• 제목/요약/키워드: Pharmacological Treatment

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NF-κB and Therapeutic Approach

  • Lee, Chang-Hoon;Kim, Soo-Youl
    • Biomolecules & Therapeutics
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    • 제17권3호
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    • pp.219-240
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    • 2009
  • Since NF-${\kappa}B$ has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of ${\kappa}B$ (NF-${\kappa}B$) in inflammatory signaling for decades. The various molecular components of NF-${\kappa}B$ transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-${\kappa}B$ pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-${\kappa}B$ signaling pathway for many therapeutic applications. However, a gene knock-out study for $IKK{\beta}$ in the NF-${\kappa}B$ pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte $IKK{\beta}$ accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of $IKK{\beta}$ appears to be beneficial to reduce HCC. This article will update issues of the NF-${\kappa}B$ pathway and inhibitors regulating this pathway.

A Pharmacological Advantage of Ursodeoxycholic Acid in Cytoprotection in Primary Rat Microglia

  • Joo, Seong-Soo;Hwang, Kwang-Woo;Lee, Do-Ik
    • Molecular & Cellular Toxicology
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    • 제1권1호
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    • pp.40-45
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    • 2005
  • Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

The Protective Effect of Paeoniae Radix Extract against 1-methyl-4-Phenylpyridium-induced Apoptosis on SK-N-MC Neuroblastoma Cells

  • Chae, Ki-Heon;Song, Yun-Kyung;Lim, Hyung-Ho
    • 대한한의학회지
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    • 제26권4호
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    • pp.74-86
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    • 2005
  • Background: There are increasing neuro-degenerative disorders with aging. Paeoniae Radix(PR) possesses various pharmacological effects such as sedative, analgesic, anti-inflammatory, anti-stress and neuro-protective actions. Also antiaging and anti-cancer effects of PR were reported. Our purpose was to investigate whether PR is useful on the treatment of Parkinson's disease, one of the neuro-degenerative disorders. Objective: We investigated whether Paeonia Radix possesses a protective effect against 1-methyl-4 phenylpyridine(MPP+)-induced cytotoxicity in neuronal cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, flow cytometry, DNA fragmentation assay, reverse transcription-polymerase chain reaction(RT-PCR), and Western blotting were performed on SK-N-MC neuroblastoma cells. Results: Cells treated with MPP+ exhibited several apoptotic features, while cells pre-treated with Paeonia Radix prior to MPP+ exposure showed s decrease in the occurrence of apoptotic features. Conclusions: These results suggest that Paeonia Radix may exert a protective effect against MPP+-induced apoptosis in SK-N-MC neuroblastoma cells.

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Antioxidant Activity and Anti-inflammatory Effect of Extracts from Paulownia tomentosa in LPS-stimulated RAW264.7 macrophage cells

  • Jo, Na-Young;Kim, Ki-Tae
    • 대한한의학회지
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    • 제40권4호
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    • pp.72-83
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    • 2019
  • In this study, we investigated the antioxidant and anti-inflammatory effect of the Paulownia tomentosa extracts (PTE). The total polyphenol and flavonoid contents of PTE were 148.98±1.84 mg GAE/g extract, and 115.33±4.16 mg CE/g extract, respectively. The PTE showed that strong antioxidant activity via -diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ABTS radical scavenging activity and FRAP assay. The anti-inflammatory activity was evaluated on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. PTE remarkably reduced protein expression of inducible nitric oxide (iNOS), resulting in inhibition of production of nitric oxide (NO). Additionally, pre-treatment of PTE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Moreover, PTE significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation in macrophages. The PTE showed high antioxidant and anti-inflammatory activity. These data suggest that PTE has pharmacological activity and may be useful for the development of anti-inflammatory agents.

Antioxidants and Anti-inflammatory Effects of Fermented Houttuynia cordata Thunb and Scoria Mixture Extract

  • Lee, Sung-Gyu;Kang, Sangmoon;Lee, Kee-Young;Park, Kwang-Lyul;Kang, Hyun
    • 대한의생명과학회지
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    • 제23권4호
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    • pp.355-361
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    • 2017
  • In this study, antioxidant and anti-inflammatory of fermented Houttuynia cordata Thunb and scoria mixture extract were investigated in vitro. Radical-scavenging activities of the ethanol extracts were examined by using ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS)) radicals assay. Consequently, we confirmed that fermented Houttuynia cordata Thunb and scoria mixture extract dependent removed DPPH and ABTS radical. Also, to confirm anti-inflammatory activity of ethanol extract, we treated fermented Houttuynia cordata Thunb and scoria mixture extract on BV-2 cell with LPS. The result showed that fermented Houttuynia cordata Thunb and scoria mixture extract concentration-dependent inhibited NO production. Therefore, fermented Houttuynia cordata Thunb and scoria mixture extract showed inhibition radical oxygen activities and inflammatory and have available for a pharmacological composition on neuritis-protection and treatment.

