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1.
Antioxidants (Basel) ; 12(6)2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37371901

RESUMEN

Blue light is reported to be harmful to eyes by inducing reactive oxygen species (ROS). Herein, the roles of Peucedanum japonicum Thunb. leaf extract (PJE) in corneal wound healing under blue light irradiation are investigated. Blue-light-irradiated human corneal epithelial cells (HCECs) show increased intracellular ROS levels and delayed wound healing without a change in survival, and these effects are reversed by PJE treatment. In acute toxicity tests, a single oral administration of PJE (5000 mg/kg) does not induce any signs of clinical toxicity or body weight changes for 15 days post-administration. Rats with OD (oculus dexter, right eye) corneal wounds are divided into seven treatment groups: NL (nonwounded OS (oculus sinister, left eye)), NR (wounded OD), BL (wounded OD + blue light (BL)), and PJE (BL + 25, 50, 100, 200 mg/kg). Blue-light-induced delayed wound healing is dose-dependently recovered by orally administering PJE once daily starting 5 days before wound generation. The reduced tear volume in both eyes in the BL group is also restored by PJE. Forty-eight hours after wound generation, the numbers of inflammatory and apoptotic cells and the expression levels of interleukin-6 (IL-6) largely increase in the BL group, but these values return to almost normal after PJE treatment. The key components of PJE, identified by high-performance liquid chromatography (HPLC) fractionation, are CA, neochlorogenic acid (NCA), and cryptochlorogenic acid (CCA). Each CA isomer effectively reverses the delayed wound healing and excessive ROS production, and their mixture synergistically enhances these effects. The expression of messenger RNAs (mRNAs) related to ROS, such as SOD1, CAT, GPX1, GSTM1, GSTP1, HO-1, and TRXR1, is significantly upregulated by PJE, its components, and the component mixture. Therefore, PJE protects against blue-light-induced delayed corneal wound healing via its antioxidative, anti-inflammatory, and antiapoptotic effects mechanistically related to ROS production.

2.
J Med Food ; 25(1): 12-23, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35029511

RESUMEN

Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of Prunus mume (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is at least partially mediated by the increase in fecal parameters as seen in the low-fiber diet-induced constipation model rats. This study aims at investigating the laxative effects of citric acid-enriched aqueous extracts of rPM, uPM, and its active compounds, such as citric acid and malic acid, on loperamide-induced constipation rat models. Animal studies were conducted with loperamide-induced constipation animal models. The results showed that rPM and citric acid, the major organic acid compounds, significantly improved stool parameters (number, weight, and water content of the stools) generated in loperamide-induced constipation rats, without adverse effects of diarrhea. The gastrointestinal (GI) motility was activated fully in the rPM- and citric acid-treated rats than in rats treaded with loperamide alone. In addition, when rPM and citric acid were added to RAW264.7 cells and used to treat loperamide-induced constipation model rats, the secretion of prostaglandin E2 (PGE2) increased significantly in cells and tissue. Furthermore, rPM and citric acid decreased the expression of the aquaporin 3 (AQP3) in the rat colons. Our results demonstrated that rPM and citric acid, the major organic acid compound in rPM, can effectively promote defecation frequency and regulate PGE2 secretion and AQP3 expression in the colon, providing scientific evidence to support the use of rPM as a therapeutic application.


Asunto(s)
Laxativos , Prunus , Animales , Acuaporina 3 , Ácido Cítrico/uso terapéutico , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Loperamida , Prostaglandinas/uso terapéutico , Prostaglandinas E/uso terapéutico , Ratas
3.
Curr Issues Mol Biol ; 43(3): 2177-2188, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34940126

