decreased heart rate and decreased LF/HF by reducing LF> In unanesthetized rabbits, stimulation of the vestibular system induced by rotation or caloric increased heart rate and increased LF/HF by increasing LF> Also electrical stimulation of the vestibular nerve produced the same of effects as rotation or caloric in anesthetized rabbits. These results suggest that Stimulation of the vestibular system increased heart rate not by inhibiting the parasympathetic nerve but by activating the sympathetic nerve.

• 한국패류학회지
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• 제25권1호
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• pp.15-22
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• 2009

Because it is known that bivalve hearts contain various modulatory systems activated by neuroendocrine substances, it was examined whether different classes of endogenous and synthetic drugs of neuroendocrinological importance can influence cardiac functions of the Pacific oyster Crassostrea gigas. Cholinergically active agents acetylcholine and carbachol increased heart rates while diminishing cardiac contractility. Adrenergically active substances norepinephrine (NE) and epinephrine (Epi) also induced heart rate increase and contractility decrease. An $\alpha_1$-adrenergic receptor-selective agonist phenyephrine (PE) failed to modulate either parameter. The Epi-induced heart rate increase and contractile depression were both blocked significantly by non-selective $\beta_1/\beta_2$-adrenergic antagonist propranolol. A $\beta_1$-selective antagonist atenolol prevented Epi-induced heart rate decrease but not the contractile depression, suggesting possible $\beta_2$ receptors for Epi-induced contractile depression. The three autacoids examined exerted discrete responses: histamine increased heart rate and depressed contraction; $\gamma$-amino-butyric acid increased both parameters; serotonin failed to change either parameter. The 5 piscine anesthetic agents examined, MS-222, benzocaine, quinaldine, urethane, pantocaine and pentobarbital, all failed to influence the cardiac function of oysters. Collectively, activities of neuroendocrinologically acting agents in mammals showed unexpected and distinct activities from those in mammalian cardiovascular systems. These results obtained from substances of different physiological functions can serve as a basis for understanding neuroendocrine control of the heart function in Pacific oyster.

• 대한약침학회지
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• 제23권1호
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• pp.1-7
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• 2020

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.101-107
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• 2004

Repeated administration of psychostimulants such as amphetamines increases locomotor activity in rodents. These drugs, including methamphetamine, enhance dopaminergic neurotransmission and result in hyper-locomotion and behavioral sensitization. It is well known that the existence of a complex balance between the cholinergic and dopaminergic systems in the central nervous system. Thus, behavioral sensitization by methamphetamine may be related to the expression of the M1 muscarinic acetylcholine receptors gene. The present study investigated the changes of M1R mRNA in hyperlocomotor activity and behavioral sensitization by methamphetamine (2 mg/kg) in mice. Our results showed that M1R mRNA expression was increased in the frontal cortex and the hippocampus region (the CA2 region) in the acute methamphetamine administered group compared to the saline administered group. In the chronic group, M1R mRNA expression was increased in the frontal cortex ill1d the hippocampus regions (CA2 and DG regions) in melt1amphetamine administered group compared to saline control group. These results indicate that acute or chronic treatment of mathamphetamine leads to the region-specific changes in mRNA expression levels of M1R. Therefore, Therefore, the present result suggests that M1R may play a role in modulating of methamphetamine-induced behavioral sensitization in mice.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.182-190
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• 2007

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the aged related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents like piracetam and cholinesterase inhibitors like $Donepezil^{\circledR}$ are used in situations where there is organic disorder in learning abilities, but the resulting side-effects associated with these agents have limited their utility. Foeniculum (F.) vulgare Linn. is widely used in Indian traditional systems of medicines and also as a house remedy for nervous debility. The present work was undertaken to assess the potential of F. vulgare as a nootropic and anti-cholinesterase agent in mice. Exteroceptive behavioral models such as Elevated plus maze and Passive avoidance paradigm were employed to assess short term and long term memory in mice. To delineate the possible mechanism through which F. vulgare elicits the anti-amnesic effects, its influence on central cholinergic activity was studied by estimating the whole brain acetylcholinesterase activity. Pretreatment of methanolic extract of fruits of F. vulgare Linn. for 8 successive days, ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging induced memory deficits in mice. F. vulgare extract significantly decreased transfer latencies of young mice and aged mice, increased step down latency and exhibited significant anti-acetyl cholinesterase effects, when compared to piracetam, scopolamine and control groups of mice. F. vulgare might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly.

