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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 19, Issue 4 - Oct 2011
Volume 19, Issue 3 - Jul 2011
Volume 19, Issue 2 - Apr 2011
Volume 19, Issue 1 - Jan 2011
Selecting the target year
Syndecan as a Messenger to Link Diabetes and Cancer
Kim, Sung-Jin ; Raman, Os Sethu ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 267~273
DOI : 10.4062/biomolther.2011.19.3.267
Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed.
Herbs for the Treatment of Insomnia
Kim, Chung-Soo ; Han, Jin-Yi ; Kim, Seung-Hwan ; Hong, Jin-Tae ; Oh, Ki-Wan ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 274~281
DOI : 10.4062/biomolther.2011.19.3.274
Pharmacological approaches have been included in conventional medical treatment for insomnia or sleep disorders. However, long-term use of frequently prescribed medications can often lead to habituation, critical withdrawal symptoms and/or side effects. Some individuals with insomnia or trouble sleeping have used complementary and alternative medicine (CAM) therapies to treat their conditions. Recently, CAMs or herbs have been attractive alternative medications to many patients with sleep disorders who may be averse to using conventional drugs. We reviewed the most widely available sleep-promoting herbs commonly used in the western and oriental countries.
Sirt1 Promotes DNA Damage Repair and Cellular Survival
Song, Seung-Hyun ; Lee, Mi-Ok ; Lee, Ji-Seon ; Oh, Je-Sok ; Cho, Sung-Uk ; Cha, Hyuk-Jin ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 282~287
DOI : 10.4062/biomolther.2011.19.3.282
Sirt1, a nicotinamide adenine dinucleotide (
)-dependent histone deacetylase, is known to deacetylate a number of proteins that are involved in various cellular pathways such as the stress response, apoptosis and cell growth. Modulation of the stress response by Sirtuin 1 (Sirt1) is achieved by the deacetylation of key proteins in a cellular pathway, and leads to a delay in the onset of cancer or aging. In particular, Sirt1 is known to play an important role in maintaining genomic stability, which may be strongly associated with a protective effect during tumorigenesis and during the onset of aging. In these studies, Sirt1 was generated in stably expressing cells and during the stimulation of DNA damage to examine whether it promotes survival. Sirt1 expressing cells facilitated the repair of DNA damage induced by either ionizing radiation (IR) or bleomycin (BLM) treatment. Fastened damaged DNA repair in Sirt1 expressing cells corresponded to prompt activation of Chk2 and
-H2AX foci formation and promoted survival. Inhibition of Sirt1 enzymatic activity by a chemical inhibitor, nicotinamide (NIC), delayed DNA damage repair, indicating that promoted DNA damage repair by Sirt1 functions to induce survival when DNA damage occurs.
Neuroprotective Effect of L-Theanine on Aβ-Induced Neurotoxicity through Anti-Oxidative Mechanisms in SK-N-SH and SK-N-MC Cells
Jo, Mi-Ran ; Park, Mi-Hee ; Choi, Dong-Young ; Yuk, Dong-Yeun ; Lee, Yuk-Mo ; Lee, Jin-Moo ; Jeong, Jae-Hwang ; Oh, Ki-Wan ; Lee, Moon-Soon ; Han, Sang-Bae ; Hong, Jin-Tae ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 288~295
DOI : 10.4062/biomolther.2011.19.3.288
Amyloid beta (
)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on
-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited
-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa-B. L-theanine also signifi cantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50
/ml) concomitantly attenuated
)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on
-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.
Comparison of Leukotriene Receptor Antagonist and Theophylline in Addition to Inhaled Corticosteroid in Adult Asthma: A Meta-Analysis
Fang, Huijuan ; Wang, Jianmiao ; Jin, Di ; Cao, Yong ; Xu, Yongjian ; Xiong, Weining ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 296~301
DOI : 10.4062/biomolther.2011.19.3.296
This meta-analysis was performed to evaluate the difference of the therapeutic effi cacy and adverse effects of leukotriene receptor antagonist and theophylline added to inhaled corticosteroids in adult asthma. Databases were searched for studies published through Nov, 2010. Randomized-controlled trials containing inhaled corticosteroids plus leukotriene receptor antagonist and inhaled corticosteroids plus sustained-release theophylline for asthma therapy were selected. For each report, data were extracted to the outcomes analyzed: mean change in morning peak expiratory flow, mean change in evening peak expiratory flow, mean change in morning forced expiratory volume in 1 sec, mean change in daily short bete2-agonist use, asthma exacerbation and adverse effects. Four assessable trials including 182 asthmatic patients were identified. Inhaled corticosteroids plus leukotriene receptor antagonist was superior to inhaled corticosteroids plus theophylline therapy in improving morning peak expiratory flow in asthmatics (mean difference 19.08 [95% confidence interval 13.37-23.79] l/min, p<0.001) and morning forced expiratory volume in 1 sec in asthmatics (mean difference 0.09 [95% confidence interval 0.03-0.14] liter, p=0.001). In evening peak expiratory flow, daily short bete2-agonist use, asthma exacerbation and adverse effects, there was no significant difference between these two therapies (All p>0.05). Our meta-analysis showed that the combination of inhaled corticosteroids plus leukotriene receptor antagonist resulted in more improvement in both peak expiratory flow and forced expiratory volume in 1 sec in the morning than inhaled corticosteroids plus sustained-release theophylline in adult asthmatics. Further trials are necessary to evaluate the dominant effects of the former combination.
