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Ardisia silvestris is a traditional medicinal herb used in Vietnam and several other countries. However, the skin-protective properties of A. silvestris ethanol extract (As-EE) have not been evaluated. Human keratinocytes form the outermost barrier of the skin and are the main target of ultraviolet (UV) radiation. UV exposure causes skin photoaging via the production of reactive oxygen species. Protection from photoaging is thus a key component of dermatological and cosmetic products. In this research, we found that As-EE can prevent UV-induced skin aging and cell death as well as enhance the barrier effect of the skin. First, the radical-scavenging ability of As-EE was checked using DPPH, ABTS, TPC, CUPRAC, and FRAP assays, and a 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was used to examine cytotoxicity. Reporter gene assays were used to determine the doses that affect skin-barrier-related genes. A luciferase assay was used to identify possible transcription factors. The anti-photoaging mechanism of As-EE was investigated by determining correlated signaling pathways using immunoblotting analyses. As-EE had no harmful effects on HaCaT cells, according to our findings, and As-EE revealed moderate radical-scavenging ability. With high-performance liquid chromatography (HPLC) analysis, rutin was found to be one of the major components. In addition, As-EE enhanced the expression levels of hyaluronic acid synthase-1 and occludin in HaCaT cells. Moreover, As-EE dose-dependently up-regulated the production of occludin and transglutaminase-1 after suppression caused by UVB blocking the activator protein-1 signaling pathway, in particular, the extracellular response kinase and c-Jun N-terminal kinase. Our findings suggest that As-EE may have anti-photoaging effects by regulating mitogen-activated protein kinase, which is good news for the cosmetics and dermatology sectors.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hymenocallis littoralis (Jacq.) Salisb. Also known as Pancratium littorale Jacq. And Hymenocallis panamensis Lindl., is a medicinal plant from the family Amarylideceae used for emetic and wound healing and has manifested anti-neoplastic, anti-oxidant, and anti-viral properties. AIM OF THE STUDY: The aim of this paper is to investigate the anti-inflammatory potential and molecular mechanism of H. littoralis against lipopolysaccharide (LPS)-induced macrophages and in vivo HCl/EtOH-induced gastritis mucosal injury models. MATERIALS AND METHODS: The production of pro-inflammatory cytokines and mediators was evaluated by Griess assay, RT-PCR, and real-time PCR. Moreover, the relevant proteins of mitogen-activated protein kinases (MAPKs) including ERK, JNK, p38, c-Jun, and c-Fos were detected using immunoblotting. RESULTS: We demonstrated that H. littoralis prominently dampened production of nitric oxide (NO) in LPS-, poly I:C-, or pam3CSK-stimulated RAW264.7 cells; down-regulated the expression levels of interleukin 6 (IL-6) and inducible nitric oxide synthase; and markedly attenuated the luciferase activities of AP-1 reporter promoters. Moreover, H. littoralis administration prominently downregulated c-Fos and c-Jun phosphorylation as well as JNK1, ERK2, and MKK7 overexpression in HEK 293T cells. Furthermore, H. littoralis displayed anti-inflammatory effects in the HCl/EtOH-induced gastritis mice model. CONCLUSIONS: Cumulatively, these results demonstrated that H. littoralis exerts eminently anti-inflammatory activities in LPS-stimulated RAW264.7 cells in vitro and in HCl/EtOH-induced gastritis mice models in vivo. These activities could be attributed to its modulatory effects on the MAPK signaling pathway.
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Amaryllidaceae , Gastritis , Liliaceae , Animales , Antiinflamatorios/efectos adversos , Etanol/uso terapéutico , Gastritis/inducido químicamente , Gastritis/tratamiento farmacológico , Gastritis/metabolismo , Lipopolisacáridos/toxicidad , Ratones , FN-kappa B/metabolismo , Extractos Vegetales/efectos adversosRESUMEN
CONTEXT: Among the plants in the genus Barringtonia (Lecythidaceae) used as traditional medicines to treat arthralgia, chest pain, and haemorrhoids in Indonesia, Barringtonia racemosa L. and Barringtonia acutangula (L.) Gaertn. have demonstrated anti-inflammatory activity in systemic inflammatory models. OBJECTIVE: The anti-inflammatory activity of Barringtonia angusta Kurz has not been investigated. We prepared a methanol extract of the leaves and stems of B. angusta (Ba-ME) and systemically evaluated its anti-inflammatory effects in vitro and in vivo. MATERIALS AND METHODS: RAW264.7 cells stimulated with LPS or Pam3CSK4 for 24 h were treated with Ba-ME (12.5, 25, 50, 100, and 150 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated. Luciferase reporter gene assay, western blot analysis, overexpression experiments, and cellular thermal shift assay were conducted to explore the mechanism of Ba-ME. In addition, the anti-gastritis activity of Ba-ME (50 and 100 mg/kg, administered twice per day for two days) was evaluated using an HCl/EtOH-induced gastritis mouse model. RESULTS: Ba-ME dose-dependently suppressed NO production [IC50 = 123.33 µg/mL (LPS) and 46.89 µg/mL (Pam3CSK4)] without affecting cell viability. Transcriptional expression of iNOS, IL-1ß, COX-2, IL-6, and TNF-α and phosphorylation of Src, IκBα, p50/105, and p65 were inhibited by Ba-ME. The extract specifically targeted the Src protein by binding to its SH2 domain. Moreover, Ba-ME significantly ameliorated inflammatory lesions in the HCl/EtOH-induced gastritis model. DISCUSSION AND CONCLUSIONS: The anti-inflammatory activity of Ba-ME is mediated by targeting of the Src/NF-κB signalling pathway, and B. angusta has potential as an anti-inflammatory drug.
