ABSTRACT
Background and Objectives: This study aimed at investigating the laxative effects of a standardized aqueous extract of Dendropanax morbiferus H. Lév. on two different constipation rat models. Materials and Methods: Animal studies were conducted with low-fiber diet-induced and loperamide-induced constipation animal models, and isolated colons were used in ex vivo analysis to determine the changes in colonic motility caused by D. morbiferus H. Lév. leaf extract (DPL). Results: The results showed that DPL administration significantly improved certain reduced fecal parameters (number, weight, and water content of the stools) in a both low-fiber diet and loperamide-induced constipation models without adverse effects of diarrhea. The laxative effect of DPL was confirmed to improve the charcoal excretion time upon DPL treatment in a low-fiber diet or loperamide-induced constipation model through gastrointestinal (GI) motility evaluation using the charcoal meal test. In addition, when DPL was administered to RAW264.7 cells and loperamide-induced constipation model rats, the production of prostaglandin E2 (PGE2) increased significantly in cells and tissue. Furthermore, DPL dose-dependently stimulated the spontaneous contractile amplitude and frequency of the isolated rat colon. Conclusion: Although our study did not provide information on the acute or chronic toxicity of DPL, our results demonstrated that DPL can effectively promote defecation frequency and rat colon contraction, providing scientific evidence to support the use of DPL as a therapeutic application. However, further toxicity studies of DPL are needed prior to the initiation of clinical trials and clinical applications.
Subject(s)
Laxatives , Plant Extracts , Animals , Constipation/chemically induced , Constipation/drug therapy , Gastrointestinal Motility , Laxatives/pharmacology , Laxatives/therapeutic use , Loperamide/pharmacology , Loperamide/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , RatsABSTRACT
PURPOSE: Previously, we demonstrated that the specific ratio of Korean multi-herbal formula (SR-5) exhibits hepatoprotective properties against ethanol-induced hepatic damage in rats. Chronic and excessive alcohol consumption is a major etiological factor involved in gastric disease and ulcer development induced by the inflammatory response and oxidative stress. METHODS: The present study evaluated the gastroprotective effects of SR-5 (100, 150, and 200 mg/kg) against hydrochloride acid/ethanol (HCl/EtOH)-induced and indomethacin/hydrochloride acid (INDO/HCl)-induced gastritis in a mouse model and the mechanisms involved. RESULTS: All the tested doses of SR-5 significantly inhibited gastric lesions in the HCl/EtOH-induced ulcer model mice. Similarly, all the tested doses of SR-5 significantly inhibited gastric lesions in the INDO/HCl-induced ulcer model mice. Furthermore, mice pretreated with SR-5 had significantly increased gastric levels of enzymatic and nonenzymatic antioxidants, namely, catalase (CAT) and glutathione (GSH), with concomitant reductions in malondialdehyde (MDA) and reactive oxygen species (ROS) levels compared with those in the HCl/EtOH or INDO/HCl group. SR-5 suppressed the expression of nuclear factor-kappa B (NF-κB)/p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) to their normal values. CONCLUSION: These findings are the first to demonstrate the powerful protective effect of SR-5 against gastric injury development and provide hope for clinical application.
ABSTRACT
BACKGROUND: We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored. METHODS: The present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models. RESULTS: The results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta. CONCLUSION: Chronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.
Subject(s)
Antihypertensive Agents/pharmacology , Hypertension, Renal/drug therapy , Hypertension/drug therapy , Plant Extracts/pharmacology , Animals , Blood Pressure/drug effects , Disease Models, Animal , Drug Therapy, Combination , Male , Nitrites/metabolism , Plant Leaves , Rats , Rats, Sprague-Dawley , Rats, Wistar , Republic of Korea , RubusABSTRACT
Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.
