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Uncontrolled hemorrhage remains a critical threat in trauma and surgery. This study developed a novel hemostatic composite by encapsulating Peganum harmala L. seed extract (PH) with known hemostatic properties into lipid nanocapsules (PH-LNCs) and then embedding them within a polyvinyl alcohol-chitosan-polyethylene glycol-glycerol (PVA-CS-PEG-G) matrix. The composite was physically crosslinked via the dual processes of freezing-thawing and thermal crosslinking and exhibited robust mechanical properties reaching 0.434 ± 0.014 MPa and elasticity of 40.685 % ± 4.04. It also demonstrated excellent biocompatibility, surface morphology, physical stability, and ex-vivo skin deposition/permeation were assessed. The characterization of PH-LNCs revealed optimal PH-LNC formation and successful integration into the composite with particle size, zeta potential, and PDI were approximately 45.45 ± 24 nm, -16.3 ± 1.4 mV, and 0.374 ± 0.1, respectively. In vitro studies highlighted enhanced blood clotting and platelet adhesion, while in vivo experiments confirmed superior hemostatic efficacy in a mouse tail amputation model. The composite's soft texture, conformability, and mechanical strength make it a promising candidate for effective traumatic wound management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC 50  = 0.90 ± 0.10 μM) was much better than that of the positive control (acyclovir, IC 50  = 1.12 ± 0.15 μM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Peganum harmala L., a traditional medicinal plant in China, is renowned for its significant alkaloid content in seeds and roots exhibiting a wide range of pharmacological activities, including antidepressant, antiseptic, and antiviral. However, the volatile composition of the herb remained unclear. Apart from that, the extraction of volatile compounds through essential oil presents challenges due to the low yield and the degradation of volatile active compounds at high temperatures. This study used multiple sample preparation methods including headspace (HS), needle trap device (NTD), and liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds from the areal part of P. harmala L.. A total of 93 compounds were identified with NTD facilitating the first detection of harmine among the volatile organic compounds. Through network pharmacology and protein interaction analysis, the compounds' potential therapeutic targets of the compounds were explored, and 23 key targets were obtained (AKT1, ALB, PTGS2, MAOA, etc). KEGG pathway enrichment analysis indicated significant involvement in neuroactive ligand-receptor interactions and serotonergic synapses. The results enhanced the understanding of P. harmala's pharmacological mechanisms and supported its ethnopharmacological use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Six alkaloids peharmalines F-K, along with 14 known ones, were isolated from the aerial part of Peganum harmala L.. The structures of the isolated compounds were determined based on their HR-ESI-MS data, extensive NMR spectroscopic analyses, and ECD calculations. 3-(4-Hydroxyphenyl)quinoline exhibited potent antiproliferative activity against the HepG-2 cell lines with an IC 50 value of 3.05 μM. Norharmane displayed a moderate inhibition against A549 and HepG-2 cells with IC 50 values of 16.45 μM and 17.27 μM, respectively., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the present study, a magnetic molecularly imprinted polymer (MMIP) was synthesized for the extraction of harmaline from Peganum harmala by dispersive solid-phase microextraction (DSPME). The MMIP for selective and intelligent extraction of harmaline with excellent functionality and high selectivity was synthesized using the sol-gel method with functionalized superparamagnetic core-shell nanoparticles, ethylene glycol dimethacrylate (EDMA) as a cross-linker, methacrylic acid (MAA) as a functional monomer, and 2,2-azobisisobutyronitrile (AIBN) as a porogen. To study the properties and morphology of the coated polymer, FT-IR spectroscopy, FESEM, TEM images, and VSM were used. The DSPME-HPLC-UV equipment was used to quantify and analyze the data obtained from harmaline extraction. In this research, the efficiency of the synthesized polymer in harmaline extraction was modeled and optimized using the response surface methodology based on central composite design (RSM-CCD). In addition, for modeling the isotherm of harmaline sorption by the MMIP, Langmuir and Freundlich isotherm equations were used. The obtained results showed that the extraction of harmaline with the MMIP was well described with Freundlich isotherm. The results of the validation of the method showed that the measurement of harmaline in the concentration range of 1.0-4000 ng mL -1 followed a linear relationship (R 2  = 9986.0). Moreover, the accuracy or repeatability index (% RSD) was determined to be < 10, and the LOQ and LOD values were 0.526 and 0.158 ng mL -1 , respectively. The results of this study showed that the DSPME technique by using the synthesized MMIP as an effective sorbent with high efficiency and capacity could be utilized for pre-concentration and extraction of harmaline from