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Ayahuasca tea is a hallucinogenic beverage used for religious purposes in Brazil and many other countries that has therapeutic potential in the treatment of some mental health disorders. In the context of psychedelic research, quantification of the tea’s main alkaloids prior to its administration in animal or human studies is essential. For this reason, this study aims to provide information regarding the stability of the main ayahuasca alkaloids (dimethyltryptamine, DMT; harmine, HRM; tetrahydroharmine, THH; harmaline, HRL) in three different conditions: (1) A year stored in a refrigerator either in plastic or glass containers, (2) seven days at 37 °C to reproduce usual mail transportation, and (3) after three freeze–thaw cycles. Samples were quantified after a dilute-and-shoot procedure using liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). There was no significant degradation of DMT concentration over time in all tested conditions. Harmala alkaloids (THH, HRL, and HRM) showed important variations after long-term and high-temperature storages. Although DMT has proven to be stable in all studied conditions, the harmala alkaloids revealed intense degradation and even concentration increment. This may be caused by degradation, alkaloid inter-conversion, and leaching from tea precipitate material. Therefore, ayahuasca quantification before administration in controlled sets is mandatory.

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called “neo-shamanic” ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.

Currently, the main pillars in treating breast cancer involve tumorectomy pursued by hormonal, radio, or chemotherapies. Nonetheless, these approaches exhibit severe adverse effects and might suffer from tumor recurrence. Therefore, there is a considerable demand to fabricate an innovative controlled-release nano-delivery system to be implanted after tumor surgical removal to guard against cancer recurrence. In addition, combining platinum-based drugs with phytochemicals is a promising approach to improving the anticancer activity of the chemotherapeutics against tumor cells while minimizing their systemic effects. This study designed polycaprolactone (PCL)-based electrospun nanofiber mats encapsulating nedaplatin (N) and Peganum harmala alkaloid-rich fraction (L). In addition to physicochemical characterization, including average diameters, morphological features, degradation study, thermal stability, and release kinetics study, the formulated nanofibers were assessed in terms of cytotoxicity, where they demonstrated potentiated effects and higher selectivity towards breast cancer cells. The dual-loaded nanofiber mats (N + L@PCL) demonstrated the highest antiproliferative effects against MCF-7 cells with a recorded IC50 of 3.21 µg/mL, as well as the topmost achieved selectivity index (20.45) towards cancer cells amongst all the tested agents (N, L, N@PCL, and L@PCL). This indicates that the dual-loaded nanofiber excelled at conserving the normal breast epithelial cells (MCF-10A). The combined therapy, N + L@PCL treatment, resulted in a significantly higher percent cell population in the late apoptosis and necrosis quartiles as compared to all other treatment groups (p-value of ≤0.001). Moreover, this study of cell cycle kinetics revealed potentiated effects of the dual-loaded nanofiber (N + L@PCL) at trapping more than 90% of cells in the sub-G1 phase and reducing the number of cells undergoing DNA synthesis in the S-phase by 15-fold as compared to nontreated cells; hence, causing cessation of the cell cycle and confirming the apoptosis assay results. As such, our findings suggest the potential use of the designed nanofiber mats as perfect implants to prevent tumor recurrence after tumorectomy.

Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.

