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1.
Int J Pharm ; 650: 123722, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38110012

RESUMEN

Chronic wounds have become a serious global health issue. In this study, we investigated the effect of increasing fucoidan (FD) concentration on the characteristics of nanofibers and their wound healing potential at in vitro as well as in vivo level. The results showed that increasing FD content (0.25 to 1 %) led to an significant increase in nanofiber diameter (487.7 ± 125.39 to 627.9 ± 149.78 nm), entrapment efficiency (64.26 ± 2.6 to 94.9 ± 3.1 %), and water uptake abilities (436.5 ± 1.2 to 679.7 ± 11.3 %). However, the in vitro biodegradation profile decreased with an increase in FD concentration. Water vapor transmission rate analysis showed that it was within the standard range for all FD concentrations. Nanofibers with 1 % PVA/DX/FD exhibited slow-release behavior, suggesting prolonged FD availability at the wound site. In vivo studies in rats with full-thickness wounds demonstrated that applying 1 % FD-enriched PVA/DEX nanofibers significantly (p < 0.0001) improved mean wound area closure. These findings suggest that FD-enriched nanofibers have immense potential as a wound dressing material in future if explored further.


Asunto(s)
Antibacterianos , Nanofibras , Ratas , Animales , Antibacterianos/farmacología , Dextranos/farmacología , Alcohol Polivinílico , Cicatrización de Heridas
2.
J Tradit Complement Med ; 10(1): 60-69, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31956559

RESUMEN

BACKGROUND AND AIM: Luteolin belongs to flavone group of flavonoids, present in many plants with potent antioxidant, anti-inflammatory and anti-proliferative effects. The objective of present study was to investigate protective effect of luteolin on injury induced inflammation via Monosodium urate (MSU) crystals induced and Acetaminophen (AMP) induced liver injury in rats. EXPERIMENTAL PROCEDURE: Protective effect of luteolin was observed by measurement of rat paw edema, lysosomal enzymes, antioxidants status and cytokine level. Measurement of uric acid level and neutrophil infiltration were done in AMP induced liver injury in rats. Luteolin was tested at 30 and 50 mg/kg doses and compare with colchicine. RESULTS AND CONCLUSION: Luteolin significantly decreases paw edema in dose dependent manner compare to control group in MSU crystal-induced rats. Luteolin (50 mg/kg) was showed significant decrease in serum level of oxidative and lysosomal enzymes, proinflammatory cytokines i.e. tumor necrosis factor (TNF)-α (39.28 ±â€¯3.17), interleukin (IL)-1ß (12.07 ±â€¯1.24), and IL-6 (24.72 ±â€¯2.52) in MSU crystal-induced rats. In AMP induced liver injury, tissue uric acid level and myeloperoxidase were decreased significantly after treatment with luteolin as well as N-acetylcysteine. Serum level of liver enzymes was significantly reduced after treatment with luteolin. Histological observation of ankle joints and liver was support to protective effect of luteolin at both doses. In conclusion, luteolin showed anti-inflammatory effect through restoration of cytokine level, lysosomal enzymes level and antioxidants status. The reduction of liver tissue uric acid content may be one of the mechanisms for protective effect of luteolin. It can contribute to reduce injury induced inflammation.

3.
Pak J Pharm Sci ; 31(4): 1355-1361, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30033420

RESUMEN

Current study aims to evaluate the wound healing effect with apparent mechanism and determination of flavonoid (quercetin) from ethanol extract of Ipomea carnea jacq. leaves, family Convolvulaceae. The wound healing effect of ethanol extract from I. carnea jacq. leaves screened by excision and incision wound methods in rats. Five groups (Negative control, vehicle control, 2.5%w/w, 5% w/w ethanol extract ointment and 5%w/w Reference Ointment Povidone-iodine group) of rats (n-6) were experimentally wounded at dorsal portion of rats. The 5% w/w ointment of ethanol extract found significant wound contraction at 18-20th days, greater tensile strength, and biochemical parameters. Ethyl acetate fraction of ethanolic extract was analysed by RP-HPLC and retention time was found 3.042 min. The percentage of quercetin was found in I. carnea leaves as 0.842%. The results were supported by histopathological studies which showed augment in terms of collagen fibers, fibroblast and new blood vessels. The results were evidently exhibited the traditional uses of I. carnea leaves for wound healing effects. The healing effect may be attributed by presence of flavonoid and other compounds present in the leaves with free radical scavenging mechanism.


