The use of biofield energy therapy as complementary and alternative medicine in human health care system: a narrative review and potential mechanisms.

INTRODUCTION: There has been accumulating interest in the application of biofield therapy as complementary and alternative medicine (CAM) to treat various diseases. The practices include reiki, qigong, blessing, prayer, distant healing, known as biofield therapies. This paper aims to state scientific knowledge on preclinical and clinical studies to validate its potential use as an alternative medicine in the clinic. It also provides a more in-depth context for understanding the potential role of quantum entanglement in the effect of biofield energy therapy. CONTENT: A comprehensive literature search was performed using the different databases (PubMed, Scopus, Medline, etc.). The published English articles relevant to the scope of this review were considered. The review gathered 45 papers that were considered suitable for the purpose. Based on the results of these papers, it was concluded that biofield energy therapy was effective in treating different disease symptoms in preclinical and clinical studies. SUMMARY: Biofield therapies offer therapeutic benefits for different human health disorders, and can be used as alternative medicine in clinics for the medically pluralistic world due to the growing interest in CAM worldwide. OUTLOOK: The effects of the biofield energy therapies are observed due to the healer's quantum thinking, and transmission of the quantum energy to the subject leads to the healing that occurs spiritually through instantaneous communication at the quantum level via quantum entanglement.

Vitamin D3 supplementation improves spatial memory, muscle function, pain score, and modulates different functional physiological biomarkers in vitamin D3 deficiency diet (VDD)-induced rats model.

BACKGROUND: Vitamin D Deficiency is recognized as a pandemic, which is associated with high mortality. An inadequate level of vitamin D is associated with autoimmune diseases, hypertension, and cancer. The study was aimed to assess the pharmacological effects of chronic vitamin D3 supplementation on the manipulation diet regiment of deprived cholecalciferol (vitamin D3 deficient diet, VDD) rats. METHODS: Memory performance (Y-maze task), muscular function (muscle grip strength), and pain score (pressure application measurement meter) were measured. Functional biomarkers were measured using ELISA method in different matrix viz. in serum (parathyroid hormone; PTH, calcitonin, thyroxine, and C-reactive protein; CRP, 25-OH Vit D3), and in CSF (klotho and ß-endorphin). 25-OH Vit D3 was also estimated in liver and kidney homogenate using ELISA. Vitamin D receptor (VDR) was measured spectrophotometrically in liver and adipose tissue. RESULTS: VDD-induced rats showed a decrease in number of entries and time spent in the novel arm and spontaneous alternations in the Y-maze task. Significant improvements of neuromuscular function and pain score after addition of vitamin D3. In comparison to the VDD group, VDR expression (liver) and active metabolites of vitamin D3 (25-OH vit.D3) in serum were significantly higher by 48.23% and 280%, respectively. The PTH and CRP levels were significantly reduced by 32.5% and 35.27%, respectively, whereas calcitonin was increased by 36.67% compared with the VDD group. Klotho and ß-endorphin expressions in cerebrospinal fluid were significantly elevated by 19.67% and 133.59%, respectively, compared to VDD group. CONCLUSIONS: Overall, the results indicate that supplementation of cholecalciferol significantly improved spatial memory impairment, VDR expression, and may provide an opportunity to manage vitamin D deficiencies.

The role of biofield energy treatment on psychological symptoms, mental health disorders, and stress-related quality of life in adult subjects: A randomized controlled clinical trial.

