This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly ...
This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of $GAD_{65/67}$ over a broader range of doses. PA increased ${\alpha}$- and ${\beta}$-subunits protein levels, but decreased ${\gamma}$-subunit protein levels in $GABA_A$ receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via $GABA_A$-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.
This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of $GAD_{65/67}$ over a broader range of doses. PA increased ${\alpha}$- and ${\beta}$-subunits protein levels, but decreased ${\gamma}$-subunit protein levels in $GABA_A$ receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via $GABA_A$-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.
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문제 정의
However, as with the development of many nascent pharmacological strategies, there is still limited information on the pharmacological studies of PA in the sleep disorder treatments such as insomnia. Therefore, the present study was to determine the sedative-hypnotic effects of PA on pentobarbital-induced sleeping behaviors. In addition, we defined the mediation of γ-aminobutyric acid (GABA)-ergic systems to understand the possible mechanisms.
가설 설정
This complex and varied expression supports the hypothesis that GABA may play a role in cellular and synaptic differentiation. Thus, we hypothesize that these results suggest the stimulation of receptors affects their expression.
제안 방법
Immunoreactive bands were developed with a BM chemiluminescence detection kit (Roche Diagnostics, Mannheim, Germany). The quantitative analysis of detected bands was performed with densitometric scanning, and all values were normalized to the amount of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in the sample, which was measured as follows. All of the immunoblots were stripped, incubated with sheep anti-GAPDH (1:2,500 in TBS containing 0.
, 2005). The ultimate goal of the present study was to determine the hypnotic effects of PA on pentobarbital-induced sleeping behaviors, and also to elucidate the possible underlying mechanism of sleep, possibly via GABAA-ergic transmission and Cl- channel activation. Both in vivo and in vitro studies were conducted to evaluate hypnotic effects of PA.
대상 데이터
Fetal bovine serum (FBS) and Dulbecco's Modified Eagle Medium (DMEM) were obtained from GIBCO (Grand Island, NY, USA).
(Chengdu, Sichuan, China). Muscimol (Tocris Bioscience, Bristol, UK), pentobarbital sodium (Hanlim Pharm. Co. Ltd., Seoul, Korea), diazepam (Samjin Pharm. Seoul, Korea), dimethyl sulfoxide (DMSO, Amresco, Solon, Ohio, USA) were also purchased, respectively. Fetal bovine serum (FBS) and Dulbecco's Modified Eagle Medium (DMEM) were obtained from GIBCO (Grand Island, NY, USA).
Ten to twelve mice were used for each treatment group. All experiments were carried out between 1:00 and 5:00 pm.
The animals used for behavioral experiments were ICR male mice (purchased from Samtako, Osan, Korea), weighing 20-25 g, in groups of 10-15. Animals were housed in acrylic cages (45×60×23 cm) with water and food available ad libitum under an artificial 12-h light/dark cycle (light on at 7:00 am), at the relative humidity (50-52%) and at a constant temperature (22 ± 2°C).
데이터처리
The data are expressed as mean ± S.E.M. The significance of the effects of the compounds was assessed by analysis of variance (ANOVA).
M (n=10). The signifi cance of the effects of the compounds was assessed using analysis of variance (ANOVA). Where there was significant variability, the individual values were compared using Dunnett’s- test.
M (n=10). The signifi cance of the effects of the compounds was assessed using analysis of variance (ANOVA). Where there was significant variability, the individual values were compared using Dunnett’s- test.
이론/모형
The concentration of protein in the supernatant was determined, and then the supernatant was used for Western blot analysis. The concentration of total protein was determined by the modified Lowry method using bovine serum albumin as a standard. The samples were stored at -20°C for further use.
성능/효과
In conclusion, our study provided evidence that PA enhanced hypnotic effects in pentobarbital-treated mice. Additionally, this invention illustrates the enhancement may result from Cl- channel activation and GABAA-ergic transmission.
