Publications by authors named "Kenroh Sasaki"

34 Publications

Synthesis and evaluation of trypanocidal activity of derivatives of naturally occurring 2,5-diphenyloxazoles.

Bioorg Med Chem 2021 Jul 12;42:116253. Epub 2021 Jun 12.

Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.

African trypanosomiasis is a zoonotic protozoan disease affecting the nervous system. Various natural products reportedly exhibit trypanocidal activity. Naturally occurring 2,5-diphenyloxazoles present in Oxytropis lanata, and their derivatives, were synthesized. The trypanocidal activities of the synthesized compounds were evaluated against Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. congolense, and T. evansi. Natural product 1 exhibited trypanocidal activity against all the species/subspecies of trypanosomes, exhibiting half-maximal inhibitory concentrations (IC) of 1.1-13.5 μM. Modification of the oxazole core improved the trypanocidal activity. The 1,3,4-oxadiazole (7) and 2,4-diphenyloxazole (9) analogs exhibited potency superior to that of 1. However, these compounds exhibited cytotoxicity in Madin-Darby bovine kidney cells. The O-methylated analog of 1 (12) was non-cytotoxic and exhibited selective trypanocidal activity against T. congolense (IC = 0.78 µM). Structure-activity relationship studies of the 2,5-diphenyloxazole analogs revealed aspects of the molecular structure critical for maintaining selective trypanocidal activity against T. congolense.
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http://dx.doi.org/10.1016/j.bmc.2021.116253DOI Listing
July 2021

Hyaluronidase and degranulation inhibitors from the edible roots of Oenanthe javanica including seric acids F and G that were obtained by heating.

Biosci Biotechnol Biochem 2021 Feb;85(2):369-377

Department of Pharmacognosy, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai, Japan.

Oenanthe javanica is a vegetable grown in East Asia and Australia in which the roots and aerial parts are boiled together to make certain traditional dishes. Nineteen compounds (1-19) were isolated from O. javanica roots and the chemical structures of 2 new norlignans were determined. The inhibitory effects of the compounds on hyaluronidase and degranulation in RBL-2H3 cells were evaluated to determine antiallergic and antiinflammation activities. Saponins (2-4) and the new norlignan seric acid G (12) were among the active compounds identified. Seric acid G (12), a methoxy derivative of seric acid F (11), was obtained as an interconverting mixture of 3:1 trans-cis isomers. Seric acids F and G (11, 12) were derived from seric acids C (10) and E, respectively, by decarboxylation and dehydration reactions that occurred during heating. It was confirmed by HPLC analysis that all eleven of the O. javanica cultivars contained seric acid C (10).
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http://dx.doi.org/10.1093/bbb/zbaa042DOI Listing
February 2021

Isolation and evaluation of trypanocidal activity of sesquiterpenoids, flavonoids, and lignans in Artemisia sieversiana collected in Mongolia.

J Nat Med 2020 Sep 3;74(4):750-757. Epub 2020 Jul 3.

National University of Mongolia, Ulaanbaatar, Mongolia.

Artemisia sieversiana is an annual herbaceous plant distributed throughout Central and East Eurasia and is regarded as an undesirable forage plant in Mongolia. It affects livestock, so information about its chemical composition is needed. We isolated three new sesquiterpenoids (1-3) and known compounds from A. sieversiana and investigated their activities. The absolute configuration of 1 was established using single-crystal X-ray diffraction crystallography, and its configuration differed from those of reported compounds with similar structures. Two additional new sesquiterpenoids (2 and 3) with similar structures were identified, and their configurations were determined. The trypanocidal activities of the isolated compounds (1-18) against Trypanosoma congolense and the pathogen responsible for fatal trypanosomosis in animals were estimated. Flavonoids and lignans were identified as active compounds with IC values ranging from 2.9 to 90.2 µM.
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http://dx.doi.org/10.1007/s11418-020-01429-2DOI Listing
September 2020

A new hexenoic acid glycoside with cytotoxic activity from the leaves of .

Nat Prod Res 2020 May 13:1-6. Epub 2020 May 13.

Pharmacognosy Department, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

A new hexenoic acid glycoside () together with known compounds, flavonol glycosides (-), iridoid glycoside (), megastigmane glycoside (), and amino acid () were isolated from the leaves of . by resin column chromatography and preparative HPLC. Their structures were determined based on spectroscopic analysis, including HRFABMS and NMR (H and C, H-H COSY, HMQC, and HMBC) data. All compounds tested for cytotoxicity were active (IC < 50 μM) with IC values ranging from 1.97 to 32.85 μM against human colon adenocarcinoma cell line, compared to etoposide (IC 1.19 μM).
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http://dx.doi.org/10.1080/14786419.2020.1765345DOI Listing
May 2020

Hyaluronidase inhibitory saponins and a trypanocidal isoflavonoid from the aerial parts of Oxytropis lanata.

