著者

Meng Wang Yating Tu Chun Liu Hui Cheng Mengxiao Zhang Qinglin Li

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1385-1393, 2023-10-01 (Released:2023-10-01)

参考文献数

33

被引用文献数

1

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Cutaneous melanoma is an aggressive cancer, which is the most common type of melanoma. In our previous studies, gambogenic acid (GNA) inhibited the proliferation and migration of melanoma cells. Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been shown to have inhibitory effects in a variety of cancers. However, the mechanisms in melanoma progression need to be further investigated. In the current study, we investigated the inhibitory effect of GNA on melanoma and its molecular mechanism through a series of cell and animal experiments. We found that GNA could improve epithelial mesenchymal transition by up-regulating the expression of the lncRNA MEG3 gene, thereby inhibiting melanoma metastasis in vitro and in vivo.

著者

Shinya Inoue Yasufumi Oshima Kentaro Kogure

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.11, pp.1635-1638, 2023-11-01 (Released:2023-11-01)

参考文献数

9

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Hyaluronic acid (HA) is a hydrophilic supra-macromolecule, with a molecular weight (MW) 1000000<. HA is recognized as a biomaterial for skin moisturization. HA solution is typically injected into the skin using a needle. However, needle injection is invasive and does not result in homogeneous distribution of HA over a large area of skin. Therefore, non-invasive and effective technologies for homogenous intradermal delivery of HA are needed. Recently, we demonstrated the use of iontophoresis (ItP) for non-invasive intradermal delivery of various macromolecules, such as small interfering RNA (siRNA) (MW: 12000) and antibodies (MW: 150000). Based on our previous studies, we hypothesized that HA can also be delivered non-invasively into the skin by ItP. In this study, we applied ItP to fluorescence-labeled HA (MW: 600000–1120000 and 1200000–1600000) on rat dorsal skin. Following treatment, fluorescence was observed to be widely distributed in the skin, demonstrating successful intradermal delivery of HA via ItP. In addition, the relative moisture content and elasticity of skin treated with ItP/HA was temporarily higher than that of control skin. This is the first report demonstrating successful non-invasive intradermal delivery of HA and improvement of skin conditions by high-molecular weight HA delivered by ItP. In conclusion, ItP would be a useful technology for non-invasive intradermal delivery of high-molecular weight HA for treatment of skin diseases and cosmetology applications.

著者

Kazuki Nagashima Kojiro Hiruma Eri Nakamura Machiko Watanabe Yuko Sekine

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b23-00530, (Released:2023-11-16)

参考文献数

27

被引用文献数

1

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Overdose has become a global social problem. The Japanese government requires gatekeeper training to detect and prevent indicators of overdose and suicide. However, knowledge of necessary factors for the gatekeeper of overdose (patient intervention) is limited. This study aimed to investigate the characteristics of individuals who experienced intervening persons expected to overdose, and to identify the factors required of gatekeepers. A Google form was used to survey 298 pharmacists and registered sellers in Japan. We searched for factors by logistic analysis. Knowledge of prescription drugs used for overdose was higher among pharmacists than among registered sellers. Conversely, pharmacists and registered sellers had similar knowledge about OTC drugs. Overall multivariate logistic regression analysis revealed countermeasures against overdose at their workplace (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 2.25–7.15, P  <  0.01) and knowledge that overdose is on the rise (OR: 1.93, 95% CI: 1.04–3.69, P  <  0.05) to be significantly associated with intervention experience as a gatekeeper. Countermeasures against overdose at their workplace (OR: 2.40, 95% CI: 1.10–5.25, P  <  0.05) in pharmacists and years of work experience (OR: 1.13, 95% CI: 1.04–1.24, P  <  0.05), countermeasure against overdose at their workplace (OR: 3.43, 95% CI: 1.18–10.0, P  <  0.05), and willingness to participate in study sessions and workshops on overdose (OR: 3.50, 95% CI: 1.51–8.10, P  <  0.05) in registered seller were significantly associated with intervention experience as a gatekeeper. These results are useful evidences for countermeasures and gatekeeper training for overdose at pharmacies and drugstores in the community.