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Antiinflamatorios/administración & dosificación , Barringtonia , Sistemas de Liberación de Medicamentos/métodos , Gastritis/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Familia-src Quinasas/antagonistas & inhibidores , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/metabolismo , Relación Dosis-Respuesta a Droga , Gastritis/inducido químicamente , Gastritis/metabolismo , Células HEK293 , Humanos , Masculino , Metanol/administración & dosificación , Metanol/metabolismo , Ratones , Ratones Endogámicos ICR , FN-kappa B , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Hojas de la Planta , Tallos de la Planta , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Familia-src Quinasas/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever. AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages. MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS. RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1ß, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1ß and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin. CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
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Antiinflamatorios/farmacología , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Rutaceae/química , Quinasa Syk/metabolismo , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Ciclooxigenasa 2/genética , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Etanol/toxicidad , Gastritis/inducido químicamente , Gastritis/tratamiento farmacológico , Gastritis/patología , Células HEK293 , Humanos , Ácido Clorhídrico/toxicidad , Inflamación/genética , Interleucina-1beta/genética , Lipopolisacáridos/toxicidad , Masculino , Metanol/química , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.
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Antiinflamatorios/farmacología , Etanol/química , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Rosaceae/química , Familia-src Quinasas/antagonistas & inhibidores , Animales , Gastritis/tratamiento farmacológico , Gastritis/metabolismo , Gastritis/patología , Células HEK293 , Humanos , Inflamación/genética , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Biológicos , Óxido Nítrico/biosíntesis , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Familia-src Quinasas/metabolismoRESUMEN
Inflammation is a complex protective response of body tissues to harmful stimuli. Acute inflammation can progress to chronic inflammation, which can lead to severe disease. Therefore, this research focuses on the development of anti-inflammatory drugs, and natural extracts have been explored as potential agents. No study has yet examined the inflammation-associated pharmacological activity of Potentilla glabra Var. mandshurica (Maxim.) Hand.-Mazz ethanol extract (Pg-EE). To examine the mechanisms by which Pg-EE exerts anti-inflammatory effects, we studied its activities in lipopolysaccharide (LPS)-treated murine macrophage RAW264.7 cells and an HCl/EtOH-induced gastritis model. LPS-triggered nitric oxide (NO) release and mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) in RAW264.7 cells were suppressed by Pg-EE in a dose-dependent manner. Using a luciferase assay and western blot assay, we found that the NF-κB pathway was inhibited by Pg-EE, particularly by the decreased level of phosphorylated proteins of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunits (p65 and p50), inhibitor of kappa B alpha (IκBα), p85, and Src. Using an overexpression strategy, cellular thermal shift assay, and immunoprecipitation analysis, we determined that the anti-inflammatory effect of Pg-EE was mediated by the inhibition of Src. Pg-EE further showed anti-inflammatory effects in vivo in the HCl/EtOH-induced gastritis mouse model. In conclusion, Pg-EE exerts anti-inflammatory activities by targeting Src in the NF-κB pathway, and these results suggest that Pg-EE could be used as an anti-inflammatory herbal medicine.