RESUMEN

Scutellaria L. (family Lamiaceae) includes approximately 470 species found in most parts of the world and is commonly known as skullcaps. Scutellaria L. is a medicinal herb used as a folk remedy in Korea and East Asia, but it is difficult to identify and classify various subspecies by morphological methods. Since Scutellaria L. has not been studied genetically, to expand the knowledge of species in the genus Scutellaria L., de novo whole-genome assembly was performed in Scutellaria indica var. tsusimensis (H. Hara) Ohwi using the Illumina sequencing platform. We aimed to develop a molecular method that could be used to classify S.indica var. tsusimensis (H. Hara) Ohwi, S. indica L. and three other Scutellaria L. species. The assembly results for S.indica var. tsusimensis (H. Hara) Ohwi revealed a genome size of 318,741,328 bp and a scaffold N50 of 78,430. The assembly contained 92.08% of the conserved BUSCO core gene set and was estimated to cover 94.65% of the genome. The obtained genes were compared with previously registered Scutellaria nucleotide sequences and similar regions using the NCBI BLAST service, and a total of 279 similar nucleotide sequences were detected. By selecting the 279 similar nucleotide sequences and nine chloroplast DNA barcode genes, primers were prepared so that the size of the PCR product was 100 to 1000 bp. As a result, a species-specific primer set capable of distinguishing five species of Scutellaria L. was developed.


Asunto(s)
Biomarcadores , Scutellaria/clasificación , Scutellaria/genética , Especificidad de la Especie , Biología Computacional/métodos , Código de Barras del ADN Taxonómico , Genes de Plantas , Genómica/métodos , Anotación de Secuencia Molecular , Fenotipo , RNA-Seq
4.
Medicina (Kaunas) ; 57(11)2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34833365

RESUMEN

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.


Asunto(s)
Laxativos , Extractos Vegetales , Animales , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Motilidad Gastrointestinal , Laxativos/farmacología , Laxativos/uso terapéutico , Loperamida/farmacología , Loperamida/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas
5.
Antioxidants (Basel) ; 10(11)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34829588

RESUMEN

We previously demonstrated that urban particulate matter (UPM) exposure decreases the migration activity and survival of human corneal epithelial cells (HCECs). Herein, we investigated the potential to improve the corneal wound-healing ability of Peucedanum japonicum Thunb. leaf extract (PJE) and its active components on UPM-induced ocular surface damage in vitro and in vivo. PJE effectively assisted wound healing without altering HCEC survival and enhanced catalase (CAT), heme oxygenase 1 (HO1) and glutathione peroxidase 1 (GPX1) antioxidant gene expression. A corneal wound was uniformly induced on the right eye in all experimental animals and divided into eight groups such as two control groups (wounded right eye group-NR and non-wounded left eye group-NL), UPM treated group and PJEs (25, 50, 100, 200, 400 mg/kg) treated groups. Corneal abrasion model rats exposed to UPM showed delayed wound healing compared to unexposed rats, but wound healing was dose-dependently enhanced by PJE oral administration. Seventy-two hours after wound generation, inflammatory cells, apoptotic cells and interleukin-6 (IL-6) expression were increased substantially after UPM exposure, but PJE treatment significantly reduced the wound to an almost normal level while enhancing re-epithelialization without changing corneal thickness. Next, we tried to identify the key molecules for enhancing wound healing through fractionation. The major compounds in the fraction, confirmed by high-performance liquid chromatography (HPLC), were chlorogenic acid (CA), neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA). Each type of CA isomers showed slightly different half maximal effective (EC50) and maximal effective (ECmax) concentrations, and their mixtures synergistically enhanced HCEC migration. Thus, corneal abrasion wound recovery after UPM exposure improved after PJE treatment, and the active PJE components were identified, providing an important basis to develop therapeutics for ocular surface damage using PJE.

6.
Dose Response ; 19(4): 15593258211044329, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34690616

RESUMEN

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.

7.
BMC Complement Med Ther ; 21(1): 271, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34711215

RESUMEN

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.


Asunto(s)
Antihipertensivos/farmacología , Hipertensión Renal/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Masculino , Nitritos/metabolismo , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Ratas Wistar , República de Corea , Rubus
8.
J Med Food ; 24(3): 258-266, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33739883