Asunto(s)
Modelos Animales de Enfermedad , Ipomoea/química , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Piel/lesiones , Cicatrización de Heridas/efectos de los fármacos , Animales , Colágeno/metabolismo , Etanol , Femenino , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Masculino , Pomadas , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Ratas , Ratas Wistar , Piel/metabolismo , Piel/patología
4.
Avicenna J Phytomed ; 6(5): 578-591, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27761428

RESUMEN

OBJECTIVE: Martynia annua L. (M. annua), (Martyniaccae) has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea), (Fabaceae) has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M. annua leaves and aerial parts of T. purpurea. MATERIALS AND METHODS: Methanol fraction of M. annua (MAF-C) and ethyl acetate fraction of T. purpurea (TPF-A) were evaluated for healing potential in dead-space and burn wound models. An ointment (5% w/w) of MAF-C and TPF-A, pongamol (0.2 and 0.5% w/w) and luteolin (0.2 and 0.5% w/w) was applied topically twice a day. The effects were compared with Povidone Iodine ointment with respect to protein, collagen content, enzymatic assay and histopathological finding of granuloma tissues. RESULTS: Ethanol extracts of M. annua and T. purpureawere exhibited total flavonoid contents of 126.2 ± 4.69 and 171.6 ± 6.38 mg (quercetin equivalent), respectively. HPLC fingerprinting confirmed the presence of luteolin in M. annua and quercetin in T. purpurea. TPF-A and MAF-C ointments (5% w/w) significantly increases the hydroxyproline and protein contents. Luteolin and pongamol ointments were also found to be effective in both wound models. CONCLUSION: Our findings suggested that 5% w/w ointment of TPF-A and MAF-C fractions were more effective than isolated flavonoids in wound healing which may be due to synergistic interactions between the flavonoids and other constituents.

5.
J Ayurveda Integr Med ; 7(1): 14-22, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27297505

RESUMEN

BACKGROUND: Bambusa vulgaris (Family: Poaceae) used in Ayurveda for paralytic complaints, inflammatory disorders and externally to skin disorders. It has various medicinal uses with good nutritional composition and a rich source of vitamins, proteins, amino acid, beta-carotene and phenolic compounds. OBJECTIVE: The present study was aimed to evaluate wound healing and anti-inflammatory potential of ethanol extract of B. vulgaris leaves in rats. MATERIALS AND METHODS: The B. vulgaris leaves were evaluated for wound healing on incision and excision wound methods. Anti-inflammatory effect was evaluated by measurement of paw edema in carrageenan-induced inflammation in rats. Ethyl acetate (BVL-A) and aqueous (BVL-B) fractions from the ethanol extract of leaves were screened for wound healing effects by measuring tensile strength and biochemical parameters in incision wound method. The wound contraction area, antioxidant status and histopathological studies were done in excision wound method. RESULTS: Tensile strength and hydroxyproline level of 5% w/w ointment of BVL-A and BVL-B treated groups were found significantly (P < 0.01) higher and comparable to the reference group. The histopathological study showed the proliferation of collagen, fibrous tissue, and capillaries with epidermal covering at the margin of the wound. The percent inhibition of paw edema was significantly decrease by increasing concentration of BVL-A and BVL-B fractions. In addition, it was found that B. vulgaris possesses antioxidant properties, by its ability to increase antioxidants level. CONCLUSIONS: The results obtained in the present study were indicated that ethyl acetate fraction of B. vulgaris leaves inhibits paw edema and accelerates cutaneous wound healing.

