• Natural Product Sciences
• /
• 제24권1호
• /
• pp.59-65
• /
• 2018

An isoform of NADPH oxidase (NOX), NOX2 is a superoxide-generating enzyme involved in diverse pathophysiological events. Although its potential as a therapeutic target has been validated, there is no clinically available inhibitor. Herein, NOX2-inhibitory activity was screened with the constituents isolated from Schisandra chinensis, which has been reported to have antioxidant and reactive oxygen species (ROS)-scavenging effects. Among the partitions prepared from crude methanolic extract, a chloroform-soluble partition showed the highest NOX2-inhibitory activity in PLB-985 cell-based NOX2 assay. A total of twenty nine compounds (1 - 29) were identified from the chloroform fraction, including two first isolated compounds; dimethyl-malate (25) and 2-(2-hydroxyacetyl) furan (27) from this plants. Of these constituents, two compounds (gomisin T, and pregomisin) exhibited an NOX2-inhibitory effect with the $IC_{50}$ of $9.4{\pm}3.6$, and $62.9{\pm}11.3{\mu}M$, respectively. They are confirmed not to be nonspecific superoxide scavengers in a counter assay using a xanthine-xanthine oxidase system. These findings suggest the potential application of gomisin T (6) and other constituents of S. chinensis to inhibit NOX2.

• Natural Product Sciences
• /
• 제2권1호
• /
• pp.1-8
• /
• 1996

Flavonoids are widely distributed polyphenol compounds in plant kingdom and known to possess varieties of biological/pharmacological activities in vitro and in vivo. A search for antiinflammatory/immunoregulatory flavonoids as potential therapeutic agents has been continued, since serious side effects of currently used nonsteroidal and steroidal antiinflammatory drugs limit their long term uses for the inflammatory disorders. In this reserch, various flavonids were isolated and tested for their in vivo antiinflammatory activity and in vitro inhibitory activity of lymphocyte proliferation. Using a mouse ear edema assay, it was found that certain flavones/flavonols possess mild antiinflammatory activity and a C-2,3-double bond might be essential. Isoflavones were less active. These flavonoids inhibited in vitro lymphocyte proliferation, relatively specific for T-cell proliferation $(IC_{50}=1-10\;{\mu}M)$ and the inhibition was reversible. We have also tested several biflavonoid derivatives, since we recently found that biflavones were phospholipase $A_2$ inhibitors. It was demonstrated that biflavones such as ochnaflavone and ginkgetin inhibited lymphocyte proliferation induced by both concanavaline A and lipopolysaccharide. The inhibition was irreversible in contrast to that of flavones/flavonols. And antiinflammatory activity of biflavonoids are discussed.

• 한국약용작물학회지
• /
• 제20권2호
• /
• pp.129-135
• /
• 2012

The feature of asthma are airway inflammation (AI), reversible airway obstruction, and an increased sensitivity to bronchoconstricting agents, elevated airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. This study was performed to investigate if oral administration of $Scutellaria$ $baicalensis$ Georgi water extracts (SBG) have the antiasthmatic potential for the treatment of asthma. Asthmatic HI and AHR were induced by systemic sensitization to ovalbumin (OVA) with intratracheal instillation with 0.1 mg/mL of diesel exhaust particles (DEP) suspension once a week for 10 weeks in BALB/c mice. SBG was orally administered with the concentraion of 200 mg/kg 5 days a week for 10 weeks. Long-term SBG treatment suppressed the eosinophil infiltration into airways from blood, the asthmatic AI and AHR by attenuating the production of cytokine IL-4, IL-5 and IL-13, histamine and OVA-specific IgE. Our data suggest that SBG has inhibitory effects on AI and AHR in a mouse model of asthma, may act as a potential Th2 cytokine antagonist, and may have a therapeutic effect on allergic asthma.

• Journal of Microbiology and Biotechnology
• /
• 제19권6호
• /
• pp.622-628
• /
• 2009

In the present study, the therapeutic potential of purified and well-characterized bacteriophages was evaluated in thermally injured mice infected with Klebsiella pneumoniae B5055. The efficacy of five Klebsiella phages (Kpn5, Kpn12, Kpn13, Kpn17, and Kpn22) was evaluated on the basis of survival rate, decrease in bacterial counts in different organs of phage-treated animals, and regeneration of skin cells as observed by histopathological examination of phage-treated skin. Toxicity studies performed with all the phages showed them to be non-toxic, as no signs of morbidity and mortality were observed in phage-treated mice. The results of the study indicate that a single dose of phages, intraperitoneally (i.p.) at an MOI of 1.0, resulted in significant decrease in mortality, and this dose was found to be sufficient to completely cure K. pneumoniae infection in the burn wound model. Maximum decrease in bacterial counts in different organs was observed at 72 h post infection. Histopathological examination of skin of phage-treated mice showed complete recovery of burn infection. Kpn5 phage was found to be highly effective among all the phages and equally effective when compared with a cocktail of all the phages. From these results, it can be concluded that phage therapy may have the potential to be used as stand-alone therapy for K. pneumoniae induced burn wound infection, especially in situations where multiple antibiotic-resistant organisms are encountered.