著者

Yoshihito Kasanami Takashi Yamamoto Tomoyoshi Miyamoto Sumio Matzno Mikio Sakakibara Masahiro Iwaki Atsufumi Kawabata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.12, pp.1699-1705, 2023-12-01 (Released:2023-12-01)

参考文献数

34

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Community pharmacists may play a key role in promoting deprescribing of potential inappropriate medications (PIMs) that are highly prevalent among community-dwelling elderly with dementia. To characterize PIMs categories that need a special attention for dementia patients, in the present study, we analyzed the anonymized pharmacy claims data of patients aged 65 years and older (n = 333869) who visited nationwide 905 community-based pharmacies of Sugi Pharmacy Co., Ltd. during December 1–31, 2019. A dementia group was defined as patients who received typical dementia medications marketed in Japan, i.e., donepezil, galantamine, memantine or rivastigmine, and a non-dementia group was defined as patients who received no such medications. After propensity score matching on the basis of patients’ age, gender and home healthcare insurance usage, the data of 11486 patients in each group were subjected to logistic regression analyses, to identify PIMs categories particularly important for dementia patients. Univariate analysis indicated that the proportions of dementia patients who received 1 and 2≤ of PIMs were significantly (p < 0.001) greater than those of non-dementia patients (odds ratios were 1.35 and 1.47, respectively). Multivariate analyses identified 5 categories of PIMs that were significantly more frequently prescribed in dementia patients, i.e., ‘H2 blockers,’ ‘drugs for overactive bladder,’ ‘anti-diabetes drugs’ and ‘sulpiride’ listed as PIMs categories for non-specific cases (adjusted odds ratios (aORs): 1.29, 1.91, 1.17, and 1.38, respectively), in addition to ‘antipsychotics’ listed only for dementia patients (aOR: 4.29). These results provide useful information to establish strategies for pharmacist-led deprescribing of PIMs in dementia patients.

著者

Sabrina Dahlizar Mika Futaki Akie Okada Wesam Radhi Kadhum Hiroaki Todo Kenji Sugibayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.3, pp.327-333, 2018-03-01 (Released:2018-03-01)

参考文献数

24

被引用文献数

10 13

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Palmitoyl-glycine-histidine (Pal-GH) is a new low molecular weight gelling agent. It exhibits thixotropic behavior, low viscosity, and high dissolving properties for a wide range of hydrophilic to lipophilic drugs. Orally administered ivermectin (IVM) is used to treat scabies. However, this treatment is associated with well-known side effects, thus a study is awaited to search for alternative routes of administration. Although a topical formulation of IVM could be a candidate, it requires whole body application except the head and face for several hours on a daily basis. Therefore, in this study, we prepared a gel spray formulation containing IVM as an approach for application to large skin areas with a single spray application without further contact with the applied formulation. Pal-GH gel spray formulations were prepared from its aqueous solution by a heating and cooling method. Rheological behavior and physical appearance (spraying, spreading ability, volume of spraying, and homogeneity) of the prepared formulations were evaluated. Pal-GH gel with propylene glycol demonstrated impressive rheological properties (typical thixotropic behavior) with high hysteresis area among all the tested Pal-GH gels and spreading ability. The obtained IVM concentration in the skin after topical application of 0.1% IVM-containing Pal-GH formulation onto hairless rats was much higher than the reported therapeutic concentration obtained from oral administration in humans. These results suggested that topical application of IVM using a Pal-GH gel spray formulation could be an alternative to the conventional oral forms for the scabies treatment.

著者

Shoma Oki Sou Kageyama Kayo Machihara Takushi Namba

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.12, pp.1787-1796, 2023-12-01 (Released:2023-12-01)

参考文献数

33

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Obesity is characterized by the excessive accumulation of fat to adipose tissue, which is related to abnormal increasing white adipose tissue (WAT) in the body, and it upregulates the risk of multiple diseases. Here, kuanoniamine C, which is a pyridoacridine alkaloid, suppressed the differentiation of pre-adipose cells into white adipocytes via the modulation of mitochondrial function, and inhibited WAT expansion in the early phase of high-fat-diet-induced obesity model. Pharmacological analysis revealed that inhibition of mitochondrial respiratory complex II, which new target of kuanoniamine C, activated reactive oxygen species (ROS)–extracellular signal-regulated kinase (ERK)–β-catenin signaling, and this signaling was antagonized by insulin-, IBMX-, and dexamethasone-induced adipogenesis. Therefore, the kuanoniamine C might prevent abnormal WAT expansion even when eating a diet that is not calorie restricted.