Fitoterapia 2020 Sep 6;145:104608. Epub 2020 May 6.

Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.

A chemical examination of an extract from the aerial part of Oxytropis lanata led to the isolation and identification of 36 compounds, including saponins, isoflavonoids, oxazoles, and glycosides. The three among them were previously unreported oleanane-type saponins. In trypanocidal screening, 5,7,4'-trihydroxyisoflavone showed inhibitory activity against Trypanosoma congolense (IC = 10.5 μM), the causative agent of African trypanosomosis in animals; this activity was similar to that of active compounds from the roots of this plant. O. lanata is known to be a traditional medicinal plant in Mongolia for the treatment of inflammatory diseases. The anti-hyaluronidase effect of saponins 3, 5, 8, and 9, (IC = 0.15-0.22 mM) was stronger than that of sodium cromoglicate, which was used as a reference drug (IC = 0.37 mM). The chemical structures of the new saponins were determined based on HRFABMS, H and C NMR, H-H COSY, HMQC, HMBC, and ROESY spectroscopic data along with chemical procedures.
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http://dx.doi.org/10.1016/j.fitote.2020.104608DOI Listing
September 2020

Indirubin promotes adipocyte differentiation and reduces lipid accumulation in 3T3‑L1 cells via peroxisome proliferator‑activated receptor γ activation.

Mol Med Rep 2020 Mar 16;21(3):1552-1560. Epub 2020 Jan 16.

Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981‑8558, Japan.

The peroxisome proliferator‑activated receptor γ (PPARγ) plays an important role in insulin sensitivity and adipocyte differentiation. It is known as ligand‑receptor that improves insulin sensitivity in type 2 diabetes mellitus. Several kinds of indigo plant have been already used to treat diabetes in oriental traditional medicine, but its mechanism has not been clarified yet. To investigate the effect of indirubin, which is a component of Polygonum tinctorium on the cell differentiation and adipprocess in 3T3‑L1 cells, 3T3‑L1 cells were cultured to determine the effect of cell differentiation and glucose uptake with indirubin. As a result, Indirubin compound enhanced adipocyte differentiation in 3T3‑L1 cells similar to rosiglitazone. This effect was terminated by cotreatment with GW9662, a PPARγ antagonist. In mature 3T3‑L1 adipocytes, the lipid droplet size and accumulation were reduced by this compound. The basal and insulin‑stimulated glucose uptakes were also significantly increased. In addition, indirubin treatment significantly enhanced estrogen level by 1.64‑fold with mature adipocytes which can be attributed to its aromatase activity. Conclutionaly, this finding suggested that indirubin is a potential anti‑diabetic compound for type 2 diabetes mellitus by promoting adipocyte differentiation and glucose uptake via PPARγ.
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http://dx.doi.org/10.3892/mmr.2020.10946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003043PMC
March 2020

Inhibitory Effects of Phenylpropanoid Derivatives from Oenanthe javanica on Antigen-Stimulated Degranulation in RBL-2H3 Cells.

J Nat Prod 2019 06 24;82(6):1518-1526. Epub 2019 May 24.

Department of Pharmacognosy , Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558 , Japan.

Two diacyldaucic acids (1 and 2), an α,β-unsaturated γ-lactone-type lignan (3) and its derivatives (4-6), and 12 known compounds were isolated from a traditional East Asian vegetable, Oenanthe javanica. The absolute configuration of 1 was validated by obtaining (+)-osbeckic acid through acid hydrolysis. The absolute configurations of 3-5 were determined by comparing their experimental and computed ECD data. The conclusion was supported by applying the phenylglycine methyl ester method to 3. Compound 6 was obtained as an interconverting mixture of isomers in a 3:1 trans- cis ratio. Several water-soluble components (1, 3, and 6) showed concentration-dependent inhibitory effects on antigen-stimulated degranulation in RBL-2H3 cells without producing any direct cytotoxicity against RBL-2H3 or HeLa cells.
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http://dx.doi.org/10.1021/acs.jnatprod.8b01054DOI Listing
June 2019

Acylated Lignans Isolated from Brachanthemum gobicum and Their Trypanocidal Activity.

J Nat Prod 2019 04 21;82(4):774-784. Epub 2019 Mar 21.

Department of Pharmacognosy , Tohoku Medical and Pharmaceutical University , Aoba-ku, Sendai 981-8558 , Japan.