Background: Western and Eastern cultures have practiced biofield energy therapy for thousands of years, but empirical research on effectiveness of this therapy is relatively nascent. Study was aimed to assess the safety and efficacy of biofield therapy on psychological symptoms and mental health disorders in adult subjects. Methods: Seventy-seven participants (39 male and 38 female) underwent clinical trial. This trial was simple randomized, placebo-controlled, parallel-group, open-label, and single-center with subjects, who have one or more psychological symptoms. Two sessions of biofield energy attunement were given in-person at day 0 and 90 for 3 min (treatment group, n = 35) and others allocated to naive attunement (placebo group, n = 42). Subjects were assessed psychological questionnaire scoring using standard scale of assessment and levels of physiological biomarkers in serum were determined by parameter-specific ELISA. Results: Perceived psychological symptoms/scores (asthenia, sleep disturbances, anxiety, depression, stress, confusion, future fearness, sexual desireness, motivation, confidence, emotional trauma, etc.) were significantly (p ≤ 0.0001) improved in the treatment group than placebo control group. Furthermore, physiological biomarkers: vitamins (B12, C, and D3 metabolites), immune biomarker (CD8+CD28-), neurotransmitters (acetylcholine, noradrenaline, and dopamine), hormones (oxytocin, 17-ß-estradiol, and insulin), and antiaging protein (klotho) levels were significantly (p ≤ 0.001) increased in treatment group than placebo. Proinflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8) and oxidative stress biomarkers (isoprostane and oxidized LDL) were reduced in treatment group compared with placebo. Conclusions: Results suggest that experimenter's biofield energy plays a significant role in information transfer processes that contribute to individual's state of physical, mental, emotional, and spiritual well-being as well as improved overall health and quality of life.

Simultaneous identification and quantification of pentacyclic triterpenoids and phenolic compounds from the leaves of Boswellia serrata using LC-MS/MS tandem mass spectrometry.

Boswellia serrata (B. serrata) is an important medicinal plant widely used as dietary supplements to provide a support for osteoarthritic and inflammatory diseases. The occurrence of triterpenes in leaves of B. serrata is very little or none. Therefore, the qualitative and quantitative determination of phytoconstituents (triterpenes and phenolics) present in the leaves of B. serrata is very much needed. The aim of this study was to develop an easy, rapid, efficient and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method for the identification and quantification of the compounds present in the leaves extract of B. serrata. The purification of ethyl acetate extracts of B. serrata was performed by solid phase extraction method, followed by HPLC-ESI-MS/MS analysis. Chromatographic parameters of the analytical method included negative electrospray ionization (ESI-) with a flow of 0.5 mL/min in gradient mode consisting of acetonitrile (A) and water (B) containing 0.1% formic acid, at 20 °C. Total 19 compounds (13 triterpenes and 6 phenolic compounds) were separated, and simultaneously quantified using a validated LC-MS/MS method with high accuracy and sensitivity. Good linearity was obtained with r2 > 0.973 in the calibration range. The overall recoveries were in a range between 95.78 and 100.2% with relative standard deviations (RSD) below 5% for the entire procedure of matrix spiking experiments. Overall, there was no ion suppression from the matrix. The quantification data showed that the total amount of triterpenes and phenolic compounds in the leaves of B. serrata ethyl acetate extract samples ranged from 14.54 to 102.14 mg/g and 2.14 to 93.12 mg/g of dry extract, respectively. This work provides, for the first time, a chromatographic fingerprinting analysis on the leaves of B. serrata. A rapid, efficient, and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and used for the both identification and quantification of triterpenes and phenolic compounds in the leaves extracts of B. serrata. The method established in this work can be used as quality-control method for other market formulations or dietary supplements containing leaf extract of B. serrata.

Evaluate the Safety and Efficacy of a Biofield Energy Treated Proprietary Dietary Supplement (TRI 360™) on Psychological Symptoms, Mental Disorders, Emotional Well-being, and Quality of Life in Adult Subjects.

