The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri

In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (\u3e 97%) in comparison to the pure SCE (~ 42%), or the physical mixture (~ 47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (\u3e 90%), compared to the pure SBE (~ 21%), or the physical mixture (~ 24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents

Drug-Phospholipid Complex-loaded Matrix Film Formulation for the Enhanced Transdermal Delivery of Quercetin

A novel quercetin-phospholipid-complex(QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. The QPLC formulation, prepared using a solvent-evaporation method, was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF)or QPLC QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The films were also functionally characterized for in vitro diffusion of quercetin through a dialysis membrane and ex vivo permeability of quercetin across rat skin. Finally, the anti-inflammatory activity of the films was evaluated on carrageenan-induced paw edema in Wistar albino rats. The experimental design identified the optimal formulation and process variables for the preparation of QPLC. The validation of the obtained model using these values confirmed the suitability and robustness of the model. The physical-chemical characterization of the prepared QPLC supported the formation of a stable complex. The solubility analysis of QPLC showed a 22-fold increase in quercetin aqueous solubility, compared to pure quercetin. The dissolution results exhibited a significantly higher rate and extent of quercetin dissolution from QPLC compared to that of pure quercetin. The permeability of quercetin from Q-MF and QPLC-MF across rat skin mirrored those obtained from the dissolution studies. Topical application of QPLC-MF exhibited a significant (p\u3c0.05) inhibition of carrageenan-induced paw edema in rats compared to that of Q-MF. This study provides a promising combination approach, i.e., phospholipid-based complexation and transdermal film formulation for improved transdermal delivery of quercetin and similar pharmacologically active phytoconstituents

PREDICTION OF ACTIVITY SPECTRA OF SUBSTANCES ASSISTED PREDICTION OF BIOLOGICAL ACTIVITY SPECTRA OF POTENTIAL ANTI-ALZHEIMER'S PHYTOCONSTITUENTS

Objective: To predict the biological activity of certain phytoconstituents for their anti-AD effects.Methods: Several phytoconstituents were selected on the basis of reported literature. The anti-AD activities of selected phytoconstituents were predicted by employing canonical simplified molecular-input line-entry system obtained from PubChem using PASS online.Results: Several phytoconstituents were predicted to have effects better than marketed drugs under some or the other out of the chosen six areas of pharmacological intervention. On the other hand, several new avenues were predicted in which the in vitro and in vivo evaluation of the phytoconstituents can be made on the basis of PASS predicted activities.Conclusion: PASS is an important tool for virtually screening the compounds of interest for the biological activities of interest. This helps the researchers to streamline the research. However, PASS has its own share of limitations amidst a multitude of merits

Antipyretic activity of azima tetracantha in experimental animals

In the present study, the ethanolic leaf extract of Azima tetracantha Lam (A. tetracantha) was investigated for antipyretic activity in rats using Brewer’s yeast induced Pyrexia. The leaves of A. tetracantha were collected from Ponnamaravathi and cut into small pieces and shade dried. The dried powdered leaves (100 gm) were extracted in a Soxhlet apparatus by using 95% ethanol. Albino rats weighing (200-250g) were taken for the experiment divided into four groups of six animals each. Group 1 received 3% aqueous suspension of gum Acacia (1 ml/200g) as vehicle orally, group 2 and group 3 received ethanolic leaf extract of A. tetracantha 100 and 200 mg/kg with 3% aqueous suspension of gum Acacia orally and the group 4 served as standard received paracetamol 25 mg/kg with 3% aqueous suspension of gum Acacia orally. The subcutaneous injection of yeast suspension markedly elevated the rectal temperature after 18h of administration. Treatment with A. tetracantha extract at a dose of 100, 200 mg/kg decreased the rectal temperature of the rats in dose dependent manner. This effect was maximal at dose of 200 mg/kg and it caused significant lowering of body temperature (P< 0.01) up to 4 hour after its administration. The antipyretic effect started as early as 1h and the effect was maintained for 4h, after its administration. Both the standard drug paracetamol 25 mg/kg and tested drug A. tetracantha extract were significantly reduced the yeast elevated rectal temperature, at 2nd, 3rd and 4th hour compared to control group

Larix decidua Bark as a Source of Phytoconstituents: An LC-MS Study

Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of larch bark was performed using mixtures of ethanol/water. Furthermore, the phytochemical composition of larch bark extract was studied using LC-MS(n) methods and the main constituents were identified as flavonoids, spiro-polyphenols, and procyanidins. To confirm the identification by LC-MS semi-preparative HPLC was performed in order to isolate the main constituents and verify the structures by \ub9H-NMR. Antioxidant properties were studied using an in vitro approach combining DPPH assay and LC-MS in order to establish different roles of the various classes of phytochemicasl of the extract. DPPH activity of some of the isolated compounds was also assessed. The overall results indicate this waste material as a good source of antioxidant compounds, mainly procyanidins, whichresulted the most active constituents in the DPPH assay

Comparative chemomapping of phytoconstituents from different extracts of globe artichoke - Cynara scolymus L.