Wound healing is a major healthcare concern, and complicated wounds may lead to severe outcomes such as septicemia and amputations. To date, management choices are limited, which warrants the search for new potent wound healing agents. Natural products loaded in poly (lactic-co-glycolic acid) (PLGA) coated with chitosan (CS) constitute a promising antibacterial wound healing formulation. In this work, harmala alkaloid-rich fraction (HARF) loaded into PLGA nanoparticles coated with chitosan (H/CS/PLGA NPs) were designed using the emulsion-solvent evaporation method. Optimization of the formulation variables (HARF: PLGA and CS: PLGA weight ratios, sonication time) was performed using the 33 Box–Behnken design (BBD). The optimal NPs were characterized using transmission electron microscopy (TEM) and Attenuated Total Reflection Fourier-Transformed Infrared Spectroscopy (ATR-FTIR). The prepared NPs had an average particle size of 202.27 ± 2.44 nm, a PDI of 0.23 ± 0.01, a zeta potential of 9.22 ± 0.94 mV, and an entrapment efficiency of 86.77 ± 4.18%. In vitro drug release experiments showed a biphasic pattern where an initial burst of 82.50 ± 0.20% took place in the first 2 h, which increased to 87.50 ± 0.50% over 72 h. The designed optimal H/CS/PLGA NPs exerted high antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.125 and 0.06 mg/mL, respectively) compared to unloaded HARF (MIC of 0.50 mg/mL). The prepared nanoparticles were found to be biocompatible when tested on human skin fibroblasts. Moreover, the wound closure percentage after 24 h of applying H/CS/PLGA NPs was found to be 94.4 ± 8.0%, compared to free HARF and blank NPs (68.20 ± 5.10 and 50.50 ± 9.40%, respectively). In conclusion, the three components of the developed nanoformulation (PLGA, chitosan, and HARF) have synergistic antibacterial and wound healing properties for the management of infected wounds.

In order to find new, less toxic and eco-friendly pest control agents, natural products are considered to be alternative options of potentially active compounds. In this context, the aim of the present study was the isolation and structural elucidation of the β-carboline and quinazoline alkaloids of Peganum harmala L. seeds. Silver nanoparticles (AgNPs) were prepared using alkaloids through a green synthesis procedure. Harmala alkaloids and their AgNPs showed considerable insecticidal and growth inhibitory activities against khapra beetle, Trogoderma granarium (Everts) (Coleoptera: Dermestidae). On a toxicity bioassay using treated filter papers, the total harmala alkaloids (THAs) were the most toxic followed by harmaline, harmine and harmalol, where LC 50’s ranged between (30.6–61.7 µg/cm 2 ) and (24.4–46.1 µg/cm 2 ) 24 h post-treatment against larvae and adults, respectively. The two quinazolines, vasicine and vasicinone, showed moderate to weak activities. At 48 h post-exposure, efficacy of all alkaloids was increased. When tested as AgNPs (size 22.5–66.2 nm diameter), toxicity of alkaloids, especially the β-carbolines, was strongly increased, where LC 50 values ranged between (4.7–11.4 µg/cm 2 ) and (4.1–10.2 µg/cm 2 ) 48 h post-treatment against larvae and adults, respectively. Feeding the 2nd instar larvae AgNPs-treated grains at sublethal concentrations led to significant drawbacks on the normal growth and development of the insect. These effects appeared as a high percentage of malformed larvae and pupae, a prolonged life span and a significant reduction in adult emergence. Results suggest the potential of using harmala alkaloids and their AgNPs as a natural approach for controlling T. granarium .

Background The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala’s alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116 colorectal cancer cells. Methods and results P. harmala’s alkaloid was extracted from harmala seeds. HCT-116 cells were treated with P. harmala’s alkaloid extract, HAR and HAL. Cytotoxicity was determined by MTT assay, apoptotic activity detected via flow cytometry and acridine orange (AO)/ethidium bromide (EB) dual staining, and cell cycle distribution analyzed with flow cytometry. The mRNA expression of Bcl-2-associated X protein ( Bax ) and glycogen synthase kinase-3 beta ( GSK3β ) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3β and p53 proteins, were determined by western blotting. The findings indicated that, P. harmala’s alkaloids extract, HAR and HAL were significantly cytotoxic toward HCT116 cells after 24 and 48 h of treatment. We showed that P. harmala’s alkaloid extract induce apoptosis and cell cycle arrest at G2 phase in the HCT116 cell line. Downregulation of GSK3β and Bcl-2 and upregulation of Bax and p53 were observed. Conclusion The findings of this study indicate that the P. harmala’s alkaloid extract has anticancer activity and may be further investigated to develop future anticancer chemotherapeutic agents.

