• 제목/요약/키워드: Therapeutic candidate

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지구자(枳椇子)에탄올추출물이 B16F10흑색종세포의 멜라닌생성에 대한 효과 (Effect of Hovenia dulcis Thunb. Ethanol Extract on the Melanogenesis in B16F10 Melanoma Cell)

  • 김준호;문대원;최미은;임규상;문연자;우원홍
    • 동의생리병리학회지
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    • 제23권2호
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    • pp.337-342
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    • 2009
  • Acquired pigmentary skin diseases such as abnormal melanogenesis, vitiligo, chloasma and inflammatory pigmentation are related to regulate the melanin production, In this study, an ethanol extract of Hovenia dulcis Thunb.(EHD) makedly inhibited melanin biosynthesis and suppressed, the protein expression of tyrosinase, tyrosinase-related protein 1(TRP-1), and tyrosinase-related protein 2(TRP-2) in B16F10 cells. On the other hand, EHD did not inhibit mushroom tyrosinase activity. These results indicate that EHD may contribute to the inhibition of melanin biosynthesis through regulating tyrosinase activity and expression, and serve as a new candidate in the design of new skin-whitening or therapeutic agents.

Antiplatelet and Antithrombotic Effects of the Extract of Lindera obtusiloba Leaves

  • Kim, Jun Ho;Lee, Jaemin;Kang, Soouk;Moon, Hongsik;Chung, Kyung Ho;Kim, Kyoung Rak
    • Biomolecules & Therapeutics
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    • 제24권6호
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    • pp.659-664
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    • 2016
  • Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.

Environmental Pollution and Gene Expression: Dioxin

  • Kim, Ki-Nam;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • 제1권2호
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    • pp.78-86
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    • 2005
  • Dioxins, especially 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), are ubiquitous environmental contaminants. TCDD is known that it has toxic effects in animals and humans, including chloracne, immune, reproductive and developmental toxicities, carcinogenicity, wasting syndrome and death. TCDD induces a broad spectrum of biological responses, including disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome and cancer. Many researches showed that TCDD induces gene expression of transcriptional factors related cell proliferation, signal transduction, immune system and cell cycle arrest at molecular and cellular levels. These toxic actions of TCDD are usually mediated with AhR (receptor, resulted from cell culture, animal and clinical studies). cDNA microarray can be used as a highly sensitive and informative marker for toxicity. Additionally, microarray analysis of dioxin-toxicity is able to provide an opportunity for the development of candidate bridging biomarkers of dioxin-toxicity. Through microarray technology, it is possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety.

Glutamate로 유도된 C6 glial 세포의 독성에 대한 팔물탕(八物湯)의 보호 효과 (Protective Effect of Palmul-tang on Glutamate Induced Cytotoxicity in C6 Glial cells)

  • 신용진;신선호
    • 동의생리병리학회지
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    • 제26권4호
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    • pp.475-482
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    • 2012
  • This study was designed to elucidate the mechanism of the cytoprotective effect of the Palmul-tang (PMT) on glutamate induced cytotoxicity in rat C6 glial cells. We determined the increase of cell viability by PMT on glutamate-induced death of C6 glial cell. On some experiments, glutamate induced cell death to be an apoptotic phenomena characterized by G1 arrest in cell cycle, chromatin condensation, DNA fragmentation in C6 glial cells. However, pre-treatment of PMT inhibited characteristic apoptotic phenomena. One of the main mediator of glutamate-induced cytotoxicity was known to generation of reactive oxigen species. In this study, PMT attenuated generation of reactive oxigen species by glutamate through down-regulation of NOX1 expression in C6 glial cells. Furthermore, PMT regulated Bcl2 families and caspase proteins, which contribute the cell survival or death. This study suggests that PMT may be candidate for both of therapeutic and protective prescription.

SNAP 유도성 RINm5F 세포 독성에 대한 황연 추출물의 방어효과 (Protective Effect of Coptidis Rhizoma on SNAP-Induced Cytotoxicity in Pancreatic RINm5F Cells)

  • 류도곤;권강범;양정예;김은경;김강산
    • 대한한의학회지
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    • 제24권2호
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    • pp.159-165
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    • 2003
  • Objectives : Coptidis rhizoma (CR) is an oriental medicine that has been used in many traditional prescriptions against diabetes mellitus in Korea for centuries. Our purpose was to determine the protective effect and its action mechanism of CR on the cytotoxicity of pancreatic -cell line (RINm5F cell). Methods : In this experiment, we used methods such as MTT assay for detection of cytotoxicity, DNA fragmentation assay for detection of apoptotic cell death, LDH activity assay for detection of necrotic cell death, and measurement of $DiOC_{6}$ (3) retention for detection of mitochondrial membrane potential (MMP). Background : Nitric oxide (NO) is believed to playa key role in the process of pancreatic -cell destruction leading to insulin-dependent diabetes mellitus (IDDM). Results : Exposure of RINm5F cells to chemical NO donor such as S-nitroso-N-acetylpenicillamine (SNAP) induced cytotoxic events such as DNA fragmentation and lactate dehydrogenase (LDH) release into medium. However, pretreatment of RINm5F cells with CR extract ($10~50{\mu\textrm{g}}/ml$) for 3 hours prevented SNAP-induced DNA fragmentation and LDH release into medium through the inhibition of MMP disruption. Conclusions : These results suggest that CR may be a candidate for a therapeutic or preventing agent against IDDM.