著者

Kazunori Miwa Yan Guo Masayuki Hata Yoshinori Hirano Norio Yamamoto Tyuji Hoshino

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.12, pp.897-905, 2023-12-01 (Released:2023-12-01)

参考文献数

40

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Virtual screening with high-performance computers is a powerful and cost-effective technique in drug discovery. A chemical database is searched to find candidate compounds firmly bound to a target protein, judging from the binding poses and/or binding scores. The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infectious disease has spread worldwide for the last three years, causing severe slumps in economic and social activities. SARS-Cov-2 has two viral proteases: 3-chymotrypsin-like (3CL) and papain-like (PL) protease. While approved drugs have already been released for the 3CL protease, no approved agent is available for PL protease. In this work, we carried out in silico screening for the PL protease inhibitors, combining docking simulation and molecular mechanics calculation. Docking simulations were applied to 8,820 molecules in a chemical database of approved and investigational compounds. Based on the binding poses generated by the docking simulations, molecular mechanics calculations were performed to optimize the binding structures and to obtain the binding scores. Based on the binding scores, 57 compounds were selected for in vitro assay of the inhibitory activity. Five inhibitory compounds were identified from the in vitro measurement. The predicted binding structures of the identified five compounds were examined, and the significant interaction between the individual compound and the protease catalytic site was clarified. This work demonstrates that computational virtual screening by combining docking simulation with molecular mechanics calculation is effective for searching candidate compounds in drug discovery.

著者

Xian-sen Jiang Bi-le Fu Xin-xin Yang Hong-yan Qin

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.12, pp.1769-1777, 2023-12-01 (Released:2023-12-01)

参考文献数

49

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Hepatocyte tight junctions (TJ) constituted blood–biliary barrier is the most important hepatic barrier for separating bile from the bloodstream, disruption or dysfunction of TJ barrier is involved in hepatobiliary manifestations of colitis, but the underlying mechanism is still not clear. This study aims to investigate the effect and underlying mechanism of tumor necrosis factor alpha (TNF-α) on hepatic TJ protein expression in blood–biliary barrier and identify its role in the pathogenesis of acute colitis-related cholestasis. Acute colitis rat model was induced by trinitrobenzene sulfonic acid (TNBS) intra-colonic administration. TJs expression of blood–biliary barrier was tested in colitis rats, the serum TNF-α level was also determined in order to elucidate the correlation of TNF-α and TJs. HepaRG cells were used to investigate the effect of TNF-α on TJs, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway were also evaluated in rats and TNF-α treated HepaRG cells. Acute colitis was induced in rats at 5 d post TNBS, which is accompanied with cholestasis-like alteration. Serum TNF-α level was increased in colitis rats and positively correlated with the alteration of total bile acids and bilirubin, marked decrease in TJs was found in TNF-α treated HepaRG cells and the rats, down-regulated PI3K/AKT signaling pathway were also identified in TNF-α treated HepaRG cells and the rats. The study concluded that serum TNF-α mediated the down-regulation of PI3K/AKT signaling pathway, which contributed to the reduction of TJ protein expression in acute colitis-related intrahepatic cholestasis. These findings suggest that TNF-α plays an important role in the pathogenesis of intrahepatic cholestasis of colitis.

