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1.
Plants (Basel) ; 13(1)2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38202401

RESUMEN

Daucus carota L., a member of the Apiaceae family, comprises 13 subspecies, with one being cultivated (D. carota L. ssp. sativus (Hoffm.) Arcang.) and the remaining being wild. Traditionally, the wild carrot has been recognized for its antilithic, diuretic, carminative, antiseptic, and anti-inflammatory properties and has been employed in the treatment of urinary calculus, cystitis, gout, prostatitis, and cancer. While extensive literature is available on the phytochemical, pharmacological, and therapeutic evaluations of the cultivated carrot, limited information has been published on the wild carrot. A thorough search was conducted on the phytochemical composition, folk-medicine uses, and pharmacological properties of wild carrot subspecies (Daucus carota L. ssp. carota). Various electronic databases were consulted, and the literature spanning from 1927 to early 2023 was reviewed. Thirteen wild Daucus carota subspecies were analyzed, revealing over 310 compounds, including terpenoids, phenylpropenoids, flavonoids, and phenolic acids, with 40 constituting more than 3% of the composition. This review also highlights the antioxidant, anticancer, antipyretic, analgesic, antibacterial, antifungal, hypolipidemic, and hepato- and gastroprotective properties of wild carrot subspecies. Existing in vitro and in vivo studies support their traditional uses in treating infections, inflammation, and cancer. However, further research on other subspecies is required to confirm additional applications. Well-designed preclinical and clinical trials are still necessary to establish the safety and efficacy of wild Daucus carota for human use.

2.
J Photochem Photobiol B ; 224: 112324, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34619435

RESUMEN

Visible light has long been recognized as a treatment for many diseases and an essential component of photo-induced chemotherapy. While previous data proved its inherent cytotoxicity, this study is the first to explore the use of a commercially available, high-intensity white LED light (24.5 mW.cm-2) as a treatment for skin tumors. After a 9-h exposure in vitro, the viability of Human Malignant Melanoma cells (A375) decreased by around 70%. Western blot analysis suggested an apoptotic cell death confirmed by the upregulation of Bax, cleaved PARP/caspase-3/8, cytochrome c, and t-bid. Additionally, cellular ROS accumulation and DNA damage were induced upon irradiation with blue light. When tested on a DMBA/TPA skin carcinogenesis model, a 90-min exposure to white light thrice weekly resulted in a significant decrease in tumor volumes/incidence compared to control and cisplatin groups, and restored normal morphological features, as confirmed by histopathology. Toxicological evaluation of ight-treated animals indicated a 100% survival rate, no skin irritation, no signs of discomfort or changes in body weight/behavior, and no toxicities to vital organs. Although these results must be confirmed by further studies, this research showed that short-exposure by commercially available high-intensity white LED light irradiation may be a promising approach for the treatment of superficial malignancies.


Asunto(s)
Luz , Fototerapia/métodos , Neoplasias Cutáneas/terapia , Animales , Apoptosis/efectos de la radiación , Western Blotting , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología
3.
J Ethnopharmacol ; 270: 113743, 2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33359187

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders. AIM OF THE STUDY: The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon. MATERIALS AND METHODS: Dried Cannabis flowers were extracted with ethanol without any purification procedures to simulate the extracts sold by underground dealers in Lebanon. GC/MS was performed to identify chemical components of the cannabis oil extract (COE). In vivo anti-inflammatory effect of COE was evaluated by using carageenan- and formalin-induced paw edema rat models. TNF-α production were determined by using LPS-activated rat monocytes. Anti-inflammatory markers were quantified using Western blot. RESULTS: Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, ß-Myrecene and D-Limonene) and sesquiterpenes (ß-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model. CONCLUSION: The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Cannabis/química , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/química , Carragenina/toxicidad , Modelos Animales de Enfermedad , Edema/sangre , Edema/inducido químicamente , Edema/patología , Flores/química , Formaldehído/toxicidad , Inflamación/sangre , Inflamación/inducido químicamente , Inflamación/patología , Líbano , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/química , Cultivo Primario de Células , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
4.
J Ethnopharmacol ; 253: 112545, 2020 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-31918014

