• Journal of Ginseng Research
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• v.23 no.2 s.54
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• pp.81-87
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• 1999

The effect of saponin and non-saponin of Panax Red Ginseng on the blood pressure and nitric oxide production were investigated in the conscious free moving one-kidney, one-clip Goldbaltt hypertensive (lK, 1C-GBH) rats. Mean blood pressure in the control and lK, 1C-GBH rats was decreased by the administration of ginseng saponin (100 mg/kg, i.v.). The hypotensive effect induced by ginseng saponin was reached maximum at 2-4 minutes and was slowly recovered to the initial level of blood pressure. Also ginseng saponin induced reflex tachycardia in the conscious both rats. Contrast to the response induced by ginseng saponin, hypotensive effect induced by non-saponin of panax ginseng is minimal. Plasma nitric oxide concentration was increased by the treatment of ginseng saponin (100 mg/kg, i.p for 5 days) in both rats. It has been shown by western blotting that the expression level of the protein for endothelial nitric oxide synthase (eNOS) in the aorta of rats was not increased by the treatment of ginseng saponin (100 mg/kg, i.p). However, eNOS activity in aortic homogenates of both rats were increased by the treatment of ginseng saponins. From the above results, the hypotensive effect of saponin was greater than that of non-saponin of Panax Red Ginseng. The lowering effect of blood pressure by ginseng saponin may be due to the increase of plasma nitric oxide concentration via the increase of endothelial nitric oxide synthase activity in the renovascular hypertensive and control rats.

• Tuberculosis and Respiratory Diseases
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• v.62 no.4
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• pp.308-313
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• 2007

Background: The nitric oxide (NO) released by inducible NO synthase (iNOS) plays an important role in the pathophysiology of sepsis. Corticosteroids also play a role in the hemodynamic and inflammatory reactions in sepsis. Both have been shown to have a relationship theoretically, but their correlation and clinical impacts have rarely been evaluated. Methods: 26 patients with sepsis and 14 healthy controls were enrolled in this study. The initial random plasma total NO and the serum cortisol levels were measured. The same measurements were serially carried out on the $3^{rd}$, $5^{th}$, and $7^{th}$ days. Results: The initial total plasma levels of NO and cortisol were higher in the patients with sepsis than in the healthy controls. The total NO levels were higher in patients with severe sepsis than in the those with mild sepsis. There was a correlation between the total NO and cortisol level throughout the study. Conclusion: In patients with sepsis, the levels of plasma NO and cortisol were well correlated during the first week of sepsis, which suggests an interrelationship. However, the clinical and pathogenetic implications await further evaluation.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.165-172
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• 2005

The aim of this study was to determine the roles of ET-1 and NO on uterine blood flow in pregnancy. Uterine arteries were isolated from 17 nonpregnant and 12 pregnant women. Nonpregnant group included patients with median age of $48.6{\pm}2.3$ years who underwent hysterectomy, because of myoma. Pregnant group included patients with median age of $31.3{\pm}1.4$ years undergoing cesarean delivery. ET-1 and ET-2 induced concentration-dependent contraction in isolated nonpregnant and pregnant uterine arteries. The contractile response and maximal contraction were increased in pregnant uterine arteries. In nonpregnant uterine arteries, there was no contraction in response to ET-3, whereas pregnancy induced concentration-dependent contraction by ET-3. Tissue nitrite/nitrate level and immunohistochemical staining of eNOS and iNOS were increased in pregnant uterine arteries, compared with nonpregnant uterine arteries. In addition, the expressions of eNOS and iNOS mRNA were significantly increased in pregnancy. Moreover, contractions by ET isopeptides, including ET-1, were enhanced, and immunohistochemical staining of ET-1 and ET-1 mRNA expression was increased in pregnant uterine arteries. These results suggest that NO production by increased NOS activity, especially eNOS activity, is related to placental and uterine blood flow. Furthermore, ET-1 appears to play a pathophysiological role in pregnant complications such as hypertension.

• Journal of Life Science
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• v.27 no.1
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• pp.8-14
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• 2017

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.29-38
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• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.576-587
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• 2009

Background: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. Material and Method: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM), The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor $N{\omega}$-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. Result: The mean infarct size (%) in the rats with AMI was $21.3{\pm}0.62%$. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. Conclusion: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

• Biomedical Science Letters
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• v.25 no.3
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• pp.267-274
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) to recognize pathogen-associated molecular patterns (PAMPs). PAMPs stimulate TLRs to initiate specific immunoactivity. The activation of TLRs signaling leads to the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of dehydrocostus lactone (DHL), which is a natural sesquiterpene lactone derived from various medicinal plants, iNOS expression induced by LPS (TLR4 agonist), MALP-2 (TLR2 and TLR6 agonist), or Poly[I:C] (TLR3 agonist) were examined. DHL suppressed the iNOS expression induced by LPS, MALP-2, or Poly[I:C]. DHL also inhibited nitrite production induced by LPS, MALP-2, or Poly[I:C]. These results suggest that DHL can modulate TLRs signaling pathways resulting in anti-inflammatory effect.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.198-198
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• 2002

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.270.3-271
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• 2001

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.32 no.3
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• pp.13-22
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• 2019

Objectives : Armeniacae semen is the seed of Prunus armenica L. var. ansu MAXIM, and this is classified into Rosaceae. Armeniacae semen has been used for centuries in traditional oriental medicine for the treatment of pain and inflammatory diseases. Amygdalin is the major compound of Armeniacae semen, and it is now being used for the treatment of pain and cancer. Methods : In the present study, we compared the effects of an aqueous extract of Armeniacae semen and a solution of amygdalin extracted from Armeniacae semen on lipopolysaccharide(LPS)-stimulated prostaglandin E2 synthesis and nitric oxide production in mouse BV-2 microglial cells. For this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, reverse transcription-polymerase chain reaction(RT-PCR), prostaglandin E2 immunoassay and nitric oxide detection were performed on mouse BV-2 microglial cells. Results : In the present study, an aqueous extract of Armeniacae semen and an amygdalin solution extracted from Armeniacae semen suppressed prostaglandin E2 synthesis and nitric oxide production by inhibiting the LPS-induced enhancement of cyclooxygenase-2(COX-2) mRNA and the inducible nitric oxide synthase mRNA in mouse BV-2 cells. For the cyclooxygenase-1(COX-1) expression, an aqueous extract of Armeniacae semen showed a more potent suppression effect compared to the amygdalin solution. However, the amygdalin solution more potently suppressed the LPS-induced COX-2 mRNA expression compared to the aqueous extract of Armeniacae semen. Conclusions : As a result, aqueous extract of Armeniacae semen and amygdalin exert anti-inflammatory and analgesic effects.