Background: The demand for "energy healing" is growing rapidly in the United States and other developed countries. To date, scanty clinical trials have been conducted to evaluate its clinical safety, efficacy, and cost-effectiveness. Primary Study Objective: The study aimed to investigate the safety and efficacy of the Blessed TRI 360TM capsule (Biofield Energy Treated Proprietary Dietary Supplement Capsules Powered by the Trivedi Effect®). Methods/Design: A total of 77 adult subjects (male and female) aged 20-45 years with one or more psychological symptoms were enrolled in the trial. The subjects were randomized into two groups: placebo control and treatment group. The treatment group (n = 35) received the Blessed TRI 360TM capsule twice a day, once in the morning and once in the evening. The placebo control group (n = 42) did not receive any treatment/capsule. Setting: An open-label, single-center, randomized controlled trial (RCT). Participants: Adult human subjects (male and female) with one or more psychological symptoms. Intervention: Biofield energy treated proprietary capsule. Primary Outcome Measures: Psychological questionnaire scores and functional physiological biomarkers. Results: Psychological and mental health symptoms were statistically and significantly reduced in the subjects taking the Blessed TRI 360TM capsule compared to the placebo group on both days 90 and 180. Furthermore, levels of functional physiological biomarkers were higher in the intervention group compared to the placebo group: vitamins (C, B12, and D3 active metabolites), neurotransmitters (acetylcholine, noradrenaline, and dopamine), hormones (17-ß-estradiol, oxytocin, and insulin), antioxidant enzyme (catalase), and anti-aging protein (klotho). Additionally, proinflammatory cytokines (TNF-α, IL-1ß, IL-8, IFN-γ, and IL-2), progesterone, and oxidative stress markers (MDA and oxidized-LDL) were lower in the Blessed TRI 360TM group than the placebo group after the intervention. Conclusions: Altogether, the Blessed TRI 360TM dietary supplement capsule was found to be safe and tolerable. It significantly improved psychological symptoms and mental disorders and simultaneously improved different functional physiological biomarkers that led to an improvement in the overall health and quality of life of the adult subjects. Clinical Trial Registration Number: ECR/147/Inst/GJ/2013/RR-16.

Efficacy of a novel proprietary dietary supplement (TRI 360TM) on psychological symptoms and stress-related quality of life in adult subjects: A randomized controlled clinical trial.

Nowadays, diet plays an increasingly important role in normal physiology and mental health. Recently, many studies have shown that more use of dietary supplements in mental and psychological disorders. Study objective was to investigate safety and efficacy of proprietary nutraceutical combination (TRI 360TM) on psychological symptoms in adult human subjects with one or more psychological symptoms in open-label, single-center, parallel-group, randomized controlled trial. Eighty-four participants aged 20-45 years with psychological symptoms were completed this trial. Participants were randomly assigned to placebo and treatment groups. Treatment group received TRI 360TM capsules twice a day. TRI 360TM was well-tolerated and didn't show treatment-related adverse-events upto 180 days. All assessed perception scorings on psychological symptoms like fatigue, mental stress, sleep disturbance, anxiety, depression, emotional trauma, mood changes, self-confidence, willpower, and motivation were very significantly (p ≤ 0.0001) improved in TRI 360TM participants than placebo control group. Furthermore, significantly (p ≤ 0.001) increased levels of functional biomarkers: vitamin C and D3 metabolites, neurotransmitters, hormones, antiaging protein (klotho) level; and decreased proinflammatory cytokines and oxidative stress marker, malondialdehyde in TRI 360TM group than placebo. According to these findings, the use of TRI 360TM supplementation as a potentially safe therapeutic option for reducing psychological symptoms in healthy adults.

Investigation of Molecular Properties that Influence the Permeability and Oral Bioavailability of Major ß-Boswellic Acids.