Eight isovaleryllignans (1-4 and 8-11), three isovalerylphenylpropanoids (5-7), three known lignans (12-14), and four known compounds were isolated from an extract of the aerial part of Brachanthemum gobicum. The structures of the isolated compounds were elucidated based on NMR and MS data analyses. The enantiomers of compounds 1-3, 5, 8, and 9 were isolated using chiral-phase HPLC, and the absolute configurations of 1a/1b-3a/3b, 5a/5b, 8a/8b, and 9a/9b were elucidated from their optical rotations and ECD spectra; the other lignans were assumed to be racemic or scalemic by chiral-phase HPLC analyses and optical rotation data. Some of the acylated lignans (racemic mixtures) (1-4, 8, 9, and 12-14) exhibited moderate inhibitory activities against Trypanosoma congolense, the causative agent of nagana disease in animals.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00670DOI Listing
April 2019

Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity.

J Nat Med 2019 Jun 7;73(3):633-640. Epub 2019 Mar 7.

School of Engineering and Applied Sciences, National University of Mongolia, P.O.B.-617/46A, Ulaanbaatar, 14201, Mongolia.

Pulsatilla species are known as "Yargui", and their flowers are traditionally used in Mongolia as a tonic and for the treatment of inflammatory diseases. By chemical investigation of P. flavescens flowers, 21 flavonoids, including a new chalcone C-glucoside, chalconaringenin 2'-O-β-D-glucopyranosyl-5'-β-D-glucopyranoside, and two new flavanone C-glucosides, (2R)- and (2S)-naringenin 8-β-D-glucopyranosyl-4'-O-β-D-glucopyranoside, were isolated. The absolute configurations of the seven flavanone glucosides were elucidated by ECD spectra. For the isolated compounds, inhibitory activity against Babesia caballi and Theileria equi, which cause fatal diseases in horses, was estimated. Although most of the isolated chalcone and flavanone derivatives did not show any anti-piroplasm activity, all the isolated flavone and flavonol derivatives showed moderate effects against B. caballi and/or T. equi.
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http://dx.doi.org/10.1007/s11418-019-01294-8DOI Listing
June 2019

Astragalus root induces ovarian β‑oxidation and suppresses estrogen‑dependent uterine proliferation.

Mol Med Rep 2018 Dec 19;18(6):5198-5206. Epub 2018 Sep 19.

Department of Pharmacognosy, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981‑8558, Japan.

Continuous estrogen stimulation in the uterus has been known to cause excess proliferation of the functional layer of endometrium, resulting in endometrial hyperplasia and leading to infertility. Estrogens can modulate other nuclear receptor signaling pathways, such as peroxisome proliferator‑activated receptors (PPARs). Astragalus root (AsR) has exhibited strong PPARα agonistic activity. Female Imprinting Control Region mice were fed a powder diet that included 5% AsR hot water extract or 0.1% bezafibrate as a positive control for 56 days to investigate AsR effects on the reproductive tract, ovary and uterus. AsR resulted in upregulation of the expression of uterine and ovarian PPARα mRNA by 2.5‑fold, and 1.5‑fold, respectively, compared with controls. AsR significantly increased ovarian expression levels of mitochondrial 2,4‑dienoyl‑CoA reductase (mDECR), an auxiliary enzyme involved in β‑oxidation. AsR‑fed mice also exhibited a significant increase in blood estradiol levels and tended to have higher ovary weight. AsR resulted in significantly decreased uterine weight and mDECR expression levels. It has been reported that a PPARα agonist suppresses the development of estrogen‑dependent endometrial hyperplasia. These findings raise the possibility that AsR suppresses estrogen‑dependent endometrial hyperplasia and ovarian dysfunction leading to infertility.
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http://dx.doi.org/10.3892/mmr.2018.9493DOI Listing
December 2018

Lanostane triterpenoids from Fomitopsis officinalis and their trypanocidal activity.

J Nat Med 2018 Mar 7;72(2):523-529. Epub 2018 Feb 7.

Department of Pharmacognosy, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai, 981-8558, Japan.

Fomitopsis officinalis is a medicinal fungus, known as 'Agarikon', and is used traditionally in the treatment of asthma and rheumatism in Mongolia. The investigation of the chemical constituents of F. officinalis led to the isolation of 4 new lanostane triterpenoids together with 4 known triterpenoids. Inhibitory activity against Trypanosoma congolense, which causes fatal diseases in animals including livestock, was estimated for the isolated compounds. Compounds 2-5 and 8 exhibited moderate inhibition activities with IC values ranging from 7.0-27.1 µM.
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http://dx.doi.org/10.1007/s11418-018-1182-1DOI Listing
March 2018

Flavonoid and Galloyl Glycosides Isolated from Saxifraga spinulosa and Their Antioxidative and Inhibitory Activities against Species That Cause Piroplasmosis.