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus libani A. Rich (C. libani) is majestic evergreen Mediterranean conifer growing in the mountains of Lebanon. The ethnobotanical and traditional uses of cedar wood oil traces back to ancient times for the treatment of various ailments including cancer. Previous work in our laboratories revealed that himachalol (7-HC), a major sesquiterpene isolated from C. libani, possesses potent cytotoxic activity against various human cancer cell lines as well as promising anti-inflammatory effect in isolated rat monocytes. AIM OF THE STUDY: The present study aims to elucidate the mechanism of action behind the cytotoxic activity of 7-HC against murine melanoma cells (B16F-10) and evaluates its chemopreventive effect against chemically-induced skin carcinogenesis in mice. MATERIALS AND METHODS: 7-HC was extracted and purified from Cedrus libani wood. Cell viability was evaluated using WST-1 kit. Cell cycle analysis and apoptosis were assessed by Flow cytometry using propidium iodide (PI) and fluorescein Isothiocyanate (FITC)-conjugated Annexin V/PI staining respectively. Apoptosis related protein were quantified using western blot. The chemopreventive activity of 7-HC was evaluated for 20 weeks using a DMBA/TPA induced skin carcinogenesis model in Balb/c mice. RESULTS: 7-HC displayed a potent anti-proliferative activity against the melanoma cells with an IC50 of 8.8 µg/ml and 7.3 µg/ml at 24 and 48 h, respectively. Co-treatment with Cisplatin did not show any synergistic or additive effect on cell viability. Flow cytometry analysis using PI revealed that 7-HC treatment (5 and 10 µg/ml) induces the accumulation of cells in the sub-G1 phase and causes a decline in cell populations in the S and G2/M phases. Annexin/PI staining also reveals that 7-HC treatment significantly increases the percentage of cells undergoing early and late apoptosis. Western blot analysis shows that 7-HC treatment decreases the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic protein Bax. A reduction in the level of phosphorylated Erk and Akt was also observed. 7-HC via topical (2.5%), intraperitoneal (10, 25 and 50 mg/kg) or gavage (50 mg/kg) treatment revealed a significant decrease in papilloma volume with no adverse effect on liver and kidney function. CONCLUSIONS: The present study demonstrates that 7-HC treatment protects against chemically-induced skin carcinogenesis, promotes cell cycle arrest and induces apoptosis partially through an inhibition of both the MAPK/Erk and PI3K/Akt pathways.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Benzocicloheptenos/farmacología , Melanoma Experimental/tratamiento farmacológico , Sesquiterpenos Policíclicos/farmacología , Neoplasias Cutáneas/prevención & control , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Benzocicloheptenos/administración & dosificación , Benzocicloheptenos/aislamiento & purificación , Cedrus/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Concentración 50 Inhibidora , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Fosfatidilinositol 3-Quinasa/metabolismo , Sesquiterpenos Policíclicos/administración & dosificación , Sesquiterpenos Policíclicos/aislamiento & purificación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Tiempo
5.
Sci Rep ; 9(1): 12855, 2019 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-31492934

RESUMEN

Cedrus libani is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce C. libani oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC50 8.1 µg/mL) and colon (HT-29, IC50 10.1 µg/mL; Caco-2, IC50 9.9 µg/mL) with ovarian (Sk-OV-3, IC50 > 50 µg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8-10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Cedrus/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Antineoplásicos Fitogénicos/química , Células CACO-2 , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Edema/prevención & control , Células HT29 , Miembro Posterior/efectos de los fármacos , Miembro Posterior/patología , Humanos , Masculino , Estructura Molecular , Extractos Vegetales/química , Ratas Sprague-Dawley
6.
Biomed Pharmacother ; 103: 443-452, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29674280