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Antiinflamatorios/farmacología , Etanol/química , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Potentilla/química , Familia-src Quinasas/antagonistas & inhibidores , Enfermedad Aguda , Animales , Gastritis/patología , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Biológicos , FN-kappa B/metabolismo , Óxido Nítrico/biosíntesis , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcripción Genética/efectos de los fármacos , Familia-src Quinasas/metabolismoRESUMEN
Atherosclerosis is a major cause of coronary heart disease. As a result of the development of atherosclerotic lesions, the walls of blood vessels become thicker and inhibit blood circulation. Atherosclerosis is caused by a high-fat diet and vascular injury. Chronic arterial inflammation plays an important role in the pathogenesis of atherosclerosis. In particular, secretion of the pro-atherogenic cytokine tumor necrosis factor-α induces expression of endothelial adhesion molecules including P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1), which mediate attachment of circulating monocytes and lymphocytes. In this study, we examined the anti-atherosclerotic effect of sorghum, which is known to have anti-oxidant and anti-inflammatory activity. A 50% ethanol extract of Sorghum bicolor L. Moench fermented with Aspergillus oryzae NK (fSBE) was used for experiments. In vitro expression of endothelial adhesion molecules VCAM-1 and ICAM-1 and pro-inflammatory factor cyclooxygenase-2 was significantly decreased and that of the anti-atherogenic factor heme oxygenase-1 significantly increased by fSBE (P < 0.05). At the in vivo level, we examined fat droplets of liver tissue, and aortic thickness via histological analysis, and determined the blood lipid profile through chemical analysis. fSBE at a dose of 200 mg/kg significantly improved blood and vascular health (P < 0.05). Taken together, these results demonstrate that fSBE has potential as a therapeutic anti-atherosclerotic agent.
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Aterosclerosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Sorghum/química , Animales , Modelos Animales de Enfermedad , Humanos , Molécula 1 de Adhesión Intercelular , Masculino , RatonesRESUMEN
Isoflavone itself is less available in the body without the aid of intestinal bacteria. In this study, we searched for isoflavone-transforming bacteria from human fecal specimens (n = 14) using differential selection media. Isoflavone-transforming activity as the production of dihydrogenistein and dihydrodaidzein was assessed by high-performance liquid chromatography and we found Lactobacillus rhamnosus, named L. rhamnosus vitaP1, through 16S rDNA sequence analysis. Extract from Pueraria lobata (EPL) and soy hypocotyl extract were fermented with L. rhamnosus vitaP1 for 24 and 48 h at 37°C. Fermented EPL (FEPL) showed enhanced anti-tyrosinase activity and antioxidant capacities, important suppressors of the pigmentation process, compared with that of EPL (p < 0.05). At up to 500 µg/ml of FEPL, there were no significant cell cytotoxicity and proliferation on B16-F10 melanoma cells. FEPL (100 µg/ml) could highly suppress the content of melanin and melanosome formation in B16-F10 cells. In summary, Lactobacillus rhamnosus vitaP1 was found to be able to biotransform isoflavones in EPL. FEPL showed augmented anti-melanogenic potential.
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Isoflavonas/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Extractos Vegetales/metabolismo , Pueraria/química , Antioxidantes/análisis , Biotransformación , Cromatografía Líquida de Alta Presión , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Inhibidores Enzimáticos/análisis , Heces/microbiología , Fermentación , Humanos , Lacticaseibacillus rhamnosus/clasificación , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/aislamiento & purificación , Melaninas/antagonistas & inhibidores , Monofenol Monooxigenasa/antagonistas & inhibidores , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Glycine max/química , Temperatura , Factores de TiempoRESUMEN
Sorghum [Sorghum bicolor (L.) Moench] is a major cereal crop. Despite the wide cultivation of sorghum, its stalks are used as hay and silage. The plant has numerous bioactive compounds including cosmeceutical ingredients. Thus, we investigated the antimelanogenic and SSE that is prepared from the stalk of Sorghum bicolor L. (SSE) after ethanol (EtOH) extraction. Based on the antioxidant capacity, antityrosinase activity, and suppression of the protein expression levels of matrix metalloproteinase (MMP)-1, -2, and -3 in human neonatal foreskin HDF-N cells, a 50% EtOH extraction of SSEs showed antimelanogenic and antiwrinkle potential. To enrich the cosmeceutical potential of SSE, a fermentation process was applied to SSE with the use of the fungus Aspergillus oryzae NK ( f SSE). On additional fermentation, the cosmeceutical potential of SSE increased with further enhancement of antityrosinase activity and suppression of MMP-1, -2, and -3 protein expression. SSE contains p-coumaric acid, and its level was enriched by the fermentation process. Collectively, SSE and its fermented product can serve as good ingredients in new cosmeceutical compounds.