real and complex samples., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Di(2-ethylhexyl) adipate (DEHA) is a widely used plasticizer and prevalent environmental contaminant. In this study, DEHA concentrations in the milk, cheese, and butter samples wrapped with food-grade commercial polyethylene films and stored at 4 °C for 30 days were detected using gas chromatographic analysis. Also, the effects of exposure to a high dose of DEHA for a long duration on the liver, brain, and heart of Wistar rats were assessed. Besides, the possible beneficial effect of Peganum harmala oil (PGO), in relieving DEHA induced adverse effects was explored. For this purpose, four groups (8 rats/group) were orally given physiological saline, PGO (320 mg/kg bwt), DEHA (2000 mg/kg bwt), or PGO + DEHA for 60 days. The results revealed that the DEHA concentrations in the tested dairy products were ordered as follows: (butter > cheese > milk). Notably, the detected levels in butter were higher than the specific migration limit in foods. DEHA induced a significant increase in the serum levels of glucose, alanine transaminase, aspartate transaminase, acetylcholine esterase, creatine kinase-myocardium bound, malondialdehyde, tumor necrosis factor-α, and interleukin-1β. But, significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia were evident following DEHA exposure. A significant reduction in the serum level of superoxide dismutase, reduced glutathione, and brain-derived neurotrophic factor was recorded. Besides, a significant downregulation in hepatic CYP2E1, brain glial fibrillary acidic protein, and cardiac troponin I gene expression was noticed. Moreover, DEHA exposure induced a significant decrease in Bcl-2 immunolabeling, but Caspase-3 immunoexpression was increased. On the contrary, PGO significantly recused DEHA injurious impacts. Therefore, PGO could represent a promising agent for preventing DEHA-induced hepatotoxicity, neurotoxicity, and cardiotoxicity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is a relentlessly progressive neurodegenerative disease featured by the over-expanded polyglutamine (polyQ)-induced protein aggregation. Using Caenorhabditis elegans (C. elegans) as a model system, we show that water soluble polysaccharide extracted from the herb Peganum harmala L. (PS1) not only reduces polyQ aggregation but also alleviates the associated neurotoxicity. Genetic and pharmacologic analysis suggested that PS1 treatment acts though proteasome-mediated protein degradation pathway to inhibit polyQ aggregation. Notably, the efficacy of PS1 is aroused specifically by co-incubation with live Escherichia coli OP50, which is the sole food source for worms. Further UPLC-Q-TOF/MS analysis determined the bioactivity of polyQ inhibition, which is composed of several oligosaccharides, including stachyoses, verbascoses, trisaccharides and tetrasaccharides composed of galacturonic acids. Together, our study revealed a potential drug target for further HD treatment and pinpointed the possibility that the secreted metabolites produced from bacteria treated with various compounds may provide direct beneficial effect to human bodies., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020. Published by Elsevier B.V.)

Bioanalytical questions are more and more solved by bioassays directly in situ the planar separation. If compared to chemical derivatization in situ, several reagent applications on the same chromatogram make the workflow for enzymatic and biological assays more complex. Hence, if compared to piezoelectric spraying of chemical derivatization reagents, an assay transfer to the piezoelectric spraying technique was much more challenging. Important aspects were investigated, i.e., plate pre-wetting, spraying nozzle type and applied volumes for microorganism suspension as well as enzyme and substrate-chromogenic solutions. Finally, with the newly developed piezoelectric spraying procedures for the application of biological (Aliivibrio fischeri) and enzymatic (acetyl- and butyrylcholinesterase) assays, several obstacles of the state-of-the-art automated immersion were avoided such as the (1) required high volumes of solutions, (2) tailing of highly water-soluble zones upon slow plate withdrawal, (3) zone distortion or shift observed after previous buffer salt applications or long/slow immersion times/speeds, (4) gradual inactivation of the enzyme solution along with its ongoing re-use, and (5) lack of covering the whole plate surface. The benchmarking of both techniques also showed that simplicity remains the key argument for immersion. As proof of concept, piezoelectrically sprayed autograms were compared with those of immersion, by taking the example of Peganum harmala (P. h.) seed extract. The plate background and thus homogeneity of the applied solutions were found to be almost comparable. Three bands among the pronounced fluorescent bands were responsible for the most antibacterial activity of P. h. seed extract in the A. fischeri bioassay and were also inhibiting the AChE. These AChE and three further BChE inhibitors were detected, whereby the AChE inhibition was twice as strong as the BChE inhibition. By their in situ HRMS spectra, the active