The present study aimed to determine the possible mechanisms of the peripheral antinociception of the aqueous extracts of Dicranopteris linearis (AEDL), Melastoma malabathricum (AEMM) and Bauhinia purpurea (AEBP) leaves in mice. Briefly, the antinociceptive profile of each extract (300, 500, and 1000 mg/kg; subcutaneous (s.c.)), was established using the abdominal constriction test. A single dose (500 mg/kg) of each extract (s.c.) was pre-challenged for 10 min with various pain receptors' antagonists or pain mediators' blockers and 30 min later subjected to the antinociceptive assay to determine the possible mechanism(s) involved. Based on the results obtained, all extracts exerted significant (p < 0.05) antinociceptive activity with dose-dependent activity observed only with the AEMM. Furthermore, the antinociception of AEDL was attenuated by naloxone, atropine, yohimbine and theophylline; AEMM was reversed by yohimbine, theophylline, thioperamide, pindolol, reserpine, and 4-chloro-DL-phenylalanine methyl ester hydrochloride; and of AEBP was inhibited by naloxone, haloperidol, yohimbine and reserpine. In conclusion, the antinociceptive activity of those extracts possibly involved the activation of several pain receptors (i.e. opioids, muscarinic, ${\alpha}_2$-adrenergic and adenosine receptors, adenosine, H3-histaminergic and $5HT_{1A}$, dopaminergic receptors).
It has been reported that administration of Ginseng powder to the Guinea pig reduces anaphylactic shook induced by horse serum (Lee, 1939). However, Lee et al. (1960) and Paik et al. (1976) have demonstrated that Ginseng increases capillary permeabilites and histamine release from the mast cell. These facts suggest that Ginseng acts directly on the bronchial muscle causing it to dilate. Recently, a number of investigators(Kidakawa & Iwasiro 1963; Takagi et al. 1973) have reported that Ginseng reverses acetylcholine- or histamine- induced contraction in the isolated Guinea pig ileum. We, therefore, undertook the present study to examine if Ginseng relaxes the spasm of bronchial muscle induced by acetylcholine or histamine. We have also attempted to identify the mechanism of the Ginseng effect. Male Guinea Pig was sacrificed by a blow on the head, The trachea was removed and sectioned with scissors into about 12 rings. After the 'C' shaped ring of cartilage was sectioned the one end of ring was tied to the bottom of the incubation bath and the other end was connected to a force transducer (FTO 3C) to record tension on a Polygraph. When the antispasmodic action of Ginseng effect was first examined in the normal trachea which was not treated by the drug. And then the Ginseng effect was tested in the muscle treated by histamine hydrochloride, acetylcholine hydrochloride or barium chloride. The results indicate that Ginseng alcohol extract relaxes the contraction of isolated tracheal muscle induced by histamine $(1{\mu}g/ml{\sim}10{\mu}g/ml)$, acetylcholine $(1{\mu}g/ml{\sim}5{\mu}g/ml)$ and barium chloride (1.5 mg/ml). The mechanism of this action is in Pa.1 due to nonspecific antimuscarinic and antihistaminic effect and in part by predominant action in the adrenergic ${\beta}-receptor$ although the ${\alpha}-receptor$ is also involved. We, therefore, conclude that Ginseng can be act as a bronchodilator.
In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.
Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.
Zakaria Zainul Amiruddin;Neelendran M;Pubalan S;Sulaiman MR;Fatimah CA
Advances in Traditional Medicine
/
v.6
no.3
/
pp.186-195
/
2006
The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.
Vasoactive intestinal peptide (VIP) is a very potent dilatator and a nonadrenergic, noncholinergic (NANC) neurotransmitter or neuromodulator in the peripheral and the central nervous systems. The mechanisms of action of VIP were examined in aortic circular and in uterine longitudinal smooth muscle strips of the rat. The effects of sympathetic neurotransmitter were investigated in gastric and aortic circular muscle strips of the mouse and the rat. The effects of silver spike point, SSP, low frequency electrical stimulations of VIP, sympathetic neurotransmitter and $\beta$-endorphin were examined in plasma, serum and 24h urine from the healthy volunteer. In gastric smooth muscle strips from the mouse, adrenergic neurotransmitter norepinephrine was inhibitory effected, followed by caused phasic and tonic contraction to the, muscrine receptor agonist carbachol and acetylcholine, respectively. In urine from the healthy volunteer, both norepinephrine and epinephrine were significantly decreased in continue type and low frequency (3 Hz) of SSP electrical stimulations. The contractile responses to S-HT in uterine longitudinal smooth muscle strips of the rats were completely decreased by a VIP 1 $\mu$M. The contractile responses to PGF2$\alpha$ were not decreased by a VIP. In plasma and serum from the healthy volunteer, both VIP and $\beta$-endorphin were significantly increased in continue type and low frequency (3 Hz) of SSP electrical stimulations. Therefore, this study demonstrate that VIP has the capacity to relax vascular or gastric smooth muscles in part by stimulating the generation of NO, and silver spike point low frequency electrical stimulation has the capacity both to decrease sympathetic neurotransmitters and to increase VIP, $\beta$-endorphin.
Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.
The present study was attempted to investigate the effects of total ginseng saponin (G75), panaxadiol-type (PDS) and panaxatriol-type saponin (PTS) on contractile responses of vasoconstrictors in aortic smooth muscle stripes of normotensive (NR) and spontaneous hypertensive rats (SHR). Phenylephrine (an adrenergic $\alpha$$\_$1/-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in both NR and AHR aorta, respectively. Phenylephrine- and high potassium-induced contractile responses were greater in NA than those in SHR aortic smooth muscle stripes. In NR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and PTS (300 $\mu$g/ml), respectively whereas phenylephrine (10$\^$-6/ M)-induced contractile responses were markedly inhibited. In SHR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and moderate doses of PTS (150-300 $\mu$g/ml), respectively but greatly blocked by high concentration of PTS (600 $\mu$g/ml). Phenylephrine (10$\^$-6/ M)-induced contractile responses were inhibited in a dose dependent fashion (150-600 $\mu$g/ml) by the pretreatment with PTS while not altered in the presence of GTS (300 $\mu$g/ml) and PDS (300 $\mu$g/ml), respectively. Taken together, these experimental results suggest that ginseng saponins cause vascular relaxation through blockade of adrenergic $\alpha$$\_$1/-receptors and some unknown mechanisms, and that there is some difference in sensitivity of vascular smooth muscle between NR and SHR in responses to ginseng saponins. It seems that panaxatriol type of some ginseng saponins has the greatest potency in vascular relaxation.
Our purpose was to know whether photo-induced adequate nitric oxide (PIANO)-mediated relaxation of rat aorta is involved in cyclic GMP increment as well as inhibition of phosphatidylinositide hydrolysis due to phenylephrine (PE). Isometric tension was measured in vitro in response to either agents that modulate NO production or release NO by photolysis of photosensitizing agents in rat aorta that had been contracted with PE submaximally. PIANO-mediated relaxation was accompanied by increment of cyclic GMP, which was dependent on the intensity and duration of light exposure and concentration of photosensitizers. Phosphatidylinositide (PI) turnover augmented by PE was significantly inhibited by PIANO. These findings indiate that cGMP increment is responsible for PIANO-mediated relaxation and which may account for the inhibition of PI turnover due to ${\alpha}-adrenergic$ receptor stimulation.
This study is to provide evidence-based recommendations for the most-effective treatments of benign prostatic hyperplasia based on patient preference or clinical need, and to meta-analyze the Korean literatures for the development of BPH treatment guidelines. For these analyses, extensive literature searches (208 articles), with priority given to the Korean Journal of Urology, were conducted from 1960 to August, 1996. Meta-analysis, like all statistical analysis, has two main functions: data summarization (qualitative meta-analysis) and smoothing o. pattern recognition (quantitative meta-analysis). As well, critical reviews and syntheses with the mean and 90-percent confidence intervals for the likelihood were used to evaluate empirical evidence and significant outcomes of the BPH treatment literatures (106 articles). For this task, the Methodologic Panel for BPH Guidelines was composed of multidisciplinary experts in the field. The results of the study were summarized as follows: For all that watchful waiting is an appropriate treatment strategy for the majority of patients with prostatism, we couldn't find the Korean literatures which carried this article. The literatures on alpha-1-adrenergic receptor blockers provide no evidence to suggest that any one alpha blocker is more effective than another. The finasteride reduces the size of the prostate, on average, and leads to a small yet perceptible reduction in sysptoms. Of all treatment options, prostate surgery with transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), and so on, offers the best chance for symptom improvement. However, surgery also has the highest rates of significant complications. Therefore, surgery need not always be a treatment of last resort. Balloon dilation of the prostatic urethra is clearly less effective than surgery in relieving symptoms, but it is associated with fewer complications. Emerging technologies for treating BPH include lasers, coils, stents, thermal therapy and hyperthermia. Established technologies will also be reanalyzed as results of new trials are reported. Although this study has some limitations due to lacking for good quality literatures, ' it provides a cornerstone for our medical research. It represents the most current scientific knowledge regarding the clinical epidemiology including treatment of BPH. It will be revised and updated as needed.
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