RESUMEN
A chemical investigation of the sponge Verongula cf. rigida led to the isolation of 13 merosesquiterpenes, among which quintaquinone (2), 5-epi-nakijiquinone L (3), and 3-farnesyl-2-hydroxy-5-methoxyquinone (4) were isolated and reported here for the first time. Particularly, compound 2 is the first member of merosesquiterpenes with a polyketide side chain substituted on C-19. All of the isolated compounds were examined for steroid 5α-reductase inhibitory activity. Cyclospongiaquinone 1 (5) showed a strong activity in the same range as that of standard finasteride.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Finasterida/farmacología , Sesquiterpenos/aislamiento & purificación , Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Animales , Finasterida/química , Finasterida/aislamiento & purificación , Humanos , Masculino , Estructura Molecular , Poríferos/química , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
Three new xanthones (1-3), together with five known ones (4-8), were isolated from whole herb of Swertia bimaculata. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New isolates were evaluated for their anti-5α-reductase activity. The results revealed that all new compounds showed weak activity with reductase inhibitions of 40.5 ± 2.8, 38.6 ± 2.5, and 48.9 ± 3.0%, respectively.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Swertia/química , Xantonas/aislamiento & purificación , Xantonas/farmacología , Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/farmacología , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Xantonas/químicaRESUMEN
Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and anti-inflammatory activities and 5α-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-α-l-rhamnopyranosyl-(1â6)-ß-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1-3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti-inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-α and 5α-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/farmacología , Fenoles/química , Fenoles/farmacología , Hojas de la Planta/química , Rubiaceae/química , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular , Citocinas/biosíntesis , Activación Enzimática/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Masculino , Ratones , Estructura Molecular , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologíaRESUMEN
The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Simulación del Acoplamiento Molecular , Physalis , Extractos Vegetales , Hiperplasia Prostática , Animales , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Physalis/química , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Estructura Molecular , Ácido Clorogénico/farmacología , Ácido Clorogénico/aislamiento & purificación , Próstata/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
This study was conducted to evaluate the promoting effect of Ishige sinicola, an alga native to Jeju Island, Korea, on hair growth. When vibrissa follicles were cultured in the presence of I. sinicola extract for 21 days, I. sinicola extract increased hair-fiber length. After topical application of I. sinicola extract onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. The I. sinicola extract significantly inhibited the activity of 5α-reductase. Treatment of immortalized vibrissa dermal papilla cells (DPCs) with I. sinicola extract resulted in increase of cell proliferation, which was accompanied by the increase of phospho-GSK3ß level, ß-catenin, Cyclin E and CDK2, whereas p27kip1 was down-regulated. In particular, octaphlorethol A, an isolated component from the I. sinicola extract, inhibited the activity of 5α-reductase and increased the proliferation of DPCs. These results suggest that I. sinicola extract and octaphlorethol A, a principal of I. sinicola, have the potential to treat alopecia via the proliferation of DPCs followed by the activation of ß-catenin pathway, and the 5α-reductase inhibition.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Folículo Piloso/efectos de los fármacos , Cabello/efectos de los fármacos , Phaeophyceae/química , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Animales , Proliferación Celular/efectos de los fármacos , Femenino , Cabello/crecimiento & desarrollo , Folículo Piloso/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fenoles/aislamiento & purificación , Fenoles/farmacología , Ratas , Ratas Sprague-Dawley , Ratas Wistar , República de Corea , Vibrisas/efectos de los fármacos , Vibrisas/metabolismo , beta Catenina/efectos de los fármacos , beta Catenina/metabolismoRESUMEN
The dried fruits of Evodia rutaecarpa Bentham have been used widely as a herbal medicine for the treatment of inflammatory disorders and abdominal pain. Benign prostatic hyperplasia (BPH) is a nonmalignant disease characterized by overgrowth of prostates. Despite the pharmacological efficacy of the fruits of E. rutaecarpa against various diseases, their effects against BPH have not been reported. Here, we investigated the inhibitory activity of a 70% ethanol extract of E. rutaecarpa (EEER) against BPH, and its underlying mechanisms regarding cell growth of BPH using BPH-1 cells. An in vitro 5α-reductase activity assay showed that EEER exhibited inhibitory activity against 5α-reductase. In BPH-1 cells, EEER treatment inhibited cell viability and reduced the expression of the proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA), cyclin D1, and phosphor-ERK1/2 proteins. Moreover, EEER also induced apoptosis, with chromatin condensation, apoptotic bodies, and internucleosomal DNA fragmentation. Regarding its underlying mechanisms, EEER exacerbated the activation of caspase-8 and caspase-3 in a concentration-dependent manner and eventually caused the cleavage of PARP. Taken together, these data demonstrated that EEER had a potent 5α-reductase inhibitory activity and that EEER treatment in BPH-1 cells inhibited cell viability via caspase-8- and caspase-3-dependent apoptosis. Therefore, EEER may be a potential phytotherapeutic agent for the treatment of BPH.