zones in the P. h. seed extract were assigned to be the AChE-inhibiting β-carboline alkaloids, harmine, harmaline and ruine, as well as the BChE-inhibiting quinazoline alkaloids, vasicine and deoxyvasicine, and the β-carboline alkaloid harmol. For the first time, the found inhibitors were calculated equivalently to the well-known ChE-inhibitor physostigmine, and thus, piezoelectric spraying was proven to be suited for quantifications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An orthogonal two dimensional analysis method based on high performance liquid chromatography (HPLC) separation and electrospray ionization-ion mobility spectrometry (ESI-IMS) detection was developed for the analysis of alkaloid compounds from Peganum harmala L. seeds. Reverse phase (RP) and hydrophilic interaction chromatography (HILIC) were compared for the most optimal performance using three different chromatographic columns. The experimental results suggest that HILIC mode is a better option for combining with the ESI-IMS system for higher sensitivity and ease in hyphenating. Under optimized conditions, alkaloids from different extraction phases were determined by means of the established HPLC-IMS method. More compounds from Peganum harmala L. seed extracts were differentiated on the HPLC-ESI-IMS system by their retention time and drift time than by HPLC or ESI-IMS alone, and thirteen alkaloids were tentatively identified based on m/z and fragment ions using ultra-high-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Hence, our results indicate that this method can be considered to be advantageous over traditional absorbance detection methods for resolving complex mixtures because of complementary separation steps, elevated peak capacity, and higher sensitivity., (Copyright © 2018. Published by Elsevier B.V.)

Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indole alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala. Their structures and absolute configurations were elucidated through spectroscopic analyses and quantum chemistry calculations. Notably, (±)-peganumalines A (1) represent a pair of rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon skeleton. All isolates were tested for antiproliferative and antibacterial activities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A thin-layer chromatography (TLC)-bioautographic method was developed with the aim to detect dipeptidyl peptidase IV (DPP IV) inhibitors from plant extracts. The basic principle of the method is that the enzyme (DPP IV) hydrolyzes substrate (Gly-Pro-p-nitroaniline) into p-nitroaniline (pNA), which diazotizes with sodium nitrite, and then reacts with N-(1-naphthyl) ethylenediamine dihydrochloride in turn to form a rose-red azo dye which provides a rose-red background on the TLC plates. The DPP IV inhibitors showed white spots on the background as they blocked enzymolysis of the substrate to produce pNA. The method was validated with respect to selectivity, sensitivity, linearity, precision, recovery, and stability after optimizing key parameters including plate type, time and temperature of incubation, concentration of substrate, enzyme and derivatization reagents, and absorption wavelength. The results showed good lineary within amounts over 0.01-0.1μg range for the positive control, diprotin A, with the coefficient of determination (r(2))=0.9668. The limits of detection (LOD) and quantification (LOQ) were 5 and 10ng, respectively. The recoveries ranged from 98.9% to 107.5%. The averages of the intra- and inter-plate reproducibility were in the range of 4.1-9.7% and 7.6-14.7%, respectively. Among the nine methanolic extracts of medicinal herbs screened for DPP IV inhibitors by the newly developed method, Peganum nigellastrum Bunge was found to have one white active spot, which was then isolated and identified as harmine. By spectrophotometric method, harmine hydrochloride was found to have DPP-IV inhibitory activity of 32.4% at 10mM comparing to that of 54.8% at 50μM for diprotin A., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Non-specific lipid transfer proteins (ns-LTPs), ubiquitously found in various types of plants, have been well-known to transfer amphiphilic lipids and promote the lipid exchange between mitochondria and microbody. In this study, an in silico analysis was proposed to study ns-LTP in Peganum harmala L., which may belong to ns-LTP1 family, aiming at constructing its three-dimensional structure. Moreover, we adopted MEGA to analyze ns-LTPs and other species phylogenetically, which brought out an initial sequence alignment of ns-LTPs. In addition, we used molecular docking and molecular dynamics simulations to further investigate the affinities and stabilities of ns-LTP with several ligands complexes. Taken together, our results about ns-LTPs and their ligand-binding activities can provide a better understanding of the lipid-protein interactions, indicating some future applications of ns-LTP-mediated transport., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Alkaloids comprise one of the largest groups of plant secondary metabolites including vinca alkaloids. The ability of six alkaloids from Veratrum lobelianum, one from Veratrum