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1.
Biol Pharm Bull ; 31(11): 2114-20, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18981583

ABSTRACT

Platycodin D (PD) isolated from Platycodi Radix has been reported to have anti-inflammatory and anti-tumor activities. In this study, we have investigated anti-inflammatory activities of prosapogenin D (PrsD) and prosapogenin D methyl ester (PrsDMe) of PD. The results indicated that PrsDMe concentration-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, however, PrsD did not inhibit NO production in LPS-induced macrophages. Furthermore, PrsDMe inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) without appreciable cytotoxic effects. In the transfectant RAW 264.7 cells, PrsDMe was observed to reduce the level of nuclear factor-kappaB (NF-kappaB) activity. PrsDMe also inhibited the degradation of an inhibitory protein called inhibitor kappaB (IkappaB). Therefore, it was suggested that PrsDMe inhibited the expression of LPS-induced iNOS and COX-2 genes by suppressing NF-kappaB activation at the transcriptional level. Also, PrsDMe showed carrageenan-induced acute anti-inflammatory activity and the adjuvant-induced anti-arthritic activity in mice. In conclusion, we suggest that these compounds exert an anti-inflammatory effect through the regulation of the NF-kappaB pathway. The different activities of PD, PrsD and PrsDMe are based on the structure of the sugar substituent or methyl group at the C28-carboxyl position.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , NF-kappa B/antagonists & inhibitors , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Experimental/metabolism , Blotting, Western , Cyclooxygenase 2/biosynthesis , Dinoprostone/biosynthesis , Edema/drug therapy , Edema/metabolism , Electrophoretic Mobility Shift Assay , Genes, Reporter , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred ICR , Molecular Structure , NF-kappa B/genetics , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/biosynthesis , Platycodon/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Saponins/chemistry , Saponins/therapeutic use , Transfection , Triterpenes/chemistry , Triterpenes/therapeutic use
2.
Arch Pharm Res ; 30(4): 475-80, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17489364

ABSTRACT

A novel proteinase fraction, SPP-501, was purified from the earthworm, Eisenia andrei, and its antithrombotic effects compared with those of urokinase and t-PA (tissue type-plasminogen activator) in a thrombosis model, induced by the insertion of a stainless wire coil into the inferior vena cava. SPP-501, urokinase and t-PA were administrated once a day for 14 days. On the oral administration of SPP-501, as well as urokinase and t-PA, the thrombus weight was dramatically decreased. The euglobulin lysis time (ELT) was also shortened by SPP-501, but urokinase and t-PA failed to dissolve the euglobulin clot. Conversely, urokinase and t-PA produced detectable fibrinogen/fibrin degradation products (FDP), but SPP-501 did not. Thrombin induced platelet aggregation was desensitized in the SPP-501 treatment groups. With a high dose of SPP-501 (45 mg/kg), the APTT (activated partial thromboplastin time) was prolonged. These results suggest that SPP-501 shows both antithrombotic and fibrinolytic activities when orally administered.


Subject(s)
Fibrinolytic Agents/therapeutic use , Oligochaeta/enzymology , Peptide Hydrolases/therapeutic use , Venous Thrombosis/drug therapy , Administration, Oral , Animals , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Male , Platelet Aggregation/drug effects , Rats , Rats, Sprague-Dawley , Whole Blood Coagulation Time
3.
Eur J Pharmacol ; 537(1-3): 1-11, 2006 May 10.
Article in English | MEDLINE | ID: mdl-16631160