RESUMEN

From 25% to 50% of adults are affected by prehypertension. Prehypertension increases the risk of hypertension and affects the heart and systemic vascular system. Food mixed tree essence of Dendropanax morbifera called Hwangchil in Korean and immature fruit of Rubus coreanus, called Bokbunja (HDR-2), have been studied for safety and effectiveness against prehypertension studies. This study was a randomized double-blind placebo-controlled multicenter clinical trial lasting 19 months from October 2017 to May 2019. The 88 subjects who enrolled in the study were divided into two groups. The treatment group was provided HDR-2 and the other group took a placebo. Both HDR-2 and placebo were in the form of capsules, and the dose was 900 mg per day. Subjects took HDR-2 or placebo capsules once a day for 8 weeks before dinner. The primary observational indicators were systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the secondary observational indicators were mean arterial pressure (MAP), mean pulse pressure, pulse rate, angiotensin-converting enzyme activity, renin activity, aldosterone, and highly sensitive-C reactive protein. The number of measurements was three times: the first visit in the screening week, the second visit in 4 weeks, and the third visit was after 8 weeks. Significant study results showed that the SBP and MAP of the HDR-2 group after 8 weeks were lower than those of the placebo group. Adverse events were not significantly different between the two groups. In conclusion, these results suggest that HDR-2 may be a useful intervention for the management of prehypertension. The protocol was registered in the Korean Clinical Trial Registration system (http://cris.nih.go.kr; registration number: KCT0004300).


Asunto(s)
Hipertensión , Prehipertensión , Adulto , Antihipertensivos/farmacología , Presión Sanguínea , Método Doble Ciego , Humanos , Hipertensión/tratamiento farmacológico , Extractos Vegetales/farmacología
9.
Molecules ; 25(24)2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339214

RESUMEN

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.


Asunto(s)
Ácido Elágico/química , Lipólisis/efectos de los fármacos , Extractos Vegetales/farmacología , Rubus/química , Termogénesis/efectos de los fármacos , Adipogénesis/genética , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa , Regulación hacia Abajo/efectos de los fármacos , Ácido Elágico/administración & dosificación , Ácido Elágico/aislamiento & purificación , Ácido Elágico/farmacología , Lipogénesis/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/veterinaria , PPAR alfa/genética , PPAR alfa/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Rubus/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
10.
J Food Biochem ; 44(11): e13464, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32969076

RESUMEN

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.


Asunto(s)
Rubus , Envejecimiento de la Piel , Animales , Ácido Elágico/farmacología , Melaninas , Ratones , Extractos Vegetales/farmacología
11.
Lipids Health Dis ; 19(1): 166, 2020 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-32646501

RESUMEN

BACKGROUND: Rubus coreanus (R. coreanus) possesses properties that may decrease cholesterol levels. METHODS: The effects of unripe R. coreanus (uRC) consumption on low-density lipoprotein (LDL) and total cholesterol levels related to decreased circulating apolipoprotein (Apo) B and oxidized LDL levels were evaluated. This randomized, double-blind, placebo-controlled study included subjects with borderline-high cholesterol levels (between 200 and 239 mg/dL) who consumed one capsule daily containing 600 mg of freeze-dried uRC extract (n = 39) or the placebo (n = 38). RESULTS: After 12 weeks, the uRC group showed reductions of 21.23 ± 4.36 mg/dL in total cholesterol levels (P = 0.007) and 15.61 ± 4.16 mg/dL in LDL cholesterol levels (P = 0.032). In addition, significantly greater reductions in Apo B levels were observed in the uRC group (- 3.48 ± 3.40 mg/dL), but Apo B levels were increased in the placebo group (6.21 ± 2.84 mg/dL; P = 0.032). Furthermore, a remarkably lower oxidized LDL level was detected in the uRC group (57.76 ± 2.07 U/L) than in the placebo group (66.09 ± 3.47 U/L) after 12 weeks of consumption (P = 0.044). CONCLUSIONS: Because of its cholesterol-lowering effect, uRC shows great promise as a therapeutic agent for subjects with borderline-high total blood cholesterol levels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03649620 (8/28/2018, retrospectively registered).


Asunto(s)
Anticolesterolemiantes/farmacología , Apolipoproteína B-100/sangre , Colesterol/sangre , Lipoproteínas LDL/sangre , Rubus/química , Anticolesterolemiantes/química , Apolipoproteína A-I/sangre , Método Doble Ciego , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/dietoterapia , Lípidos/sangre , Masculino , Persona de Mediana Edad , Placebos , Rubus/fisiología
12.
Int J Mol Sci ; 21(14)2020 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-32674521

RESUMEN

We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.


Asunto(s)
Conjuntiva/efectos de los fármacos , Córnea/efectos de los fármacos , Epitelio Corneal/efectos de los fármacos , Material Particulado/efectos adversos , Retina/efectos de los fármacos , Animales , Línea Celular , Conjuntiva/metabolismo , Córnea/metabolismo , Modelos Animales de Enfermedad , Síndromes de Ojo Seco/inducido químicamente , Epitelio Corneal/metabolismo , Fluoresceína/farmacología , Humanos , Incidencia , Interleucina-6/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Retina/metabolismo , Lágrimas/efectos de los fármacos , Lágrimas/metabolismo
13.
BMC Complement Med Ther ; 20(1): 190, 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32571292

RESUMEN

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.


