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Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation

  • Yeon Jin Lee;Jin Yong Song;Su Hyun Lee;Yubin Lee;Kyu Teak Hwang;Ji-Yun Lee
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.303-312
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    • 2024
  • Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone-treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

Effect of Banhasasim-tang on the Hepatic and Splenic Toxicity induced by Doxorubicin (반하사심탕(半夏瀉心湯)이 Doxorubicin에 의해 유발(誘發)된 간장(肝臟) 및 비장(脾臟) 독성(毒性)에 미치는 영향(影響))

  • Hwang, Hui-Jeung;Shin, Min-Kyu;Kwak, Min-Ah;Lee, Yun-Hee;Kim, Sang-Chan;Byun, Joon-Seok
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.8 no.1
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    • pp.9-21
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    • 2002
  • Object The effect of Banhasasim-tang extracts on the hepatic, splenic toxicity and induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Method The changes of body weigh, organ weights of liver and spleen were observed with blood GOT and GPT level. Results 1. Increase of absolute and relative liver weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in Doxorubicin treatment group were significantly decreased in Banhasasim-tang extracts dosing groups. 2. Decrease of absolute and relative spleen weight observed in Doxorubicin treatment group were dose dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group.

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Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity

  • Gou, Dongxia;Pei, Xuejing;Wang, Jiao;Wang, Yue;Hu, Chenxing;Song, Chengcheng;Cui, Sisi;Zhou, Yifa
    • Journal of Ginseng Research
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    • v.44 no.5
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    • pp.717-724
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    • 2020
  • Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

Studies on Antihyperliperlipemic and Antioxidant Activity of Allium cepa L. (양파(Allium cepa L.)의 항고지혈 및 항산화 활성에 관한 연구)

  • Lee, Byeong-Joo;Kim, Gyung-Wan;Chung, Myung-Hyun
    • Korean Journal of Pharmacognosy
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    • v.28 no.4
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    • pp.198-208
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    • 1997
  • This Study was attempted to investigate the effect of Allium cepa L. (onion) on the activities of GOT and GPT, the levels total lipids, triglyceride, total cholesterol, phospholipid and ${\beta}-lipoprotein$ in the serum and the increase ratio of body and liver weight in the experimentally induced hyperlipemic rats. The activities of S-GOT and S-GPT were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the high lipid-diet control group. The levels of total lipids. Triglyceride, total cholesterol and phospholipids were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the control group, respectively. However, the level of ${\beta}-lipoprotein$ was significantly decreased in dose of onion juice 3 ml/head. The levels of triglyceride and total cholesterol in the liver were significanatly decreased in dose of onion juice 3 ml/head. Increase ratio of the body and liver weight were significantly decreased in dose of onion juice 3 ml/head. Anti-fatigue activity of onion juice were studied in mice using the swimming performance method. The potencies of anti-fatigue acti-vities was significantly found in 1.2 ml/head. p.o. of onion juice. The methanol extract and juice extract of onion was significantly found to have an antioxidative activity on the air oxidation of linoleic acid as compared to the 3-butyl-4-hydroxyanisole and ${\alpha}-tocopherol$.

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Relieving effect for respiratory inflammation of Sojadodamgangki-tang (소자도담강기탕(蘇子導痰降氣湯)의 호흡기 염증 완화효과)