ABSTRACT

Platycodi Radix is the root of Platycodon grandiflorum and it is widely used in the traditional Oriental medicine as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Platycodin D is the major constituent of triterpene saponins in the root. This study investigates apoptosis by platycodin D in immortalized human keratinocytes (HaCaT). Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream level, but not IKK-alpha. Pretreated-N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), a potent NF-kappaB inhibitor, could suppress the induction of apoptosis and activation of NF-kappaB of HaCaT cells by platycodin D. We also demonstrated that platycodin D-mediated apoptosis of HaCaT cells upregulates Fas receptor and Fas ligand (FasL) expression, but did not exhibit p53 activation. HaCaT cells were also transfected with pFLF1, which preserves the promoter region of Fas receptor gene containing NF-kappaB binding site. On incubation with platycodin D, the NF-kappaB activity related to Fas receptor increased in a dose-dependent manner. Among the major transcription elements on Fas receptor and FasL promoter, NF-kappaB activation was shown to have an essential role in the expression of the death receptor such as FasL. These results suggest that platycodin D has the ability to induce apoptosis in HaCaT cells through the upregulation of Fas receptor and FasL expression via to NF-kappaB activation in the transcriptional level. These results demonstrate that the NF-kappaB activation plays a crucial role in the induction of apoptosis in human HaCaT cells on treatment with platycodin D.


Subject(s)
Apoptosis/drug effects , Keratinocytes/drug effects , NF-kappa B/metabolism , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Caspase 3 , Caspase 8 , Caspases/metabolism , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , DNA Fragmentation , Fas Ligand Protein , Gene Expression Regulation/drug effects , Humans , I-kappa B Kinase , In Situ Nick-End Labeling , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , RNA, Messenger/metabolism , Tumor Necrosis Factors/genetics , Tumor Necrosis Factors/metabolism , fas Receptor/genetics , fas Receptor/metabolism
4.
Biol Pharm Bull ; 28(6): 1043-8, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15930742

ABSTRACT

We investigated the intestinal absorption enhancing effect of the saponins from the root bark of Aralia elata (SRBAE) in Caco-2 cell monolayers and rats. SRBAE at concentrations of 0.04% and 0.08% (w/v) decreased the transepithelial electrical resistance (TEER) values and increased the paracellular uptake of chondroitin sulfates (CSs) having different molecular weights (MW 500, 4500, and 18000) in a dose-dependent manner. We also evaluated the cytotoxicity of SRBAE to determine its proper concentration as an absorption enhancer. MTT assay and trypan blue exclusion test indicated that the cytotoxicity of SRBAE at concentrations of 0.04% and 0.08% was negligible. CS (MW 18000) was orally administered with or without SRBAE to rats. The oral administration of SRBAE (250 mg/kg) in 1 h increased the intestinal absorption of CS, by 4.9-fold versus the control (CS alone). Histological examination of the gastrointestinal tissues showed that SRBAE did not cause any damage to tissues. In conclusion, our results suggest that SRBAE acts as an efficient absorption enhancer and makes it easier for hydrophilic molecules to penetrate the intestinal epithelium.


Subject(s)
Aralia , Chondroitin Sulfates/metabolism , Intestinal Absorption/drug effects , Plant Bark , Plant Roots , Saponins/pharmacology , Animals , Biological Transport/drug effects , Biological Transport/physiology , Caco-2 Cells , Humans , Intestinal Absorption/physiology , Male , Rats , Rats, Sprague-Dawley , Saponins/isolation & purification
5.
Biol Pharm Bull ; 28(3): 523-6, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15744082

ABSTRACT

Araloside A, a potent inhibitor of gastric lesion and ulcer formation in rats, was isolated from the root bark of Aralia elata through a bioassay-guided separation procedure. The compound exhibited significant reduction of HCl.ethanol-induced gastric lesions and aspirin-induced gastric ulcers at oral doses of 50 and 100 mg/kg, respectively. These activities are comparable to those of cimetidine.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Aralia , Oleanolic Acid/analogs & derivatives , Saponins/therapeutic use , Stomach Ulcer/drug therapy , Animals , Anti-Ulcer Agents/isolation & purification , Male , Oleanolic Acid/isolation & purification , Oleanolic Acid/therapeutic use , Plant Bark , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Roots , Rats , Rats, Sprague-Dawley , Saponins/isolation & purification , Stomach Ulcer/pathology
6.
World J Gastroenterol ; 11(47): 7430-5, 2005 Dec 21.
Article in English | MEDLINE | ID: mdl-16437712

ABSTRACT

AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats. METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is a promising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increased mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.