BACKGROUND AND OBJECTIVES: Boswellic acids (BAs) include ß-boswellic acid (BA), 3-acetyl-ß-boswellic acid, 11-keto-ß-boswellic acid, 3-acetyl-11-keto-ß-boswellic acid, ß-boswellic alcohol, and 3-acetyl-11-hydroxy-ß-BA from Boswellia species, and are the main active ingredients of Boswellia serrata extracts (BSE). BSE have been used for the treatment of different inflammatory diseases; however, their pharmaceutical development has been severely limited by their poor oral bioavailability. The aims of this study were to investigate the molecular properties of six BAs, and to determine their experimental aqueous solubility, partition coefficient (Log P), gastrointestinal stability, adsorption-desorption kinetics, and permeability studies. METHODS: The physicochemical properties of six BAs were obtained from SMILES representations using ChemDraw, and MarvinSketch. The molecular properties were also determined experimentally. The permeability studies were performed using parallel artificial membrane permeability assay (PAMPA), and Caco-2 cells. RESULTS: The experimental Log P values of BAs correlated well (R2 = 0.94) with the calculated Log P values. Metabolic stability data confirmed that BAs were found to be unstable in simulated gastrointestinal fluids and intestinal S9 fractions. The apparent permeability (Papp) range of BAs in both PAMPA and Caco-2 for the apical (AP) to basolateral (BL) was in the range of 0.52 ± 0.05 × 10-6 to 2.84 ± 0.14 × 10-6cm/s. The efflux ratio of Papp (BL → AP) to Papp (AP → BL) for all BAs was < 2 in Caco-2 cells, suggesting greater permeability in the absorptive direction. Caco-2 cell adsorption studies confirmed the accumulation of BAs (35-55%) inside the enterocytes. These compounds exhibited a strong correlation between PAMPA and Caco-2 cell monolayer permeation data. CONCLUSIONS: The results of the present study have shown an empirical relationship between the molecular properties and intestinal absorption of BAs for the first time.

Betulinic Acid, the first lupane-type triterpenoid isolated via bioactivity-guided fractionation, and identified by spectroscopic analysis from leaves of Nyctanthes arbor-tristis: its potential biological activities in vitro assays.

Betulinic acid was first time isolated via bioactivity-guided fractionation from ethyl acetate extract of Nyctanthes arbor-tristis leaves. Its structure was established by FTIR, 1H and 13C- nuclear magnetic resonance and high-resolution mass spectrometry. It had shown excellent inhibition of anti-inflammatory properties with IC50 of 10.34 µg/mL (COX-1), 12.92 µg/mL (COX-2), 15.53 µg/mL (5-LOX), 15.21 µg/mL (Nitrite), 16.65 µg/mL (TNF-α), and also exhibited potent antioxidant activity with IC50 of 18.03 µg/mL. The anticancer activity of betulinic acid was evaluated against different human cancer cell lines. It showed significant cytotoxicity against various cancer cell lines with an IC50 of 6.53 (HepG2), 9.34 (A549), 14.92 (HL-60), 16.90 (MCF-7), 17.07 (HCT-116), 13.27 (PC-3), and 12.55 µM (HeLa). This is the first report on isolation and identification of the unreported lupane-type triterpenoid, betulinic acid from leaves of Nyctanthes arbor-tristis, which showed potent anti-inflammatory, antiproliferative, and antioxidant activity in vitro assays.

Role of Vital Trace Elements in Nanocurcumin-Centered Formulation: A Novel Approach to Resuscitate the Immune System.

The present paper described the immunomodulatory potential of novel nanocurcumin-based formulation enriched with trace elements and vitamins on cyclophosphamide-induced immunosuppression in rat model. Major immune-related assays were monitored such as hemagglutination assay, delayed-type hypersensitivity (DTH) reaction, cellular immune response, IgG, IgE, IgM, cerebrospinal fluid biomarkers, hematological study, antioxidant profile, and lipid biomarkers. Chemical characterization of novel formulation showed retention time (R t ) 18.98 of curcumin, while LC-MS data revealed the presence of the curcumin mass at m/z 369.01 [M + H]+ (calculated for C21H21O6+, 369.13). This novel formulation exhibited significantly (p ≤ 0.001) increased primary and secondary antibody titer by 72.41% and 33.25%, respectively, while DTH response being improved by 87.50% (p ≤ 0.01). However, CD4+, CD8+, and CD28+ counts were significantly (p ≤ 0.05) increased by 76.46%, 68.21%, and 19.29%, respectively, while the concentrations of IgE, IgM, and IgG were significantly (p ≤ 0.05) increased by 40%, 28.43%, and 38.75%, respectively. CSF biomarkers analysis showed a decreased level of corticosterone, dopamine, serotonin, and tau protein by 29.38%, 51.73%, 29.93%, and 4.87%, respectively. Antioxidant enzymes such as CAT, GPx, and SOD were increased by 43.74%, 49.00%, and 40.84%, respectively, and non-enzymatic component, GSH, was increased by 55.52%. Similarly, free radical LPO was significantly (p ≤ 0.05) decreased by 40.37%, and acute inflammatory marker, MPO concentration, was reduced by 31.14%, compared with the disease control group. In addition, supportive hematology and lipid profile analysis showed promising results with improved overall animal profile. Thus, trace elements in novel formulation can be used in the various pharmacological activities and as dietary supplement due to its wide properties.