RESUMEN

ß-2-himachalen-6-ol (HC), a novel sesquiterpene derived from Lebanese wild carrot, was shown to possess a remarkable anticancer activity. The present study investigates the in vitro anticancer activity of HC and its effect on papillomas induced using a DMBA/TPA skin carcinogenesis mouse model. HaCaT-ras II-4 epidermal squamous cell viability was assessed using WST-1 kit. Cell cycle was analyzed by flow cytometry, and pro/anti-apoptotic proteins were measured using western blot. Mice papillomas were induced by DMBA and promoted with TPA for 18 weeks. At week 12, animals were divided into four groups: HC topically treated (5%Top), HC intraperitoneally treated (25 mg/kg; HC25), Cisplatin treated (2.5 mg/kg), and control (DMSO treated). Papilloma yield, volume, histology, and mice weight and liver function were assessed. HC treatment decreased significantly cell survival (IC50 = 7 and IC90 = 40 µg/ml) and increased significantly cells undergoing late apoptosis and necrosis. It also significantly decreased the levels of pro-caspase-3, p53, Bcl-2, p-Erk/Erk and p-Akt/Akt and increased p21 and Bax proteins. Treatment with HC25, HC5%Top or Cisplatin showed a significant decrease in papilloma yield and volume. Only Cisplatin treatment caused a significant decrease in body weight and increase in serum ALT. In conclusion, ß-2-himachalen-6-ol induced significant tumor shrinkage, an effect partly mediated via promoting apoptosis through inhibition of the MAPK/ERK and PI3K/AKT pathways, with no significant toxicity to laboratory mice.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Carcinogénesis/efectos de los fármacos , Sesquiterpenos/uso terapéutico , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Antineoplásicos Fitogénicos/farmacología , Carcinogénesis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Endogámicos BALB C , Sesquiterpenos/farmacología , Neoplasias Cutáneas/metabolismo , Resultado del Tratamiento
7.
Chem Biol Interact ; 275: 162-170, 2017 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-28782499

RESUMEN

Previous studies in our laboratory showed that Daucus carota oil extract (DCOE) possesses in vitro and in vivo anticancer activities. Chemical analysis of DCOE led to the isolation of ß-2-himachalen-6-ol (HC) which exhibited potent anticancer activity against colon, breast, brain and skin cancer cells. The present study investigates the anticancer activity of HC against SW1116 colon cancer cell lines, and evaluates its effect in a 1,2-dimethylhydrazine (DMH) colon carcinogenesis black6 mice model. The SW1116 colon cancer cell line was treated with HC (1, 5, 10 and 25 µg/ml) and cell viability was evaluated with WST 1 assay kit. Cell cycle analysis was carried out by flow cytometry, and pro/anti-apoptotic proteins were measured using western blot. The effect of intraperitoneal (IP) treatment with HC (10, 25 and 50 µg/ml) in mice was assessed using the DMH colon carcinogenesis model with Cisplatin (2.5 µg/kg; IP) as a positive control. Blood samples were collected for assessment of liver toxicity and colon tumor incidence and size were studied histologically. HC showed a dose-dependent decrease in cell survival with an IC50 of 18 and 14.5 µg/ml after 24 and 48 h respectively. Flow cytometry analysis revealed that 10 µg/ml HC increased the number of cells undergoing necrosis (18.05%) and late apoptosis (15.66%). At HC 25 µg/ml more cells shifted toward necrosis (58.01%) and late apoptosis (30.47%). Western blot analysis revealed a significant decrease in p-Erk, p-Akt, pro-caspase-3 and Bcl-2 and an increase in p53, p21, Bax and PARP proteins. Mice treatment (IP) with HC caused a significant decrease in tumor incidence and size. Similar effects were observed with cisplatin treatment. In conclusion, HC treatment (low dose) induced cell cycle arrest and promoted apoptosis via inhibition of the MAPK/ERK and PI3K/AKT pathways. HC treatment also had antitumor effect in vivo with no significant toxicity to laboratory mice.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Sesquiterpenos/toxicidad , Transducción de Señal/efectos de los fármacos , 1,2-Dimetilhidrazina , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Daucus carota/química , Daucus carota/metabolismo , Activación Enzimática/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sesquiterpenos/química , Sesquiterpenos/uso terapéutico
9.
BMC Complement Altern Med ; 17(1): 36, 2017 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-28073348