Subject(s)
Artemisia , Duodenogastric Reflux/complications , Gastritis/drug therapy , Plant Extracts/pharmacology , Animals , Cholagogues and Choleretics , Duodenogastric Reflux/chemically induced , Gastritis/etiology , Male , Rats , Rats, Sprague-Dawley , Taurocholic Acid
7.
Int Immunopharmacol ; 4(8): 1039-49, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15222978

ABSTRACT

Platycodon D (PD) and D3 (PD3) isolated from Platycodon grandiflorum has been previously reported to show anti-inflammatory activities in rats. In this study, the production of proinflammatory cytokines, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) was examined in a macrophage like cell line, RAW 264.7 cells, in the presence of PD and PD3, oligosaccharide derivatives of oleanolic acid. RAW 264.7 cells activated with lipopolysaccharide (LPS; 1 microg/ml) and recombinant interferon-gamma (rIFN-gamma; 50 U/ml) were treated with various doses of PD and PD3 for 24 h. Supernatants were analyzed for the production of NO and TNF-alpha using Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. NO was inhibited in a dose-dependent manner by PD and PD3 (IC50 of platycodin D approximately 15 uM, IC50 PD3 approximately 55 uM). The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation. Secretion of TNF-alpha was also increased up to 8 h postactivation, suggesting that PD may stimulate TNF-alpha synthesis or inhibit degradation of TNF-alpha mRNA. Oleanolic acid was without effect on both the production of NO and secretion of TNF-alpha. These data suggest a dichotomous regulation of these important proinflammatory mediators by PD and PD3.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Nitric Oxide/biosynthesis , Platycodon , Saponins/pharmacology , Triterpenes/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Blotting, Western , Cell Line , Mice , Nitric Oxide/antagonists & inhibitors , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Plant Roots/chemistry , Saponins/chemistry , Time Factors , Triterpenes/chemistry , Tumor Necrosis Factor-alpha/biosynthesis
8.
Arch Pharm Res ; 26(3): 214-23, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12723935

ABSTRACT

The present study was conducted to investigate the effects of green tea extract (GTE) on arteral blood pressure and contractile responses of isolated aortic strips of the normotensive rats and to establish the mechanism of action. The phenylephrine (10(-8) approximately 10(-5) M)-induced contractile responses were greatly inhibited in the presence of GTE (0.3 approximately 1.2 mg/mL) in a dose-dependent fashion. Also, high potassium (3.5 x 10(-2) approximately 5.6 x 10(-2) M)-induced contractile responses were depressed in the presence of 0.6 approximately 1.2 mg/mL of GTE, but not affected in low concentration of GTE (0.3 mg/mL). However, epigallocatechin gallate (EGCG, 4 approximately 12 microg/mL) did not affect the contractile responses evoked by phenylephrine and high K+. GTE (5 approximately 20 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient. Interestingly, the infusion of a moderate dose of GTE (10 mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study demonstrate that intravenous GTE causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic alpha1-receptors. GTE also causes the relaxation in the isolated aortic strips of the rat via the blockade of adrenergic alpha1-receptors, in addition to the unknown direct mechanism. It seems that there is a big difference in the vascular effect between GTE and EGCG.


Subject(s)
Blood Pressure/drug effects , Catechin/analogs & derivatives , Catechin/pharmacology , Muscle, Smooth, Vascular/drug effects , Tea , Vasoconstriction/drug effects , Animals , Aorta/drug effects , Aorta/physiology , Blood Pressure/physiology , In Vitro Techniques , Male , Muscle, Smooth, Vascular/physiology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Leaves , Rats , Rats, Sprague-Dawley , Vasoconstriction/physiology
9.
Biol Pharm Bull ; 26(4): 429-33, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12673020