6.
Int J Biol Macromol ; 91: 1110-9, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27344952

RESUMEN

The Apigenin (APN) was isolated from ethanolic extract of M. alba leaves and screened by in-vivo wound models (Diabetic and Dead space) in rats. Apigenin loaded hydrogel (HGs) was prepared using gellan gum-chitosan (GGCH) with PEG as a cross linker and characterized for various parameter like AFM, swelling property, entrapment efficiency and drug release. Further performance of hydrogel was evaluated by wound healing activity tested against wound contraction, collagen content, dried granuloma weights and antioxidant activity. The percent entrapment efficiency of optimized hydrogel found to be 87.15±1.20. APN loaded GGCH-HGs were able to release 96.11% APN in 24h. The level of superoxide dismutase (SOD) and catalase were found increased significantly in granuloma tissue of APN treated group. APN GGCH-HGs found higher wound healing effect in diabetic as well as normal wound tissues with significant antioxidant activity. Results proven the utility of prepared hydrogel (APN loaded GGCH-HGs) seems to be highly suitable for wound healing due to its unique properties of biocompatibility, biodegradability, moist nature and antioxidant effectiveness.


Asunto(s)
Apigenina/farmacología , Quitosano/química , Diabetes Mellitus/fisiopatología , Liberación de Fármacos , Hidrogeles/química , Polisacáridos Bacterianos/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Apigenina/química , Colágeno/metabolismo , Portadores de Fármacos/química , Femenino , Masculino , Hojas de la Planta/química , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Piel/metabolismo
7.
Int J Biol Macromol ; 87: 449-59, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26955748

RESUMEN

Aim of this research was to prepare hyaluronic acid-modified-cellulose acetate phthalate (HAC) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). HAC copolymer was synthesized and confirmed by fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. HAC NPs with 5-FU were prepared using HAC copolymer and compared with 5-FU loaded cellulose acetate phthalate (CAP) NPs. NPs were characterized by atomic force microscopy (AFM), particle size, zeta potential, polydispersity index, entrapment efficiency, in-vitro release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). HAC NPs were found slower release (97.30% in 48h) than (99.25% in 8h) CAP NPs. In cytotoxicity studies, showed great cytotoxic potential of 5-FU loaded HAC NPs in A549, MDA-MD-435 and SK-OV-3 cancer cellline. HAC NPs showing least hemolytic than CAP NPs and 5-FU. Area under curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and time to reach maximum plasma concentration Tmax), were observed 4398.1±7.90µgh/mL, 145.45±2.25µg/L, 45.74±0.25h, 72±0.50h, respectively of HAC NPs and 119.92±1.78µgh/mL, 46.38±3.42µg/L, 1.2±0.25h, 0.5±0.02h were observed in plain 5-FU solution. In conclusion, HAC NPs is effective deliver carrier of 5-FU for lung cancer.


Asunto(s)
Celulosa/análogos & derivados , Portadores de Fármacos/química , Fluorouracilo/química , Ácido Hialurónico/química , Nanopartículas/química , Adipatos/química , Animales , Línea Celular Tumoral , Celulosa/química , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Fluorouracilo/farmacocinética , Hemólisis/efectos de los fármacos , Humanos , Masculino , Tamaño de la Partícula , Ratas
8.
Drug Deliv ; 23(5): 1525-35, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25417834

RESUMEN

The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.


Asunto(s)
Celulosa/análogos & derivados , Dextranos/administración & dosificación , Fluorouracilo/administración & dosificación , Nanopartículas/química , Tensoactivos/administración & dosificación , Administración Cutánea , Celulosa/administración & dosificación , Celulosa/química , Dextranos/química , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Fluorouracilo/química , Humanos , Tensoactivos/química
9.
Asian Pac J Trop Med ; 6(4): 253-9, 2013 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-23608325

RESUMEN

OBJECTIVE: To evaluate wound healing potential of flavonoid fractions of Martynia annua (M. annua) Linn. leaves in diabetic rats on the basis of folkloric information and preliminary study. METHODS: The flavonoid compound luteolin and apigenin were isolated from dried leaves of plant by column chromatography. The two concentrations (0.2% and 0.5% w/w) of luteolin and flavonoid fraction were selected for topically applied as ointment on diabetic wound. The Povidone Iodine Ointment USP was used as a reference. On 18th days, protein content, hydroxyproline and antioxidants (SOD, CAT and GSH) level in granuloma tissues were determined. RESULTS: The results showed that, percent wound contraction were observed significantly (P<0.01) greater in MAF fraction and 0.5% w/w of luteolin treatment groups. Presence of matured collagen fibres and fibroblasts with better angiogenesis were observed in histopathological studies. CONCLUSIONS: In conclusion, our findings suggest that flavonoid fraction (MAF) and luteolin (0.5% w/w) may have potential benefit in enhancing wound healing in diabetic condition, possibly due to free-radical scavenging activity of plant.