著者

Hongye Han Takeshi Akiyoshi Tokio Morita Toshiaki Tsuchitani Momoko Nabeta Kodai Yajima Ayuko Imaoka Hisakazu Ohtani

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.12, pp.1745-1752, 2023-12-01 (Released:2023-12-01)

参考文献数

41

被引用文献数

1

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Jabara juice and its component narirutin inhibit the activity of organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1, which are considered to play significant roles in the intestinal absorption of fexofenadine. In this study, we investigated the effects of jabara juice on the intestinal absorption of fexofenadine in mice and the inhibitory effects of jabara juice and narirutin on the permeation of fexofenadine using Caco-2 cell monolayers and LLC-GA5-COL300 cell monolayers. In the in vivo study, the area under the plasma concentration–time curve (AUC) of fexofenadine in mice was increased 1.8-fold by jabara juice. In the permeation study, 5% jabara juice significantly decreased the efflux ratio (ER) of fexofenadine for Caco-2 monolayers. Furthermore, the ERs of fexofenadine and digoxin, which is a typical substrate of P-glycoprotein (P-gp), for LLC-GA5-COL300 cell monolayers were decreased in a concentration-dependent manner by jabara juice extract, suggesting that jabara juice may increase the intestinal absorption of fexofenadine by inhibiting P-gp, rather than by narirutin inhibiting OATPs. The present study showed that jabara juice increases the intestinal absorption of fexofenadine both in vivo and in vitro. The intestinal absorption of fexofenadine may be altered by the co-administration of jabara juice in the clinical setting.

著者

Hideyoshi Harashima

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.12, pp.1648-1660, 2023-12-01 (Released:2023-12-01)

参考文献数

81

被引用文献数

1

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This review paper summarizes progress that has been made in the new field of “Controlled Intracellular Trafficking.” This involves the development of new systems for delivering plasmid DNA (pDNA), small interfering RNA (siRNA), mRNA, proteins, their escape from endosomes, the mechanism for how they enter the nucleus, how they enter mithochondria and how materials subsequently function within a cell. In addition, strategies for delivering these materials to a selective tissue after intravenous administration was also intensively investigated not only to the liver but also to tumors, lungs, adipose tissue and the spleen. In 2020, a new mRNA vaccine was developed against coronavirus disease 2019 (COVID-19), where ionizable cationic lipids were used as a delivery system. Our strategy to identify an efficient ionizable cationic lipids (iCL) based on a lipid library as well as their applications concerning the delivery of siRNA/mRNA/pDNA is also described.

著者

Ayano Iwazaki Kimie Imai

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.11, pp.1716-1719, 2022-11-01 (Released:2022-11-01)

参考文献数

12

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We studied the effect of dietary fibers (DFs) on the levels of free hypoglycemic agents in vitro, i.e., glimepiride and the biguanides buformin and metformin. The levels of free buformin and free metformin were not affected by mixtures of DFs, i.e., cellulose, chitosan, pectin (PE), and glucomannan (GM), in fluids of pH 1.2 and 6.8 (similar to the pH of the stomach and intestines, respectively). However, the free biguanide level was significantly reduced by mixing with PE or sodium alginate (AL), in water. The free glimepiride level was reduced in the mixture of AL, PE, and GM (in a solution with a pH of 6.8). The changes in aqueous AL solution pH seemed to reflect the free metformin levels. Therefore, the effects of DFs on free drug levels were dependent on drug type, hypoglycemic agent, and mixing solution. In this study, the oral regimen concentrations of the drug and DFs were used. Based on these results, it is important to consider the interactions between hypoglycemic agents and DFs.

著者

Shota Oyama Mao Tomita Moeka Hata Yu Mikame Tsuyoshi Yamamoto Eishi Ashihara Asako Yamayoshi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.71, no.11, pp.819-823, 2023-11-01 (Released:2023-11-01)