Asunto(s)
Antihipertensivos/farmacología , Aorta Torácica/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Extractos Vegetales/farmacología , Rubus/química , Vasodilatadores/farmacología , Animales , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Ratones , Hojas de la Planta/química , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , República de Corea , Organismos Libres de Patógenos Específicos
14.
Nutrients ; 12(3)2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32110925

RESUMEN

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.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Colesterol/metabolismo , Ácido Elágico/farmacología , Hidroximetilglutaril-CoA Reductasas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Extractos Vegetales/farmacología , Rubus/química , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Animales , Antioxidantes/metabolismo , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Dieta Alta en Grasa , Ácido Elágico/uso terapéutico , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Hipercolesterolemia/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo , Fosforilación/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
15.
Mol Med Rep ; 16(6): 9573-9578, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29039529

RESUMEN

Helicobacter pylori (H. pylori) infection activates pro­inflammatory mediators, including interleukin (IL)­8 and vascular endothelial growth factor (VEGF) in gastric epithelial cells. 1­Tetradecanol (1­TD) has been purified from Dendropanax morbifera Leveille; its physiological activities are poorly understood. The present study assessed whether 1­TD has an effect on H. pylori­mediated inflammation in AGS gastric epithelial cells. 1­TD reduced IL­8 production by AGS cells in response to H. pylori in a significant and dose­dependent manner, as measured by ELISA. Western blot analysis demonstrated that 1­TD also suppressed the activation of nuclear factor­κB, and two mitogen activated protein kinase species (p38 and extracellular signal­regulated kinase 1/2), but not c­Jun N­terminal kinase in H. pylori­infected AGS cells. As predicted, VEGF expression and hypoxia inducible factor­1α stabilization induced by H. pylori in AGS cells were inhibited by 1­TD. In addition, 1­TD directly inhibited the growth of H. pylori in a dose­dependent manner, as investigated by measuring the optical density. These findings indicated that 1­TD may be a potential preventive or therapeutic agent for H. pylori­induced gastric inflammation.


Asunto(s)
Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/fisiología , Interleucina-8/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Biomarcadores , Línea Celular , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Mucosa Gástrica/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo
16.
Eur J Pharmacol ; 799: 135-142, 2017 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-28167257

RESUMEN

Tetradecanol is a straight-chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30µM) reduced specifically the growth of T cells such as EL-4 T cell and isolated murine CD4+ T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin-2 (IL-2), a potent T cell growth factor. Tetradecanol significantly inhibited IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4+ T cells activated with anti-CD3 and anti-CD28 antibodies. Next, we examined the effect of tetradecanol on the transcriptional activity related to IL-2 production in T cells. Tetradecanol decreased PMA/Io-induced promoter activity of NF-κB in EL-4 T cells, but did not show any significant effects on the promoters of activator protein 1 (AP-1) and nuclear factor of activated T cells (NF-AT). Tetradecanol inhibited IκBα degradation and nuclear translocation of NF-κB subunit, p65 in PMA/Io-activated EL-4 T cells. These results suggest that tetradecanol might have immunosuppressive effects on T cell mediated disorders. Using a chronic allergic contact dermatitis model induced by repeated application of oxazolone, we showed that tetradecanol reduced ear thickness induced by oxazolone.


Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Alcoholes Grasos/farmacología , Interleucina-2/metabolismo , FN-kappa B/metabolismo , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dermatitis por Contacto/complicaciones , Dermatitis por Contacto/tratamiento farmacológico , Alcoholes Grasos/uso terapéutico , Femenino , Células HeLa , Humanos , Hipersensibilidad/complicaciones , Interleucina-2/biosíntesis , Interleucina-2/genética , Masculino , Ratones , Inhibidor NF-kappaB alfa/metabolismo , Proteolisis/efectos de los fármacos , Linfocitos T/metabolismo , Transcripción Genética/efectos de los fármacos
17.
J Med Food ; 19(9): 870-81, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27331439

RESUMEN

Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation-induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 receptor and resulting inhibition of cAMP activity.


