Effects of Passiflora incarnata and Valeriana officinalis in the control of anxiety due to tooth extraction: a randomized controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy of Valeriana officinalis L. and Passiflora incarnata L. to control anxiety, surgical discomfort, and changes in vital signs of patients undergoing extraction of two unilateral third molars. MATERIALS AND METHODS: This study is a randomized, triple-blinded clinical trial. Fifty-four patients were allocated into three groups (Valeriana officinalis L., Passiflora incarnata L., and placebo). Anxiety levels were assessed using the State-Trace Anxiety Inventory (STAI) index, surgical discomfort using the QCirDental, and through the measurement of vital signs. The surgical times evaluated were before (T0), during (T1), and after surgery (T2). RESULTS: There was evidence that both Valeriana officinalis L. and Passiflora incarnata L., reduced STAY-S scores between T0 and T2 (p < .05), unlike placebo (p = .129). There was no change in surgical discomfort in all groups over time, and vital signs presented variable results. CONCLUSION: Phytotherapy drugs showed a reduction in anxiety state compared to the placebo group during third molar extraction procedure.  CLINICAL TRIAL REGISTRATION: klRBR-6kcxvrc, March 10, 2022.

In Vitro Metabolism of Six C-Glycosidic Flavonoids from Passiflora incarnata L.

Several medical plants, such as Passiflora incarnata L., contain C-glycosylated flavonoids, which may contribute to their efficacy. Information regarding the bioavailability and metabolism of these compounds is essential, but not sufficiently available. Therefore, the metabolism of the C-glycosylated flavones orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin was investigated using the Caco-2 cell line as an in vitro intestinal and epithelial metabolism model. Isovitexin, orientin, and isoorientin showed broad ranges of phase I and II metabolites containing hydroxylated, methoxylated, and sulfated compounds, whereas schaftoside, isoschaftoside, and vitexin underwent poor metabolism. All metabolites were identified via UHPLC-MS or UHPLC-MS/MS using compound libraries containing all conceivable metabolites. Some structures were confirmed via UHPLC-MS experiments with reference compounds after a cleavage reaction using glucuronidase and sulfatase. Of particular interest is the observed cleavage of the C-C bonds between sugar and aglycone residues in isovitexin, orientin, and isoorientin, resulting in unexpected glucuronidated or sulfated luteolin and apigenin derivatives. These findings indicate that C-glycosidic flavones can be highly metabolized in the intestine. In particular, flavonoids with ortho-dihydroxy groups showed sulfated metabolites. The identified glucuronidated or sulfated aglycones demonstrate that enzymes expressed by Caco-2 cells are able to potentially cleave C-C bonds in vitro.

Sleep-inducing effect of Passiflora incarnata L. extract by single and repeated oral administration in rodent animals.

Social cost of insomnia in modern society is gradually increasing. Due to various social phenomena and lifestyles that take away the opportunity of good quality of sleep, problems of insomnia cannot be easily figured out. Prescription of sleeping pills for insomnia patients can cause other inconveniences due to their side effects beyond their intended purposes. On the other hand, Passiflora incarnata L. (PI) has been widely used in South America for several centuries, showing effectiveness for sleep, sedation, anxiety, and so on in the civilian population. However, reports on the treatment efficacy of this herbal medicinal plant for insomnia patients through standardization as a sleeping agent have been very rare. Therefore, we obtained leaves and fruits of PI (8:2 by weight) as powder to prepare an extract. It was then applied to C6 rat glioma cells to quantitate mRNA expression levels of GABA receptors. Its sleep-inducing effect was investigated using experimental animals. PI extract (6 µg/ml) significantly decreased GABA receptors at 6 hr after treatment. Immobility time and palpebral closing time were significantly increased after single (500 mg/kg) or repeated (250 mg/kg) oral administration. In addition, blood melatonin levels were significantly increased in PI extract-treated animals after both single and repeated administrations. These results were confirmed through several repeated experiments. Taken together, these results confirmed that PI extract had significant sleep-inducing effects in cells and animals, suggesting that PI extract might have potential for treating human insomnia.

Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models.

Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and, Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health. Patients with Alzheimer's disease are also known to suffer from severe sleep disturbance. Meanwhile, vitexin is a key ingredient in Passiflora incarnata L (passion flower, PF) extract, which is known to help with sleep. This medicinal plant has been used as a folk remedy for sedation, anxiety and sleep since centuries ago, but the standardization work has not been done and the extent of the effect has not been clearly demonstrated. For this reason, we tried to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. Here, we found that vitexin, which is the main bioactive component of ethanol extracts from leaves and fruits (ratio; 8:2) of PF, confirmed the improvement of neurogenesis (DCX) of DBA/2 mice repeated PF oral administration by immunohistochemistry (IHC) and western blot analysis. PF-treated group showed increased the neurotrophic factor (BDNF) in the hippocampus compared with that of vehicle-treated group, but the inflammation markers Iba-1 (microglial marker) and COX-2 were inconsistent between the groups. However, we found COX-2 signal is essential for hippocampal neurogenesis according to the additional IHC experiments using COX-2 inhibitor and pIkappaB have shown. In addition, although prescription sleeping pills have been reported to show significant changes in appetite and metabolic rate from time to time, no changes in the feeding behavior, body weight, metabolic rate and body composition of the animals were observed by administration of PF. Interestingly, we found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.

Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review.

Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John's wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.

Validación del método de determinación de flavonoides en tabletas de Passiflora incarnata L / Validation of flavonoid quantification method in Passiflora incarnata L. tablets

OBJETIVO: validar el método de cuantificación de flavonoides en las tabletas de Passiflora incarnata L., utilizando como patrón quercetina. MÉTODOS: se evaluó la especificidad, linealidad, exactitud, precisión y robustez según las recomendaciones de la USP 30 y el Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED). RESULTADOS: en las condiciones practicadas en este trabajo el método es selectivo; resultó lineal en un rango de 60 a 140 por ciento de concentración de flavonoides. Mostró exactitud y precisión con coeficiente de variación global de 0,67 por ciento. No varió significativamente cuando se modificaron las condiciones de análisis. CONCLUSIONES: el método analítico, en las condiciones practicadas, es fiable y permite obtener resultados apropiados para el uso que se pretende(AU)

INTRODUCTION: to validate the flavonoid quantification method on Passiflora incarnata L. tablets by using quercetine as standard. METHODS: selectivity, linearity, accuracy, precision and robustness were evaluated, using USP 30 and the regulations of the Center for the State Control of Drug Quality (CECMED). RESULTS: under the conditions of this study, the method is selective, linear in a range of 60 to 140 percent of flavonoid concentration. It showed accuracy and precision with global relative standard deviation of 0.67 percent. The results did not significantly vary when the analytical conditions changed. CONCLUSIONS: under the established conditions, this method is reliable and allows obtaining appropriate results for the intended use(AU).

Validación del método de determinación de flavonoides en tabletas de Passiflora incarnata L / Validation of flavonoid quantification method in Passiflora incarnata L. tablets

Objetivo: validar el método de cuantificación de flavonoides en las tabletas de Passiflora incarnata L., utilizando como patrón quercetina. Métodos: se evaluó la especificidad, linealidad, exactitud, precisión y robustez según las recomendaciones de la USP 30 y el Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED). Resultados: en las condiciones practicadas en este trabajo el método es selectivo; resultó lineal en un rango de 60 a 140 por ciento de concentración de flavonoides. Mostró exactitud y precisión con coeficiente de variación global de 0,67 por ciento. No varió significativamente cuando se modificaron las condiciones de análisis. Conclusiones: el método analítico, en las condiciones practicadas, es fiable y permite obtener resultados apropiados para el uso que se pretende(AU)

Introduction: to validate the flavonoid quantification method on Passiflora incarnata L. tablets by using quercetine as standard. Methods: selectivity, linearity, accuracy, precision and robustness were evaluated, using USP 30 and the regulations of the Center for the State Control of Drug Quality (CECMED). Results: under the conditions of this study, the method is selective, linear in a range of 60 to 140 percent of flavonoid concentration. It showed accuracy and precision with global relative standard deviation of 0.67 percent. The results did not significantly vary when the analytical conditions changed. Conclusions: under the established conditions, this method is reliable and allows obtaining appropriate results for the intended use(AU)

The efficacy of passiflora incarnata linnaeus in reducing dental anxiety in patients undergoing periodontal treatment.