J Nat Prod 2017 09 23;80(9):2416-2423. Epub 2017 Aug 23.

School of Engineering and Applied Sciences, National University of Mongolia , Ulaanbaatar 14201, Mongolia.

Eight new flavonoid-based 3'-O-β-d-glucopyranosides (1-8) and three new galloyl glucosides (9, 11, 12), were isolated from the aerial parts of Saxifraga spinulosa, along with 25 known compounds. The structures of the new compounds were elucidated by spectroscopic methods. Most of the isolated compounds exhibited potent DPPH radical-scavenging activities. Further, their inhibitory activities were evaluated against Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi, protozoan parasites that cause piroplasmosis in livestock. The results indicated that several of these compounds showed growth-inhibitory effects on such organisms that cause piroplasmosis.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00142DOI Listing
September 2017

Antioxidant Flavonols and Phenolic Compounds from Atraphaxis frutescens and Their Inhibitory Activities against Insect Phenoloxidase and Mushroom Tyrosinase.

J Nat Prod 2016 Dec 8;79(12):3065-3071. Epub 2016 Dec 8.

Department of Pharmacognosy, Tohoku Medical and Pharmaceutical University , 4-1 Komatsushima 4-chome, Aoba-ku, Sendai 981-8558, Japan.

Chemical investigation of the aerial parts of Atraphaxis frutescens resulted in the isolation of five 7-methoxyflavonols with pyrogallol B-ring moieties (1-5), a fisetinidol glucoside (13), and a benzyl glycoside (18), together with 26 known compounds including flavonoids, phenylpropanoid amides, anthraquinone glycosides, lignans, and a benzyl derivative. The principal chemical structural feature of the isolated compounds was either a pyrogallol or catechol B-ring moiety, and they showed potent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. To assess the effects of these antioxidants on biological enzymes, their inhibitory effects against an insect phenoloxidase and a mushroom tyrosinase were evaluated. This study indicated that insect phenoloxidase was inhibited by phenylpropanoid amides and that mushroom tyrosinase was inhibited by the characteristic 7-methoxyflavonol 3-O-rhamnopyranosides.
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http://dx.doi.org/10.1021/acs.jnatprod.6b00720DOI Listing
December 2016

Trypanocidal Activity of 2,5-Diphenyloxazoles Isolated from the Roots of Oxytropis lanata.

J Nat Prod 2016 11 31;79(11):2933-2940. Epub 2016 Oct 31.

Department of Pharmacognosy, Tohoku Medical and Pharmaceutical University , 4-1 Komatsushima 4-chome, Aoba-ku, Sendai 981-8558, Japan.

Eleven 2,5-diphenyloxazole derivatives (1-11), together with six known isoflavonoid derivatives, were isolated from the roots of Oxytropis lanata. The 2,5-diphenyloxazole (1) obtained proved to be identical to a standard sample used as a scintillator and liquid laser dye. The other oxazole derivatives isolated were found to have one to four hydroxy and/or O-methyl groups in their phenyl rings. Seven of the oxazole derivatives obtained are new (3-9). The inhibitory activity of the isolated compounds was evaluated against Trypanosoma congolense, the causative agent of African trypanosomosis in animals. Oxazoles with di- and trihydroxy groups showed trypanocidal activity, and 2-(2',3'-dihydroxyphenyl)-5-(2″-hydroxyphenyl)oxazole (4) exhibited the most potent inhibitory activity (IC 1.0 μM).
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http://dx.doi.org/10.1021/acs.jnatprod.6b00778DOI Listing
November 2016

Abietane-type diterpenoids from the roots of Caryopteris mongolica and their cholinesterase inhibitory activities.

Phytochemistry 2016 Oct 10;130:152-8. Epub 2016 Jun 10.

School of Engineering and Applied Sciences, National University of Mongolia, POB-617, Ulaanbaatar-46A, 14201, Mongolia.

Eleven abietane-type diterpenoids and two known abietanes were isolated from the roots of Caryopteris mongolica, and their structures were characterized. The absolute configurations at C-5 and C-10 were determined from the NMR data, including from the nuclear Overhauser effect and CD spectra, and the absolute configuration of C-16 in the hydroxypropyl group was determined via a modified Mosher's method. Furthermore, the previously unknown absolute configuration of the C-15 of cyrtophyllone B was determined to be in an R-configuration using X-ray crystallography. To estimate the preventive effects of the isolates for neurodegenerative disease development, their inhibitory activities against acetylcholinesterase (AChE) from human erythrocytes and butyrylcholinesterase (BChE) from horse serum were evaluated.
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http://dx.doi.org/10.1016/j.phytochem.2016.05.011DOI Listing
October 2016

Boiogito Increases the Metabolism of Fatty Acids in Proximal Tubular Cells through Peroxisome Proliferators-Activated Receptor (PPAR) α Agonistic Activity.

