• Advances in Traditional Medicine
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• 제7권4호
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• pp.409-417
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• 2007

We investigated the effect of Arogh, a polyherbal formulation (PHF) on animal models of anxiety based on exploratory behavior. The anxiolytic activity of polyherbal formulation (30, 100, 300 and 500 mg/kg) was studied using various behavioural paradigms such as elevated plus maze (EPM), light/dark apparatus (LDA), open field apparatus (OFA), hole board apparatus (HBA). Diazepam (1 mg/kg) was used as a standard anxiolytic drug. The effect of PHF (100 and 300 mg/kg) on serotonin, dopamine and noradrenaline mediated behaviour was studied by lithium induced head twitches in rats, haloperidol induced catalepsy in mice and clonidine induced hypothermia in rats respectively. In EPM, PHF (100, 300 and 500 mg/kg) significantly (P < 0.05) increased the time spent in open arms and the number of entries in open arms. In LDA, PHF (100, 300 and 500 mg/kg) significantly (P < 0.05) increased the time spent in lit zone. In OFA, PHF (100, 300 and 500 mg/kg) significantly (P < 0.05) increased the number of assisted rearing and the number of squares traversed. In HBA, PHF (100, 300 and 500 mg/kg) significantly (P < 0.05) increased the number of head poking. In lithium induced head twitches, PHF (100 and 300 mg/kg) significantly (P < 0.05) decreased the number of head twitches. In haloperidol induced catalepsy, PHF (300 mg/kg) decreased the duration of catalepsy significantly (P < 0.05) at 60 min. In clonidine-induced hypothermia, PHF (300 mg/kg) did not modify the effect. Drugs must be carefully assessed on EPM test and therefore in the present study EPM is supported by other tests. Present study indicates that Arogh, a polyherbal formulation possess anxiolytic activity. It diminished serotonergic transmission and decreased the duration of catalepsy indicating potentiation of dopaminergic transmission. Thus, Arogh a polyherbal formulation contains bioactive principles which possess anxiolytic activity and modified 5-HT and DA mediated behaviour.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

• Advances in Traditional Medicine
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• 제7권3호
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• pp.261-273
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• 2007

We investigated the antihypertensive effect of Pet ether extract (PE) of ginger rhizome; its toluene fraction (TF) and Korean ginseng extract (KGE) in deoxycorticosterone acetate (DOCA) - salt induced and fructose induced hypertensive rats. In DOCA model, DOCA (25 mg/kg, once a week; s.c) was administered in uninephrectomised animals for 4 w. PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were evaluated for their antihypertensive effect. In the fructose model, drinking water was replaced with fructose (10%) for five weeks to induce hypertension. PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were assessed for its antihypertensive effect in fructose model. After completion of the treatment schedule, vascular reactivity to various agonists like 5-HT, noradrenaline, adrenaline, phenylbiguanide and acetylcholine were recorded in rats of both the models. A cumulative dose response curve (CDRC) of 5-HT was carried out in isolated rat fundus strip of the fructose induced hypertensive rats. Chronic administration of PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o), and KGE (30 mg/kg/day; p.o) significantly reduced the blood pressure in DOCA salt whereas PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) reduced the blood pressure in fructose induced hypertensive rats. Treatment with PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) in fructose model for five weeks shifted the CDRC towards the right on rat fundus. The mechanism of action may partly involve the serotonergic antagonistic property.

• 정신신체의학
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• 제21권2호
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• pp.81-92
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• 2013

새로운 항우울제가 개발되고 임상에서 정신과적 질환뿐만이 아니라 만성통증증후군, 섬유근통증증후군, 두통 등의 많은 정신신체질환 그리고 신체질환자의 적응장애 및 우울증 등의 자문조정정신의학 영역에서도 다양하게 자주 사용되고 있다. 다양한 정신의학적 질환을 치료하기 위해 처방하는 새로운 항우울제의 사용 시 치료중단의 가장 큰 원인은 약물부작용이다. 이 논문은 현재 우리나라에서 널리 사용되고 있는 새로운 항우울제 사용 시 나타나는 부작용들 중 정신신체의학과 자문조정정신의학영역에서 관심을 가져야 할 매우 빈번하게 나타나는 세 가지 부작용인 오심과 구토, 체중증가, 성기능장애에 대한 발생기전, 발생빈도, 그리고 약물학적 처치를 위주로 한 해결방안을 알아보았다. 저자는 이 논문을 통하여 정신건강의학과 의사만이 아니라 정신신체의학 영역에 관심을 가지거나 자문조정정신의학과 연계되는 타과 영역의 의사들이 새로운 항우울제를 사용할 때 빈번하게 나타나서 삶의 질을 떨어뜨리고 치료중단을 일으킬 수 있는 이 약물들의 부작용을 잘 인지함으로써 이를 조기에 발견하고 적절히 해결하여 환자 치료에 도움을 주고자 하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.525-538
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2005년도 추계학술대회
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• pp.49-66
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• 2005

Panax ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized Morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. GTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, we hypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum ($\mu$-receptors) and mouse vas deferens($\delta$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H ($\kappa$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS Prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced cAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.151-156
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• 2004