Cellular Signaling Molecules Associated with Peptidoglycan-Induced CCL3 Up-Regulation
Kim, Kang-Seung ; Rhim, Byung-Yong ; Eo, Seong-Kug ; Kim, Koan-Hoi ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 302~307
DOI : 10.4062/biomolther.2011.19.3.302
Peptidoglycan (PGN) is detected in inflammatory cell-rich regions of human atheromatous plaques. The present study investigated the effects of PGN on CC chemokine ligand 3 (CCL3) expression, which is elevated in the atherosclerotic arteries, and determined cellular factors involved in PGN-mediated CCL3 up-regulation in mononuclear cells, with the goal of understanding the molecular mechanisms of inflammatory responses to bacterial pathogen-associated molecular patterns in diseased arteries. Exposure of human monocytic leukemia THP-1 cells to PGN resulted in enhanced secretion of CCL3 and profound induction of the CCL3 gene transcript. Both events were abrogated by oxidized 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine, an inhibitor of Toll-like receptors 2/4. Pharmacological inhibitors such as U0126, SP6001250, Akt inhibitor IV, rapamycin, RO318220, diphenyleneiodonium chloride, and N-acetylcysteine also significantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not influence CCL3 expression. We propose that PGN contributes to enhanced CCL3 expression in atherosclerotic plaques and that Toll-like receptors (TLR2), Akt, mTOR, mitogen-activated protein kinase, and reactive oxygen species are involved in that process.
The Influence of Circadian Gene Per2 on Cell Damaged by Ultraviolet C
Liu, Yanyou ; Wang, Yuhui ; Jiang, Zhou ; Xiao, Jing ; Wang, Zhengrong ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 308~314
DOI : 10.4062/biomolther.2011.19.3.308
It has been shown that circadian genes not only play an important role on circadian rhythms, but also participate in other physiological and pathological activities, such as drug dependence, cancer development and radiation injury. The Per2, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. In the present study, we applied mPER2-upregulated NIH3T3 cells to reveal the relationship of mPer2 and the cells damaged by ultraviolet C (UVC). NIH3T3 cells at the peak of the expression of mPer2 induced by phorbol 12-myristate 13-acetate (PMA) demonstrated little damage by UVC evaluated by MTT assay, cell growth curves and cell colony-forming assay, compared with that at the nadir of the expression of mPer2. Overexpression of mPER2, accompanied p53 upregulated, also demonstrated protective effect on NIH3T3 cells damaged by UVC. These results suggest that mPer2 plays a protective effect on cells damaged by UVC, whose mechanism may be involved in upregulated p53.
Effects of Alpha 1- and Alpha 2-Adrenoreceptor Stimulation on Galanin mRNA Expression in Primary Cultured Superior Cervical Ganglion Neurons
Xing, Yi ; Chen, Xiuying ; Liu, Zhen ; Li, Hao ; Liu, Huaxiang ; Li, Zhenzhong ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 315~319
DOI : 10.4062/biomolther.2011.19.3.315
Galanin (Gal) is a 29-amino-acid neuropeptide which is expressed in superior cervical ganglion (SCG) neurons and plays a trophic role in the adult animal and acts as an inhibitory modulator of cholinergic and noradrenergic neurotransmission. Whether activation or inhibition of alpha-adrenoreceptors infl uences Gal mRNA expression in SCG neurons remains unknown. Here, we have evaluated the possible regulation of Gal mRNA expression with acute (4 h) and chronic (4 days) stimulation of alpha 1- and alpha 2-adrenoreceptor agonists or antagonists in primary cultured SCG neurons. The results showed that the amount of Gal mRNA expression in cultured SCG neurons increased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor antagonist yohimbine compared with control SCG neurons at the same time point, whereas the amount of Gal mRNA expression decreased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor agonist clonidine as compared with that in control group. All these effects were not dose-dependent on the administration of alpha 2-adrenoreceptor agonist clonidine or alpha 2-adrenoreceptor antagonist yohimbine. Alpha 1-adrenoreceptor agonist phenylephrine or antagonist prazosin chronic stimulation did not have effects on Gal mRNA expression. Acute exposure of these agents did not have effects on Gal mRNA expression. The present study showed that Gal may be regulated by activation or inhibition of alpha 2-adrenoreceptors, but not alpha 1-adrenoreceptors in sympathetic neurons.