Biol Pharm Bull 2016 ;39(1):143-7

Department of Pharmacognosy, Tohoku Pharmaceutical University.

The promotion of fatty acid metabolism, to which peroxisome proliferators-activated receptor (PPAR) α contributes, has been suggested to participate in maintaining the function of renal proximal tubular epithelial cells (PTECs). The loading of fatty acids to PTECs could result in cell inflammation and cell death. A "Kampo" medicine, Boiogito (BO), is used to treat overweight women exhibiting chronic fatigue and edema in the lower extremities or knees. BO improves renal function by reducing the portion of fatty acids, thereby preventing damage to PTECs. In this study, BO and Astragalus Root (AsR), a constituent crude drug of BO, were administered orally to intravenously bovine serum albumin (BSA)-administered mice to evaluate the PPARα-cAMP responsive element binding protein (CREB) binding protein (CBP) complex binding activity and/or mRNA expression of PPARα, as quantified by enzyme-linked immunosorbent assay (ELISA) and/or polymerase chain reaction (PCR). Increases in PPARα-CBP complex binding activity and the expression of PPARα mRNA were observed not only in BO-administered mice but also in AsR-administered mice, accompanied by a decrease in the amount of renal fatty acid.
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http://dx.doi.org/10.1248/bpb.b15-00678DOI Listing
October 2016

Investigation into hippocampal nerve cell damage through the mineralocorticoid receptor in mice.

Mol Med Rep 2015 Nov 1;12(5):7211-20. Epub 2015 Oct 1.

Department of Pharmacognosy, Tohoku Pharmaceutical University, Sendai, Miyagi 981‑8558, Japan.

Stress‑associated neuropsychiatric disease is associated with glucocorticoid levels; however, the behavior of mineralocorticoid receptors (MR) under conditions of stress remain to be elucidated. Steroid receptors in the brain are classified into glucocorticoid receptors (GR) and/or MR, exhibiting a difference in affinity for corticosteroids. The hippocampus is one of the most stress‑susceptible regions in the brain. In the present study, it was investigated whether the two steroid receptors affect hippocampal neuron damage. The effect of fludrocortisones (FD) on hippocampal neurons caused by FD‑containing cholesterol pellets subcutaneously embedded in the backs of mice (FD pellet group, 80 mg cholesterol and 20 mg FD) was investigated. A significant extension of the tail length by ~2.22 fold was observed in the FD pellet group compared with that in the control group as elucidated via the comet assay. Cytotoxicity (pyknosis and degranulation) and DNA fragmentation due to the death of nerve cells were observed using Kluver‑Barrera staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with the sham group mice, hippocampal neuron damage was observed in the adrenalectomized mice and the damage was suppressed by the combinatorial use of spironolactone, which suggested MR‑induced hippocampal neuron damage. In conclusion, the present study clearly indicated a regional difference in vulnerability and/or sensitivity to corticosteroids. MR sensitivity to corticosteroids was high in the CA3 region and pyramidal cells of the hippocampus, which may therefore be vulnerable to corticosteroids. Thus, it is clearly suggested that MR function is important in the stress response.
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http://dx.doi.org/10.3892/mmr.2015.4406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626142PMC
November 2015

An antibacterial ortho-quinone diterpenoid and its derivatives from Caryopteris mongolica.

Bioorg Med Chem Lett 2015 Jun 24;25(12):2555-8. Epub 2015 Apr 24.

School of Engineering and Applied Sciences, National University of Mongolia, POB-617, Ulaanbaatar-46A, Mongolia.

To identify antibacterial components in traditional Mongolian medicinal plant Caryopteris mongolica, an ortho-quinone abietane caryopteron A (1) and three its derivatives caryopteron B-D (2-4) were isolated from the roots of the plant together with three known abietanes demethylcryptojaponol (5), 6α-hydroxydemethyl cryptojaponol (6), and 14-deoxycoleon U (7). The chemical structures of these abietane derivatives were elucidated on the basis of spectroscopic data. Compounds 1-4 had C-13 methylcyclopropane substructures, and 2-4 had a hexanedioic anhydride ring C instead of ortho-quinone in 1. The stereochemistry of these compound was assumed from NOE spectra and ECD Cotton effects. Compounds 1 and 5-7 showed antibacterial activities against the Gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Micrococcus luteus, being 1 the more potent.
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http://dx.doi.org/10.1016/j.bmcl.2015.04.048DOI Listing
June 2015

Cholinesterase-inhibitory diterpenoids and chemical constituents from aerial parts of Caryopteris mongolica.