RESUMEN

BACKGROUND: Previous studies in our laboratory showed that the Lebanese Daucus carota ssp. carota (wild carrot) oil extract possesses in vitro and in vivo anticancer activities. The present study aims to examine the cytotoxic effect of Daucus carota oil fractions on human epidermal keratinocytes and evaluate the chemopreventive activity of the pentane diethyl ether fraction on DMBA/TPA induced skin carcinogenesis in mice. METHODS: Wild carrot oil extract was chromatographed to yield four fractions (F1, 100% pentane; F2, 50:50 pentane:diethyl ether; F3, 100% diethyl ether; F4 93:7 chloroform:methanol). The cytotoxic effect of fractions (10, 25, 50 and 100 µg/mL) was tested on human epidermal keratinocytes (non-tumorigenic HaCaT cells and tumorigenic HaCaT-ras variants) using WST a ssay. Cell cycle phase distribution of tumorigenic HaCaT-ras variants was determined by flow cytometry post-treatment with F2 fraction. Apoptosis related proteins were also assessed using western blot. The antitumor activity of F2 fraction was also evaluated using a DMBA/TPA induced skin carcinoma in Balb/c mice. RESULTS: All fractions exhibited significant cytotoxicity, with HaCaT cells being 2.4-3 times less sensitive than HaCaT-ras A5 (benign tumorigenic), and HaCaT-ras II4 (malignant) cells. GC-MS analysis revealed the presence of a major compound (around 60%) in the pentane/diethylether fraction (F2), identified as 2-himachalen-6-ol. Treatment of HaCaT-ras A5 and HaCaT-ras II4 cells with F2 fraction resulted in the accumulation of cells in the sub-G1 apoptotic phase and decreased the population of cells in the S and G2/M phases. Additionally, F2 fraction treatment caused an up-regulation of the expression of pro-apoptotic (Bax) and down-regulation of the expression of anti-apoptotic (Bcl2) proteins. A decrease in the phosphorylation of AKT and ERK was also observed. Intraperitoneal treatment with F2 fraction (50 or 200 mg/kg) in the DMBA/TPA skin carcinogenesis mouse model showed a significant inhibition of papilloma incidence (mice with papilloma), yield (number of papilloma/mouse) and volume (tumor relative size) at weeks 15, 18 and 21. CONCLUSION: The present data reveal that F2 fraction has a remarkable antitumor activity against DMBA/TPA-induced skin carcinogenesis, an effect that may be mediated through inhibition of the MAPK/ERK and PI3K/AKT pathways.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Daucus carota/química , Queratinocitos/citología , Sustancias Protectoras/administración & dosificación , Neoplasias Cutáneas/prevención & control , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Apoptosis/efectos de los fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Fase G1/efectos de los fármacos , Humanos , Queratinocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/fisiopatología , Acetato de Tetradecanoilforbol/toxicidad , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
10.
J Ethnopharmacol ; 190: 59-67, 2016 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-27240746