Immunomodulatory potential of nanocurcumin-based formulation.

Vitamins, minerals, and nanocurcumin play a substantial role in various nutraceutical/pharmaceutical formulations that are widely used in therapeutics, cosmetics, and dietary supplements. The current study aimed to investigate the comparative in vitro immunomodulatory effect of a novel nanocurcumin-based formulation with curcumin in LPS-induced cytokine expression, NK cells' activity, and phagocytosis. The proinflammatory cytokines (TNF-α, IL-1ß, and MIP-1α) and NK cells' activity were measured in cell supernatants using ELISA assay; however, phagocytosis activity was performed using colorimetric analysis. The chemical characterization of novel nanocurcumin-based formulation using LC-MS (R t 19.02 min) and mass spectra analysis (m/z 369.04) confirmed the presence of the curcumin in highest peak concentration. MTT assay in three tested cell-lines showed that the formulation was found non-toxic at all the tested concentrations. The expression of TNF-α, IL-1ß, and MIP-1α in splenocytes was significantly (p ≤ 0.001) inhibited. Besides, the NK cells' activity and phagocytosis (macrophage) were increased significantly (p ≤ 0.001). Overall, the promising results of this study indicated the significant immunomodulatory effect of nanocurcumin-based formulation compared to the curcumin, which could be used against various inflammatory disorders such as allergy, asthma, autoimmune diseases, coeliac disease, inflammatory bowel disease, etc.

Effect of a Novel Ashwagandha-based Herbomineral Formulation on Pro-inflammatory Cytokines Expression in Mouse Splenocyte Cells: A Potential Immunomodulator.

BACKGROUND: Herbomineral formulations are momentous in an audience of worldwide by virtue of their holistic approach to life. These formulations are widely used as complementary therapies in immunocompromised patients including cancer. Still, there is the need of cost-effective and safe herbomineral-based formulation that can modulate immune response by the regulation of cytokines cascades. OBJECTIVE: Current study, we investigated immunomodulatory effect of TEBEH in LPS-induced cytokines expression levels in mouse splenocytes in vitro. MATERIALS AND METHODS: The most effective and safe concentrations of TEBEH were chosen by determining the cell viability of splenocytes using MTT assay. The pro-inflammatory cytokines such as TNF-α, IL-1ß, MIP-1α, and IFN-γ were measured in cell supernatants using ELISA. RESULTS: MTT data showed TEBEH formulation was found safe up to 10.53 µg/mL. At noncytotoxic concentrations (0.00001053-10.53 µg/mL), TEBEH significantly (P ≤ 0.001) inhibited the expressions of TNF-α, IL-1ß, and MIP-1α in mouse splenocytes as compared with vehicle control. CONCLUSION: In summary, TEBEH may indeed promote an anti-inflammatory environment by suppression of pro-inflammatory cytokines. These observations indicated that TEBEH has potential effects in downregulating the immune system and might be developed as a useful anti-inflammatory product for various inflammatory disorders. SUMMARY: The present study was undertaken to evaluate an immunomodulatory effect of the herbomineral formulation in LPS-induced mouse splenocytes with the measurement of cytokines expression such as TNF-α, IL-1ß, MIP-1α and IFN-γ. The results showed that the expression of TNF-α, IL-1ß, and MIP-1α was significantly down-regulated while, IFN-γ was significantly up-regulated in mouse splenocytes. It is hypothesized that modulation of the proinflammatory cytokines might occur via NF-κB pathway. Therefore, the herbomineral test formulation might act as an effective anti-inflammatory and immunomodulatory product, and this can be used as a complementary and alternative treatment for the prevention of various types of inflammatory and auto-immune disorders Abbreviations used: LPS: Lipopolysaccharide, IL: Interleukin; NF-κB: Nuclear factor kappa-B, TNF-α: Tumor necrosis factor alpha, MIP-1α: Macrophage inflammatory protein-1α, IFN-γ: Interferon, MTT: 3-(4,5-diamethyl-2-thiazolyl)-2, 5-diphenyl-2Htetrazolium), ELISA: Enzyme linked immune sorbent assay, ANOVA: Analysis of variance.