Effect of Berberine on MUC5AC Mucin Gene Expression and Mucin Production from Human Airway Epithelial Cells
Sikder, Md. Asaduzzaman ; Lee, Hyun-Jae ; Lee, Su-Yel ; Bae, Heung-Seog ; Kim, Jang-Hyun ; Chang, Gyu-Tae ; Lee, Choong-Jae ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 320~323
DOI : 10.4062/biomolther.2011.19.3.320
We conducted this study to investigate whether berberine signifi cantly affects MUC5AC mucin gene expression and mucin production induced by epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-
) from human airway epithelial cells. Confl uent NCI-H292 cells were pretreated with varying concentrations of berberine for 30 min and then stimulated with EGF, PMA or TNF-
for 24 h. MUC5AC mucin gene expression and mucin production were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Berberine was found to inhibit the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-
. Berberine also inhibited the production of MUC5AC mucin protein stimulated by the same inducers. This result suggests that berberine can regulate the expression of mucin gene and production of mucin protein, by directly acting on human airway epithelial cells.
Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica
Ko, Hyun-Jeong ; Jin, Jeong-Ho ; Kwon, Oh-Song ; Kim, Jong-Taek ; Son, Kun-Ho ; Kim, Hyun-Pyo ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 324~330
DOI : 10.4062/biomolther.2011.19.3.324
Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders, especially respiratory inflammation, in Chinese medicine. Previously, phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity in vitro and in vivo. In this study, the effects of BL on lung inflammation including bronchitis were examined in vitro and in vivo. BL (10-100
/ml) inhibited nitric oxide (NO) production of lipopolysaccharide (LPS)-treated alveolar macrophages, MH-S cells, primarily by down-regulating inducible NO synthase. BL also inhibited production of the proinflammatory cytokines, TNF-
and IL-6. Against an animal model of pleural cavity inflammation, BL (200-400 mg/kg) significantly inhibited 5 h and 24 h carrageenan-induced pleurisy in rats when administered orally. Additionally, BL inhibited experimental bronchitis induced by intratracheal instillation of LPS to rats. Taken together, these results indicate that BL may be effective for the treatment of human lung inflammation as well as bronchitis.
Anti-Inflammatory Effects of Hexane Fraction from White Rose Flower Extracts via Inhibition of Inflammatory Repertoires
Lee, Hwa-Jeong ; Kim, Han-Seok ; Kim, Seung-Tae ; Park, Dong-Sun ; Hong, Jin-Tae ; Kim, Yun-Bae ; Joo, Seong-Soo ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 331~335
DOI : 10.4062/biomolther.2011.19.3.331
In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-
, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-
) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-
and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.
Antioxidative Constituents of the Aerial Parts of Galium spurium
Yang, Seok-Won ; Park, Sae-Rom ; Ahn, Dal-Rae ; Yang, Jae-Heon ; Kim, Dae-Keun ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 336~341
DOI : 10.4062/biomolther.2011.19.3.336
As part of an ongoing search for natural plants with antioxidant compounds by measuring the radical scavenging effect on 1,1-diphenyl- 2-picrylhydrazyl (DPPH), a total extract of the twigs of Galium spurium L. (Rubiaceae) was found to show potent antioxidant activity. Subsequent activity-guided fractionation of the methanolic extract led to the isolation of nine compounds, asperulosidic acid methyl ester (1), asperuloside (2), caffeic acid (3), kaempferol-3-O-L-rhamnopyranoside (4), quercetin-3-O-[
-D-glucopyranoside] (5), isorhamnetin-3-O-glucopyranoside (6), quercetin-3-O-
-L-rhamnopyranoside (7), kaempferol-3-O-[
-D-glucopyranoside] (8), and quercetin (9). Their structures were elucidated by spectroscopic studies. Compounds 1, 3-8 were isolated for the first time from this plant. Among them, compounds 3 and 9 showed the significant radical scavenging effects on DPPH, and compounds 3 and 7 showed the potent riboflavin originated superoxide quenching activities.