RESUMEN

Daucus carota ssp. carota, also known as wild carrot, is a commonly used herb in Lebanese folk medicine to treat several ailments including cancer. Previous studies in our laboratories showed that the Daucus carota oil extract (DCOE) and subsequent fractions exhibit antioxidant, anti-inflammatory and anti-cancer activities. In this study, we report the isolation and identification of the major compound responsible for the anti-cancer activity of DCOE along with the mechanism of action involved. GC-MS and NMR spectroscopy revealed the identity of the major compound as ß-2-himachalen-6-ol, a novel sesquiterpene unique to the Lebanese wild carrot. ß-2-Himachalen-6-ol demonstrated potent anti-cancer activity against B16F-10, Caco-2, MB-MDA-231, A549 and SF-268 cancer cells (IC50 13-4µg/ml; 58-18µM), with SF-268 cells being the most sensitive. The sesquiterpene was shown to induce cell death through apoptosis (flow cytometry), decrease 2D cell motility (wound healing assay) and 3D invasion, as well as increase cell adhesion in SF-268 cells. Additionally, ß-2-himachalen-6-ol showed very low toxicity in mice with an LD50>6000mg/kg body weight. In conclusion, the present data demonstrate that ß-2-himachalen-6-ol is a potential multi-mechanistic chemotherapeutic drug with high potency and safety.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Daucus carota/química , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Apoptosis/efectos de los fármacos , Células CACO-2 , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Humanos , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Invasividad Neoplásica , Neoplasias/patología , Fosforilación , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/toxicidad , Transducción de Señal/efectos de los fármacos , Factores de Tiempo
11.
BMC Complement Altern Med ; 15: 384, 2015 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-26497894

RESUMEN

BACKGROUND: Salvia libanotica (S. Libanotica) is a commonly used herb in folk medicine in Lebanon and the Middle East. The present study aimed to assess the scientific basis for the therapeutic use of S. libanotica in glycemia and to evaluate its effects on lipemia and abdominal fat. METHODS: Animals were fed a high-fat diet and allocated into a control and three experimental groups (GI, GII and GIII) receiving incremental doses of the plant water extract in drinking water (50, 150 and 450 mg/Kg body weight respectively) for six weeks. RESULTS: The intake of S. libanotica extract was associated with a significant decrease in fasting serum glucose (102.9 ± 10.8 in GII and 87.5 ± 6.4 in GIII vs. 152.1 ± 7.9 mg/dl in controls) and a two fold increase in fasting serum insulin (GIII) and liver glycogen content (GII and GIII). Group III also had better glucose tolerance following intraperitoneal glucose challenges. Additionally, the plant extract intake produced a significant improvement in serum HDL (34.4 ± 2.4 in GIII vs. 27.2 ± 1.9 mg/dl in controls) and HDL/LDL cholesterol ratio (2.79 ± 0.32 in GII and 3.02 ± 0.31 in GIII vs. 1.74 ± 0.18 in controls), as well as a decrease in abdominal fat. CONCLUSION: The current study is the first to demonstrate that the chronic intake of S. libanotica infusion helps in the prevention of high fat-induced hyperglycemia and dyslipidemia. This supports the plant use as a remedy for the prevention of type 2 diabetes and cardiovascular diseases.


Asunto(s)
Glucemia/efectos de los fármacos , Lípidos/sangre , Extractos Vegetales/farmacología , Salvia , Grasa Abdominal/efectos de los fármacos , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Prueba de Tolerancia a la Glucosa , Glucógeno/metabolismo , Insulina/sangre , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley
12.
Pharm Biol ; 53(9): 1285-94, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25856705

RESUMEN

CONTEXT: Wild carrot, Daucus carota L. ssp. carota (Apiacae), is widely distributed throughout the world and has various uses in traditional medicine in Lebanon. OBJECTIVE: The present study aimed to fractionate and analyze the chemical composition of the Daucus carota oil extract (DCOE) fractions and to evaluate their antioxidant and hepatoprotective properties in vitro and in vivo. MATERIALS AND METHODS: DCOE was chromatographed on silica gel column to produce four fractions: pentane (F1), 50:50 pentane:diethyl ether (F2), diethyl ether (F3), and 93:7 chloroform: methanol (F4). Qualitative and quantitative analyses of oil fractions were performed by GC-MS and HPLC techniques. The in vitro antioxidant properties were assessed using DPPH, FIC, and ferric-reducing antioxidant power (FRAP) assays. The hepatoprotective property was determined by examining the levels of serum markers (alanine transaminase (ALT) and aspartate transaminase (AST)) and hepatic antioxidant (superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST)) enzymes in CCl4-intoxicated mice pretreated with intraperitoenal 50, 100, or 200 mg/kg b.w. of the oil fractions for 5 d. RESULTS: GCMS analysis of F2 revealed the presence of 2-himachalen-6-ol (61.4%) which is reported for the first time in Daucus carota species. F3 and F4 were rich in phenolics and flavonoids and demonstrated significant DPPH activity (IC50 = 0.29 and 0.38 mg/ml, respectively) and high FRAP values (225.11 and 437.59 µmol FeSO4/g, respectively). The sesquiterpene-rich fraction F1 had the highest FIC ability (IC50 = 0.28 mg/ml). Pretreatment with F1 and F4 reversed the CCl4-induced decrease in SOD, CAT, and GST levels and reduced significantly hepatic damage. DISCUSSION AND CONCLUSION: The current results suggested that wild carrot oil fractions exhibited a unique chemical composition and possessed significant antioxidant activities as well as hepatoprotective effects against CCl4-induced hepatotoxicity.


Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Daucus carota , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Biomarcadores/sangre , Compuestos de Bifenilo/química , Tetracloruro de Carbono , Fraccionamiento Químico , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cromatografía Líquida de Alta Presión , Citoprotección , Daucus carota/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Enzimas/sangre , Cromatografía de Gases y Espectrometría de Masas , Hígado/enzimología , Hígado/patología , Ratones Endogámicos BALB C , Oxidación-Reducción , Fitoterapia , Picratos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Aceites de Plantas/química , Aceites de Plantas/aislamiento & purificación , Plantas Medicinales
13.
Asian Pac J Cancer Prev ; 16(2): 761-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25684522

RESUMEN

BACKGROUND: In this study, we used Daucus carota oil extract (DCOE) to target acute myeloid leukemia (AML) cells. All the AML cell lines tested were sensitive to the extract while peripheral mononuclear cells were not. Analysis of mechanism of cell death showed an increase in cells positive for annexinV and for active caspases, indicating that DCOE induces apoptotic cell death in AML. Inhibition of the MAPK pathway decreased sensitivity of AML cells to DCOE, indicating that cytotoxicity may be dependent on its activity. In conclusion, DCOE induces selective apoptosis in AML cells, possibly through a MAPK-dependent mechanism.


Asunto(s)
Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Daucus carota/química , Leucemia Mieloide Aguda/tratamiento farmacológico , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Western Blotting , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Células Tumorales Cultivadas
14.
Artículo en Inglés | MEDLINE | ID: mdl-25694787

RESUMEN

Tragopogon porrifolius (Asteraceae), commonly referred to as white salsify, is an edible herb used in Lebanese folk medicine to treat cancer and liver dysfunction. In this study, we investigated the antioxidant activity of Tragopogon porrifolius methanolic extract, both in vitro and in vivo, in addition to its hepatoprotective and anticancer activities. Total phenolic and flavonoid contents were measured and found to be 37.0 ± 1.40 mg GAE/g and 16.6 ± 0.42 mg QE/g dry weight, respectively. In vitro antioxidant assays revealed an FRAP value of 659 ± 13.8 µmol Fe(2+)/g of extract and DPPH IC50 value 15.2 µg/mL. In rats subjected to CCl4-induced hepatotoxicity, significant increase in CAT, SOD, and GST levels was detected. The highest dose of the extract (250 mg/kg) recorded a fold increase of 1.68 for SOD, 2.49 for GST, and 3.2 for CAT. The extract also showed substantial decrease in AST (57%), ALT (56%), and LDH (65%) levels. Additionally, the extract caused a dose-dependent decrease in cell viability and proliferation. In conclusion, the methanolic extract of T. porrifolius displayed a relatively high antioxidant activity both in vitro and in vivo as well as hepatoprotective potential against liver toxicity in rats and anticancer effect on MDA-MB-231 and Caco-2 cells.