Subject(s)
Ellagic Acid/chemistry , Lipolysis/drug effects , Plant Extracts/pharmacology , Rubus/chemistry , Thermogenesis/drug effects , Adipogenesis/genetics , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Adipose Tissue, White/pathology , Animals , Biomarkers/metabolism , Body Weight/drug effects , Diet, High-Fat , Down-Regulation/drug effects , Ellagic Acid/administration & dosage , Ellagic Acid/isolation & purification , Ellagic Acid/pharmacology , Lipogenesis/genetics , Male , Mice , Mice, Inbred C57BL , Obesity/drug therapy , Obesity/veterinary , PPAR alpha/genetics , PPAR alpha/metabolism , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Rubus/metabolism , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolismABSTRACT
In this study, we carried out a comparative evaluation of antiaging and anti-melanogenesis activities of raspberry extracts (Rubus occidentalis L.) according to their stage of ripening (uRo: unripe raspberry, Ro: ripe raspberry), and analyzed the active component (ellagic acid) present in these extracts. Our results showed higher inhibitory effects of the uRo extract in terms of elastase and collagenase activities than Ro extract. In the CCD-986sk cells, uRo extract significantly inhibited MMP-1 activity by 18% and increased the rate of type 1 pro-collagen synthesis by 25%. Besides, treatment with uRo extract significantly inhibited α-melanocyte-stimulating hormone-induced melanin synthesis and tyrosinase activity in B16F10 mouse melanoma cells. Overall, uRo was a more potent mediator of antiaging and anti-melanogenesis effects than Ro extract. Further analysis showed that the functional effects of uRo could be attributed to its 18.5 times higher ellagic acid content than that in Ro extract. PRACTICAL APPLICATIONS: This study reported the differential effect of the raspberry extracts depending on their stage of ripening. To the best of our knowledge, this was the first study to report the antiaging, anti-wrinkle, and anti-pigmentation effects of the uRo extracts. We showed that the extracts from the uRo have an overall better antiaging and skin-whitening effect than ripe ones. The effects were attributed to high ellagic acid content in uRo. We believed that our study makes a significant contribution to the literature because the outcome of the study has both, cosmetic as well as therapeutic implications.
Subject(s)
Rubus , Skin Aging , Animals , Ellagic Acid/pharmacology , Melanins , Mice , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: Many clinical trials on antihypertensive drugs have confirmed the usefulness of these drugs in regulating blood pressure effectively. However, all the drugs usually require long-term use; thus, economic burdens as well as some adverse effects, including headache, diarrhea, skin rash, edema, fever, and liver and kidney dysfunction, accompany their use. Therefore, we attempted to identify natural medications for treating hypertension. We investigated the antihypertensive effects of Dendropanax morbiferus H. Lév. extract (DP), enzymatically hydrolyzed DP extract (Hy-DP) and 5% unripe Rubus coreanus Miq. ethanol extract (5-uRCK). METHODS: Extracts of the unripe R. coreanus were made using 20 volumes of 5% ethanol at 100 °C for 4 h. The dried leaves of D. morbiferus were subjected to enzymatic hydrolysis by protease, trypsin, bromelain and papain to increase L-arginine and GABA levels. Vasorelaxant effects of these extracts were evaluated on rat aorta precontracted with phenylephrine. In addition, hippocampal neurons, RAW 264.7 macrophages and human umbilical vein endothelial cells (HUVECs) were used to exam nitric oxide (NO) production and NO synthase (NOS) gene expression. RESULTS: DP, Hy-DP and 5-uRCK dose-dependently relaxed isolated rat aortic rings contracted with phenylephrine; however, Hy-DP was more effective than DP. L-NAME and ODQ differentially inhibited Hy-DP- and 5-uRCK-induced relaxation; both L-NAME and ODQ completely blocked 5-uRCK-mediated relaxation. Endothelium-denuded aortic ring relaxation was induced much less by 5-uRCK than by Hy-DP. Therefore, 5-uRCK and Hy-DP induced vascular relaxation by endothelium-dependent and partially endothelium-dependent mechanisms, respectively. Hy-DP and 5-uRCK induced eNOS gene expression and NO production in endothelial cells but did not change iNOS/nNOS expression or NO production in macrophages or neuronal cells. Both Hy-DP and 5-uRCK effectively induced vascular relaxation via similar but slightly different mechanisms. The best effective combination was investigated after mixing Hy-DP and 5-uRCK at different ratios. The 2:1 Hy-DP:5-uRCK mixture inhibited ACE, cGMP- and cAMP-dependent phosphodiesterase activity and vascular relaxation better than the other mixtures. CONCLUSION: In conclusion, Hy-DP and 5-uRCK exert antihypertensive effects through different endothelium-dependent or endothelium-independent mechanisms. These findings may greatly help elucidate the mechanisms of clinical efficacy of Hy-DP:5-uRCK mixtures used for blood pressure regulation.
