• Journal of Pharmaceutical Investigation
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• 제33권3호
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• pp.171-178
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterzed by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. The purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$, and AUC. Administration of metformin in normal and diabetic rats treated with Laminaria japonica diet showed significant decrease in AUC, $C_{max},\;and\;k_a$, and increase in $t_{max}$, compared to those with normal diet. This might result from adsortion of metformin on components of Laminaria japonica, causing delayed absorption. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by long-term Laminaria japonica diet.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.19-29
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• 1996

The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

• 생약학회지
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• 제48권3호
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• pp.179-186
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• 2017

Pyrrosia lingua which belongs to Polypodiaceae has been used as a traditional medicine for the treatment of urinary system inflammation, urination disorder, and bronchitis. However, there are not enough phytochemical and pharmacological studies of P. lingua up to now. Here in this study, the protective effect of MeOH extract of whole plant of Pyrrosia lingua (MPL) against 2% glucose-induced toxicity was investigated using Caenorhabditis elegans (C. elegans) model system. We found that MPL significantly extended the lifespan of wild-type nematode under normal culture condition. MPL also effectively recovered the decreased lifespan caused by 2% glucose-toxicity. In addition, MPL efficiently attenuated the increased glucose concentration inside of nematode. Further studies evaluating diabetes-related factors revealed that MPL reduced both intracellular ROS and lipid accumulation which were up-regulated under 2% glucose supplement condition. Our data also showed that MPL improved the 2% glucose-induced shortened body movement of nematode. Lastly, we carried out genetic studies using several single gene knockout mutants to establish the possible target of MPL. Our results demonstrated that genes such as daf-2 and daf-16 were responsible for the protective activity of MPL against 2% glucose-induced toxicity. These results indicate that MPL exerts protective action against 2% glucose via regulation of insulin/IGF-1 sinaling pathway and FOXO activation.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.113-120
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$ and AUC. Administration of glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.309-316
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• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• 대한약리학회지
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• 제9권2호
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• pp.1-6
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• 1973

Although numerous drugs are available for the treatment of superficial fungi infections of skin, the clinical effects of the majority of such drugs are not satisfactory. In the hope of searching the effective drugs for superficial fungi infections, authors studied whether Veratrum rhizoma extracts had any effect on fungi, with water extract (VRWE), ethanol extract (VREE) and methanol extract (VRME) from Veratrum album L. var. grandiflorum Max. In in vitro studies, the spores of fungi were inoculated on Sabouraud's glucose agar media which contained three extracts of Veratrun rhizoma in each concentration of $500\;{\mu}g/ml$, $1,000\;{\mu}g/ml$ and $5,000\;{\mu}g/ml$ respectively, and the growth of the fungi were observed for 3 weeks. The species of the fungi used in these experiments were Epidermophyton floccosum, Microsporum canis, Microsporum nanum, Microsporum gypseum, Microsporum cookei, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Trichophyton verrucosum. The results of the studies were as follows: 1. The growth of M. canis, M. nanum, T mentagrophytes and T. tonsurans were slightly inhibited by VRWE $1,000\;{\mu}g/ml$, and with VRWE $5,000\;{\mu}g/ml$, the growth of E. floccosum, M. gypseum and T. rubrum were slightly inhibited, moderate inhibition on the growth of M. canis, M. nanum, M. cookei, T. mentagrophytes and T. tonsurans were showed by VRWE $5,000\;{\mu}g/ml$. 2. With $500\;{\mu}g/ml$ of VREE, the inhibition on growth of E. floccosum, M. nanum and M. gypseum were slight, however significant inhibition on the growth of M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed. The growth of M. nanum and M. gypseum were moderately inhibited, and significant inhibition on the growth of E. floccosum, M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed by VREE $1,000\;{\mu}g/ml$. By VREE $5,000\;{\mu}g/ml$, the growth of all tested fungi were significantly inhibited except T. verrucosuia being showed slight inhibition. 3. Significant inhibition on the growth of M. canis, T, mentagrophytes, T. rubrum and T. tonsurans were noted, and moderate inhibition of M. nanum, slight inhibition of E. floccosum and M. gypseum in growth were observed by VRME $500\;{\mu}g/ml$. The growth of E. floccosum, M. canis, M. nanum, M. cookei, T. mentsgrophytes, T. rubrum and T. tonsurans were significantly inhibited by VRME $1,000\;{\mu}g/ml$, and that of M. gypseum was moderate. With $5,000\;{\mu}g/ml$ of VRME, significant inhibition on the growth of E. floccosum, M. canis, M. nanum, M. gypseum, M. cookei, T mentagrophytes, T. rubrum and T. tonsurans were observed, and T. verrucosum was showed only slight inhibition. From the above results, it was found that the extracts of organic solvents from Veratrum rhizoma (VREE & VRME) exerted significant antifungal activity, and their effects were probably derived from the pharmacological action of steroidal alkaloids.

