Lead impurities in traditional herbal medicinal products with Plantago lanceolata L., folium (Ribwort Plantain leaves) available in Polish pharmacies - toxicological risk assessment for adults.

Traditional herbal medicinal products (THMP) with Plantago lanceolata L., folium (Ribwort Plantain Leaves) are well-known and very popular among the European population. The aim of our study was the toxicological risk assessment for adults of Pb impurities in THMP with Plantago lanceolata L. obtained from pharmacies in Poland. The estimations of Pb impurities in the single dose (22.1 - 50.7 ng/single dose) and in the daily dose (ng/day) were based on the worst-case scenario (WCS), i.e. based on the posology recommended by manufacturers. The estimated daily exposure (ng/day) meets the standards of the ICH Q3D (R1) guideline on elemental impurities (5.0 µg/day) according to the Pb levels (all results were below 250 ng/day). It can be concluded that all investigated THMPs with Plantago lanceolata L., folium available in pharmacies from Poland should not represent any health risk to the adults.

The Level of Cadmium Impurities in Traditional Herbal Medicinal Products with Plantago lanceolata L., folium (Ribwort Plantain Leaves) Available in Polish Pharmacies - Comprehensive Toxicological Risk Assessment Including Regulatory Point of View and ICH Q3D Elemental Impurities Guideline.

Plantago lanceolata L., folium (ribwort plantain) is an active pharmaceutical ingredient in traditional herbal medicinal products (THMP) available in pharmacies as a demulcent for the symptomatic treatment of oral or pharyngeal irritations and associated dry cough. This kind of THMP is widely applied among the European population; however, recently, voices have been heard in the public about alleged cadmium impurities. The idea of our study was a comprehensive risk assessment of the Cd impurity exposure and its effect on human health. Our assessment strategy was based on regulatory aspects (raw results versus limits set by FAO/WHO for herbal medicines) and toxicological risk assessment approach based on ICH Q3D guideline for elemental impurities in final pharmaceutical products. The cadmium was determined by electrothermal atomization atomic absorption spectrometry based on our previously described methodology. Obtained results show that all analysed THMP with P. lanceolata L., folium available in the Polish pharmacies contain cadmium impurities, but at a very low level (ranged 0.73 - 20.6 µg/L). The content of Cd in a single dose (ng/single dose) is also very low and is not a threat to patients. The estimated maximum daily exposure (ng/day) of Cd based on the 'worst-case scenario' (maximum concentrations by oral administration) meets the standards of ICH Q3D guideline (all results were below oral permitted daily exposure; PDE for Cd, i.e. < 5.0 µg/day). It can be concluded that all analysed samples of THMP with P. lanceolata L., folium should not represent any health hazard to the patients due to cadmium levels. To the best of our knowledge, this is the first study about Cd impurity level in THMP with P. lanceolata L., folium (ribwort plantain leaves) available in European pharmacies.

A new flavonoid, a new phenylethanoid glycoside and related compounds isolated from the inflorescences of Plantago lanceolata L.

For the first time inflorescences of a plant species from the genus Plantago (Pantaginaceae)-Plantago lanceolata L. (Ribwort Plantain), a known medicinal plant, were subjected to studies of phenolic compounds, which resulted in an isolation of two new compounds: a flavonoid-isorhamnetin 3-O-α-L-4C1-arabinopyranosyl-(1→2)-ß-D-4C1-glucopyranoside) (1) and a phenylethanoid glycoside-2-(3,4-dihydroxyphenyl)ethyl O-α-L-arabinofuranosyl-(1→2)-[α-L-1C4-rhamnopyranosyl-(1→3)][E-caffeoyl-1→4]-ß-D-4C1-glucopyranoside (14), along with fourteen known compounds-eight flavonoids (2-9) and six phenylethanoid glycosides (10-13, 15-16). The chemical structures were established by 1 D and 2 D NMR and HRESIMS spectral methods. The known phenylethanoids were the same as reported for leaves or aerial parts of P. lanceolata or other Plantago species. The flavonoids appeared to be only flavonols, mainly isorhamnetin 3-O- and 3,4'-O- glycosides, and thus completely different from flavones, mainly luteolin and apigenin glucuronides, previously reported in the leaves. The possible medicinal and chemotaxonomic relevance of the phenolics found in P. lanceolata inflorescences were taken into consideration.

Application of the Life Cycle Management of Analytical methods concept to a HPTLC-DPPH assay method for acteoside content in industrial extracts of Plantago lanceolata L.