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Proliferación Celular/efectos de los fármacos , Evodia , Extractos Vegetales/farmacología , Próstata/efectos de los fármacos , Hiperplasia Prostática/tratamiento farmacológico , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Evodia/química , Frutas , Humanos , Masculino , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Próstata/enzimología , Próstata/patología , Hiperplasia Prostática/enzimología , Hiperplasia Prostática/patología , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
Two new phenylpropanoids (1-2), together with two known lignans (3-4), were isolated from whole herb of Swertia atroviolacea. The structures of the new metabolites were established on the basis of detailed spectroscopic analysis. Compounds 1 and 2 were evaluated for their anti-5α-reductase activity. The results revealed that 1 and 2 showed weak activity with reductase inhibitions of 45.6 ± 2.8% and 38.4 ± 2.5%, respectively.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Fenilpropionatos/aislamiento & purificación , Swertia/química , Inhibidores de 5-alfa-Reductasa/farmacología , Lignanos/aislamiento & purificación , Fenilpropionatos/química , Fenilpropionatos/farmacologíaRESUMEN
A double-blind, randomized, placebo-controlled clinical trial assessed the efficacy and safety of Ageratum conyzoides in treating benign prostatic hypertrophy (BPH). In this study, 109 men with medically diagnosed BPH, aged 41-76 years, were administered the investigational product, A. conyzoides extract at a dose of 250 mg/d or placebo, q.d. for 12 weeks. The primary outcome measures were the International Prostate Symptom Score (IPSS), daily urinary frequency and safety evaluations. The secondary outcome measures were testosterone, dihydrotestosterone, oestradiol, sex hormone binding globulin (SHBG), Dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels, and prostate specific antigen (PSA), lipids, blood glucose, the Aging Male's Symptom (AMS) Score and sexual function assessed by Derogatis Interview for Sexual Functioning-Self Report (DISF-SR). The effect of A. conyzoides L extract on gene expression of 5-alpha-reductase in human prostate cells was also investigated to elucidate a potential mechanism of action. The clinical study, showed a significant reduction in total IPSS score (p < 0.01) and day- and night-time urinary frequency (P < 0.01) over time after treatment with A. conyzoides. Steroid hormones, SHBG, PSA levels, lipids, and blood glucose remained within healthy reference range in both groups. There were no changes in AMS or DISF-SR in either group. Gene arrays demonstrated that A. conyzoides extract was effective in reducing the expression of mRNA coding for 5-alpha-reductase types 2 and 1 in human prostate epithelial cells. The overall results indicate that A. conyzoides may be an effective treatment for reducing symptoms of BPH in healthy men, in part, through inhibition of 5-alpha-reductase enzyme activity. © 2017 BioFactors, 43(6):789-800, 2017.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Ageratum/química , Antiinflamatorios/farmacología , Colestenona 5 alfa-Reductasa/genética , Próstata/efectos de los fármacos , Hiperplasia Prostática/tratamiento farmacológico , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Adulto , Anciano , Antiinflamatorios/aislamiento & purificación , Biomarcadores/sangre , Glucemia/metabolismo , Línea Celular , Colestenona 5 alfa-Reductasa/metabolismo , Sulfato de Deshidroepiandrosterona/sangre , Dihidrotestosterona/sangre , Método Doble Ciego , Estradiol/sangre , Humanos , Hidrocortisona/sangre , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Extractos Vegetales/química , Próstata/metabolismo , Próstata/patología , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/genética , Hiperplasia Prostática/patología , Globulina de Unión a Hormona Sexual/genética , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangre , Resultado del Tratamiento , Micción/efectos de los fármacosRESUMEN
Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Antagonistas de Receptores Androgénicos/farmacología , Proliferación Celular/efectos de los fármacos , Colestenona 5 alfa-Reductasa/metabolismo , Cynanchum , Extractos Vegetales/farmacología , Próstata/efectos de los fármacos , Hiperplasia Prostática/prevención & control , Receptores Androgénicos/efectos de los fármacos , Testosterona , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Antagonistas de Receptores Androgénicos/aislamiento & purificación , Animales , Colestenona 5 alfa-Reductasa/genética , Cynanchum/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Tamaño de los Órganos , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Próstata/enzimología , Próstata/patología , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/enzimología , Hiperplasia Prostática/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas Sprague-Dawley , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Factores de TiempoRESUMEN