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Cosméticos/farmacología , Extractos Vegetales/farmacología , Pigmentación de la Piel/efectos de los fármacos , Sorghum/química , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Cosméticos/química , Ácidos Cumáricos , Fermentación , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Melanoma , Metaloproteasas/metabolismo , Ratones , Células 3T3 NIH , Extractos Vegetales/química , Tallos de la Planta/química , Propionatos/química , Envejecimiento de la Piel/efectos de los fármacosRESUMEN
Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng, displays immunostimulatory and antitumor activities. Even though numerous studies have been reported, the mechanism as to how RGAP is able to stimulate the immune response is not clear. In this study, we aimed to explore the mechanism of molecular activation of RGAP in macrophages. RGAP treatment strongly induced NO production in RAW264.7 cells without altering morphological changes, although the activity was not strong compared to LPS-induced dendritic-like morphology in RAW264.7 cells. RGAP-induced NO production was accompanied with enhanced mRNA levels of iNOS and increases in nuclear transcription factors such as NF-κB, AP-1, STAT-1, ATF-2, and CREB. According to pharmacological evaluation with specific enzyme inhibitors, Western blot analysis of intracellular signaling proteins and inhibitory pattern using blocking antibodies, ERK, and JNK were found to be the most important signaling enzymes compared to LPS signaling cascade. Further, TLR2 seems to be a target surface receptor of RGAP. Lastly, macrophages isolated from RGS2 knockout mice or wortmannin exposure strongly upregulated RGAP-treated NO production. Therefore, our results suggest that RGAP can activate macrophage function through activation of transcription factors such as NF-κB and AP-1 and their upstream signaling enzymes such as ERK and JNK.
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Activación de Macrófagos/efectos de los fármacos , Panax/química , Polisacáridos/farmacología , Factor de Transcripción Activador 2 , Animales , Línea Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Immunoblotting , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas RGS/deficiencia , Proteínas RGS/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismoRESUMEN
The Rheum palmatum L., a traditional medicine in Korea, was screened for their estrogenic activity in a recombinant yeast system with a human estrogen receptor (ER) expression plasmid and a reporter plasmid used in a previous study. The EC50 values of the n-hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions of the methanolic extract of R. palmatum in the yeast-based estrogenicity assay system were 0.145, 0.093, 0.125, 1.459, 2.853 microg/mL, respectively, with marked estrogenic activity in the dichloromethane fraction. Using an activity-guided fractionation approach, five known anthraquinones, chrysophanol (1), physcion (2), emodin (3), aloe-emodin (4) and rhein (5), were isolated from the dichloromethane fraction. Compound 3 had the highest estrogenic relative potency (RP, 17bestradiol = 1.00) (6.3 x 10(-2)), followed by compound 4 (3.8 x 10(-3)), compound 5 (2.6 x 10(-4)), a compound 1 (2.1 x 10(-4)). Also, compound 3 and fraction 3 (which contained compound 3) of the dichloromethane fraction of R. palmatum showed strong cytotoxicity in both ER-positive (MCF-7) and-negative (MDA-MB-231) breast cancer cell lines.
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Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/farmacología , Receptores de Estrógenos/efectos de los fármacos , Rheum , Antraquinonas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Emodina/análogos & derivados , Emodina/farmacología , Moduladores de los Receptores de Estrógeno/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Raíces de Plantas , Receptores de Estrógenos/genética , Proteínas Recombinantes/efectos de los fármacos , Rheum/químicaRESUMEN
The medicinal plant extracts commercially used in Asia were screened for their estrogenic and antiestrogenic activities in a recombinant yeast system featuring both a human estrogen receptor (ER) expression plasmid and a reporter plasmid. Pueraria lobata (flower) had the highest estrogenic relative potency (RP, 7.75×10(-3); RP of 17ß-estradiol=1), followed by Amomum xanthioides (1.25×10(-3)). Next potent were a group consisting of Glycyrrhiza uralensis, Zingiber officinale, Rheum undulatum, Curcuma aromatica, Eriobotrya japonica, Sophora flavescens, Anemarrhena asphodeloides, Polygonum multiflorum, and Pueraria lobata (root) (ranging from 9.5×10(-4) to 1.0×10(-4)). Least potent were Prunus persica, Lycoppus lucidus, and Adenophora stricta (ranging from 9.0×10(-5) to 8.0×10(-5)). The extracts exerting antiestrogenic effects, Cinnamomum cassia and Prunus persica, had relative potencies of 1.14×10(-3) and 7.4×10(-4), respectively (RP of tamoxifen=1). The solvent fractions from selected estrogenic or antiestrogenic herbs had higher estrogenic relative potencies, with their RP ranging from 9.3×10(-1) to 2.7×10(-4) and from 8.2×10(-1) to 9.1×10(-3), respectively. These results support previous reports on the efficacy of Oriental medicinal plants used or not used as phytoestrogens for hormone replacement therapy.