J Nat Med 2015 Oct 22;69(4):471-8. Epub 2015 Apr 22.

Department of Pharmacognosy, Tohoku Pharmaceutical University, 4-1 Komatsushima 4-chome, Aoba-ku, Sendai, 981-8558, Japan,

A diterpenoid diglucoside (12,19-di-O-β-D-glucopyranosyl-11-hydroxyabieta-8,11,13-triene-19-one), isoscutellarein 7-O-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranoside, isoscutellarein 7-O-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(p-E-coumaroyl)]-β-D-glucopyranoside, hypolaetin 7-O-[6″-O-(E-caffeoyl)]-β-D-glucopyranoside, and 15 known compounds were isolated from aerial parts of the Mongolian medicinal plant Caryopteris mongolica. The cholinesterase-inhibitory activities of the constituents were estimated. The abietane diterpenoids (12-O-demethylcryptojaponol and 6α-hydroxydemethylcryptojaponol) showed potent inhibitory activity against acetylcholinesterase from human erythrocytes and electric eel, and against butyrylcholinesterase from horse serum.
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http://dx.doi.org/10.1007/s11418-015-0908-6DOI Listing
October 2015

Effect of natural flavonoids, stilbenes and caffeic acid oligomers on protein glycation.

Biomed Rep 2014 Sep 25;2(5):628-632. Epub 2014 Jun 25.

Tohoku Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.

The aim of the present study was to identify the inhibitory activity of natural flavonoids, stilbenes and caffeic acid oligomers on protein glycation. Antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity. The production of 3-deoxyglucosone (3-DG) and advanced glycation end products (AGEs) by glycation reactions were determined by high-performance liquid chromatography and fluorescence, respectively. Certain flavonoids, stilbenes and caffeic acid oligomers prevented AGE production and the IC values of the compounds were compared. These examined compounds are assumed to suppress AGE generation by inhibiting the increase in 3-DG production through a specific unknown mechanism in the early phase of the Maillard reaction, by inhibiting the generation of active oxygen in the later phase and by suppressing the progression of the reaction. Regular, daily consumption of these compounds in the form of a food or extract is expected to aid in the prevention or inhibition of non-enzymatic amino acid glycation in the living body, which is possibly associated with aging, diabetic complications, arteriosclerotic diseases and Alzheimer's disease, and they may also be effective agents in cosmetics promoting anti-aging.
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http://dx.doi.org/10.3892/br.2014.304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106577PMC
September 2014

Monoterpene glycosides, phenylpropanoids, and acacetin glycosides from Dracocephalum foetidum.

Phytochemistry 2014 May 28;101:91-100. Epub 2014 Feb 28.

Department of Pharmacognosy, Tohoku Pharmaceutical University, 4-1 Komatsushima 4-chome Aoba-ku, Sendai 981-8558, Japan.

Chemical investigation of the acetone extract from the aerial parts of the Mongolian medicinal plant Dracocephalum foetidum resulted in the isolation of three limonene glycosides, a caffeic acid trimer, four rosmarinic acid glucosides, and five acacetin acyl glycosides, together with 13 known natural products. The chemical structures of all of the compounds were determined by spectroscopic analyses. Among these compounds three showed hyaluronidase inhibitory activity. In addition, one other compound showed stronger 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity than the positive control Trolox, whereas three other compounds demonstrated a similar activity to that of Trolox.
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http://dx.doi.org/10.1016/j.phytochem.2014.02.007DOI Listing
May 2014

Phytochemical constituents of Mongolian traditional medicinal plants, Chamaerhodos erecta and C. altaica, and its constituents prevents the extracellular matrix degradation factors.

J Nat Med 2013 Oct 9;67(4):867-75. Epub 2013 Feb 9.

Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.

Activity-guided isolation of the n-butanol fraction of Chamaerhodos erecta and water soluble fraction of C. altaica resulted in the isolation of 39 compounds, including new compounds identified as 4,5-dihydroxybenzaldehyde-3-O-β-D-glucopyranoside (1) from C. erecta and quercetin-3-O-β-D-glucuronopyranosyl-4'-O-β-D-glucopyranoside (2) from C. altaica. A total of 37 other compounds were identified based on physico-chemical properties and spectroscopic data. Antioxidative activity was evaluated using a DPPH radical-scavenging method, hyaluronidase inhibitory activity, and advanced glycation end products production inhibitory activity of isolated compounds. Some flavonols (4, 6, 9-11, 14, 15), catechins (18, 19), an amino acid (20), a lignan glucoside (23), and tannins (29-39) exhibited potential a free radical scavenging activity while the new compound (1) showed weak activity. A catechin (18) and some of the tannins (32, 33, 35, 36, 38) had moderate hyaluronidase inhibitory activity. Some of flavonoids and tannins prevented advanced glycation end products production, and the IC₅₀ of compounds 3, 9, 14-16, 33, 34, 36, 38, and 39 were determined.
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http://dx.doi.org/10.1007/s11418-013-0748-1DOI Listing
October 2013

Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells.