15.
J Med Food ; 18(7): 745-52, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25599142

RESUMEN

Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been used in folk medicine throughout the world and recently was shown to possess anticancer and antioxidant activities. This study aims to determine the anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell proliferation. Flow cytometric analysis indicated that both fractions induced sub-G1 phase accumulation and increased apoptotic cell death. Western blot revealed the activation of caspase-3, PARP cleavage, and a considerable increase in Bax and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with either fraction markedly decreased the levels of both phosphorylated Erk and Akt. Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added inhibition of cell survival suggesting an effect of F1 or F2 through the phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest and apoptosis in HT-29 cells through the suppression of mitogen-activated protein kinase (MAPK)/Erk and PI3K/Akt pathways.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias del Colon/patología , Daucus carota/química , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Pentanos/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Adenocarcinoma/patología , Apoptosis/efectos de los fármacos , Células CACO-2 , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/enzimología , Quinasas MAP Reguladas por Señal Extracelular/análisis , Fase G1/efectos de los fármacos , Células HT29 , Humanos , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/análisis
16.
BMC Complement Altern Med ; 14: 387, 2014 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-25300932

RESUMEN

BACKGROUND: Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. METHODS AND RESULTS: Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest cytotoxicity against both cell lines. Flow cytometric analysis revealed that both fractions induced the accumulation of cells in the sub-G1 phase, increase in apoptotic cell death and chromatin condensation. The increase in apoptosis in response to treatment was also apparent in the increase in BAX and the decrease in Bcl-2 levels as well as the proteolytic cleavage of both caspase-3 and PARP as revealed by Western blot. Furthermore, treatment of MDA-MB-231 cells with either fraction significantly reduced the level of phosphorylated Erk but did not show any effect on phosphorylated Akt. The combined treatment with a potent PI3K inhibitor (wortmannin) and F1 or F2 fraction had a synergistic inhibitory effect on cell survival which shows that these two drugs work on different pathways. CONCLUSIONS: These results suggest that the pentane-based fractions of DCOE possess potential anti-cancer activity that is mainly mediated through the Erk pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/fisiopatología , Ciclo Celular/efectos de los fármacos , Daucus carota/química , Extractos Vegetales/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Pentanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo
17.
Appetite ; 72: 1-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24099703

RESUMEN

Tragopogon porrifolius (white salsify) is an edible plant commonly used in folk medicine in Lebanon and neighbouring countries. This study investigates the effect of the aqueous extract of the aerial part of T. porrifolius on lipemia and appetite regulation using a rat model. Food intake, abdominal fat percentage, blood lipid profile, liver weight and liver enzymes were assessed following 4 weeks of extract intake via drinking water (50, 100, or 250 mg/kg body weight) in standard high-carbohydrate and high-fat dietary conditions. In a separate study, the short term effect of a preload of T. porrifolius extract on food intake was evaluated. Results showed that consumption of the plant extract for a period of four weeks resulted in a marked improvement of the lipid profile (triglycerides, total cholesterol, LDL and HDL cholesterol). Body weight, food intake and intra-abdominal fat were also lower in animals given the plant extract (100 and 250 mg/kg). In addition, T. porrifolius extract preload produced a dose dependent decrease in food intake observed over 24h. The intake of T. porrifolius aqueous extract therefore improved lipemia and increased satiety in rats with no visible adverse effects.


Asunto(s)
Apetito/efectos de los fármacos , Ingestión de Energía/efectos de los fármacos , Hiperlipidemias/tratamiento farmacológico , Lípidos/sangre , Fitoterapia , Respuesta de Saciedad/efectos de los fármacos , Tragopogon , Grasa Abdominal/metabolismo , Animales , Regulación del Apetito/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Dieta Alta en Grasa , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Hiperlipidemias/sangre , Hiperlipidemias/etiología , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Saciedad/efectos de los fármacos , Triglicéridos/sangre
18.
Chemotherapy ; 60(5-6): 302-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26088465