nigrum and three from Peganum nigellastrum to modify transport activity of MDR1 was studied. Flow-cytometry in a multidrug-resistant human MDR1-gene-transfected mouse lymphoma cells (L5178Y) was applied. The inhibition of multidrug resistance was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Veralosinine and veranigrine were the most effective resistance modifiers. In a checkerboard method veralosinine and veranigrine enhanced the antiproliferative effects of doxorubicin on MDR cells in combination. The structure-activity relationships were discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The β-carboline alkaloids of Peganum harmala L were extracted through a bioassay-guided fractionation and their antimicrobial activities were investigated. Results revealed significant differences (P>0.05) between compounds depending on the microorganism tested and the application method. When examined individually, harmine was the most effective against Proteus vulgaris, Bacillus subtilis and Candida albicans where inhibition zones ranged between 21.2 and 24.7 mm. Potentiality of the alkaloids was increased when applied as binary mixtures suggesting a kind of synergistic interaction with inhibition zones reaching 31.5mm with the total alkaloidal extract. We recommended the use of such compounds as new antimicrobial biorationals., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Peganum harmala seed extracts have been frequently reported to possess antibacterial potential through in vitro studies, but in vivo studies have acquired less attention. The present study was therefore designed to investigate its efficacy on the course of colibacillosis and effects of long-term feeding on selected parameters of general health in chickens. Two experiments were conducted in this regard. Experiment 1 (a pilot study) was performed to determine the dose of a field strain of Escherichia coli (O1:K1) required to induce clinical symptoms in 4- and 15-d-old specific-pathogen-free chickens. A successful induction of colibacillosis, in terms of clinical signs, mortality, and pathological lesions in addition to reisolation of the pathogen was observed by inoculating 4- and 15-d-old chicks with 4.3 log(10) and 6.4 log(10) cfu of E. coli, respectively, by intraperitoneal injection. Using these doses experiment 2 (main study) consisting of a single experiment with 3 parts was performed. Parts A and B generated the information regarding efficacy of the extract against infection in 4- and 15-d-old chickens applying different treatment schemes, whereas the effects of continuous feeding of the extract were assessed in part C. Whereas no protective effect of the extract could be recorded in young chickens, significant differences (P < 0.05) with regard to BW, clinical score, gross lesion score, and total granulocyte counts were observed in 15-d-old birds. Bacterial recovery per gram of tissue and reisolation frequency were lower in treated birds. The continuous feeding of the extract for 6 wk resulted in an augmentation in relative liver weight and depletion in alkaline phosphatase, protein, albumin, and globulin. It can be concluded that the crude extract of Peganum harmala possesses limited antimicrobial activity against E. coli in vivo and long-term continuous feeding may induce undesired effects. Furthermore, the study underlines the value of in vivo experiments and the diverse picture that herbal products, in this case Peganum harmala, may deliver by testing them against specific pathogens.

The present work describes the mechanisms involved in the vasorelaxant effect of harmine and harmaline. These alkaloids induce in a dose-dependent manner the relaxation in the aorta precontracted with noradrenaline or KCl. However, the removal of endothelium or pre-treatment of intact aortic ring with L-NAME (inhibitor of NOSe synthetase) or with indomethacin (non-specific inhibitor of cyclo-oxygenase), reduces significantly the vasorelaxant response of harmaline but not harmine. According to their IC50 values, prazosin (inhibitor of alpha-adrenorecepteors) reduces the vasorelaxant effect only of harmaline, whereas, pre-treatment with IBMX (non-specific inhibitor of phosphodiesterase) affects both the harmaline and harmine-responses. Inhibitions of L-type voltage-dependent Ca2+ channels (VOCs) in endothelium-intact aortic rings with diltiazem depress the relaxation evoked by harmaline as well as by harmine. Pre-treatment with harmaline or harmine (3, 10 or 30 microM) shifted the phenylephrine-induced dose response curves to the right and the maximum response was attenuated indicating that the antagonist effect of both alkaloids on alpha1-adrenorecepteors was non-competitive. These two alkaloids also exert an antioxidant activity by scavenging the free radical generated by DPPH. Therefore, the present results suggest that the vasorelaxant effect of harmaline but not harmine is related to its action on the prostacyclin pathway and on the endothelial cells to release NO. However, both alkaloids can act as blockers VOCs, as inhibitors of phosphodiesterase resulting in an increase of the second messenger (cAMP and cGMP) levels and finally reduce the levels of free radicals in tissues.