• Title/Summary/Keyword: pharmaceutical effects

검색결과 3,550건 처리시간 0.032초

Age-Dependent Sensitivity to the Neurotoxic Environmental Metabolite, 1,2-Diacetylbenzene

  • Hoang, Ngoc Minh Hong;Kim, Sungjin;Nguyen, Hai Duc;Kim, Minjo;Kim, Jin;Kim, Byoung-Chul;Park, Daeui;Lee, Sujun;Yu, Byung Pal;Chung, Hae Young;Kim, Min-Sun
    • Biomolecules & Therapeutics
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    • 제29권4호
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    • pp.399-409
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    • 2021
  • 1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

Intrathecal administration of naringenin improves motor dysfunction and neuropathic pain following compression spinal cord injury in rats: relevance to its antioxidant and anti-inflammatory activities

  • Fakhri, Sajad;Sabouri, Shahryar;Kiani, Amir;Farzaei, Mohammad Hosein;Rashidi, Khodabakhsh;Mohammadi-Farani, Ahmad;Mohammadi-Noori, Ehsan;Abbaszadeh, Fatemeh
    • The Korean Journal of Pain
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    • 제35권3호
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    • pp.291-302
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    • 2022
  • Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Ginsenoside Rg1 promotes neurite growth of retinal ganglion cells through cAMP/PKA/CREB pathways

  • Ye-ying Jiang ;Rong-yun Wei;Kai Tang;Zhen Wang;Ning-hua Tan
    • Journal of Ginseng Research
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    • 제48권2호
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    • pp.163-170
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    • 2024
  • Background: Mechanisms of synaptic plasticity in retinal ganglion cells (RGCs) are complex and the current knowledge cannot explain. Growth and regeneration of dendrites together with synaptic formation are the most important parameters for evaluating the cellular protective effects of various molecules. The effect of ginsenoside Rg1 (Rg1) on the growth of retinal ganglion cell processes has been poorly understood. Therefore, we investigated the effect of ginsenoside Rg1 on the neurite growth of RGCs. Methods: Expression of proteins and mRNA were detected by Western blot and qPCR. cAMP levels were determined by ELISA. In vivo effects of Rg1 on RGCs were evaluated by hematoxylin and eosin, and immunohistochemistry staining. Results: This study found that Rg1 promoted the growth and synaptic plasticity of RGCs neurite by activating the cAMP/PKA/CREB pathways. Meanwhile, Rg1 upregulated the expression of GAP43, Rac1 and PAX6, which are closely related to the growth of neurons. Meantime, H89, an antagonist of PKA, could block this effect of Rg1. In addition, we preliminarily explored the effect of Rg1 on enhancing the glycolysis of RGCs, which could be one of the mechanisms for its neuroprotective effects. Conclusion: Rg1 promoted neurite growth of RGCs through cAMP/PKA/CREB pathways. This study may lay a foundation for its clinical use of optic nerve diseases in the future.

Effects of Binders on Pharmaceutical Properties of Aspirin Tablets

  • Kwon, Kwang-Hyen;Shin, Young-Hee;Lee, Chi-Ho
    • Journal of Pharmaceutical Investigation
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    • 제15권3호
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    • pp.140-150
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    • 1985
  • The influences of three binders, hydroxypropyl cellulose(HPC), microcrystalline cellulose (MCC) and polyvinylpyrrolidone(PVP), on the transmittance of compression pressure from upper punch to lower punch and the disintegration of aspirin tablets prepared by direct compression were studied. The optimum concentration of three binders for the disintegration of aspirin tablets was about 20w/w% and several physical properties of the powder and tablets were also investigated. The tablet machine was specially made for the measurement of compression pressure of the tablets.

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Inhibitory Constituents against HIV-1 Protease from Agastache rugosa

  • Min, Byung-Sun;Masao-Hattori;Lee, Hyeong-Kyu;Kim, Young-Ho
    • Archives of Pharmacal Research
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    • 제22권1호
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    • pp.75-77
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    • 1999
  • Two diterpenoid compounds, agastanol (1) and agastaquinone (2), were isolated from the roots of Agastache rugosa (Labiatae). Compound 1 and 2 showed significant inhibitory effects against human immunodeficiency virus type 1 (HIV-1) protease activity with $IC_{50}$ values of 360 and $87{\mu}M$, respectively.

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결정형(Habit)이 아스피린과 페나세틴의 용출 속도에 미치는 영향 (Effect of Crystal Form(Habit) on Dissolution Rate of Aspirin and Phenacetin)

  • 조지운;손영택
    • Journal of Pharmaceutical Investigation
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    • 제20권2호
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    • pp.65-71
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    • 1990
  • Some studies reported physicochemical factors of drugs affecting solubility and dissolution rate. However, few have been reported about pharmaceutical application of crystal forms (habits). Therefore, using acetylsalicylic acid and phenacetin as model substances, we monitored the effects of crystal forms on the dissolution rates.

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황정 에탄올 추출물의 비만 조절 유전자에 대한 효과 (Effects of ethanol extract of Polygonatum sibiricum rhizome on obesity-related genes)

  • 전우진;이도섭;손서연;서윤지;연승우;강재훈
    • 한국식품과학회지
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    • 제48권4호
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    • pp.384-391
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    • 2016
  • 선행연구(12,13)에 따르면 10주간 ID1216을 투여한 비만 마우스에서 체중과 체지방이 감소하였고 이는 SIRT1-$PGC1{\alpha}$의 발현을 조절하여 나타나는 것으로 확인하였다. 본 연구는 $SIRT1-PGC1{\alpha}-PPAR{\alpha}$의 하위 기전인 UCPs, ACO, aP2의 발현 조절에 ID1216이 영향을 미쳐 그 효과를 나타내는 것을 추가로 확인한 것에 의미가 있다. 또한 10주간 ID1216을 투여한 비만 마우스의 혈액 분석 결과에서도 혈중 중성지방, LDL, HDL total cholesterol등의 혈중 지방질 수치가 개선됨과 동시에 free fatty acid의 농도는 감소하였는데 이는 ID1216이 HSL과 같은 지방질분해효소의 활성을 조절하여 중성지방의 분해과정에 관여하기는 하나 에너지 대사와 지방산 산화 과정에도 복합적으로 관여하여 최종적으로 나타내는 비만 대사 조절 효과에 의한 것으로 판단된다. 따라서 ID1216은 $SIRT1-PGC1{\alpha}-PPAR{\alpha}$ pathway를 촉진시켜 세포와 조직 수준에서 열발생(thermogenesis)에 관여하는 유전자인 UCP1, UCP2, UCP3의 발현을 증가시켰고 ${\beta}$-oxidation에 관여하는 유전자인 ACO와 aP2의 발현도 증가시켰으며 또한 지방분해(lypolysis)에 관여하는 유전자인 ATGL과 HSL의 발현을 증가시키는 분자생물학적 기전을 나타내어 체지방 감소 효과를 나타내는 것으로 확인되었다.