参考文献数

22

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Exosomes are a type of extracellular vesicles that contain diverse molecules and are present in our body fluids. They play a crucial role in transporting materials and transmitting signals between cells. Currently, there have been numerous reports on the use of exosomes in drug delivery systems (DDS). However, most existing methods for utilizing exosomes in DDS require the isolation and purification of exosomes, which raises concerns about yield and potential damage to the exosomes. Recently, we have developed a novel DDS called “ExomiR-Tracker” that harnesses exosomes without the need for isolation and purification. This system aims to deliver nucleic acid drugs effectively. ExomiR-Tracker consists of an anti-exosome antibody equipped with nona-D-arginines (9 mer) and nucleic acid drugs which have complementary sequence of target microRNA (anti-miR). In this study, we modified ExomiR-Tracker by incorporating branched nona-D-arginines (9 + 9 mer) molecules (referred to as Branch ExomiR-Tracker) and evaluated its efficacy in lung adenocarcinoma cells (A549 cells). The improved complex formation ability and enhanced cellular uptake of anti-miR, demonstrated by our findings, highlight the advantages of incorporating branched oligoarginine peptides into the ExomiR-Tracker platform. These results represent significant progress in revealing the effectiveness of Branch ExomiR-Tracker against adhesive cancer cells, which has not been shown to be effective with the conventional Linear ExomiR-Tracker.

著者

Megumi Yamamoto Yuma Ito Masaki Fukui Kazuya Otake Yoshimichi Shoji Tatsuya Kitao Hiroaki Shirahase Eiichi Hinoi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1435-1443, 2023-10-01 (Released:2023-10-01)

参考文献数

35

被引用文献数

1

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Osteoporosis is treated with oral and parenteral bone resorption inhibitors such as bisphosphonates, and parenteral osteogenic drugs including parathyroid hormone (PTH) analogues and anti-sclerostin antibodies. In the present study, we synthesized KY-054, a 4,6-substituted coumarin derivative, and found that it potently promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity at 0.01–1 µM in mouse-derived mesenchymal stem cells (ST2 cells) and rat bone marrow-derived mesenchymal stem cells (BMSCs). In the ovariectomized (OVX) rats, KY-054 (10 mg/kg/d, 8 weeks) increased plasma bone-type ALP activity, suggesting in vivo promoting effects on osteoblast differentiation and/or activation. In dual-energy X-ray absorption (DEXA) scanning, KY-054 significantly increased the distal and diaphyseal femurs areal bone mineral density (aBMD) that was decreased by ovariectomy, indicating its beneficial effects on bone mineral contents (BMC) and/or bone volume (BV). In micro-computed tomography (micro-CT) scanning, KY-054 had no effect on metaphysis trabecular bone loss and microarchitecture parameters weakened by ovariectomy, but instead increased metaphysis and diaphysis cortical bone volume (Ct.BV) and cortical BMC (Ct.BMC) without reducing medullary volume (Med.V), resulting in increased bone strength parameters. It is concluded that KY-054 preferentially promotes metaphysis and diaphysis cortical bone osteogenesis with little effect on metaphysis trabecular bone resorption, and is a potential orally active osteogenic anti-osteoporosis drug candidate.

著者

Yasuhiro Yamamoto Hiromi Koma Sayaka Nishii Tatsurou Yagami

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.4, pp.402-412, 2017-04-01 (Released:2017-04-01)

参考文献数

46

被引用文献数

5 5

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Heat shock protein 70 (Hsp70) is not only a molecular chaperone in cytosol, but also presents in synaptic plasma membranes. To detect plasmalemmal Hsp70 (pl-Hsp70), neurons were immunostained with anti-Hsp70 antibody without permeabilization and fixation. Dotted immunofluorescent signals at neuronal cell bodies and neurites indicated the localization of Hsp70 on the neuronal cell surface. To target only pl-Hsp70, but not cytosolic Hsp70, the anti-Hsp70 antibody was applied without permeabilization in the primary culture of rat cortical neurons. The antibody induced neuronal cell death in a concentration-dependent manner. The anti-Hsp70 antibody activated ubiquitin-proteasome pathway, but inactivated caspase-3. A lag time was required for the neurotoxicity of anti-Hsp70 antibody. Hydrogen peroxide was increased in the anti-Hsp70 antibody-treated neurons during the lag time. Catalase suppressed the anti-Hsp70 antibody-reduced cell viability via the plausible inhibition of hydrogen peroxide generation. One of down-streams of hydrogen peroxide exposure is activation of the mitogen-activated protein kinase (MAPK) signaling cascade. The neurotoxicity of anti-Hsp70 antibody was partially ascribed to c-Jun N-terminal kinase among MAPKs. In conclusion, the anti-Hsp70 antibody targeted pl-Hsp70 on the neuronal cell surface and induced neuronal cell death without complement. Furthermore, hydrogen peroxide appeared to mediate the neuronal cell death, which was accompanied with the enhancement of the ubiquitin–proteasome pathway and the suppression of caspase in a different fashion from the known cell death.

