Objectives : The purpose of this study was to find the protective effects of garlic on the halogenated hydrocarbon induced hepatotoxicities, and the possible protection mechanisms involved. Methods : Male Sprague-Dawley rats received garlic (0.5%) or regular diet, for 4 weeks. This was followed by a single dose of corn oil (the controls), carbon tetrachloride (400mg/kg body weight) and trichloroethylene (2,000mg/kg body weight) being administered to each diet group. Blood samples were collected 24 hours fellowing the administration, and the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALD activities measured. The liver samples were studied for their cytochrome P450 and CYP2E1 contents, lipid peroxidation and histopathology. Results : rho results for the group receiving the 9.5% garlic diet showed a slight decrease of CYP2E1 expression compared with the regular diet group. Carbon tetrachloride was significantly decreased the CYP2E1 contents in both the regular and garlic diet groups, but the trichloroethylene remained unchanged. Garlic did not decrease the lipid peroxidation of the liver in the control group, but attenuated the increase of lipid peroxidation caused by carbon tetrachloride. Garlic attenuated the increase of both the serum AST and ALT activities caused by carbon tetrachloride. The histopathelogical observations also showed that garlic attenuated centrilobular necrosis and vacuolar degenerative changes significantly in the carbon tetrachloride treated group. Conclusions : The results indicate that garlic attenuates the carbon tetrachloride-induced hepatotoxicity, through the prevention of the metabolic activation and lipid peroxidation.
Duck viral hepatitis is an acute, highly infectious viral disease of young dacklings aged from two days to three weeks. The significant lesion associated with the disease was enlarged liver including necrotic foci and numerous hemorrhagic spots. We have isolated five strains of duck hepatitis virus (DHV) from field cases showing about 20% mortality with a sign of opisthotonos. When a-day-old ducklings were intramuscularly inoculated with one of the isolates, 92% of the birds were died within 5 days. We attempted to develop an attenuated strain of duck hepatitis virus (DHV) using one of the isolates by serial chicken embryo passages. The propagation of DHV in chicken embryos was carried 140 passages. The virus titer increased gradually from the $21^{st}$ through the $50^{th}$ passage, but there was no significant increase of virus titer in subsequent passages after then. Through the serial passages, the virulence of the virus for chicken embryos was gradually increased but decreased for ducklings. The pathogenicity of the virus for ducklings was preserved up to the $21^{st}$ passage but disappeared at the $50^{th}$passage. An attenuated Korean isolate which was passaged 140 times in chicken embryos gave good protection in ducklings against both challenge infection to a Korean virulent strain and to a DHV-DRL strain, a type 1 reference strain of DHV, which indicated that the Korean isolates could be classified as DHV type 1. And the above results suggest that an attenuated Korean isolate can be used for developing a live DHV vaccine.
Enhanced activity of renin-angiotensin-aldosterone system has been suggested as a cause of the high blood pressure in certain forms of experimental hypertension. In spontaneously hypertensive rats, however, increased activity of the system has not been found, and even suppressed renin angiotensin system has been reported in the spontaneously hypertensive rat. In the present experiments it was attempted to explore the possible alteration of the short loop negative feedback control in the hypertensive rat. Experiments have been done in the anesthetized spontaneously hypertensive rats(SHR) as well as in normotensive Wistar and Sprague Dawley rats as control. Responses of the plasma renin activity to the intravenous L-isoproterenol were dose dependent, in both SHR and normotensive control rats. Hypotensive responses to smaller do sea of L-isoproterenol were more accentuated in SHR than in the normotensive control rats. Angiotensin If given intravenously suppressed plasma renin activity in a dose dependent fashion in both groups. However, these suppressive responses were significantly attenuated in SHR as compared with the normotensive control rats. Treatment with angiotensin I-converting enzyme inhibitor did not correct the attenuated responses of the plasma renin activity to angiotensin II in SHR. Intravenous infusion of arginine vasopressin also produced a dose-dependent suppression of plasma renin activity in both groups. The responses to arginine vasopressin were also significantly attenuated to the normotensive control rats. In the sodium-depleted SHR, arginine vasopressin did not suppress plasma renin activity, whereas the suppressive responses to arginine vasopressin in the normotensive control rats were not different from the untreated control rats. These data suggest that there may be a derangement in the short loop negative feedback control of the renin-angiotensin system in spontaneously hypertensive rat.