The use of algae as a foodstuff is rapidly expanding worldwide from the East Asian countries, where they are also used for medical care. Harmala alkaloids (HAlk) are a family of bioactive compounds found in the extracts of some plants, including wakame ( Undaria pinnatifida ), an edible marine invasive algae. HAlks are based on a characteristic β-carboline structure with at least one amino ionizable group. In this work, we report the successful separation of a mixture of six HAlks (harmine, harmaline, harmol, harmalol, harmane, and norharmane) by capillary electrophoresis ion-trap mass spectrometry (CE-IT-MS) in less than 8 min. Optimum separation in fused-silica capillaries and detection sensitivity in positive-ion mode were achieved using a background electrolyte (BGE) with 25 mmol L −1 ammonium acetate (pH 7.8) and 10 % ( v / v ) methanol, and a sheath liquid with 60:40 ( v / v ) isopropanol–water and 0.05 % ( v / v ) formic acid. The separation method was validated in terms of linearity, limits of detection and quantification, repeatability, and reproducibility. Later, a sample pretreatment was carefully optimized to determine HAlks in commercial wakame samples with excellent recovery and repeatability. For the complex wakame extracts, the MS–MS fragmentation patterns of the different HAlks were useful to ensure a reliable identification. The complete procedure was validated using the standard-addition calibration method, determining matrix effects on the studied compounds. Harmalol, harmine, and harmaline were naturally present in the samples and were quantified at very low concentrations, ranging from 7 to 24 μg kg −1 dry algae.

This study reports a facile and eco-friendly method for the green synthesis of platinum and palladium nanoparticles (Pt NPs and Pd NPs) using Peganum harmala seed alkaloid fraction. The ζ-potential of the synthesized Pt NPs, Pd NPs and Pt–Pd NPs were −11.2 ± 0.5, −9.7 ±1.2, and −12.7 ± 2.1 mV; respectively. Transmission electron microscopy (TEM) revealed the formation of spherical-shaped nanoparticles with smooth margins. The mean diameters of the synthesized Pt NPs, Pd NPs, and Pt–Pd NPs were determined using TEM analysis and were found to be 20.3 ± 1.9, 22.5 ± 5.7, and 33.5 ± 5.4 nm, respectively. The nanoparticles’ bioreduction was confirmed by ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, and their organic contents were determined by thermal gravimetric analysis (TGA). The Pt–Pd NPs mixture showed more pronounced antioxidant activity of 843.0 ± 60 μM Trolox equivalent (TE)/mg NPs compared to the individual Pt NPs (277.3 ± 13.5 μM TE/mg NPs) and Pd NPs (167.6 ± 4.8 μM TE/mg NPs). Furthermore, the Pt–Pd NPs exhibited significant cytotoxic activities against lung cancer (A549) and breast adenocarcinoma (MCF-7) cells, IC50 of 8.8 and 3.6 µg/mL, respectively; as compared to Pt NPs (IC50 of 10.9 and 6.7 µg/mL, respectively) and Pd NPs (IC50 of 31 and 10.8 µg/mL, respectively and compared to carboplatin (IC50 of 23 and 9.5 µg/mL, respectively). Moreover, molecular docking studies were conducted to explore the possible anticancer and antioxidant mechanisms of the biogenic nanoparticles. Pt NPs, Pd NPs, and their mixture showed inhibitory activity against cysteine proteinase, which supports their high antitumor activity, but moderate antioxidant activity. In conclusion, Pd-Pt NPs mixture prepared using harmala seed alkaloid fraction showed potential as effective antineoplastic agents.

This chapter contains sections titled: History Identifying Characteristics Exposure Dose Effect Toxicokinetics Histopathology and Pathophysiology Clinical Response Diagnostic Testing Treatment References