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Protective effects of a chalcone derivative against Aβ-induced oxidative stress and neuronal damage

  • Kim, Mi-Jeong;Lee, Yoo-Hyun;Kwak, Ji-Eun;Na, Young-Hwa;Yoon, Ho-Geun
    • BMB Reports
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    • 제44권11호
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    • pp.730-734
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    • 2011
  • Amyloid ${\beta}$-peptide ($A{\beta}$-peptide)-induced oxidative stress is thought to be a critical component of the pathophysiology of Alzheimer's disease (AD). New chalcone derivatives, the Chana series, were recently synthesized from the retrochalcones of licorice. In this study, we investigated the protective effects of the Chana series against neurodegenerative changes in vitro and in vivo. Among the Chana series, Chana 30 showed the highest free radical scavenging activity (90.7%) in the 1,1-diphenyl-2- picrylhydrazyl assay. Chana 30 also protected against $A{\beta}$-induced neural cell injury in vitro. Furthermore, Chana 30 reduced the learning and memory deficits of $A{\beta}_{1-42}$-peptide injected mice. Taken together, these results suggest that Chana 30 may be a promising candidate as a potent therapeutic agent against neurodegenerative diseases.

Early-onset epileptic encephalopathies and the diagnostic approach to underlying causes

  • Hwang, Su-Kyeong;Kwon, Soonhak
    • Clinical and Experimental Pediatrics
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    • 제58권11호
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    • pp.407-414
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    • 2015
  • Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes.

Arginase II Inhibitory Activity from Crude Drugs

  • Lim, Chae-Jin;Hung, Tran Manh;Ryoo, Sung-Woo;Lee, Jeong-Hyung;Min, Byung-Sun;Bae, Ki-Hwan
    • Natural Product Sciences
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    • 제17권2호
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    • pp.113-116
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    • 2011
  • Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. In our experiment, the EtOH extracts of four-hundreds extracts drugs were investigated for the arginase inhibitory activity. Among them, four extracts exhibited over 50% inhibition of arginase II activity compared to control at a concentration of 150${\mu}g/ml$. In particular, the seed of Arctium lappa, gum-resin of Boswellia carterii, aerial part of Artemisia apiacea and rhizome of Cyperus rotundus inhibited arginase II activity, with $IC_{50}$ values of 118.4, 135.4, 123.9 and 86.7${\mu}g/ml$, respectively. In addition, four plant extracts showed less than 20% inhibition of arginase I activity at 150${\mu}g/ml$. These plants might be the potential candidate materials in the development of the novel atherosclerosis drug.

Genetic Toxicity Test of Emodin by Ames, Micronucleus, Comet Assays and Microarray Analysis Showing Differential Result

  • Go, Seo-Y.;Kwon, Kyoung-J.;Park, Sue-N.;Sheen, Yhun-Y.
    • Biomolecules & Therapeutics
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    • 제15권3호
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    • pp.192-198
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    • 2007
  • Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a major constituent of rhubarb. Although it has been claimed to have a wild spectrum of therapeutic value, its side effects, especially in human kidney cells have not been well characterized. In this study, we have carried out in vitro genetic toxicity test of emodin and microarray analysis of differentially expressed genes in response to emodin. The result of Ames test showed mutations with emodin treatment in base substitution strain TA1535 both with and without exogenous metabolic activation. Likewise, emodin showed mutations in frame shift TA98 both with and without exogenous metabolic activation. The result of COMET assay in L5178Y cells with emodin treatment showed DNA damage both with and without exogenous metabolic activation. Emodin did not increase micronuclei in CHO cells both with and without exogenous metabolic activation. 150 Genes were selected as differentially expressed genes in response to emodin by microarray analysis and these genes would be candidate biomarkers of genetic toxic action of emodin.

Inhibitory Effects of Ginsenoside Rb1 on Atopic Dermatitis-Like Skin Lesions in Mice

  • Park, Hye-Jin;Byeon, Hye-Eun;Choi, Ko-Woon;Rhee, Dong-Kwon;Lee, Kang-Ro;Pyo, Suhk-Neung
    • Journal of Ginseng Research
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    • 제34권4호
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    • pp.363-368
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    • 2010
  • Allergies are immediate hypersensitive responses to antigens and interleukin (IL)-4 is involved in the initiation and development of allergic responses. $Rb_1$ has been known to have a variety of biological activities including anti-inflammatory activity, but the effect of $Rb_1$ on allergic responses is not known yet. The present study was undertaken to examine whether $Rb_1$ has an inhibitory effect on allergic response in mouse model. In allergic mouse model, our results showed that topical application of $Rb_1$ on atopic dermatitis (AD)-like skin lesions improved skin condition and inhibited starching behaviors. In addition, $Rb_1$ application not only suppressed mRNA expression of IL-4 and IL-10, but also prevented the nuclear factor of activated T cells 1 transcription. Moreover, $Rb_1$ application suppressed IL-4's secretion. Taken together, these results suggest that $Rb_1$ has a potent inhibitory effect in AD-related T cell cytokine production and may be a candidate for therapeutic agent in allergy.