Subject(s)
Antihypertensive Agents/pharmacology , Aorta, Thoracic/drug effects , Endothelium, Vascular/drug effects , Plant Extracts/pharmacology , Rubus/chemistry , Vasodilator Agents/pharmacology , Animals , Disease Models, Animal , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Male , Mice , Plant Leaves/chemistry , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Republic of Korea , Specific Pathogen-Free OrganismsABSTRACT
Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-uRCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5-uRCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-uRCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-uRCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5-uRCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-uRCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-uRCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5-uRCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Cholesterol/metabolism , Ellagic Acid/pharmacology , Hydroxymethylglutaryl CoA Reductases/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Plant Extracts/pharmacology , Rubus/chemistry , Sterol Regulatory Element Binding Protein 2/metabolism , Animals , Antioxidants/metabolism , Body Weight/drug effects , Cholesterol/blood , Cholesterol Ester Transfer Proteins/metabolism , Diet, High-Fat , Ellagic Acid/therapeutic use , Hep G2 Cells , Hepatocytes/metabolism , Humans , Hypercholesterolemia/drug therapy , Lipid Metabolism/drug effects , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Male , Organ Size/drug effects , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Phosphorylation/drug effects , Plant Extracts/therapeutic use , Rats, Sprague-Dawley , Signal Transduction/drug effectsABSTRACT
Microalgae have recently been recognized as a valuable resource for various applications. Phaeodactylum tricornutum is a diatom that lives in marine water and has an unusually high content of lipids. In this study, we added P. tricornutum into a gelatin dope solution to examine the effect of this diatom using electrospinning. The addition of P. tricornutum extracts increased the conductivity of the dope solution but had little effect on the viscosity. Due to the increased conductivity, the fiber diameter was reduced compared with the neat gelatin nanofiber. The loading of P. tricornutum extracts was confirmed using fluorescence microscopy, and the incorporation of lipids was detected through gas chromatography. The P. tricornutum-loaded nanofiber mat exhibited anti-microbial activity against Escherichia coli and multidrug-resistant Staphylococcus aureus (MRSA). The cell viability test showed that the P. tricornutum-loaded nanofiber has no cytotoxicity. We expect that this antimicrobial P. tricornutum-loaded gelatin nanofiber mat can be applied as a wound dressing.