Analytical methods used for quality control of plants and plant extracts are based on the identification and quantification of chemical markers to manage batch reproducibility and efficacy. The aim of this work was to assess the performance of a High Performance Thin Layer Chromatography (HPTLC) method developed for quality control of industrial dry extracts of ribwort plantain (P. lanceolata L.), using 2,2-diphenyl 1-picrylhydrazyle (DPPH) effect directed chemical reaction for antioxidant activity of acteoside, a phenylethanoid glycoside commonly used as a marker for P. lanceolata L., and to demonstrate the applicability of the Life Cycle Management of Analytical Methods concept to quantitative HPTLC-DPPH methods. The first step was the determination of the Analytical Target Profile (ATP) and Target Measurement Uncertainty (TMU), taking into account the quality control requirements for such extracts and the detection method applicable range. Once the desired range was established, an evaluation of the calibration function was conducted using several calibration models. Due to the lack of reference samples, spiked samples were used to evaluate the accuracy of the method by means of Total Analytical Error (TAE) determination, using prediction intervals calculation for the selected calibration functions. Measurement Uncertainty (MU) was also estimated, allowing the final choice of the calibration function to be used for quality control, giving the most fit for purpose performance level in accordance with the product specifications. As Life Cycle Management of the method also includes its routine use, the Measurement Uncertainty was checked on spiked and unspiked extract samples with different dilution levels, in order to verify the accordance of results between spiked and unspiked samples and to prepare a replication strategy to be applied during the routine use of the method.

Stability Study and a 14-Day Oral Dose Toxicity in Rats of Plantain Leaf Extract (Plantago lanceolata L.) Syrup.

Plants have been used since antiquity to treat and prevent diseases. Plantain (Plantago lanceolata L.) is traditionally used for the treatment of the common cold and associated symptoms such as cough. This study was designed to evaluate the oral toxicity of plantain leaf extract-containing syrup. In preparation of the toxicological examination and to ensure the quality of the herbal preparation, analytical methods were developed and validated, and stability testing was performed. Physicochemical and microbial quality, thin layer chromatography patterns and high performance liquid chromatography fingerprints complied with the specifications during the entire period of stability testing. The marker substance, acteoside, remained within the stability-defining limits of 90%-110% for quantitative determinations. No hint of toxicity emerged from 14-day repeat dose toxicity testing in rats. The animals were given doses of 3, 6, or 12 mL of syrup per kg body weight by gavage twice daily. All animals showed normal appearance and behavior. Body and organ weights at the end of the study were similar to those in the control group. Overall, P. lanceolata syrup was found to be stable and non-toxic under the test conditions.

Chemical composition of essential oils from plantago lanceolata L. leaves extracted by hydrodistillation.

Extensive traditional use of medical plants leads to research dealing with chemical composition of essential oils. The aim of this work was evaluation of quality of the essential oil and extending of the knowledge about chemical composition of essential oil from ribwort (Plantago lanceolata L.) and proportional representation of compounds. Extractions of essential oils from samples of ribwort were performed by hydrodistillation. GC-MS and GC-FID techniques were used for investigation of the qualitative and semi-quantitative content of aromatic compounds in the essential oils, respectively. Major aroma constituents of ribwort leaves were groups of fatty acids 28.0-52.1 % (the most abundant palmitic acid 15.3-32.0 %), oxidated monoterpenes 4.3-13.2 % (linalool 2.7-3.5 %), aldehydes and ketones 6.9-10.0 % (pentyl vinyl ketone 2.0-3.4 %) and alcohols 3.8-9.2 % (1-octen-3-ol 2.4-8.2 %). In relative high amount were identified apocarotenoids (1.5-2.3 %) which are important constituents because of their intense fragrant. The importance is in potential manufacture control of feedstocks before producing of food supplements.

Efecto antiulceroso del extracto hidroalcohólico de Plantago lanceolata (llantén menor) sobre la úlcera gástrica inducida en ratas / Anti-ulcer effect of hydroalcoholic extract of Plantago lanceolata (plantain minor) on gastric ulcer induced in rats

Objetivo: Determinar el efecto antiulceroso del extracto hidroalcohólico de Plantago lanceolata L. (llantén menor) en animales de experimentación. Metodología: Es un estudio de tipo experimental, en donde se indujo las úlceras gástricas con indometacina a dosis única de 80 mg/kg vía subcutanea. Se realizó el análisis fitoquímico cualitativo para la determinación de metabolitos secundarios. Para la determinación del efecto antiulceroso se formaron 06 grupos: grupo control solución salina fisiológica a 4 mL/kg, grupo indometacina (I), y cuatro grupos experimentales indometacina más extracto a 200 y 400 mg/kg, omeprazol a 20 mg/kg y ranitidina a 100 mg/kg respectivamente. Se administraron los extractos y medicamentos estándar a las 24, 12 y una hora antes de la inducción de la úlcera gástrica. Se realizó el examen macroscópico y microscópico de las mucosas gástricas de todas las ratas determinándose el porcentaje de inhibición antiulceroso. Resultados: El extracto hidroalcohólico a la dosis de 200 y 400 mg/kg presentó efecto antiulceroso en los indicadores evaluados de hiperemia, edema, úlcera y hemorragias siendo estadísticamente significativos y un porcentaje de inhibición de 83,1 % y 98,9 % respectivamente en comparación al omeprazol (67,4 %) y Ranitidina (44,9 %). A nivel microscópico no se evidenciaron alteraciones histológicas significativas. Conclusiones: El extracto hidroalcohólico de Plantago lanceolata L. (llantén menor) presenta flavonoides, compuestos fenólicos, alcaloides, triterpenos y/o esteroides y presentó efecto antiulceroso a las dosis evaluadas en el modelo empleado sin signos de toxicidad aguda.