• Archives of Pharmacal Research
• /
• 제23권5호
• /
• pp.471-476
• /
• 2000

DA-8159, a new phosphodiesterase 5 inhibitor, was assessed for its erectogenic potential by a penile erection test in rats, the relaxation of isolated rabbit corpus cavernosum (CC), and estimation of the intracavernous pressure (ICP) in the anesthetized dog. Oral administration of DA-8159 (0.3 to 1 ${\mu}g/kg$ ) increased the number of erections in rats with increasing dosage, with the highest penile erection index at 10 ${\mu}g/kg$ DA-8159 induced the relaxation of phenylephrine (PHE)-induced contractions in the rabbit CC and decreased the $IC_{50}$ of the nitric oxide donor sodium nitroprusside (SNP) in a dose-dependent fashion. In pentobarbital-anesthetized dogs, the intravenous administration of DA-8159 (1~300 ${\mu}g/kg$ ) potentiated the increase in ICP induced by the intracavernosal SNP in a dose-related manner. These findings suggest that DA-8159 has significant therapeutic potential in the treatment of erectile dysfunction.

• BMB Reports
• /
• 제42권8호
• /
• pp.535-539
• /
• 2009

Voltage-gated $K^+$ (Kv) channels are widely expressed in the plasma membranes of numerous cells such as epithelial cells. Recently, it has been demonstrated that Kv channels are associated with the proliferation of several types of cancer cells. Specifically, Kv1.3 seems to be involved in cancer cell proliferation and apoptosis. In the present study, we examined the expression of Kv1.3 in immortalized and tumorigenic human mammary epithelial cells. We also evaluated the expression level of Kv1.3 in each stage of breast cancer using mRNA isolated from breast cancer patients. In addition, treatment with tetraethylammonium, a Kv channel blocker, suppressed tumorigenic human mammary epithelial cell proliferation. Therefore, Kv1.3 may serve as a novel molecular target for breast cancer therapy while its stage-specific expression pattern may provide a potential diagnostic marker for breast cancer development.

• Journal of Ginseng Research
• /
• 제36권1호
• /
• pp.16-26
• /
• 2012

Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginseng may also be potentially valuable in treating cardiovascular diseases. Research concerning cardiovascular disease is focusing on purified individual ginsenoside constituents of ginseng to reveal specific mechanisms instead of using whole ginseng extracts. The most commonly studied ginsenosides are $Rb_1$, $Rg_1$, $Rg_3$, $Rh_1$, Re, and Rd. The molecular mechanisms and medical applications of ginsenosides in the treatment of cardiovascular disease have attracted much attention and been the subject of numerous publications. Here, we review the current literature on the myriad pharmacological functions and the potential benefits of ginseng in this area. In vitro investigations using cell cultures and in vivo animal models have indicated ginseng's potential cardiovascular benefits through diverse mechanisms that include antioxidation, modifying vasomotor function, reducing platelet adhesion, influencing ion channels, altering autonomic neurotransmitters release, and improving lipid profiles. Some 40 ginsenosides have been identified. Each may have different effects in pharmacology and mechanisms due to their different chemical structures. This review also summarizes results of relevant clinical trials regarding the cardiovascular effects of ginseng, particularly in the management of hypertension and improving cardiovascular function.

• Journal of Ginseng Research
• /
• 제42권3호
• /
• pp.356-360
• /
• 2018

The fermentation of medicinal herbs facilitated by microbes is assumed to exert promising therapeutic efficacy on the absorption, bioavailability, and pharmacological effects by speeding up the making or conversion of active constituents into their metabolites. We examined the cardioprotective potential of fermented ginseng, GBCK25, against high-fat diet (HFD)-induced metabolic and functional illnesses as following the essential analysis such as electrocardiographic parameters, alterations of body and organ weights, and echocardiographic studies. The results exhibited that body weights were significantly reduced and the gain of different organ weights were partly eased by GBCK25 treatment. Echocardiography results proposed the amelioration of heart function through normalized levels of left ventricle systolic pressure, ejection fraction, and fractional shortening. These outcomes deliver straight confirmation that GBCK25 could be a potential nutraceutical source for the relief of HFD-induced obesity mediated cardiac dysfunctions.

• International Journal of Oral Biology
• /
• 제43권1호
• /
• pp.23-27
• /
• 2018

Increased intracellular levels of $Ca^{2+}$ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated $Ca^{2+}$ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a $Ca^{2+}$-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

• KSBB Journal
• /
• 제20권1호
• /
• pp.1-11
• /
• 2005

Recently, there has been extremely active in the research of stem cell biology. Stem cells have excellent potential for being the ultimate source of transplantable cells for many different tissues. Researchers hope to use stem cells to repair or replace diseased or damaged organs, leading to new treatments for human disorders that are currently incurable, including diabetes, spinal cord injury and brain diseases. There are primary sources of stem cells like embryonic stem cells and adult stem cells. Stem cells from embryos were known to give rise to every type of cell. However, embryonic stem cells still have a lot of disadvantages. First, transplanted cells sometimes grow into tumors. Second, the human embryonic stem cells that are available for research would be rejected by a patient's immune system. Tissue-matched transplants could be made by either creating a bank of stem cells from more human embryos, or by cloning a patient's DNA into existing stem cells to customize them. However, this is laborious and ethically contentious. These problems could be overcome by using adult stem cells, taken from a patient, that are treated to remove problems and then put back. Nevertheless, some researchers do not convince that adult stem cells could, like embryonic ones, make every tissue type. Human stem cell research holds enormous potential for contributing to our understanding of fundamental human biology. In this review, we discuss the recent progress in stem cell research and the future therapeutic applications.