Subject(s)
Anti-Infective Agents/pharmacology , Diatoms/chemistry , Nanofibers/chemistry , Plant Extracts/pharmacology , Animals , Anti-Infective Agents/chemistry , Cell Survival/drug effects , Drug Resistance, Multiple/drug effects , Escherichia coli/drug effects , Fibroblasts/drug effects , Gelatin/chemistry , Gelatin/pharmacology , Mice , NIH 3T3 Cells , Plant Extracts/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Wound Healing/drug effectsABSTRACT
In the present study, we examined the effect of a mixture of dietary components, including red grape extract, soy isoflavone and L-carnitine (RISC), on obesity. RISC substantially inhibited high-fat diet (HFD)-induced increase in body weight in a dose-dependent manner in C57BL/6 mice. The amount of subcutaneous and mesenteric fat was also significantly decreased by RISC treatment in HFD-fed C57BL/6 mice, whereas epididymal fat was not affected. Moreover, HFD-induced plasma leptin levels were down-regulated by RISC treatment. In these mice, RISC treatment significantly increased the plasma level of high density lipoprotein cholesterol without affecting the level of low density lipoprotein cholesterol and triglycerides. In addition, HFD-induced increase in liver weight and lipid accumulation in liver was significantly suppressed by RISC treatment in C57BL/6mice. Plasma level of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase was also inhibited by RISC treatment. These results demonstrate that RISC suppresses HFD-induced obesity and suggest that RISC supplementation might be a promising adjuvant therapy for the treatment of obesity and its complications, such as cardiovascular and non-alcoholic fatty liver diseases.
Subject(s)
Cardiovascular Diseases/prevention & control , Carnitine/pharmacology , Dietary Fats/administration & dosage , Fatty Liver/prevention & control , Glycine max/chemistry , Isoflavones/pharmacology , Obesity/prevention & control , Plant Extracts/pharmacology , Vitis/chemistry , Animals , Lipids/blood , Mice , Mice, Inbred C57BL , Obesity/etiology , Organ Size/drug effectsABSTRACT
To develop a therapeutic agent for obesity-related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l-carnitine (RGTC), and its effects on obesity, hyperlipidemia and non-alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high-fat diet (HFD)-induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration-dependently suppressed the HFD-induced increase in plasma lipids, such as low-density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD-fed C57BL/6 mice. The plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were also significantly down-regulated by RGTC treatment. These results suggest that RGTC suppressed HFD-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders.
Subject(s)
Carnitine/pharmacology , Fatty Liver/drug therapy , Hyperlipidemias/drug therapy , Obesity/drug therapy , Plant Extracts/pharmacology , Adipose Tissue/drug effects , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Body Weight/drug effects , Diet, High-Fat , Leptin/blood , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Tea/chemistry , Vitis/chemistryABSTRACT
Lipid-soluble ginseng extract was prepared by n-hexane extraction of red ginseng. BALB/c-nu mice were inoculated with human lung cancer (NCI-H460) cells to establish a human tumor xenograft model in nude mice, and the lipid-soluble ginseng extract was orally administered. The tumor inhibitory rates of the lipid-soluble ginseng extract at doses of 0.1, 0.3, and 1.0 g/kg/day were 18.9% (P < .05), 60.0% (P < .001), and 67.5% (P < .001), respectively. The oral administration of the lipid-soluble extract of red ginseng showed a potent anticancer effect in nude mice bearing human lung cancer cells in a dose-dependent manner without any apparent toxicity. This lipid-soluble ginseng extract is a potential nontoxic anticancer supplement for the prevention and intervention of lung tumor growth through an oral administration route.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Cell Proliferation/drug effects , Lung Neoplasms/drug therapy , Panax , Phytotherapy , Plant Extracts/therapeutic use , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Humans , Lipids , Mice , Mice, Inbred BALB C , Mice, Nude , Plant Extracts/pharmacology , Solubility , Xenograft Model Antitumor AssaysABSTRACT
Glabridin, a flavonoid present in licorice root, is known to have antiinflammatory and cardiovascular protective activities. The present study reports an inhibitory effect of glabridin on microglial activation. Glabridin dose-dependently attenuated lipopolysaccharide (LPS)-induced production of inflammatory mediators, including nitric oxide, tumor necrosis factor-alpha and interleukin-1beta, in BV-2 cells, a murine microglia cell line. Moreover, mRNA expression of these inflammatory mediators was also suppressed by glabridin in LPS-stimulated BV-2 cells. Further study demonstrated that glabridin inhibited LPS-induced DNA binding activity of NF-kappaB and AP-1 in BV-2 cells. Collectively, the results presented in this report demonstrate that glabridin inhibits the production of inflammatory mediators in BV-2 cells and this is mediated, at least in part, by blocking NF-kappaB and AP-1 activation. The results suggest that glabridin might be a potential therapeutic agent for the treatment of neuroinflammatory and neurodegenerative diseases.