Anticonvulsant Effect of Artemisia capillaris Herba in Mice
Woo, Tae-Seon ; Yoon, Seo-Young ; Pena, Ike Campomayor Dela ; Choi, Ji-Young ; Lee, Hye-Lim ; Choi, Yoon-Jung ; Lee, Yong-Soo ; Ryu, Jong-Hoon ; Choi, Jae-Sue ; Cheong, Jae-Hoon ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 342~347
DOI : 10.4062/biomolther.2011.19.3.342
In the present study, the anticonvulsant effects of Artemisia capillaris Herba (AC) and its major constituent, esculetin (ECT), were tested and the mechanism studied. Locomotion, Myorelaxation, motor coordination and electroshock seizure experiment were conducted in mice. To identify the anticonvulsant mechanism effect of this drug, chemical-induced seizure in mice and the ionic movement in neuroblastoma cells were also observed. The ethanol extract of AC was orally administered to mice 30 min. prior to testing and ECT was intraperitoneally injected. AC and ECT treatment did not change locomotor activities as well as activities on the rota-rod, which indicates that they did not cause a sedative and myorelaxation effect. AC and ECT treatment increased threshold of convulsion induced by electroshock. AC treatment also inhibited convulsion induced by pentylenetetrazole. In the case of strychnine however, only high dose of AC treatment inhibited convulsion. AC and ECT treatment increased the
influx into the intracellular area in a dose-dependent manner. On the other hand, bicuculline, a GABA antagonist, inhibited the
influx induced by AC and ECT. These results indicate that ECT induces the anticonvulsive effect of AC extract through the GABAergic neuron.
Aqueous Extracts of Liriope platyphylla Are Tightly-Regulated by Insulin Secretion from Pancreatic Islets and by Increased Glucose Uptake through Glucose Transporters Expressed in Liver Hepatocytes
Kim, Ji-Eun ; Nam, So-Hee ; Choi, Sun-Il ; Hwang, In-Sik ; Lee, Hye-Ryun ; Jang, Min-Ju ; Lee, Chung-Yeol ; Soon, Hong-Ju ; Lee, Hee-Seob ; Kim, Hae-Sung ; Kang, Byeong-Cheol ; Hong, Jin-Tae ; Hwang, Dae-Youn ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 348~356
DOI : 10.4062/biomolther.2011.19.3.348
Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodigenerative disorders, obesity and diabetes. The aims of this study were to study the antidiabetic effects of the aqueous extract of L. platyphylla (AEtLP) through pancreatic and extrapancreatic actions. AEtLP were orally administrated to ICR mice once a day for 7 days. Of three different concentrations of AEtLP, only 10% AEtLP were low toxic to liver, based on body weight and serum biochemical analyses. However, 10% AEtLP-treated mice displayed signifi cant reduction of the glucose concentration and increased insulin concentration; no changes were noted using 5% and 15% AEtLP. Also, the increase of glucose transporter (Glut)-1 expression in liver was dependent on the concentration of AEtLP, and was regulated by the phosphorylation of Akt. The lowest expression of Glut-3 was observed in 15% AEtLP treated mice, followed by 10% AEtLP- and 5% AEtLP-treated mice. This pattern of Glut-3 expression was roughly in accord with the phosphorylation of c-Jun N-teminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, a signifi cant rise of the superoxide dismutase activity (SOD) was detected in AEtLP-treated mice. The fi ndings suggest that AEtLP should be considered as a diabetes therapeutic candidate to induce insulin secretion from pancreatic
-cells and glucose uptake in liver cells.
Enhanced Local Anesthetic Efficacy of Bioadhesive Ropivacaine Gels
Cho, Cheong-Weon ; Choi, Jun-Shik ; Shin, Sang-Chul ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 357~363
DOI : 10.4062/biomolther.2011.19.3.357
In relieving local pains, ropivacaine has been widely used. In case of their application such as ointments and creams, it is difficult to expect their effects for a significant period of time, because they are easily removed by wetting, movement and contacting. Therefore, the new formulations that have suitable bioadhesion were needed to enhance local anesthetic effects. The effect of drug concentration and temperature on drug release was studied from the prepared 1.5% Carboxymethyl cellulose (CMC) (150MC) gels using synthetic cellulose membrane at
. As the drug concentration and temperature increased, the drug release increased. A linear relationship was observed between the logarithm of the permeability coefficient and the reciprocal temperature. The activation energy of drug permeation was 3.16 kcal/mol for a 1.5% loading dose. To increase the skin permeation of ropivacaine from CMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the ropivacaine-CMC gels. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. For the efficacy study, the anesthetic action of the formulated ropivacaine gel containing an enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. According to the rat tail-flick test, 1.5% drug gels containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed the best prolonged local analgesic effects. In conclusion, the enhanced local anesthetic gels containing penetration enhancer and vasoconstrictor could be developed using the bioadhesive polymer.
Effects of Curcumin on the Pharmacokinetics of Loratadine in Rats: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Curcumin
Li, Cheng ; Choi, Byung-Chul ; Kim, Dong-Ki ; Choi, Jun-Shik ;
Biomolecules and Therapeutics, volume 19, issue 3, 2011, Pages 364~370
DOI : 10.4062/biomolther.2011.19.3.364
The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71
and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.