Asunto(s)
Ansiedad/metabolismo , Disfunción Cognitiva/metabolismo , Extractos Vegetales/farmacología , Receptores de Serotonina/metabolismo , Rosa , Privación de Sueño/psicología , Estrés Fisiológico/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ansiedad/tratamiento farmacológico , Conducta Animal , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Corticosterona/metabolismo , AMP Cíclico/antagonistas & inhibidores , Dopamina/metabolismo , Masculino , Fitoterapia , Extractos Vegetales/uso terapéutico , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Serotonina/sangre , Sueño/fisiología , Privación de Sueño/complicaciones , Privación de Sueño/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-26904142

RESUMEN

Background. The objective of the present study was to perform a bioguided fractionation of unripe Rubus coreanus Miquel (uRC) and evaluate the lipid accumulation system involvement in its antiobesity activity as well as study the uRC mechanism of action. Results. After the fractionation, the BuOH fraction of uRC (uRCB) was the most active fraction, suppressing the differentiation of 3T3-L1 adipocytes in a dose-dependent manner. Moreover, after an oral administration for 8 weeks in HFD-induced obese mice, uRCB (10 and 50 mg/kg/day) produced a significant decrease in body weight, food efficiency ratio, adipose tissue weight and LDL-cholesterol, serum glucose, TC, and TG levels. Similarly, uRCB significantly suppressed the elevated mRNA levels of PPARγ in the adipose tissue in vivo. Next, we investigated the antiobesity effects of ellagic acid, erycibelline, 5-hydroxy-2-pyridinemethanol, m-hydroxyphenylglycine, and 4-hydroxycoumarin isolated from uRCB. Without affecting cell viability, five bioactive compounds decreased the lipid accumulation in the 3T3-L1 cells and the mRNA expression levels of key adipogenic genes such as PPARγ, C/EBPα, SREBP-1c, ACC, and FAS. Conclusion. These results suggest that uRC and its five bioactive compounds may be a useful therapeutic agent for body weight control by downregulating adipogenesis and lipogenesis.

19.
Int J Mol Med ; 35(4): 1109-18, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25672970

RESUMEN

Several recent studies have reported an association between neurodegeneration and histone modifications, such as acetylation, deacetylation and methylation. In addition, questions have been raised regarding a potential functional role for the histone acetylation enzymes in ß-amyloid (Aß)-mediated neurotoxicity, particularly the p300/CBP-associated factor (PCAF) enzyme. We recently reported the potential utility of a PCAF inhibitor in the suppression of Aß-induced neuronal cell death, although the in vivo effectiveness of the PCAF inhibitor remained unclear. In this study, we modified the PCAF inhibitor by chemical derivatization and selected compound C-30-27 as the most potent PCAF inhibitor. We demonstrated that C-30-27 selectively inhibited acetylation-dependent nuclear factor-κB (NF-κB) at Lys-122 and suppressed the NF-κB-mediated inflammatory response induced by lipopolysaccharide (LPS) or Aß in both BV2 and Neuro-2A (N2A) cells. Finally, we demonstrated that C-30-27 improved cognitive deficits, as well as the capacity for locomotion and the damaged cholinergic system in the Aß-treated rats. In conclusion, our results demonstrate that this selective PCAF inhibitor has the potential to reduce the neuroinflammatory response induced by Aß.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , FN-kappa B/metabolismo , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Acetilación/efectos de los fármacos , Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/psicología , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/química , Ratones , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas
20.
Mediators Inflamm ; 2014: 406514, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24948847

RESUMEN

Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF- κ B-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF- κ B transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF- κ B activation and IL-8 production in both TLR5- and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.


Asunto(s)
Adyuvantes Inmunológicos/química , Transducción de Señal , Acetato de Tetradecanoilforbol/química , Receptores Toll-Like/metabolismo , Animales , Células CACO-2 , Núcleo Celular/metabolismo , Croton/química , Citosol/metabolismo , Flagelina/química , Células HEK293 , Humanos , Interleucina-8/metabolismo , Ligandos , Linfocitos/citología , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Extractos Vegetales/química , Bazo/citología , Linfocitos T/inmunología , Receptor Toll-Like 5/metabolismo , Activación Transcripcional , Vacunas
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