Asunto(s)
Flavonoides/farmacología , Pedaliaceae , Fitoterapia/métodos , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Administración Cutánea , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Relación Dosis-Respuesta a Droga , Erupciones por Medicamentos/etiología , Femenino , Fibroblastos/efectos de los fármacos , Flavonoides/administración & dosificación , Flavonoides/efectos adversos , Depuradores de Radicales Libres/farmacología , Hidroxiprolina/metabolismo , Luteolina/administración & dosificación , Luteolina/efectos adversos , Luteolina/farmacología , Masculino , Pomadas , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Proteínas/metabolismo , Ratas , Ratas Wistar , Piel/química
10.
Zhong Xi Yi Jie He Xue Bao ; 9(1): 49-56, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21227033

RESUMEN

OBJECTIVE: The present study was undertaken with a view to validate the traditional use of Phyllanthus acidus (L.) Skeels fruit as a hepatoprotective agent. METHODS: The 70% ethanolic extract of P. acidus fruit (100, 200 and 400 mg/kg, p.o.), and reference drug silymarin (100 mg/kg, p.o.) were given to rats of different groups respectively once a day for 5 d and the carbon tetrachloride (CCl4) (2 mL/kg, subcutaneously) was given on days 2 and 3. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) were assessed along with liver histopathological examination. The effects on oxidative stress markers such as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also assessed in liver tissue homogenate to evaluate in vivo antioxidant activity. In addition, the effects on hexobarbitone-induced sleeping time were observed and the free radical-scavenging potential was determined by using 2, 2-diphenyl-1-picrylhydrazil (DPPH) in mice. RESULTS: P. acidus extracts and silymarin exhibited a significant hepatoprotective effect as evident from the decreases of serum AST, ALT and ALP levels and LPO and increases in the levels of TP, GSH, SOD, CAT, and GPx compared with control group (P<0.01 or P<0.05). The biochemical results were supplemented with results of histopathological sections of the liver tissues. P. acidus extracts considerably shortened the duration of hexobarbitone-induced sleeping time in mice compared with control group (P<0.01) and showed remarkable DPPH-scavenging activity. CONCLUSION: The present findings suggest that the hepatoprotective effect of P. acidus against CCl4-induced oxidative damage may be related to its antioxidant and free radical-scavenging potentials.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Hígado/efectos de los fármacos , Phyllanthus/química , Sustancias Protectoras/farmacología , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Frutas/química , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos , Ratas , Ratas Wistar
11.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-303645

RESUMEN

<p><b>OBJECTIVE</b>To evaluate the wound healing potential of fractions from ethanol extract of Martynia annua (M. annua) Linn leaves.</p><p><b>METHODS</b>Ethanol extract of M. annua Linn leaves was fractionate into three different fractions (MAF-A, MAF-B and MAF-C) which were screened for wound healing potential using two models: excision and incision on rats. The thin layer chromatography (TLC) profile of all fractions were analyzed and TLC of luteolin was also done. The Povidone-Iodine Ointment was used as reference for comparision. Excision and incision wounds were created on dorsal portion of rats for study. Wound contraction, biochemical parameters (protein level and hydroxyproline level) and histopathological study were performed in excision wound model whereas incision model was used for determination of tensile strength.</p><p><b>RESULTS</b>The wound contraction and tensile strength of skin tissues were observed significantly greater in MAF-C fraction treated group than other two fractions (P<0.01). In excision wound method (on day 18) protein content and hydroxyproline were found significantly higher in MAF-C group than control group (P<0.01). Histopathological study also showed better angiogenesis, matured collagen fibres and fibroblast cells as compared with the control group.</p><p><b>CONCLUSIONS</b>In conclusion, our findings suggest that fraction MAF-C from ethanol extract of M. annua leaves is found most effective in wound healing.</p>