  • Younji Han;Changwoo Seon;Yeonju Woo;Dong Hyuk Lee;Jin-woo Suh;Jun-Sang Yu;Joo-Hee Kim;Bo-In Kwon
    • Journal of Society of Preventive Korean Medicine
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    • v.27 no.2
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    • pp.23-33
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    • 2023
  • Objectives : Sojadodamgangki-tang and its main components are traditional korean medicinal methods for treatment of cough, sputum and dyspnea. Using a respiratory inflammatory model, we intend to reveal the anti-inflammatory effect and its immune mechanism of Sojadodamgangki-tang. Methods : We used a papain-induced respiratory inflammatory mouse model. 8-week-old female BALB/C mice were divided into 3 groups as follows: the following groups: saline control group, papain treated group (vehicle), papain and Sojadodamgangki-tang(200 mg/kg) treated group (n=4). To evaluate the anti-inflammatory effect of Sojadodamgangki-tang extracts, inflammatory cell infiltration was measured in bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF). In addition, the effects of Sojadodamgangki-tang extracts on Th2 cell population in lung were determined by using flow cytometry. Results : Sojadodamgangki-tang extracts administration reduced inflammatory cell infiltration in BALF and NALF, especially of eosinophils. Furthermore, total immunogloblin (Ig)-E levels was reduced in BALF and serum by drug administration. Interestingly, Sojadodamgangki-tang extracts treatment also decreased the Th2 cell (CD4+GATA3+) population in lung. Conclusions : Our findings indicate Sojadodamgangki-tang extracts have anti-inflammatory effects by mediating Th2 cell and B cell activation.

Anti-Inflammatory and Anti-Allergic Effects of Adenophora triphylla var. japonica Extract (잔대 추출물의 항염 및 항천식 효과)

  • Jang, Hwan Hee;Kim, Mi Ju;Cho, Su Yeon;Kim, Jung Bong;Lee, Sung Hyeon;Lee, Young Min
    • Journal of the East Asian Society of Dietary Life
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    • v.25 no.5
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    • pp.813-821
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    • 2015
  • Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. The purpose of the present study was to evaluate the anti-inflammatory and anti-asthma effects of Adenophora triphylla var. japonica extracts. We investigated the molecular mechanism underlying the effects of 80% ethanol extracts (AE) of A. triphylla on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. AE treatment inhibited pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6 as well as nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. In particular, NO and pro-inflammatory cytokine production was suppressed more effectively by aerial parts (AE-A) than roots (AE-R) of A. triphylla. Quantitative RT-PCR assay showed that AE reduced mRNA levels of iNOS and COX-2. We also evaluated the anti-asthmatic effects of AE-A in an ovalbumin (OVA)-induced BALB/c mouse model. AE-A supplementation significantly reduced the amounts of airway eosinophils, IL-4 and IL-13 levels in BALF, and IgE levels in serum as compared with untreated, OVA-induced mice. These results suggest that AE-A can be considered as a therapeutic agent to potentially relieve asthma.

Effect of Heat Processed Ginseng on Anti-Fatigue (가공 인상의 항피로효과)

  • Shin, Y.W.;Choi, H.J.;Kim, D.H.;Park, J.H.;Kim, N.J.
    • Korean Journal of Pharmacognosy
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    • v.37 no.4 s.147
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    • pp.246-252
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    • 2006
  • Processing of traditional herbal medicine is one of the pharmaceutical technique in oriental medicine. Most frequently used processing method in oriental medicine are roasting and steaming. In this studies, to elucidate the pharmacological transformation of traditional herbal medicine by means of processing them, Ginseng Radix (root of Panax ginseng, Araliaceae) was used as a sample. Processed ginseng radix (SGR, Sun Ginseng) was prepared by steaming of roots of white ginseng (GR) for 3 hours at $120^{\circ}C$. The biological activities of methanol extract of GR and SGR were investigated. According to DPPH radical scavenging effects, and inhibitory effects of xanthine oxidase and AAPH induced hemolysis, PGR exhibited more effective than those of GR in vitro. And, the antifatigue effect of GR and SGR were investigated using a weight-loading forced swimming test by monitoring swimming times and prolonged intensity exercise model rats by measuring blood biochemical parameters. GR and SGR were significantly prolonged swimming times in 8% body weight ratio loaded mice. Also, they had the inhibitory effects on the decrease of blood glucose levels, the elevation of serum creatinine, lactic acid and free fatty acid, and lactic dehydrogenase activities in forces swimming rats with 1% of the body weight attached to the neck for 3 hours. SGR was more excellent than GR on these effect. Also, these effects were transformed to the n-butanol fraction of methanol extract of SGR. From these results, it can be considered that SGR has antifatigue effect.