The role of neurohumoral mechanisms in the regulation of cardiovascular functions and the effects of ethanol (EOH) on these mechanisms were examined in hemorrhaged conscious Wistar rats. The rats were bled at a constant rate (2 ml/kg/min) through the femoral artery until mean arterial pressure (MAP) was reduced by 30 mmHg. We studied the responses to hemorrhage 1) under normal conditions (Normal), and after pretreatments with 2) neural blockade (NB), pentolinium, 3) arginine vasopressin V1-receptor antagonist (AVPX) + NB, 4) angiotensin II ATI-receptor antagonist (AngIIX) + NB, 5) combined humoral blockade (HB), and 6) neurohumoral blockade. Intravenous administration of 30% EOH (6.3 ml/kg) attenuated the baroreceptor reflex sensitivity, and enhanced the depressor action of AngIIX. During hemorrhage, NB produced a faster fall ill MAP than Normal both in the saline and EOH groups. However, HB accelerated the rate of fall in MAP only in the EOH group. The recovery from hemorrhagic hypotension was not different between NB and Normal rats, but was attenuated in HB rats in the saline group. Under NB, AngIIX, but not AVPX, retarded the recovery rate compared with NB alone. EOH attenuated the recovery of MAP after hemorrhage in Normal rats, but completely abolished the recovery in HB rats. We conclude that 1) the maintenance of MAP during hemorrhage is mediated almost entirely by the autonomic functions, 2) angiotensin II plays an important role in the recovery from hemorrhagic hypotension, but AVP assumes little importance, 3) AVP release largely depends on the changes in blood volume, whereas renin release depends on the changes in blood pressure rather than blood volume, and 4) EOH increases the dependence of cardiovascular regulation on angiotensin II and impairs the recovery from hemorrhagic hypotension through the attenuation of autonomic functions.
Leya, Mwense;Kim, Won Kyong;Ochirkhuyag, Enkhsaikhan;Yu, Eun-Chae;Kim, Young-Jee;Yeo, Yoonhwan;Yang, Myeon-Sik;Han, Sang-Seop;Lee, John Hwa;Tark, Dongseob;Hur, Jin;Kim, Bumseok
Journal of Veterinary Science
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v.22
no.2
/
pp.15.1-15.13
/
2021
Background: Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. Objectives: The study aimed to determine the protective efficacy of attenuated Salmonella strain expressing highly conserved Brucella immunogens in goats. Methods: Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 109 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. Results: Among these vaccines inoculated at 5 × 109 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Real-time polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the non-vaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. Conclusions: These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.
Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.