著者

Ning Wan Yi-Yang Jia Yi-Lin Hou Xi-Xi Ma Yong-Sheng He Chen Li Si-Yuan Zhou Bang-Le Zhang

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.7, pp.1112-1120, 2016-07-01 (Released:2016-07-01)

参考文献数

51

被引用文献数

7 8

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In this work two novel cationic lipids using natural tartaric acid as linking backbone were synthesized. These cationic lipids were simply constructed by tartaric acid backbone using head group 6-aminocaproic acid and saturated hydrocarbon chains dodecanol (T-C12-AH) or hexadecanol (T-C16-AH). The physicochemical properties, gel electrophoresis, transfection activities, and cytotoxicity of cationic liposomes were tested. The optimum formulation for T-C12-AH and T-C16-AH was at cationic lipid/dioleoylphosphatidylethanolamine (DOPE) molar ratio of 1 : 0.5 and 1 : 2, respectively, and N/P charge molar ratio of 1 : 1 and 1 : 1, respectively. Under optimized conditions, T-C12-AH and T-C16-AH showed effective gene transfection capabilities, superior or comparable to that of commercially available transfecting reagent 3β-[N-(N′,N′-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and N-[2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium chloride (DOTAP). The results demonstrated that the two novel tartaric acid-based cationic lipids exhibited low toxicity and efficient transfection performance, offering an excellent prospect as nonviral vectors for gene delivery.

著者

Masako Horiuchi Yoshiyuki Seyama

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.54, no.3, pp.294-301, 2008 (Released:2008-06-01)

参考文献数

25

被引用文献数

15 16

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Bidens pilosa L. var. radiata SCHERFF (Tachiawayukisendangusa: Musashino Miyako Bidens Pilosa (MMBP)) has been reported to have antiinflammatory and antiallergic properties in the treatment of experimental diseases. We studied the antiinflammatory and anti-allergic effects of enzymatic digested MMBP (eMMBP), MMBP treated with Cellulosine, using an experimental inflammatory and allergic model. Oral administration of eMMBP suspension in carboxy-methyl-cellulose sodium solution inhibited the production of IgE 10 days after immunization with 2,4-dinitrophenylate (DNP)-ascaris in mice. Oral administration of eMMBP suspension inhibited dye exudation in rat skin induced by passive cutaneous anaphylaxis (PCA) and chemical mediators (histamine and substance P). The effects of eMMBP on the inhibition of histamine release from mast cells induced by compound 48/80 or antigen-antibody reaction was stronger than that of the hot-water extract (HWex). Caffeic acid and flavonoids (hyperin and isoquercitrin) in eMMBP are increased more than those in HWex of MMBP, as estimated using HPLC. These results suggest that eMMBP has antiinflammatory and antiallergic activity, and that enzymatic digestion enhances its antiallergic activity by the inhibition of histamine release from the mast cells due mainly to an increase in caffeic acid and flavonoids. The enzymatic digestion of MMBP might be useful in enhancing its antiinflammatory and antiallergic activities.

著者

Yoshinobu Tsuruta Yushi Katsuyama Yuri Okano Toshiyuki Ozawa Satoshi Yoshimoto Hideya Ando Hitoshi Masaki Masamitsu Ichihashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.5, pp.725-729, 2023-05-01 (Released:2023-05-01)