• Journal of Ginseng Research
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• 제42권4호
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• pp.401-411
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• 2018

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

• Biomolecules & Therapeutics
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• 제13권1호
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• pp.26-31
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• 2005

The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.

• Journal of Ginseng Research
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• 제34권1호
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• pp.51-58
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• 2010

This study compared the effects of black, white, and red ginseng extracts (WGE, RGE, BGE, 200 mg/kg, p.o.) on learning and memory deficits associated with scopolamine treatment (SCOP, 2 mg/kg, i.p.). Tacrine (THA, 10 mg/kg, p.o.) was used as a positive control. Ginseng significantly reversed SCOP-induced memory impairment in the passiveavoidance test and also reduced escape latency in training trials of the Morris water maze test. The increased acetylcholinesterase (AChE) activity produced by SCOP was significantly inhibited by WGE and RGE (p<0.001). SCOP administration had no effect on choline acetyltransferase (ChAT) activity, but RGE and BGE significantly increased ChAT activity (p<0.05). SCOP administration increased oxidative damage in the brain. Treatment of amnesic mice with ginseng extracts decreased malondialdehyde (MDA) levels and restored superoxide dismutase (SOD) and catalase (CAT) activity to control levels. These results suggest that black ginseng enhances cognitive activity by regulation of cholinergic enzymes and antioxidant systems.

• 대한약리학회지
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• 제27권1호
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• pp.21-31
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• 1991

미주신경절단 가토에서 니코틴성약물인 nicotine과 DMPP뿐아니라 무스카린성 약물인 muscarine과 bethanechol은 측뇌실내 투여로 모두 혈압상승작용을 나타냈다. Nicotine과 DMPP에 대한 승압반응은 측뇌실내 mecamylamine처리로 현저히 감약되었으나 측뇌실내 pirenzepine처리에 의해서는 영향받지 않았고, muscarine과 bethanechol에 대한 승압반응은 pirenzepin에 의해서는 억제되나 mecamylamine에 의해서는 영향받지 않았다. 이는 뇌내의 니코틴성 수용체 및 무스카린성 수용체가 모두 혈압상승에 관여함을 가리키고 있다. Nicotine과 muscarine에 대한 승압반응은 regitine, reserpine, enalapril, saralasin, SK&F-100273, regitine과 enalapril, regitine과 saralasin의 정맥내 처리에 의해서는 억제되지 않았으며 nicotine에 대한 승압반응은 regitine과 SK&F-100273 두약물의 병용처리에 의해서 억제되었고 muscarine에 의한 승압반응은 regitine, enalapril과 SK&F-100273의 세가지 약물의 병용처리에 의해서만 억제되었다. Nicotine이나 muscarine에 의한 혈압상승상태에서 정맥내 regitine의 투여는 혈압하강을 일으켰으나 enalapril이나 SK&F-100273은 혈압하강을 일으키지 못하였다. Enalapril은 regitine처리나 regitine과 SK&F-100273병용처리 가토에서 nicotine에 의해 상승된 혈압을 하강시키지 못하였으나 SK&F-100273은 regitine처리 가토에서 nicotine에 의한 상승된 혈압을 하강시켰다. Enalapril은 이러한 SK&F-100273의 할압하강작용을 강화시키지 못하였다. Enalapril은 regitine 처리 가토에서 muscarine에 의하여 상승된 혈압은 하강시키지 못하였으나, regitine과 SK&F-100273병용처리 가토에서 muscarine에 의해 상승된 혈압은 하강시켰다. SK&F-100273은 regitine처리 가토에서 muscarine에 의해 상승된 혈압을 하강시키지 못했으나 regitine과 enalapril병용처리 가토의 상승된 혈압은 하강시켰다. 이상의 성적은 뇌실내 nicotine에 의한 혈압상승에는 말초에서 교감신경계와 vasopressin이 관여하며 muscarine에 의한 혈압상승에는 교감신경계, vasopressin 및 angiotensin계가 관여함을 시사하고 있다. Regitine의 정상 가토 혈압하강작용은 enalapril이나 SK&F-100273의 단독처리에 의해서는 영향받지 않았으나 이 두약물을 병용처리시에는 유의하게 강화되었고, 이는 가토 동맥압의 유지에 교감신경, renin-angiotensin 및 vasopressin계가 관여함을 시사하고 있다.