Anti-inflammatory Effects of Hydrogels Containing Piroxicam and Hydrolyzed Products of Scutellariae Radix on Collagen-induced Arthritis (콜라겐으로 유발된 관절염에 대한 피록시캄 및 황금 가수분해물 복합 히드로겔의 항염 효과)

  • Kim, Tae-Kyun;Ahn, Hyo-Cho;Yun, Mi-Young;Leem, Jae-Yoon;Chae, Byeong-Suk;Kim, Dae-Keun;Park, Byung-Hyun;Yang, Jae-Heon
    • YAKHAK HOEJI
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    • v.52 no.5
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    • pp.394-401
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    • 2008
  • In order to access the suppressive effects of piroxicam (PX) and hydrolyzed products of Scutellariae Radix (PSH) on arthritis, we investigated whether PSH gel could suppress the progression of collagen-induced arthritis. PX, one of nonsteroidal anti-inflammatory drugs has been used in the systemic and topical treatment in a variety of inflammatory conditions. Scutellariae Radix, one of the herbal medicines, was used for the purpose of anti-inflammatory and anti-bacterials. For the purpose of transdermal absorption of the hydrogel preparations, two classes of hydrogels (PX, PSH) were formulated with carbomer 940, diethylene glycol monoethyl ether, polyethylene glycol-8-glyceryl caprylate/caprate and triethanolamine. In carrageenan-induced edema in rat hind paws, inhibition of foot swelling was more increased in PSH than PX hydrogel. Rheumatoid factors including serum IgG, IgM and collagen specific antibody were present much lower in PSH gel treated mice than control. Histological examination revealed that PSH hydrogel inhibited infiltration of inflammatory cells into affected paw joint, compared with control. The PSH hydrogel would be a suitable preparation to increase transdermal treatment for anti-inflammatory effects on collagen-induced arthritis.

Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a Component of Polysiphonia morrowii, In Vivo and In Vitro

  • Kang, Na-Jin;Han, Sang-Chul;Kang, Hyun-Jae;Ko, Geum;Yoon, Weon-Jong;Kang, Hee-Kyoung;Yoo, Eun-Sook
    • Toxicological Research
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    • v.33 no.4
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    • pp.325-332
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    • 2017
  • 3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

Phamacopuncture and Dermal Application of Sebalgukhwa-san: Effects on Hair Growth in a Mouse Model of Alopecia

  • Ji, Min Jung;Lim, Seong Chul;Kim, Jae Soo;Lee, Hyun Jong;Lee, Yun Kyu
    • Journal of Acupuncture Research
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    • v.36 no.2
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    • pp.92-99
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    • 2019
  • Background: This study was conducted to evaluate the effects of pharmacopuncture and dermal application of Sebalgukhwa-san extracts on hair growth in an alopecia mouse model. Methods: Twenty-one C57BL/6 mice were divided into 3 groups; control group-normal saline injection or vehicle solution application, positive control group-minoxidil (MNXD), experimental group-pharmacopuncture and applied Sebalgukhwa-san (SGS) extract. The effects of the treatment on hair growth, were determined through photographs, and phototrichogram analysis by folliscope. Hair follicle morphometry by hematoxylin-eosin staining was performed, and hair growth-related protein expression of vascular endothelial growth factor, insulin like growth factor-1, and transforming growth factor-beta 1 were monitored by Western blotting. Serum levels of aspartate aminotransferase and alanine aminotransferase were measured for liver function test. Results: Body weight increased consistently in all groups. Hair growth was improved in the MNXD and SGS groups compared with the control. Hair density and thickness improved statistically significantly in the MNXD and SGS groups compared with the control p < 0.05. The number of hair follicles improved in the MNXD and SGS groups compared with the control but the size did not. The expression of vascular endothelial growth factor and insulin like growth factor-1 increased, and there was a decrease in the expression of transforming growth factor-beta 1 in the MNXD and SGS groups compared with the control, however, there was no significant difference. Sebalgukhwa-san treatment had no toxicity in liver function tests. Conclusion: Pharmacopuncture and dermal application of Sebalgukhwa-san extract may be therapeutically beneficial for the treatment of alopecia.