Effects of Caffeic Acid and Quercetin on In Vitro Permeability, Metabolism and In Vivo Pharmacokinetics of Melatonin in Rats: Potential for Herb-Drug Interaction.

BACKGROUND AND OBJECTIVES: Melatonin is a popular dietary supplement and also considered as pharmaceutical product for sleep disorders. Caffeic acid and quercetin are widely distributed in leafy vegetables, fruits, tea extract, and both are used as natural antioxidant. There is an immense concern for health researchers to study the herb/food-drug interactions of melatonin. It is mainly metabolized by CYP1A2 in human so that herbs/foods containing cytochrome P450 (CYP) inhibitors can affect pharmacokinetics of melatonin. By considering pharmacokinetic aspects, the present study was undertaken to evaluate the effects of caffeic acid and quercetin on Caco-2 cells permeability, metabolism, CYP1A inhibition in vitro assay systems and a single dose pharmacokinetics of melatonin in vivo rats. METHODS: The effects of caffeic acid and quercetin on melatonin permeability were tested in Caco-2 cells. Metabolic stability and CYP1A activity were investigated in rat liver microsomes (RLMs) using probe substrates (melatonin/phenacetin in vitro). Melatonin and phenacetin were incubated in RLMs with or without caffeic acid and quercetin, and the IC50 values were determined. The pharmacokinetics of melatonin conducted in rats after a single dose (15 mg/kg) pre-treatment with caffeic acid, quercetin and caffeic acid plus quercetin followed by oral dose of melatonin at 5 mg/kg. Analysis of all samples was with LC-MS/MS. RESULTS: Caffeic acid and quercetin did not alter Caco-2 permeability of melatonin in apical to basolateral direction and vice versa. Melatonin was metabolized in rat liver microsomes, which was inhibited by both caffeic acid and quercetin through CYP1A. The concomitant oral administration of melatonin along with 15 mg/kg of caffeic acid or quercetin or caffeic acid plus quercetin significantly (p < 0.05) increased the AUC0-t of melatonin by 30.0, 66.7 and 114.0%, respectively. The apparent oral rat plasma clearance (CL/F) of melatonin also decreased significantly (p < 0.05) by 28.78, 47.87 and 50% in presence of caffeic acid, quercetin and caffeic acid plus quercetin, respectively. CONCLUSION: These findings suggest that caffeic acid and quercetin improved oral exposure of melatonin via CYP1A inhibition pathway.

Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy.