Journal of The Korean Society of Integrative Medicine
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v.11
no.2
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pp.119-128
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2023
Purpose : The fruit of Actinidia polygama has been used in oriental medicine for the treatment of gout, rheumatoid arthritis, and inflammation. Though A. polygama exhibited anti-inflammatory activity in RAW 264.7 cells and carrageenan-induced rat paw edema, the exact mechanism for anti-inflammation was not evaluated yet. In this study, the anti-inflammatory mechanisms of A. polygama ethanol extract (APEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : WST-1 assay was applied to analyze the cytotoxic effect of APEE in RAW 264.7 cells. The productions of nitric oxide (NO) and prostaglandin (PG) E2 were analyzed by the Griess reaction and enzyme immunoassay (EIA) assay, respectively. In addition, protein expressions for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by Western blot analysis. The activated status of an inflammatory transcription factor, NF-κ B, and its upstream signaling molecules, mitogen-activated protein kinases (MAPKs), was also evaluated by Western blot analysis. Results : As a result, APEE treatment did not exhibit any cytotoxicity until the concentration of 200 ㎍/㎖. APEE treatment significantly inhibited NO and PGE2 productions as well as their enzymes, iNOS and COX-2 in a dose-dependent manner. The inflammatory transcription factor, NF-κ B, was also attenuated by APEE treatment. In addition, the phosphorylated status of MAPKs such as extracellular regulated kinase (ERK), c-jun NH2 kinase (JNK), and p38, were significantly diminished by APEE treatment in LPS stimulated RAW 264.7 cells. Conclusion : Consequently, APEE treatment significantly attenuated the production of inflammatory mediators and their enzyme expressions in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-κ B, and upstream signaling molecules, MAPKs, were also significantly attenuated by APEE treatment in LPS-activated RAW 264.7 cells. These results indicate that APEE might be a candidate to be utilized as a promising candidate for the treatment of inflammatory disorders.
Gyeong-Ran Noh;Bitna Kweon;Dong-Uk Kim;Jin‑Young Oh;Gabsik Yang;Il-Joo Jo
Journal of Convergence Korean Medicine
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v.6
no.1
/
pp.29-36
/
2024
Objectives: Psoriasis is a common chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and an excessive inflammatory response. Agents that can attenuate keratinocyte hyperproliferation and excessive inflammatory responses are considered potentially useful for the treatment of psoriasis. Daehwangmokdanpitang (DHMDPT) exhibits a broad range of bioactivities, including anti-proliferative and anti-inflammatory effects. This study aims to evaluate the anti-psoriatic potential of DHMDPT in vitro. Methods: HaCaT keratinocytes were stimulated with a mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish an in vitro psoriatic keratinocyte model. Cell viability was measured using the MTT assay. Quantitative real-time PCR (qRT-PCR) was performed to measure the mRNA levels of the hyperproliferative marker gene keratin 6 (KRT6) and inflammatory factors such as IL-6, TNF-α, and IL-23A. Additionally, chemokines including CCL5, CCL2, CCL20, and CXCL1 were measured by qRT-PCR. Results: DHMDPT attenuated M5-induced hyperproliferation, as indicated by a reduction in KRT6 expression in HaCaT keratinocytes. M5 stimulation significantly upregulated the mRNA levels of IL-6, TNF-α, and IL-23A. However, DHMDPT treatment attenuated the upregulation of IL-6 but not TNF-α or IL-23A. Additionally, DHMDPT inhibited the expression of CCL5, CCL2, and CXCL1, but not CCL20. Conclusion: DHMDPT effectively attenuated the M5-induced proliferation and inflammatory response in HaCaT keratinocytes. Therefore, DHMDPT could be an attractive candidate for future development as an anti-psoriatic agent.
Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.
Immune response to two methods of Newcastle disease virus vaccine, one inactivated and the other attenuated was observed and the data presented. (1) Administration of inactivated virus vaccine in an amount of 1.0 ml. by intramuscular route gave an appreciable immunity to Newcastle disease for a period of at least three-and-half months. (2) The chickens given attenuated virus vaccine in the drinking water produced satisfactory immunity as manifested by the fact that immunized birds showed resistance when challenged 105 days after the vaccination and maintained high degree of HI titer for a period of 75 days. (3) Vaccination with the attenuated virus vaccine in drinking water is very simple and time saving in procedure, although the duration of immunity seems to be slightly shorter than that proced by inactivated virus vaccine. The author wishes to express his appreciation, to Drs. Kyu Myung Lee, Chang Koo Lee, and Ryong Sook Kee of their suggestions and help. The author is also indebted to Dr. Chang Hi Lee, Director of Anyang Veterinary Laboratory, who allowed the use of the facilities of the laboratory, whitout which this experiment could not have been undertaken.
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