Kaurenoic acid, a Diterpene Derived from Aralia continentalis, Alleviates Lipogenesis in HepG2 Cells

  • Kim, Yu Gon;Kim, Jae Hyeon;Jo, Yong Wan;Kwun, Min Jung;Han, Chang Woo
    • 대한한의학회지
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    • 제36권4호
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    • pp.74-79
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    • 2015
  • Objectives: Here we investigated the anti-lipogenic potential of kaurenoic acid (KA), a diterpene derived from Aralia continentalis, in a cellular model of non-alcoholic fatty liver disease. Methods: HepG2 cells were treated with palmitate for 24h to induce intracellular lipid accumulation. To assess the influence of KA on steatotic HepG2 cells, various concentration of KA was co-administered. After palmitate treatment, Intracellular triglyceride content was measured. Expression level of several lipogenic genes, sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1) were measured using Western-blot analyses or RT-PCR. Results: Palmitate markedly increased intracellular triglyceride level and expression of related lipogenic genes in HepG2 cells, and which was relieved by co-administered KA. Conclusions: It is conceivable that that KA may have a pharmacological potential to reduce lipid accumulation in non-alcoholic fatty liver disease.

Nonpharmacological management and psychosocial support for children and adolescents with type 1 diabetes

  • Yoo, Jae-Ho
    • Clinical and Experimental Pediatrics
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    • 제54권2호
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    • pp.45-50
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    • 2011
  • Compared to that in the Caucasian population, type 1 diabetes mellitus (T1DM) incidence rates are very low in Koreans. Therefore, compared to the recent development of pharmacological therapy applicable to Korean children with T1DM, interest in nonpharmacological therapy and psychosocial support systems remains low, as is the development of Korean-style T1DM education programs for therapeutic application. Children who have been newly diagnosed with diabetes are placed in completely new environments for treatment. For appropriate control of diabetes, patients have to self-monitor blood glucose levels and inject insulin several times a day and must use extreme self-control when they eat foods to avoid increases in blood glucose levels. Blood glucose excursions resulting from impaired pancreatic ${\beta}$ cell functions cause mental stress due to vague fears of chronic complications of diabetes. In addition, children with diabetes cannot be excluded from the substantial amount of studies required of Korean adolescents, and the absolute shortage of time for ideal control of diabetes adds to their mental stress. Many of these patients are psychologically isolated in school where they spend most of their time, and they are not appropriately considered or supported with respect to blood glucose control in many cases. In this respect, this author will introduce some of the newest views on nonpharmacological therapy and psychosocial support systems that account for important parts of T1DM management and seek measures to apply them in conformity with the social characteristics of Korea.

Zingiber officinale Rosc.: A traditional herb with medicinal properties

  • Imtiyaz, Shaikh;Rahman, Khaleequr;Sultana, Arshiya;Tariq, Mohd;Chaudhary, Shahid Shah
    • 셀메드
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    • 제3권4호
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    • pp.26.1-26.7
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    • 2013
  • Ginger (Zingiber officinale) belonging to the family Zingiberaceae is a perennial herb. It is widely distributed in tropical Asia. In India, it is cultivated mainly in Kerala, Andhia Pradesh, Uttar Pradesh, West Bengal and Maharashtra. It is one of the most common spices, which is in use since centuries for its versatile medicinal actions like antiemetic, stomachic, expectorant, anti-inflammatory, aphrodisiac etc in traditional system of medicine (Unani, Ayurveda, and Chinese medicine). It is useful for the treatment of various gastrointestinal, pulmonary, cardiovascular and sexual disorders. The phytochemical study of ginger showed the presence of many volatile oils and oleo-resins like gingerol, zinger one, zingiberol etc. Numerous experimental and clinical trials have proven ginger for its range of therapeutic activities such as antibacterial, antidiabetic, antiemetic, hypolipidaemic, hepatoprotective etc properties. The present article aims to explore traditional Unani and pharmacological activities of this herb reported till date.

Evaluation of Salivary Cortisol and Anxiety Levels in Myofascial Pain Dysfunction Syndrome

  • Nadendla, Lakshmi Kavitha;Meduri, Venkateswarlu;Paramkusam, Geetha;Pachava, Koteswara Rao
    • The Korean Journal of Pain
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    • 제27권1호
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    • pp.30-34
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    • 2014
  • Background: Myofascial pain dysfunction syndrome (MPDS), otherwise called myofascial pain is one of the most common temporomandibular disorders, which in turn is the most common cause of orofacial pain of non-dental origin. Its etiology is multifactorial and still poorly understood. Psychological factors have been shown to play a role in the etiology. The aim of the study was to evaluate the association between anxiety and salivary cortisol levels in patients with myofascial pain. Methods: Twenty patients suffering from myofascial pain were recruited as the study group. The same number of age and sex matched healthy individuals were taken as the control group. The salivary samples collected between 9-9:15 am from both groups were analyzed for cortisol levels with the competitive enzyme-linked immunosorbent assay method. Anxiety levels of 40 patients were measured using Hamilton's anxiety scale. Results: The mean serum cortisol level of the MPDS group showed a highly significant difference (P < 0.001) from the controls. The mean anxiety scores of the MPDS group showed a highly significant difference (P < 0.001) from the controls. A positive correlation was found between anxiety and the salivary cortisol levels in MPDS patients. Conclusions: These findings suggest that anxiety plays a vital role in the etio-pathogenesis of MPDS; thus, besides pharmacological treatment, psychological support is also needed.

Ameliorative Effect of a Selective Endothelin $ET_A$ Receptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia

  • Mangat, Gautamjeet S.;Jaggi, Amteshwar S.;Singh, Nirmal
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권3호
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    • pp.201-209
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    • 2014
  • The present study was designed to investigate the efficacy of selective $ET_A$ receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from $5^{th}$ to $8^{th}$ week of L-methionine treatment). On $52^{nd}$ day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective $ET_A$ receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.