This study was carried out to evaluate the putative anxiolytic-1ike effects of the aqueous extracts of Sanjoin-tang (SJIT) and its ingredients using the elevated plus maze (EPM) test in mice. SJIT consists of five herbs, namely, Zizyphi Spinosi Semen (roasted), Glycyrrhizae Radix, Cnidii Rhizoma, Anemarrhenae Rhizoma, and Hoelen. The aqueous extracts of SJIT and each herbal drug were orally administered to ICR mice, 1 hr before evaluating behavioral activity in the EPM test, respectively. Repeated treatments (for 3 days) of the aqueous extract of SJIT (400 mg/kg) significantly increased time-spend in the open arms and arms entries into the open arms in the EPM test. Zizyphi Spinosi Semen (400 mg/kg), an ingredient of SJIT, significantly increased timespent in the open arms and arm entries into the open arms (P < 0.05). However, the other ingredient of SJIT did not show any anxiolytic-like behaviors. In addition, the anxiolytic-like effects of Zizyphi Spinosi Semen were blocked by pindolol (lO mg/kg), a $5-HT_{1A}$ receptor antagonist. These results suggest that Zizyphi Spinosi Semen (roasted) as an ingredient of SJIT plays a crucial anxiolytic role, and it acts via the serotonergic nervous system.

• The Korean Journal of Physiology and Pharmacology
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• 제3권5호
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• pp.501-505
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• 1999

Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is primarily expressed in serotonergic neurons of the raphe nuclei. Simple tandem repeat polymorphisms, typically one to four nucleotides long, are tandemly repeated several times and often characterized by many alleles. To identify the presence of polymorphic repeats, we sequenced the 5'-upstream region of the mouse TPH gene. For the detection of any allelic variants, polymerase chain reaction, nonisotopic single-strand conformation polymophism, and DNA sequencing analyses of the tandem repeat sequences were performed using genomic DNA extracted from 60 ICR mice. Two dinucleotide repeats, $5'-(AC/TG)_{22}-3'$ and $5'-(GT/CA)_{17}3',$ were identified at approximately - 5.7 kb and - 3.4 kb upstream from the transcriptional initiation site of the mouse TPH gene, respectively. Minor allelic variants, $5'-(AC/TG)_{21}-3'$ and $5'-(GT/CA)_{18}-3',$ were observed in heterozygous pairs from 3 of 60 and 1 of 60 ICR mice, respectively. The identification of these microsatellites in the mouse TPH promoter raises the possibility that identical and/or other polymorphic sequences might exist in the upstream region of the human TPH gene.

• Korean Journal of Acupuncture
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• 제23권2호
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• pp.113-123
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• 2006

Objectives: Pharmacopuncture which is a combination of acupuncture and herbal medicine helps to prevent and treat the diseases and symptoms including various pains. However, little was known about the therapeutic effects and its mechanisms on acute pain, although pharmacopuncture has been used frequently in acupuncture clinics. Acupuncture is known for producing analgesia for persistent ankle sprain pain in human. Furthermore, it also produces analgesia in a rat model of ankle sprain pain. Methods: To illuminate the underlying mechanisms of capsaicin pharmacopuncture-induced analgesia, weight bearing force (WBF) was observed on the acute ankle sprained rat model. Ankle sprain was induced in the rat by manually hyper-extending ligaments of the right ankle. Capsaicin pharmacopuncture was applied to SI6 (Yanglo) on the left forelimb (contralateral to the sprained ankle). Results: In behavioral test, capsaicin pharmacopuncture produced marked analgesic effects on acute ankle sprained animals as measured by WBF of the affected limb similar to manual acupuncture. Capsaicin pharmacopuncture was also suppressed by serotonin (5-HT) receptor antagonist methysergide (2 mg/kg, Lp.), but not by opioids receptor antagonist naltrexone (10 mg/kg, Lp.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, Lp.). Conclusion: The data suggest that capsaicin pharmacopuncture-induced analgesia is accomplished by activating the descending serotonergic inhibitory systems.

• 한국동물학회지
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• 제38권3호
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• pp.348-355
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• 1995

배추흰나비 유충 뇌에 분포하는 세로토닌 면역반응성 신경원(이하 세로토닌 세포)이 발생에 따라 형태학적으로 어떻게 분화해 나가는지를 조사하였다. 1령 유충뇌와 2령 유충뇌는 각각 20개의 세로토닌 세포를 포함하였다. 1령 유충뇌에서는 세로토닌 면역 반응성 섬유(이하 세로토닌 섬유) 한무리가 뇌교련을 형성하였고 이같은 섬유의 대부분은 반대쪽 중앙 신경망에 종지하였다. 2령 유충의 뇌에서는 세로토닌 섬유의 대부분이 뇌교련을 형성하였고 1령 유충뇌에서 보다는 그들의 수가 더 많이 관찰되었다. 이 섬유의 종말이 형성하는 보다 풍부한 arborization은 중앙 신경망의 상당한 부분을 차지하였다. 3령 유충뇌의 세로토닌 세포는 22개 였고 세로토닌 섬유들의 구성하는 뇌교련수도 3개로 증가되었으며 세로토닌 섬유의 대부분은 뇌교련을 형성하였다. 30개의 세로토닌 섬유뿐만 아니라 뇌의 전후 방향으로 달리는 세로토닌 섬유도 포함하였다.