This study aims to investigate the biological activities related to hair loss of Equisetum debile extracts, including 5α-reductase inhibition, interleukin-6 (IL-6) secretion reduction, and anti-oxidation. E. debile extracts were obtained by maceration in various solvents. Crude extract (CE) was obtained by maceration in 95% ethanol. Chlorophyll-free extract (CF) was the CE which of the chlorophyll has been removed by electrocoagulation. Hexane extract (HE), ethyl acetate extract (EA), and ethanolic extract (ET) were fraction extracts obtained from maceration in hexane, ethyl acetate, and 95% ethanol, respectively. The extracts were investigated for inhibitory activity against 5α-reductase and IL-6 secretion. Total phenolic contents (TPC) were investigated and antioxidant activities were determined by means of 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. The inhibition of lipid peroxidation was determined by the ferric thiocyanate method. The cytotoxicity of the extracts on dermal papilla cells and irritation test by hen's egg test chorioallantoic membrane assay were also investigated. All extracts could inhibit 5α-reductase and decrease IL-6 secretion in lipopolysaccharide-stimulated macrophage. The antioxidant activity of E. debile extracts was directly related to their TPC. ET which contained the highest TPC (68.8 ± 6.7 mg GA/g) showed the highest equivalent concentration (EC1) of 289.1 ± 26.4 mM FeSO4/g, TEAC of 156.6 ± 34.6 mM Trolox/g, and 20.0 ± 6.0% DPPH inhibition. However, EA exhibited the highest inhibition against lipid peroxidation (57.2 ± 0.4%). In addition, EA showed no cytotoxicity on dermal papilla cell line and no irritation on chorioallantoic membrane of hen's eggs. In conclusion, EA was suggested as the most attractive ingredients for functional food and nutraceuticals because of the high inhibitory activity against 5α-reductase, IL-6 secretion, and lipid peroxidation inhibition.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Alopecia/prevención & control , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Suplementos Dietéticos , Equisetum/química , Alimentos Funcionales , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Inhibidores de 5-alfa-Reductasa/toxicidad , Alopecia/enzimología , Alopecia/fisiopatología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/toxicidad , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/toxicidad , Benzotiazoles/química , Compuestos de Bifenilo/química , Línea Celular Tumoral , Embrión de Pollo , Cloruros/química , Colestenona 5 alfa-Reductasa/metabolismo , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/patología , Compuestos Férricos/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Fenoles/aislamiento & purificación , Fenoles/farmacología , Picratos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Neoplasias de la Próstata/enzimología , Células RAW 264.7 , Solventes/química , Ácidos Sulfónicos/químicaRESUMEN
Six sesquiterpenes: germacrone (1), zederone (2), dehydrocurdione (3), curcumenol (4), zedoarondiol (5) and isocurcumenol (6) were isolated from rhizomes of Curcuma aeruginosa Roxb. (Zingiberaceae). They inhibited 5α-reductase which converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most potent (IC(50)=0.42±0.05 mg/mL). Compound 1 was anti-androgenic in LNCaP cells when proliferation was testosterone-induced. The growth of flank gland of male Syrian hamsters is dependent on circulating androgen and when maintained with testosterone, 1 (3, 30, 100µg) inhibited growth but was ineffective against DHT. The similar activity profile was observed on the 5α-reductase inhibitor, finasteride (100 µg) treatment group. The androgen receptor binding assay showed that 1 did not bind to the androgen receptor. In conclusion, 1 showed anti-androgenic effect on in vitro and in vivo assays. One of the possible mechanisms was inhibition 5α-reductase activity. Thus, 1 is a potential lead compound for treatment of androgen-dependent disorders.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Antagonistas de Andrógenos/farmacología , Curcuma/química , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Antagonistas de Andrógenos/aislamiento & purificación , Animales , Línea Celular , Cricetinae , Finasterida/farmacología , Humanos , Concentración 50 Inhibidora , Masculino , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Rizoma , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos de Germacrano/aislamiento & purificación , Sesquiterpenos de Germacrano/farmacología , Testosterona/farmacologíaRESUMEN
Crude drugs expected to have an estrogenic effect were screened for their inhibitory activity on testosterone 5α-reductase. Testosterone 5α-reductase is an enzyme catalyzing the conversion of testosterone to dihydrotestosterone, which possesses high affinity for the androgen receptor. Among the crude drugs tested, we focused on Puerariae Flos (the flowers of Pueraria thomsonii) due to its potent inhibitory activity and suitability for commercial use. The 50% ethanolic extract of Puerariae Flos (PF-ext) showed inhibitory activity of 60.2% at 500 µg/ml against testosterone 5α-reductase. Interestingly, it was more potent than that of Puerariae Radix (roots of Pueraria lobata). PF-ext also showed in vivo anti-androgenic activity using a hair growth assay in testosterone-sensitive male C57Black/6NCrSlc strain mice. We demonstrated saponins, including soyasaponin I and kaikasaponin III, to be active components in PF-ext. In addition, hair growth promotion activity in C3H/He mice at 2 mg/mouse/day of the topical administration of PF-ext was demonstrated. Thus, Puerariae Flos is a promising crude drug for treating androgenic alopecia.