Asunto(s)
Animales , Femenino , Masculino , Antiinfecciosos Locales , Usos Terapéuticos , Sustancias de Crecimiento , Usos Terapéuticos , Extractos Vegetales , Usos Terapéuticos , Hojas de la Planta , Química , Ratas Wistar , Tracheophyta , Química , Resultado del Tratamiento , Cicatrización de Heridas
12.
J Ethnopharmacol ; 129(2): 280-2, 2010 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-20347947

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Asteracantha longifolia Nees. (Family-Acanthaceae) is a wild herb commonly used in traditional ayurvedic medicine as Kokilaaksha and the Unani drug as Talimakhana in India and Srilanka for various medicinal uses as aphrodisiac, tonic, sedative and blood diseases etc. AIM OF THE STUDY: The aim of the current study was to validate and explore the folk use of Asteracantha longifolia Nees. (AL) (Leaf part) on pharmacological grounds using haloperidol induced iron deficiency anemia for the assessment of erythropoietic activity. MATERIALS AND METHODS: Determination of iron in plant extracts was carried out using spectrophotometric method. Plant extract was obtained from crude drugs using extraction with ethanol. In vivo study, haloperidol induced iron deficiency anemia model was used in experimental studies. RESULTS: An administration of ethanolic extract of AL at the doses of 100 mg/kg and 200 mg/kg body weight, i.p., demonstrated a significant (P<0.05) increase in erythrocyte count, haemoglobin count, serum iron and serum protein etc. This effect may be due to the presence of iron (622 microg/50 mg) in extract estimated by spectrophotometric method. CONCLUSION: An ethanolic extract of AL effectively restored the hematological parameters, serum iron and serum protein and normalized the microcytic (smaller in size), anisocytosis (disturbed shape) and hypochromic RBCs. These observations could justify the inclusion of this plant in the management of iron deficiency anemia due the presence of iron and other constituents as flavonoids, terpenoids, steroids, lupeol and betulin.


Asunto(s)
Acanthaceae/química , Anemia Ferropénica/tratamiento farmacológico , Eritrocitos/metabolismo , Hematínicos/uso terapéutico , Hierro/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Anemia Ferropénica/sangre , Anemia Ferropénica/inducido químicamente , Animales , Proteínas Sanguíneas/metabolismo , Recuento de Eritrocitos , Femenino , Haloperidol , Hematínicos/farmacología , Hemoglobinas/metabolismo , Hierro/sangre , Hierro/farmacología , Masculino , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Ratas Endogámicas
13.
J Ethnopharmacol ; 108(2): 204-10, 2006 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-16806763

RESUMEN

Tephrosia purpurea is a well-known herb for its hepatoprotective, anticancer, antiulcer, antibacterial and in healing bleeding piles, etc. The present study was aimed for wound healing potential of ethanolic extract of Tephrosia purpurea (aerial part) in the form of simple ointment using three types of wound models in rats as incision wound, excision wound and dead space wound. The results were comparable to standard drug Fluticasone propionate ointment, in terms of wound contraction, tensile strength, histopathological and biochemical parameters such as hydroxyproline content, protein level, etc. Histopathological study showed significant (P<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters were observed significant (P<0.05) in comparison to control group.


Asunto(s)
Extractos Vegetales/farmacología , Tephrosia/química , Cicatrización de Heridas/efectos de los fármacos , Androstadienos/administración & dosificación , Androstadienos/farmacología , Animales , Colágeno/metabolismo , Etanol , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fluticasona , Hidroxiprolina/metabolismo , Masculino , Medicina Ayurvédica , Pomadas , Fotomicrografía , Componentes Aéreos de las Plantas/química , Extractos Vegetales/administración & dosificación , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Piel/lesiones , Piel/fisiopatología , Resistencia a la Tracción/efectos de los fármacos , Factores de Tiempo
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