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Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility

Liquid Chromatography – Mass Spectrometry (LC-MS) Analysis of Withania somnifera (Ashwagandha) Root Extract Treated with the Energy of Consciousness

Withania somnifera (ashwagandha) root extract is very popular ancient herbal medicine. The objective of the study was to characterize and evaluate the impact of The Trivedi Effect®-Biofield Energy Healing Treatment (Energy of Consciousness) on phytoconstituents present in the ashwagandha root extract using LC-MS. Ashwagandha root extract was divided into two parts. One part was denoted as the control, while the other part was defined as The Trivedi Effect® - Biofield Energy Treated sample, which received Energy of Consciousness Healing Treatment remotely from eighteen renowned Biofield Energy Healers. The LC-MS analysis of the control and treated samples showed a very close retention time (Rt), indicated that the polarity of the phytoconstituents present in the root extract are same. The numbers of peaks observed in the total ion chromatograms were 28 and 29 in the control and treated samples, respectively. The change in the peak height% of the phytoconstituents in the treated sample was altered significantly within the range of -50.91% to 118.12% compared with the control sample. Similarly, the change in the peak area% of most of the phytoconstituents in the treated ashwagandha was significantly altered within the range of -54.95% to 66.95% compared with the control sample. An additional peak was appeared in the treated sample at Rt of 5.72 minutes, which was not found in the control sample. The LC-MS spectra indicated the presence of possible withanolides like -hydroxy-2,3-dihydro-withanolide F, withanolide A, withaferine A, withanone, withanolide D, ixocarpalactone A, withanolide S, thiowithanolide, etc. in both the samples. The peak are percentage (%) was altered in the identified withanolides, but withanolide sulfoxide was increased significantly by 12.44% in the treated sample compared with the control sample. These results indicated that The Trivedi Effect® - Biofield Energy Treatment might have an impact on the intrinsic physicochemical properties of the phytoconstituents present in the ashwagandha root extract. This could be the probable cause of alteration in the peak height, peak area, and appearance of a new peak in the treated sample. As a result, the concentrations of the phytoconstituents altered in the treated sample compared with the control sample. The treated ashwagandha root extract would be helpful for designing better pharmaceutical/nutraceutical formulations which might be providing a better therapeutic response against autoimmune diseases, nervous and sexual disorders, infectious diseases, antiaging, diabetes, cancer, ulcer, immunological disorders, stress, arthritis, etc. Source: https://www.trivedieffect.com/science/liquid-chromatography-mass-spectrometry-lc-ms-analysis-of-withania-somnifera-ashwagandha-root-extract-treated-with-the-energy-of-consciousness http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=398&doi=10.11648/j.ajqcms.20170101.1

Construction and Analysis of Protein–Protein Interaction of Therapeutic Phytoconstituents of Garlic (Allium sativum) Targeting Non-small Cell Lung Cancer Protein

Background: Advances in genomics and taxonomic literature reveal that lung cancer is a polygenic disease and expose the complexity of cancer-related genes and molecular mechanisms. Several chemically synthesized drugs are used in cancer treatment, but this is still a challenging task because of their lower efficacy and side effects. In recent years, phytochemicals have played a vital role in novel drug discovery; garlic was used in this study to treat lung cancer. This study aimed to determine the specific target, pharmacological, and molecular mechanisms of garlic phytoconstituents in lung cancer treatment. Methodology: Protein–protein interaction network and KEGG signaling pathway analysis of no small cell lung cancer and garlic phytoconstituents revealed that out of 68 targets of non-small cell lung cancer, 14 were targeted by garlic phytoconstituents. Results: Only 14 phytoconstituents of Allium sativum L. have regulatory effects on 14 targets of non-small cell lung cancer. Garlic phytoconstituents have an inhibitory effect on lung cancer progression by regulating highly enriched pathways in lung cancer, such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway. Conclusion: Some garlic phytoconstituents, such as allixin, ajoene, carvacrol, and some derivative of allicin have drug-like properties that target these targets and act by regulating different molecular pathways of cancer progression. The results of this study require further in vivo or experimental studies to confirm their value in lung cancer treatment and to identify the exact binding sites of the selected targets on which ligands can bind

Ayurvedic formulations: potential COVID-19 therapeutics?

Background: While Molnupiravir and Paxlovid have recently been approved for use in some countries, there are no widely available treatments for COVID-19, the disease caused by SARS-CoV-2 infection. Herbal extracts have been used to treat respiratory clinical indications by Ayurvedic medicine practitioners with minimal adverse reactions and intense research efforts are currently under way to develop some of these formulations for COVID-19 treatment. Methods: Literature search for in silico, in vitro, in vivo, and clinical studies on the topic of Ayurvedic formulations for potential COVID-19 treatment, in order to present the current state of current knowledge by integrating information across all systems. Results: The search yielded 20 peer reviewed articles on in silico studies examining the interaction of phytoconstituents of popular Ayurvedic formulations with SARS-CoV-2 components and its receptors; five articles on preclinical investigations of the ability of selected Ayurvedic formulations to inhibit functions of SARS-CoV-2 proteins; and 51 completed clinical trials on the efficacy of using Ayurvedic formulations for treatment of mild to moderate COVID-19. Clinical data was available from 17 of the 51 trials. There was a considerable overlap between formulations used in the in silico studies and the clinical trials. This finding was unexpected as there is no clearly stated alignment between studies and the traditional pathway to drug discovery– basic discovery leading to in vitro and in vivo proof of concept, followed by validation in clinical trials. This was further demonstrated in the majority of the in silico studies where focus was on potential antiviral mechanisms, while the clinical trials were focused on patient recovery using oral treatments. In all 17 clinical trials where data was available, Ayurvedic treatments lead to a shorter period to recovery in participants with COVID-19. Conclusion: The most commonly used Ayurvedic treatments for management of respiratory symptoms associated with SARS-CoV-2 infection appear to have prophylactic and/or therapeutic properties. It would be of particular interest to assess synergistic and concomitant systemic effects and antiviral activities of individual phytoconstituents and their combinations in the Ayurvedic treatments