STATEMENT OF PROBLEM: Oral premedication used to reduce the anxiety in patients undergoing dental treatment. Passion flower has been used as a sedative that can control the dental anxiety. PURPOSE: This study determines the efficacy of Passion flower, in reducing anxiety during the dental procedures. MATERIAL AND METHODS: In this randomized- one sided blind clinical trial, 63 patients, with moderate, high and severe anxiety(according to VAS score) in need of periodontal treatment were randomly divided into 3 groups of 21.The first group was given the drop Passion flower drop and the second group were given the drop of placebo and the third group; neither drug nor placebo were given (negative control group). RESULTS were analyzed by Chi Square, Variance Analysis, Tucky and Paired-T using SPSS software. RESULTS: Mean anxiety level prior to the drug administration was 12.09±2.42 for the Passion flower group, 12.00±2.66 for the placebo group and 11.66±2.39 for the negative control group. After premedication, these values were: 8.47±2.58 for the Passion flower group, 10.52±2.11 for the placebo group and 11.23±2.34 for the negative control group. These results demonstrated a significant difference (p< 0.0001) in the anxiety levels before and after the Passion flower administration in the Passion flower group and also between the Passion flower group and the other two groups. CONCLUSION: RESULTS indicated that administration of Passion flower, as a premedication, is significantly effective in reducing the anxiety. Since this study is a pioneer on the subject, further trials with greater number of subjects are required to confirm our results.

Validação de método analítico para doseamento de flavonoides totais em cápsulas contendo extrato seco de Passiflora incarnata L / Validation of analytical method for assay of total flavonoids in capsules containing dry extract of Passiflora incarnata L

Este trabalho teve como objetivo desenvolver e validar metodologia analítica por espectrofotometria no UV para a quantificação de flavonóides totais, expressos em vitexina, em cápsulas contendo extrato seco de Passiflora incarnata L. O método foi desenvolvido a partir da metodologia de doseamento de flavonóides totais descrita na monografia do extrato seco de P. incarnata L, disponível na Farmacopeia Britânica (2010). A validação da metodologia analítica de doseamento foi realizada de acordo com a Anvisa RE N° 899/2003 e diretrizes da International Conference on Harmonization. O método mostrou-se seletivo, pois não houve interferência dos adjuvantes na leitura das absorbâncias nas soluções analisadas. Apresentou coeficiente de correlação linear (r) de 0,9999, confirmando a linearidade do método. Os valores de desvio padrão relativo, obtidos tanto para precisão, nos níveis de repetibilidade e precisão intermediária, quanto para exatidão não excederam o máximo de 15% determinado nos critérios de aceitação para métodos bioanalíticos, considerando a complexidade da matéria-prima vegetal.

The aim of this study was to develop and validate an analytical method using UV spectrophotometry to determine total flavonoids, expressed in vitexin, in capsules containing a dry extract of Passiflora incarnata L. The analytical method was based on the spectrophotometric assay described in the British Pharmacopoeia (2010), for the dry extract of P. incarnata L. The validation of this method of quantitation was done in accordance with ANVISA resolution 899/2003 and the International Conference on Harmonization guidelines. The method was selective, because there was no interference from additives in the reading of the absorbance of solutions analyzed. It showed a linear regression correlation coefficient (r) of 0.9999, confirming the linearity of the method. The values of relative standard deviation calculated for precision (both repeatability and intermediate precision) and for accuracy did not exceed the maximum of 15% allowed in the acceptance criteria for bioanalytical methods, considering the complexity of the plant raw material.

Efecto in vitro de una solución de Passiflora incarnata L. sobre la respuesta de linfocitos humanos de donantes sanos y de enfermos con inmunodeficiencia celular / In vitro effect of a Passiflora incarnata L. solution on the response of human lymphocytes from healthy donors and from patients with cellular immunodeficiency

La Passiflora incarnata L. es una especie que se ha utilizado por el hombre con diversos fines. Se estudió el efecto in vitro de un extracto fluido de esta planta sobre los linfocitos de 20 donantes voluntarios de sangre y de 20 enfermos con diagnóstico de inmunodeficiencia celular, mediante la técnica de formación de roseta activa, roseta espontánea y el ultramicrométodo inmunocitoquímico, así como en la función fagocítica de los neutrófilos. No se hallaron diferencias estadísticamente significativas entre las condiciones experimentales sin pasiflora y con pasiflora, en las técnicas de formación de rosetas ni en la expresión de los marcadores de linfocitos CD2 y CD3. Similares resultados se hallaron con la función fagocítica de los neutrófilos en la misma dilución(AU)