参考文献数

28

被引用文献数

3

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Epidermal keratinocytes protect themselves by cooperating with neighboring cells against internal and external stresses, which leads not only to the maintenance of cell homeostasis but also to the prevention of skin aging. Although it is known that nuclear factor (NF)-E2-related factor 2 (Nrf2) signaling plays a pivotal role in ameliorating oxidative stress and inflammatory responses under stress situations, it is unclear whether Nrf2 signaling in keratinocytes cooperates with neighboring cells such as dermal fibroblasts. Thus, this study was conducted to examine the influence of dermal fibroblasts on Nrf2 signaling in epidermal keratinocytes using a co-culture system. The results show that expression levels of Nrf2-regulated antioxidant factors, such as glutathione and heme oxygenase-1, in HaCaT keratinocytes (HaCaT KCs) are up-regulated in the presence of normal human dermal fibroblasts (NHDFs). In addition, the secretion of pro-inflammatory molecules, including interleukin-1α (IL-1α) and prostaglandin E2 (PGE2), is suppressed in co-cultures of NHDFs and UVB-irradiated HaCaT KCs. Interestingly, the localization of Nrf2 protein in HaCaT KCs was immediately translocated from the cytoplasm to the nucleus after the co-culture with NHDFs. These results suggest the possibility that Nrf2 signaling in keratinocytes is regulated in cooperation with dermal fibroblasts.

著者

Karin Endo Yoko Niki Yukihiro Ohashi Hitoshi Masaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.2, pp.225-231, 2021-02-01 (Released:2021-02-01)

参考文献数

21

被引用文献数

3 4

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The dermis is mainly constructed by type I collagen fibers, which provide mechanical strength to the skin by building a frame-like structure, and by elastic fibers, which provide elasticity to respond to movements of the skin. The depletion of collagen fibers and the disappearance of oxytalan fibers, which are a type of elastic fiber, are characteristic changes in photoaged skin. Prostaglandin E2 (PGE2) is one of the chemical mediators involved in inflammation and is responsible for sunburn. Furthermore, it has been reported that PGE2 attenuates the production of collagen and the expression of elastic fiber-related factors in fibroblasts. Tranexamic acid (TXA), which is an anti-inflammatory medicine that inhibits plasmin, reduces the level of PGE2 secreted following UV exposure or after inflammatory stimulation. However, few reports have verified TXA as an anti-skin aging agent. In this study, we examined the potential of TXA as an anti-skin aging agent using repetitively UVA-irradiated fibroblasts as a model for fibroblasts located in chronically sun-exposed dermis. Repetitively UVA-irradiated fibroblasts had higher secretion levels of PGE2. In addition, fibroblasts repetitively irradiated with UVA or treated with PGE2 produced disrupted collagen and fibrillin-1 fibers. Treatment with TXA improved the formation of both types of fibers by repetitively UVA-irradiated fibroblasts by restoring the expression of fiber-related proteins at the mRNA and protein levels. Thus, these results demonstrate that TXA has potential as an anti-photoaging agent.

著者

Lin-jiao Wang Wei Xi Xiao-lan Yuan Xiao-hua Yang

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c22-00843, (Released:2023-10-03)

参考文献数

31

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Dapagliflozin (DAPA), sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is used to treat Type 2 diabetes. In this study, a highly sensitive and selective analytical method based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was established and validated for the determination of DAPA in rat plasma. The separation of DAPA and internal standard (DAPA-d5) were performed on a reversed-phase ACQUITY UPLC® BEH C18 column (100×3.0 mm, 1.7 µm). The mobile phase is composed of 0.1% formic acid in water (solvent A) and methanol (solvent B) in gradient elution. Under the negative ion mode, full MS/dd-MS2 was adopted to collect data via Q-Orbitrap. DAPA was effectively separated from matrix backgrounds within 10 min, and DAPA in plasma showed a good linear relationship in the range of 10-10000 µg/L. The determination coefficient (R2) was 0.9987, and the lower limit of quantification (LLOQ) was 10 µg/L. The precision and accuracy were all less than 10%, and the extraction recovery of DAPA was 86.16%-96.06% from plasma. This study offered an efficient separation and quantification method for DAPA. The improved and validated method succeeded in evaluating the pharmacokinetics of DAPA in rat plasma samples after a single oral administration of 1 mg/kg.

著者

Ning Luo Gui-bing Chen Teng Zhang Jie Zhao Jing-nan Fu Ning Lu Tao Ma

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.2, pp.187-193, 2023-02-01 (Released:2023-02-01)

参考文献数

47

被引用文献数

1 3

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Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.