RESUMEN

Daucus carota (DC) is a herb used in folklore medicine in Lebanon to treat numerous diseases including cancer. Recent studies in our laboratory on DC oil and its fractions revealed potent anticancer activities in vitro and in vivo. The present study aims to investigate the effect of the most potent DC fraction, pentane/diethyl ether (50:50), on lung, skin, breast and glioblastoma cancer cell motility and invasion. Upon treatment, a pronounced decrease in cancer cell motility was observed in the 4 cell lines. The treatment also led to a decrease in cancer cell invasion and an increased cell adhesion. Additionally, the DC fraction caused a decrease in the activation of the ρ-GTPases Rac and CDC42, a finding that may partially explain the treatment-induced decrease in cell motility. The current study demonstrates a crucial effect of the DC pentane/diethyl ether fraction on cancer cell motility and metastasis, making it a potential candidate for cancer therapy specifically targeting cancer motility and metastasis.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Daucus carota , Éter/uso terapéutico , Invasividad Neoplásica/prevención & control , Pentanos/uso terapéutico , Extractos Vegetales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Éter/aislamiento & purificación , Éter/farmacología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Melanoma Experimental , Invasividad Neoplásica/patología , Pentanos/aislamiento & purificación , Pentanos/farmacología , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología
19.
Phytother Res ; 27(5): 737-44, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22815230

RESUMEN

Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone-methanol. The oil extract was analyzed by gas chromatography-mass spectrometry and screened for its antioxidant properties in vitro using 1,1-diphenyl-2-picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST-1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 µmol FeSO4 /g, and the IC50 values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose-dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Daucus carota/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/química , Antioxidantes/química , Muerte Celular , Línea Celular Tumoral , Proliferación Celular , Flavonoides/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Fenoles/análisis , Extractos Vegetales/química
20.
Pharm Biol ; 49(9): 955-61, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21777042

RESUMEN

CONTEXT: Daucus carota L. ssp. carota (Apiacea) is widely distributed throughout the world and has many uses in traditional medicine. OBJECTIVE: The present study investigates the chemopreventive effects of oil extract of D. carota umbels on 7,12-dimethyl benz(a)anthracene (DMBA)-induced skin cancer in mice. MATERIALS AND METHODS: D. carota oil extract (DCOE) was prepared by extracting the dried umbels with 50:50 acetone:methanol. Skin papilloma were initiated by DMBA and promoted by 12-O-tetradecanoyl phorobol-13-acetate (TPA). The extract was administered to animals via gavage (0.02 mL of 100% oil), intraperitoneal (0.3 mL of 2% oil), and topical (0.2 mL of 5, 50, and 100% oil) routes for 20 weeks. Tumor appearance, incidence, yield, and volume were compared with those of a non-treated control group. RESULTS: Topical 100% treatment delayed tumor appearance, and inhibited tumor incidence and yield by 40 and 89%, respectively. Topical 50% treatment inhibited tumor incidence and yield by 30 and 83%, respectively, whereas the 5% treatment inhibited tumor yield by 36%. Tumor volume was decreased by 99, 91, and 70% following topical treatments with 100, 50, and 5% oil, respectively. Intraperitoneal treatment inhibited tumor yield by 43%, and decreased tumor volume by 85%, whereas gavage treatment showed minimal effects on both. Intraperitoneal and topical treatment decreased infiltration and hyperplasia with an increase in the level of hyperkeratosis. CONCLUSION: These findings demonstrate that DCOE has remarkable antitumor activity against DMBA-induced skin cancer compared with non-treated animals paving the ground for further investigations.


Asunto(s)
Anticarcinógenos/farmacología , Carcinoma de Células Escamosas/prevención & control , Daucus carota/química , Papiloma/prevención & control , Extractos Vegetales/farmacología , Neoplasias Cutáneas/prevención & control , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Anticarcinógenos/química , Carcinógenos/toxicidad , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/patología , Quimioprevención/métodos , Flores , Ratones , Ratones Endogámicos BALB C , Aceites/química , Aceites/farmacología , Papiloma/inducido químicamente , Papiloma/patología , Fitoterapia , Extractos Vegetales/toxicidad , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Carga Tumoral/efectos de los fármacos
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