Passiflora incarnata L. is a species that has been used by man for various purposes. It was studied the effect in vitro of a fluid extract of this plant on lymphocytes from 20 blood donors and 20 patients with cellular immunodeficiency diagnosis, using the technique of active rosette formation, and spontaneous rosette immunocytochemical ultramicromethod and in the phagocytic function of neutrophils. We found no statistically relevant differences between experimental conditions with and without Passiflora, neither in the rosette formation techniques or the expression of lymphocyte markers CD2 and CD3. Similar results were found with the phagocytic function of neutrophils in the same dilution(AU)

Efecto in vitro de una solución de Passiflora incarnata L. sobre la respuesta de linfocitos humanos de donantes sanos y de enfermos con inmunodeficiencia celular / In vitro effect of a Passiflora incarnata L. solution on the response of human lymphocytes from healthy donors and from patients with cellular immunodeficiency

La Passiflora incarnata L. es una especie que se ha utilizado por el hombre con diversos fines. Se estudió el efecto in vitro de un extracto fluido de esta planta sobre los linfocitos de 20 donantes voluntarios de sangre y de 20 enfermos con diagnóstico de inmunodeficiencia celular, mediante la técnica de formación de roseta activa, roseta espontánea y el ultramicrométodo inmunocitoquímico, así como en la función fagocítica de los neutrófilos. No se hallaron diferencias estadísticamente significativas entre las condiciones experimentales sin pasiflora y con pasiflora, en las técnicas de formación de rosetas ni en la expresión de los marcadores de linfocitos CD2 y CD3. Similares resultados se hallaron con la función fagocítica de los neutrófilos en la misma dilución

Passiflora incarnata L. is a species that has been used by man for various purposes. It was studied the effect in vitro of a fluid extract of this plant on lymphocytes from 20 blood donors and 20 patients with cellular immunodeficiency diagnosis, using the technique of active rosette formation, and spontaneous rosette immunocytochemical ultramicromethod and in the phagocytic function of neutrophils. We found no statistically relevant differences between experimental conditions with and without Passiflora, neither in the rosette formation techniques or the expression of lymphocyte markers CD2 and CD3. Similar results were found with the phagocytic function of neutrophils in the same dilution

Multivariate analysis of the effects of soil parameters and environmental factors on the flavonoid content of leaves of Passiflora incarnata L., Passifloraceae / Análise multivariada dos efeitos dos parâmetros do solo e fatores ambientais no teor de flavonoides das folhas de Passiflora incarnata L., Passifloraceae

The aim of the present study was to evaluate the effect of soil characteristics (pH, macro- and micro-nutrients), environmental factors (temperature, humidity, period of the year and time of day of collection) and meteorological conditions (rain, sun, cloud and cloud/rain) on the flavonoid content of leaves of Passiflora incarnata L., Passifloraceae. The total flavonoid contents of leaf samples harvested from plants cultivated or collected under different conditions were quantified by high-performance liquid chromatography with ultraviolet detection (HPLC-UV/PAD). Chemometric treatment of the data by principal component (PCA) and hierarchic cluster analyses (HCA) showed that the samples did not present a specific classification in relation to the environmental and soil variables studied, and that the environmental variables were not significant in describing the data set. However, the levels of the elements Fe, B and Cu present in the soil showed an inverse correlation with the total flavonoid contents of the leaves of P. incarnata.

O objetivo deste trabalho foi avaliar os efeitos do solo (pH, macro e micronutrientes), fatores ambientais (temperatura, umidade, época do ano e período da coleta) e condições meteorológicas (chuva, sol, nublado, nublado com chuva) no teor de flavonoides das folhas de Passiflora incarnata L. (Passifloraceae), através do tratamento quimiométrico dos dados por PCA (análise de componentes principais) e HCA (análise hierárquica de agrupamentos). Os flavonoides totais foram quantificados por cromatografia líquida de alta eficiência-detecção por ultravioleta (CLAE-UV/DAD). As análises por PCA e HCA mostraram que as amostras de Passiflora não apresentam uma classificação específica em relação às variáveis estudadas e que as variáveis do meio ambiente não são relevantes para descrever o modelo estudado, porém os elementos do solo Fe, B e Cu demonstraram correlação inversa à concentração dos flavonoides totais.