후속연구
There is growing fact that the search for novel plant-derived pharmacotherapies for psychiatric illness has progressed significantly in the past decade. With time a considerable number of herbal constituents whose behavioral effects and pharmacological actions have been well characterized may be good candidates for further investigations that may ultimately lead to clinical use of these constituents. The potential benefits of herbal remedies such as St.
참고문헌 (32)
Abourashed EA Koetter U Brattstrom A 2004 In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors Phytomedicine 11 633 638 15636177
Barnard EA Skolnick P Olsen RW Mohler H Sieghart W Biggio G Braestrup C Bateson AN Langer SZ 1998 International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function Pharmacol Rev 50 291 313 9647870
Chen FP Jong MS Chen YC Kung YY Chen TJ Chen FJ Hwang SJ 2011 Prescriptions of Chinese Herbal Medicines for Insomnia in Taiwan during 2002 Evid Based Complement Alternat Med 2011 236341 19339485
Darias V Abdala S Martin-Herrera D Tello ML Vega S 1998 CNS effects of a series of 1,2,4-triazolyl heterocarboxylic derivatives Pharmazie 53 477 481 9699225
de Sousa FC Pereira BA Lima VT Lacerda CD Melo CT Barbosa-Filho JM Vasconcelos SM Viana GS 2005 Central nervous system activity of yangambin from Ocotea duckei Vattimo (Lauraceae) in mice. Phytother Res 19 282 286 16041767
Gapter L Wang Z Glinski J Ng KY 2005 Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos Biochem Biophys Res Commun 332 1153 1161 15913545
Giner EM Manez S Recio MC Giner RM Cerda-Nicolas M Rios JL 2000 In vivo studies on the anti-inflammatory activity of pachymic and dehydrotumulosic acids Planta Med 66 221 227 10821046
Kaminaga T Yasukawa K Kanno H Tai T Nunoura Y Takido M 1996 Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos , on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin Oncology 53 382 385 8784472
Lee SM Lee YJ Yoon JJ Kang DG Lee HS 2012 Effect of Poria cocos on hypertonic stress-induced water channel expression and apoptosis in renal collecting duct cells J Ethnopharmacol 141 368 376 22414475
Li G Xu ML Lee CS Woo MH Chang HW Son JK 2004 Cytotoxicity and DNA topoisomerases inhibitory activity of constituents from the sclerotium of Poria cocos Arch Pharm Res 27 829 833 15460443
Ma Y Han H Eun JS Kim HC Hong JT Oh KW 2007 Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems Biomol Ther 30 1748 1753
Ma Y Jo YJ Woo SS Hong JT Oh KW 2008 Honokiol potentiates pentobarbital-induced sleeping behaviors through GABA (A) receptor CI-channel activation J Applied Pharmacol 16 328 335
Mathews GC Bolos-Sy AM Holland KD Isenberg KE Covey DF Ferrendelli JA Rothman SM 1994 Developmental alteration in GABAA receptor structure and physiological properties in cultured cerebellar granule neurons Neuron 13 149 158 8043274
Morton GJ Kaiyala KJ Fisher JD Ogimoto K Schwartz MW Wisse BE 2011 Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice Am J Physiol Endocrinol Metab 300 E392 401 21062956
Park JH Cha HY Seo JJ Hong JT Han K Oh KW 2005 Anxiolytic-like effects of ginseng in the elevated plus-maze model: comparison of red ginseng and sun ginseng Prog. Neuropsychopharmacol. Biol. Psychiatry 29 895 900 16002200
Qu WM Yue XF Sun Y Fan K Chen CR Hou YP Urade Y Huang ZL 2012 Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice Br J Pharmacol 167 587 598 22537192
Rudolph U Mohler H 2004 Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics Annu Rev Pharmacol Toxicol 44 475 498 14744255
Spelman K Burns J Nichols D Winters N Ottersberg S Tenborg M 2006 Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators Altern Med Rev 11 128 150 16813462
Wolfman C Viola H Marder M Wasowski C Ardenghi P Izquierdo I Paladini AC Medina JH 1996 Anxioselective properties of 6,3’-dinitroflavone, a high-affinity benzodiazepine receptor ligand Eur J Pharmacol 318 23 30 9007508
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