Ashwagandha (Withania somnifera) is a very well-known herbal medicine and it was well studied for its active metabolites throughout the World. Although, nearly 40 withanolides were isolated from W. somnifera root extract, still there is remaining unidentified metabolites due to very low abundance and geographical variation. Advanced separation technology with online identification by mass and nuclear magnetic resonance (NMR) are nowadays used to find out the new compounds in the crude herbal extract. This article described the metabolite profiling of ashwagandha root hydroalcoholic extract using ultra-performance liquid chromatography coupled with a positive ion electrospray ionization tandem mass spectrometry through gas chromatography mass spectrometry (GC/MS) and NMR spectroscopy. A total of 43 possible withanolides was identified and proposed their structures based on the mass of molecular and fragment ions. GC/MS and NMR analysis indicated the presence of several known withanolides including withaferin A, withanolide D, withanoside IV or VI, withanolide sulfoxide, etc. To the best of our knowledge, dihydrowithanolide D at m/z 473 (tR 7.86 min) and ixocarpalactone A at m/z 505 (tR 8.43 min) were first time identified in the ashwagandha root hydroalcoholic extract. The current study that described the identification of withanolides with summarized literature review might be helpful for designing the experiment to identify of the new chemical constituents in Withania species.

Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells.

Phenolic compounds are common ingredients in many dietary supplements and functional foods. However, data concerning physicochemical properties and permeability of polyphenols on the intestinal epithelial cells are scarce. The aims of this study were to determine the experimental partition coefficient (Log P), and parallel artificial membrane permeability assay (PAMPA), to characterize the bi-directional transport of six phenolic compounds viz. caffeic acid, chrysin, gallic acid, quercetin, resveratrol and rutin in Caco-2 cells. The experimental Log P values of six polyphenols were correlated (R (2) = 0.92) well with the calculated Log P values. The apparent permeability (P app) range of all polyphenols in PAMPA for the apical (AP) to basolateral (BL) was 1.18 ± 0.05 × 10(-6) to 5.90 ± 0.16 × 10(-6) cm/s. The apparent Caco-2 permeability (P app) range for the AP-BL was 0.96 ± 0.03 × 10(-6) to 3.80 ± 0.45 × 10(-6) cm/s. The efflux ratio of P app (BL → AP) to P app (AP → BL) for all phenolics was <2, suggesting greater permeability in the absorptive direction. Six compounds exhibited strong correlations between Log P and PAMPA/Caco-2 cell monolayer permeation data. Dietary six polyphenols were poorly absorbed through PAMPA and Caco-2 cells, and their transepithelial transports were mainly by passive diffusion.

Evaluation of inhibitory effects of caffeic acid and quercetin on human liver cytochrome p450 activities.

When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb-drug interactions. This work was conducted to evaluate the herb-drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC50 , Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 µM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 µM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 µM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC50 > 100 µM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 µM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 µM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols.

Effects of piperine, cinnamic acid and gallic acid on rosuvastatin pharmacokinetics in rats.

The purpose of this study was to investigate the potential pharmacokinetic interactions with natural products (such as piperine (PIP), gallic acid (GA) and cinnamic acid (CA)) and rosuvastatin (RSV) (a specific breast cancer resistance protein, BCRP substrate) in rats. In Caco2 cells, the polarized transport of RSV was effectively inhibited by PIP, CA and GA at concentration of 50 µM. After per oral (p.o.) coadministration of PIP, CA and GA (10 mg/kg) significantly increased intravenous exposure (AUC(last)) of RSV (1 mg/kg) by 73.5%, 62.9% and 53.3% (p < 0.05), respectively than alone group (control). Compared with the control (alone) group, p.o. coadministration of PIP, CA and GA (10 mg/kg) significantly increased the oral exposure (AUC(last)) of RSV (5 mg/kg) by 2.0-fold, 1.83-fold (p < 0.05) and 2.34 -fold (p < 0.05), respectively. Moreover, the cumulative biliary excretion of RSV (5 mg/kg, p.o.) was significantly decreased by 53.3, 33.4 and 39.2% at the end of 8 h after p.o. co-administration of PIP, CA and GA (10 mg/kg), respectively. Taken together, these results indicate that the natural products such as PIP, CA and GA significantly inhibit RSV transport in to bile and increased the plasma exposure (AUC(last)) of RSV.