Subject(s)
Isoflavones/pharmacology , Microglia/drug effects , NF-kappa B/antagonists & inhibitors , Phenols/pharmacology , Transcription Factor AP-1/antagonists & inhibitors , Animals , Cell Line , Interleukin-1beta/metabolism , Lipopolysaccharides , Mice , Microglia/metabolism , Nitric Oxide/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Silymarin has been known to inhibit chemical-induced irritant contact dermatitis. In the present study, we report that topical application of silymarin suppresses dust mite extract (DPE)-induced atopic dermatitis (AD) in NC/Nga mice. Repeated topical application of ears with DPE caused AD-like skin lesions in NC/Nga mice. However, silymarin reduced AD-like skin lesions in these mice, resulting in decreased ear swelling and leukocyte infiltration into the ear. Moreover, our results showed that mast cell infiltration into the ear was suppressed by silymarin treatment in DPE-treated NC/Nga mice. Silymarin also reduced plasma level of IL-4 and IgE in these mice. Further study demonstrated that the mRNA expression of IL-4 was increased and that of IFN-gamma was decreased by DPE treatment in the ears of NC/Nga mice. However, DPE-induced changes in IL-4 and IFN-gamma mRNA expression were reversed by silymarin. DPE-induced increase in TNF-alpha mRNA expression was also suppressed by silymarin treatment. The results presented in this report suggest that silymarin might be beneficial for the treatment of AD.
Subject(s)
Dermatitis, Atopic/drug therapy , Silymarin/therapeutic use , Animals , Disease Models, Animal , Mice , Pyroglyphidae/chemistry , RNA, Messenger/metabolismABSTRACT
The present study reports the antiinflammatory activity of a methanol extract isolated from the stem bark of Magnolia kobus (MK). MK potently inhibited lipopolysaccharide (LPS)-induced production of nitric oxide and interleukin-1beta (IL-1beta) in RAW 264.7 cells, a murine macrophage-like cell line. The secretion of tumor necrosis factor-alpha (TNF-alpha) was also suppressed in LPS-stimulated RAW 264.7 cells although the magnitude of inhibition was weaker than that of nitric oxide and IL-1beta. The mRNA expressions of inducible nitric oxide synthase (iNOS), IL-1beta and TNF-alpha were also suppressed by MK in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced DNA binding of AP-1 and phosphorylation of c-jun N-terminal kinase (JNK) were inhibited by MK treatment in RAW 264.7 cells, whereas phosphorylation of p38 mitogen-activated protein kinase was unaffected. Moreover, topical application of MK suppressed ear swelling in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation model. Collectively, these results suggest that MK exerts antiinflammatory effects in vitro and in vivo and this might be mediated, at least in part, by blocking AP-1 and JNK activation.
Subject(s)
Anti-Inflammatory Agents/isolation & purification , Magnolia/chemistry , Phytotherapy , Plant Bark/chemistry , Plant Extracts/isolation & purification , Administration, Topical , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Cell Line , Cell Survival/drug effects , DNA/chemistry , DNA/metabolism , Ear, External/drug effects , Ear, External/pathology , Edema/chemically induced , Edema/pathology , Gene Expression/drug effects , Interleukin-1beta/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Methanol/chemistry , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Protein Binding/drug effects , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The pectic polysaccharide (angelan) of Angelica gigas Nakai is an immunostimulator that activates the immune functions of B cells and macrophages. Here we investigated the effect of angelan on tumor growth and metastasis. Angelan was found to significantly prolong the survival rate of B16F10-implanted mice and to reduce the frequency of pulmonary metastasis of B16F10 melanoma. Moreover, the combined treatment of angelan and doxorubicin (a cytotoxic anticancer agent) more effectively inhibited tumor growth and metastasis than either compound alone. In the present study, we found that angelan directly inhibited cancer cell adhesion and invasion through the extracellular matrix, in addition to activating the immune functions of B cells and macrophages. These results suggest that angelan can inhibit tumor growth and metastasis by stimulating host immunity and directly inhibiting cancer cell adhesion.