• 대한약리학회지
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• 제9권2호
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• pp.39-45
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• 1973

The majority of drugs used in the treatment of superficial fungal infections has limited values due to its low efficacy or development of resistance. For the purpose of searching efficacious agent on the superficial fungal infections induced by dermatophytes which is regarded as the most malicious one, authors examined whether Chinae Rhizoma Extracts have significant on it. Extracts from Smilax china Linne used for the study are water extract (CRWE), ethanol extract (CREE) and methanol extract (CRME). In in vitro studies, the spores of the dermatophytes were inoculated on Sabouraud's glucose agar media which contained three extracts of Chinae Rhizoma in each concentration of $500\;{\mu}g/ml$, $1,000\;{\mu}g/ml$ and $5,000\;{\mu}g/ml$ respectively, and also $1,000\;{\mu}g/ml$ of salicylic acid and undecylenic acid $1,000\;{\mu}g/ml$ as comparable drugs. The growth of the dermatophytes were observed for 3 weeks. The species of the dermatophytes used in this experiment were Epidermophyton floccosum, Microsporum canis, Microsporum cookei, Microsporum gypseum, Microsporum nanum, Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton tonsurans and Trichophyton verrucosum distributed from The Institute of Tropical Medicine in Belgium. The results of the studies were as follows: 1. The growth of M. canis, M. nanum, T. mentagrophytes, T. rubrum & T. tonsurans were slightly inhibited in CRWE $1,000\;{\mu}g/ml$ and CRWE $5,000\;{\mu}g/ml$, and only slight inhibition on the growth of E. floccosum, M. canis and M. gypseum were observed in CRWE $5,000\;{\mu}g/ml$. 2. Complete inhibition of T. rubrum, moderate inhibition of M. nanum & T. tonsurans, and slight inhibition of E. floccosunl, M. canis, M. cookei & T. mentagrophytes in growth were observed in concentration of CREE $500\;{\mu}g/ml$. The growth of M. gypseum was slightly inhibited, moderate inhibition on the growth of M. canis, M. cookei & T. mentagrophytes, and complete inhibition of E. floccosum, M. nanum, T. rubrum & T. tonsurans in growth were observeed by CREE $1,000\;{\mu}g/ml$. With $5,000\;{\mu}g/ml$ of CREE, the growth of E. floccosum, M. canis, M. cookei, M. gypseum, T. mentagrophytes, T. rubrum & T. tonsurans were completely inhibited except T. verrucosum being showed slight inhibition. 3. In CRME $500\;{\mu}g/ml$, slight inhibition of T. verrucosum, moderate inhibition of M. gypseum and complete inhibition of E. floccosum, M. canis, M. cookei, T. mentagrophytes, T. rubrum & T. tonsurans in growth were observed. The growth of E. floccosum, M. canis, M. cookei, M. gypseum, M. nanum, T. mentagrophytes, T. rubrum & T. tonsurans were completely inhibited except T. verrucosum being showed moderate inhibition in both CRME $1,000\;{\mu}g/ml$ and CRME $5,000\;{\mu}g/ml$. 4. In $1,000\;{\mu}g/ml$ of undecylenic acid, slight inhibition of T. verrucosum and complete inhibition of E, floccosum, M. canis, M. cookei, M. gypseum, M. nanum, T. mentagrophytes, T. rubrum & T. tonsurans in growth were observed. From the above results, it was found that Chinas Rhizoma Alcoholic Extracts(CREE & CRME) exerted significant antifungal activity, and their effects were probably derived from the pharmacological actions of triterpenoidal saponin and steroidal saponin.

• 약학회지
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• 제52권4호
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• pp.299-305
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• 2008

Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% for $AUC_{t}$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.103-103
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• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

• 혜화의학회지
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• 제22권1호
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• pp.145-170
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• 2013

Objectives : This study was carried out to investigate the anti inflammatory and anti allergy effects of Vitex rotundifolia Linne fil. extract(VRE). Results : 1. In vitro test, VRE was used to determine the modulation of cytokine secretion, the activation of inflammatory and allergic factor and the inhibition of gene expression. The cell survival rate of Raw 264.7 and Jurkat T cells didn't decrease and accordingly cytotoxicity wasn't observed. In anti-allergic assay, the secretion of IL-2, TNF-${\alpha}$, IL-4, IL-5 and IFN-${\gamma}$ were suppressed on Jurkat T cells induced by dust mites. And the gene expression of COX-2 was suppressed in HMC-1 stimulated by calcium ionophore A23187. In anti-inflammatory assay, the gene expression of TNF-${\alpha}$, COX-2 were suppressed on LPS-activated Raw 264.7 cells. And the secretion of IL-6 and IL-8 were suppressed on EoL-1 cells induced by dust mites. P38 and ERK activation of MAPK decreased generally. VRE showed potent inhibitory activity of NO production. 2. In vivo test, we used NC/Nga mouse induced by atopic dermatitis to observe the effects of VRE on the weight, water and feed, blood test, weight of organs, total IgE and histological change of main organs. Quantity of water and feed were not changed, therefore it didn't affect the weight directly, and no change was observed in related main organs, thus maybe there is no organ toxicity by test substances. And the symptoms were decreased significantly, and the thickness of epithelial cell layer and the number of mast cells were inhibited significantly by the difference of dosage. The number of total complete blood cells and IgE in serum were not changed significantly. Conclusion : These results suggest that VRE has anti-inflammatory and anti-allergic effects. Therefore VRE could be used effectively on improvement or treatment of atopic dermatitis. However, further study is needed to prove which component of VRE indicates effective pharmacological action.