Biol Pharm Bull 2011 ;34(3):354-9

Department of General Medicine, Kanazawa Medical University, Ishikawa 920–0293, Japan.

Neuroimaging evidence showed structural and/or functional abnormalities existing in the central nervous system, especially the hippocampus, in chronic fatigue syndrome (CFS) patients. However, its pathophysiologic mechanisms are unclear in part due to the lack of an applicable animal model. We established a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy. Thereafter, resveratrol, a polyphenolic activator of sirtuin 1, was used for treatment in this model. Daily running activity was increased by more than 20%, and the hippocampus was enlarged after 4-week resveratrol therapy. Furthermore, resveratrol inhibited neuronal apoptosis and expression of hippocampal acetylated p53 in the fatigue mice. Resveratrol also improved neurogenesis and expression of brain-derived neurotrophic factor mRNA in the hippocampus. We concluded that repeated injection of B. abortus antigen could induce hypoactivity and hippocampal atrophy in mice. Resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis.
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http://dx.doi.org/10.1248/bpb.34.354DOI Listing
November 2011

Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum.

J Nat Prod 2009 Aug;72(8):1379-84

Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.

From the aerial parts of Clinopodium chinense var. parviflorum, nine new phenylpropanoids, clinopodic acids A-I (2-10), were isolated together with a known phenylpropanoid, rosmarinic acid (1). The structures of these new compounds were elucidated on the basis of spectroscopic analysis. Clinopodic acid C (4) showed MMP-2 inhibitory activity (IC(50) 3.26 microM).
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http://dx.doi.org/10.1021/np800781tDOI Listing
August 2009

The Kampo medicines Orengedokuto, Bofutsushosan and Boiogito have different activities to regulate gene expressions in differentiated rat white adipocytes: comprehensive analysis of genetic profiles.

Biol Pharm Bull 2008 Nov;31(11):2083-9

Department of General Medicine, Kanazawa Medical University, Japan.

Three Kampo medicines, Boiogito (BOT), Bofutsushosan (BTS) and Orengedokuto (OGT), used for obese patients were investigated for their effects on adipogenesis in cultured rat white adipocytes. Administration of the three extracts suppressed adipogenesis in concentration-dependent manners (1-100 microg/ml) without any cytotoxicity. Changes in mRNA expression levels were analyzed using a Rat 230 2.0 Affymetrix GeneChip microarray system. DNA microarray analysis (total probe set: 31099) using cDNAs prepared from adipocytes revealed that BOT, BTS and OGT increased the expression of 133-150 genes and decreased the expression of 42-110 genes by > or =2-fold. We identified 329 downregulated genes and 189 upregulated genes among a total set of 514 probes (overlap: 4). Overall, genes related to cellular movement, cell death, cell growth/differentiation and immune responses were the most downregulated, while those related to lipid metabolism and cell signaling were the most upregulated. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assays were conducted to confirm the microarray results. Analysis of the clustering profiles of the microarray results revealed that BOT and BTS changed the expression levels of similar genes mainly involved in small molecule biochemistry and cell differentiation, while OGT altered 10 genes related to lipid metabolism, in contrast to the effects of BOT and BTS. We also measured mRNA expression levels of seven selected genes highly contributing to the lipid metabolism by using semiquantitative RT-PCR assay, that were acetyl-Coenzyme A carboxylase alpha (ACACA), AE binding protein 1 (AEBP1), patatin-like phospholipase domain containing 8 (PNPLA8), secretoglobin (SCGB1A1), adrenergic (ADRB3), adiponectin (ADIPOQ), monoglyceride lipase (MGLL). Beta-actin (ACTB) gene was used as an endogenous internal standard. The present findings indicate that these three herbal extracts have the potential to prevent adipogenesis in rat white adipocytes through different mechanisms via modulation of gene expression levels.
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http://dx.doi.org/10.1248/bpb.31.2083DOI Listing
November 2008

Oral Administration of Ren-Shen-Yang-Rong-Tang 'Ninjin'yoeito' Protects Against Hematotoxicity and Induces Immature Erythroid Progenitor Cells in 5-Fluorouracil-induced Anemia.

Evid Based Complement Alternat Med 2009 Jun 27;6(2):247-56. Epub 2007 Oct 27.

Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

The purpose of this study was to investigate the efficacy of four different Japanese and Chinese herbal prescriptions, Ren-Shen-Yang-Rong-Tang (Ninjin'yoeito, NYT), Chai-Hu-Gui-Zhi-Gan-Jiang-Tang (Saikokeishikankyoto, SKKT), Si-Jun-Zi-Tang (Shikunshito, SKT) and Si-Wu-Tang (Shimotsuto, SMT), which are traditionally used for anemia and fatigue, against hematotoxicity in mice treated with 5-fluorouracil (5-FU). NYT 1-100 mg kg(-1) day(-1) injected orally for 7 consecutive days before and after 5-FU injection significantly suppressed reductions in red blood cell, white blood cell and platelet counts in peripheral blood, and accelerated their recovery. Administration of SKKT also produced a slight but significant improvement in 5-FU-induced erythrocytopenia, whereas SMT and SKT could not prevent anemia. Oral injection of NYT also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 10, and markedly hastened their recovery on day 20, in a dose-dependent manner. Erythroid progenitor colonies, such as colony forming units-erythroid and burst forming units-erythroid, formed by marrow cells from mice treated with 5-FU were significantly increased by oral administration of NYT. These findings suggest that NYT has the potential to protect against hematotoxicity, and also has hematopoietic activity, through stimulation of immature erythroid progenitor cell differentiation.
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http://dx.doi.org/10.1093/ecam/nem080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686622PMC
June 2009

Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection.

Immunopharmacol Immunotoxicol 2009 Jun;31(2):238-45

Department of General Medicine, Kanazawa Medical University, Ishikawa, Japan.

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups. Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.
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http://dx.doi.org/10.1080/08923970802391525DOI Listing
June 2009

Anti-hepatitis C virus effect of citrus unshiu peel and its active ingredient nobiletin.

Am J Chin Med 2005 ;33(1):87-94

Department of Pharmacology, School of Medicine, Showa University, Japan.

We investigated the effects of water and ethyl acetate extracts of Citrus unshiu peel (Aurantii Nobilis pericarpium) on hepatitis C virus (HCV) absorption in MOLT-4 cells (a human lymphoblastoid leukemia cell line). By reverse transcription polymerase chain reaction (RT-PCR), we showed that both the ethyl acetate layer of Citrus unshiu peel extract and fraction 7 decreased HCV absorption in MOLT-4 cells. Furthermore, we demonstrated that 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) is the active ingredient that markedly inhibited HCV infection in MOLT-4 cells.
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http://dx.doi.org/10.1142/S0192415X05002680DOI Listing
June 2005

Effect of Saiko-ka-ryukotsu-borei-to on amylase activity in mice.

Biol Pharm Bull 2004 Oct;27(10):1688-90

Department of Pharmacognosy, Tohoku Pharmaceutical University, Aoba-ku, Sendai, Japan.

The effects of Saiko-ka-ryukotsu-borei-to (SRBT), a Chinese medicinal prescription, on mouse serum amylase activity were investigated in vivo. SRBT was found to not only dose- and/or time-dependently augment amylase activity, but also to increase alpha-amylase protein content and soluble starch metabolic activity. These results provide a rational basis for the clinical use of SRBT that may accompany disease therapy.
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http://dx.doi.org/10.1248/bpb.27.1688DOI Listing
October 2004

Nonopioid receptor-mediated effects of U-50,488H on [Ca(2+)]i and extracellular dopamine in PC12 cells.

J Neurosci Res 2003 Nov;74(4):598-604

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.

The present studies were carried out to determine the effects of a kappa-opioid receptor agonist on cytosolic Ca(2+) concentration, [Ca(2+)](i), and extracellular dopamine in undifferentiated PC12 cells. The kappa-opioid receptor agonist U-50,488H caused concentration-dependent increases in [Ca(2+)](i) and extracellular dopamine. Neither effect was blocked by the selective kappa-opioid receptor antagonist nor-binaltorphimine. Increases in extracellular dopamine content and [Ca(2+)](i) caused by U-50,488H were correlated positively in the presence of extracellular Ca(2+); however, reduction of extracellular Ca(2+) abolished the increase in [Ca(2+)](i), but not that in dopamine. The latter observation suggests that stimulation of exocytotic release is not the primary mechanism involved in the increase in extracellular dopamine caused by U-50,488H. Effects on dopamine synthesis or catabolism also seem unlikely because the enhancement of extracellular dopamine occurred rapidly, and the amount of a major metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), was not affected. In any event, neither the increase in [Ca(2+)](i) nor the increase in extracellular dopamine caused by U-50,488H is mediated by the kappa-opioid receptor.
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http://dx.doi.org/10.1002/jnr.10801DOI Listing
November 2003
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