ABSTRACT

Three antiinflammatory saponin components were isolated from the alkaline hydrolysate of a butanol-soluble portion of Kalopanax pictus bark extract through an in vivo activity-guided fractionation procedure. The hydrolysate showed inhibition of adjuvant induced arthritis in rats. After further fractionation, the ethyl acetate fraction exhibited antiarthritic activity, which resulted in the isolation of alpha-hederin, alpha-hederin methyl ester, and kalopanaxsaponin I. All compounds showed inhibition of vascular permeability in mice, but only alpha-hederin methyl ester showed anticarrageenan activity in rats and antiarthritic activity in rats and mice.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Butanols/isolation & purification , Kalopanax , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Saponins/isolation & purification , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Butanols/chemistry , Butanols/therapeutic use , Edema/chemically induced , Edema/drug therapy , Esters , Hydrolysis , Male , Oleanolic Acid/chemistry , Oleanolic Acid/therapeutic use , Plant Bark , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Rats , Rats, Sprague-Dawley , Saponins/chemistry , Saponins/therapeutic use
10.
Chem Pharm Bull (Tokyo) ; 50(7): 900-3, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12130847

ABSTRACT

By bioassay-guided separation, a known saponin, kalopanaxsaponin A (1) and a new saponin, pictoside A (2) were isolated from the stem bark of Kalopanax pictus as anti-inflammatory components when evaluated by vascular permeability test. Another novel saponin, pictoside B (3) was also isolated but was inactive in the test system used. The structures of pictosides A and B were elucidated as caulophyllogenin 3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranoside (2) and pictogenin (3beta,6beta,16alpha,23-tetrahydroxyolean-12-ene-28-oic acid) 3-O-alpha-L-arabinopyranoside (3), respectively, by spectral analysis and by chemical degradation. Kalopanaxsaponin A and pictoside A showed significant anti-inflammatory activity at the oral doses of 50 mg/kg.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Kalopanax/chemistry , Saponins/isolation & purification , Saponins/pharmacology , Animals , Biological Assay , Capillary Permeability/drug effects , Hydrolysis , Male , Mice , Mice, Inbred ICR , Molecular Conformation , Oligosaccharides/analysis , Spectrometry, Mass, Fast Atom Bombardment , Structure-Activity Relationship , Subcellular Fractions/chemistry
11.
Arch Pharm Res ; 25(1): 67-70, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11885695

ABSTRACT

The effects of the dried stem powder of Opuntia ficus-indica var. saboten (OF-s) were investigated on gastric lesion and ulcer models in rats. It showed significant inhibition in HCl ethanol-induced gastric lesion at the doses of 200 and 600 mg/kg p.o. and in HCl.aspirin-induced gastric lesion at 600 mg/kg p.o. OF-s also showed significant inhibition in indomethacin-induced gastric lesion at the doses of 200 and 600 mg/kg, p.o. However, it did not affect both the aspirin-induced and Shay ulcers in rats. It also did not affect gastric juice secretion, acid output and pH. These data indicate that OF-s only possesses pronounced inhibitory action on gastric lesion without antiulcer activity in rats.


Subject(s)
Ficus/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Stomach Ulcer/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Ethanol , Gastric Juice/metabolism , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Indomethacin , Male , Plant Stems/chemistry , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology
12.
Planta Med ; 68(3): 221-5, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11914958

ABSTRACT

The root of Platycodon grandiflorum has been widely used for the treatment of various chronic inflammatory diseases including airway disease in oriental medicine. The root extract of the plant has been known to be effective in the expectoration of sputum or mucus, thereby improving airway respiratory function and preventing secondary airway inflammation. In this study, we investigated the effect of platycodin D and D3, the saponin components that are anti-inflammatory components in Platycodon grandiflorum. Platycodin D and D3 increased mucin release from rat and hamster tracheal surface epithelial cell culture and also from intact rat trachea upon nebulization. The effect of platycodin D3 was stronger than that of ATP, a potent mucin secretagogue and also of ambroxole, a mucolytic drug. The results from the present study suggest that platycodin D and D3 are useful as expectorant agents in the treatment of various airway diseases.


Subject(s)
Campanulaceae , Mucins/drug effects , Saponins/pharmacology , Trachea/drug effects , Triterpenes/pharmacology , Animals , Cells, Cultured , Cricetinae , Dose-Response Relationship, Drug , In Vitro Techniques , L-Lactate Dehydrogenase/drug effects , Male , Mucins/metabolism , Plant Extracts/pharmacology , Plant Roots/chemistry , Rats , Rats, Sprague-Dawley , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Trachea/metabolism
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