Subject(s)
Angelica/chemistry , Cell Proliferation/drug effects , Melanoma, Experimental/prevention & control , Neoplasm Metastasis/prevention & control , Polysaccharides/pharmacology , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Cell Adhesion/drug effects , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Female , Injections, Intraperitoneal , Macrophages/drug effects , Macrophages/immunology , Melanoma, Experimental/mortality , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Neoplasm Metastasis/immunology , Neoplasm Metastasis/pathology , Plant Preparations/administration & dosage , Plant Preparations/pharmacology , Polysaccharides/administration & dosage , Survival Rate , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
Prodigiosin (PDG), a bacterial metabolite, is a known T cell-specific immunosuppressant. Here, we compared its inhibitory potency and mode of action with cyclosporine A (CsA) in a mouse model. PDG efficiently inhibited T cell proliferation with an IC(50) of 3.37 ng/ml, a similar dose to that of CsA (IC(50) of 2.71 ng/ml). PDG inhibited only IL-2Ralpha expression, but not IL-2 expression, whereas CsA inhibited both. Exogenously added IL-2 reversed the suppressive activity of CsA, but not that of PDG. Moreover, although both PDG and CsA markedly reduced mortality rates in lethal acute graft-versus-host disease (GVHD), the combined treatment was more effective than either drug alone. These results demonstrate that PDG and CsA have similar inhibitory potencies, but different modes of action, and suggest that PDG has potential use as a supplementary immunosuppressant in combination with CsA for the treatment of GVHD.
Subject(s)
Cyclosporine/therapeutic use , Drug Therapy, Combination , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/therapeutic use , Prodigiosin/therapeutic use , Acute Disease , Animals , Arthritis, Experimental/drug therapy , Arthritis, Experimental/etiology , Arthritis, Experimental/prevention & control , Bacteria/chemistry , Bacteria/immunology , Bacteria/metabolism , Cell Proliferation/drug effects , Cyclosporine/immunology , Cyclosporine/pharmacology , Disease Models, Animal , Drug Administration Schedule , Drug Evaluation, Preclinical/methods , Female , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Immunosuppressive Agents/immunology , Immunosuppressive Agents/pharmacology , Interleukin-2/antagonists & inhibitors , Interleukin-2/genetics , Interleukin-2/immunology , Interleukin-2 Receptor alpha Subunit , Lymphocytes/drug effects , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Prodigiosin/immunology , Prodigiosin/pharmacology , Receptors, Interleukin/antagonists & inhibitors , Receptors, Interleukin/genetics , Receptors, Interleukin/immunology , T-Cell Antigen Receptor Specificity/immunology , Time FactorsABSTRACT
An oriental herbal combination (BDX-1) was isolated from Achyranthes bidentata and Atractylodes japonica. We previously tested the clinical effectiveness of BDX-1 in rheumatoid arthritis (RA) patients and found that it has a beneficial therapeutic effect. Here, we provide experimental evidence for the effectiveness of BDX-1 on RA in murine models. The oral administration of BDX-1 was found to markedly inhibit collagen-induced arthritis, adjuvant-induced arthritis, and zymosan-induced inflammation. It also inhibited carrageenan-induced acute edema and acetic acid-induced writhing response. In addition, the biological activity of BDX-1 was found to be strongly increased by fermentation. Our results suggest that BDX-1 could be useful for the treatment of rheumatoid arthritis.