Natural harmaline acts as novel fluorescent probe for hypochlorous acid and promising therapeutic candidate for rheumatoid arthritis.

Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products.

Insights into free radicals scavenging, α-Amylase inhibition, cytotoxic and antifibrotic activities unveiled by Peganum harmala extracts.

BACKGROUND: Peganum harmala L. is used in traditional medicine to treat several health ailments. Hence, the present work aimed to investigate the DPPH free radical scavenging, α-amylase, cytotoxic, and antifibrotic effects of the hydrophilic extract and fixed oil obtained from P. harmala seeds. METHODS: The hydrophilic extract and fixed oil of P. harmala were assessed for their abilities to scavenge DPPH free radicals and inhibit α-amylase using reference bioassays. The cytotoxicity was assessed on several cancer and normal cell lines, including B16F1, Caco-2, COLO205, HeLa, Hep 3B and Hep G2, MCF-7, and HEK-293 T cells. The MTS assay was used to evaluate the antifibrotic capabilities utilizing the human hepatic stellate (LX-2) cell line. RESULTS: P. harmala plant fixed oil has potent DPPH free radical scavenging activity with an IC50 dose of 79.43 ± 0.08 µg/ml. Besides, the hydrophilic extract has a poor anti-α-amylase effect compared with the antidiabetic drug Acarbose, with IC50 doses of 398 ± 0.59 and 25.11 ± 1.22 µg/ml, respectively. In addition, the growth of MCF-7, Hep3B, HepG2, HeLa, COLO205, CaCo2, B16F1, and HeK293t was inhibited by P. harmala hydrophilic extract with IC50 doses of 121.34 ± 1.71, 268.3 ± 0.75, 297.20 ± 1.00, 155.60 ± 1.14, 150.01 ± 0.51, 308.35 ± 0.53, 597.93 ± 1.36, and 5.38 ± 0.99 µg/ml, respectively. In addition, at 1000 µg/ml, 5-Fluorouracil reduced fibrosis cells by 0.089%, while the hydrophilic extract decreased the number of LX-2 cells by 5.81%. CONCLUSION: P. harmala plant-fixed oil exhibits potential antioxidant properties. While the hydrophilic extract showed limited effectiveness as an anti-α-amylase agent and demonstrated notable cytotoxic effects against various tested cancer cell lines. Furthermore, this extract significantly reduces the number of LX-2 fibrotic cells. These findings emphasize the therapeutic potential of these products in managing various health disorders and warrant further investigation into their mechanisms of action and clinical applications.

Profiling the volatile compounds of Peganum harmala L. Based on multiple sample preparation coupled with gas chromatography-mass spectrometry analysis and explored its antidepressants-like activity.

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.

Cytotoxicity of alkaloids isolated from Peganum harmala seeds on HCT116 human colon cancer cells.

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 (GSK3ß) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3ß 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 GSK3ß 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.

Phytochemical profiling, cytotoxic, anti-migration, and anti-angiogenic potential of phenolic-rich fraction from Peganum harmala: in vitro and in ovo studies.

Peganum harmala has been extensively employed in Algerian traditional medicine practices. This study aimed to explore the impact of n-butanol (n-BuOH) extract sourced from Peganum harmala seeds on cell proliferation, cell migration, and angiogenesis inhibition. Cytotoxic potential of n-BuOH extract was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide) assay against human breast adenocarcinoma MCF-7 cells, cell migration was determined using scratch assay, and anti-angiogenic effect was evaluated through macroscopic and histological examinations conducted on chick embryo chorioallantoic membrane. Additionally, this research estimated the phytochemical profile of n-BuOH extract. Fifteen phenolic compounds were identified using Ultra-performance liquid chromatography UPLC-ESI-MS-MS analysis. In addition, the n-BuOH extract of P. harmala exhibited potent antioxidant and free radical scavenging properties. The n-BuOH extract showed potent cytotoxicity against MCF-7 cell with an IC50 value of 8.68 ± 1.58 µg/mL. Furthermore, n-BuOH extract significantly reduced migration. A strong anti-angiogenic activity was observed in the groups treated with n-BuOH extract in comparison to the negative control. Histological analysis confirmed the anti-angiogenic effect of the n-BuOH extract. This activity is probably a result of the synergistic effects produced by different polyphenolic classes.

ß-Carboline alkaloids from the roots of Peganum harmala L.

This study reports the isolation of four new ß-carboline alkaloids (1-4) and six previously identified alkaloids (5-10) from the roots of Peganum harmala L. Among these compounds, 1 and 2 were characterized as rare ß-carboline-quinazoline dimers exhibiting axial chirality. Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring, and compound 4 was a novel annomontine ß-carboline. The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations. The biosynthetic pathways of 1-3 were proposed. Additionally, the cytotoxicity of some isolates against four cancer cell lines (HL-60, A549, MDA-MB-231, and DU145) was evaluated. Notably, compound 4 exhibited significant cytotoxicity against HL-60, A549, and DU145 cells with IC50 values of 12.39, 12.80, and 30.65 µmol·L-1, respectively. Furthermore, compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC50 value of 17.32 µmol·L-1.

Myceligenerans pegani sp. nov., an endophytic actinomycete isolated from Peganum harmala L. in Xinjiang, PR China.

An endophytic actinomycete designated TRM65318T, was isolated from the root of Peganum harmala L. Its taxonomic status was determined using a polyphasic approach. Comparative 16S rRNA gene sequence analysis indicated that strain TRM65318T is phylogenetically most closely related to Myceligenerans salitolerans XHU 5031T (98.15 %) and Myceligenerans xiligouense DSM 15700T (97.78 %). The peptidoglycan belonged to type A4α. The polar lipids were phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, two unknown lipids and three glycolipids. The predominant menaquinones were MK-9(H4) and MK-9(H6) and the whole-cell sugars contained glucose, mannose and galactose. Major fatty acids were anteiso-C15 : 0, iso-C15 : 0 and C16 : 0. Strain TRM65318T had a genome size of 5881012 bp with a genome G+C content of 71.79 mol%. The average nucleotide identity and DNA-DNA hybridization values between strain TRM65318T and the most closely related species were much lower than the thresholds commonly used to define species. At the same time, differences in phenotypic and genotypic data showed that strain TRM65318T could be clearly distinguished from M. salitolerans XHU 5031T. Therefore, it is concluded that strain TRM65318T represents a novel species of the genus of Myceligenerans. The proposed name for this organism is Myceligenerans pegani sp. nov., with type strain TRM65318T (=CCTCC AA 2019057T=LMG 31679T).

Chromatographic assessment of biodiesel production from Peganum harmala seed oil using environmentally benign nano-catalysts.

This work gives a comprehensive chromatographic assessment of biodiesel generation from plant seed oil using ecologically friendly nano-catalysts. Researchers all over the world are actively looking for new ways to satisfy the urgent need for clean and renewable energy sources. The resultant biodiesel was fully characterized utilizing modern techniques like scanning electron microscopy, energy diffraction X-ray and X-ray diffraction. The biodiesel gas chromatography/mass spectrometry analysis revealed four significant peaks of fatty acid methyl esters, indicating high-quality biodiesel production. Furthermore, the biodiesel fuel qualities were discovered to be comparable with international standards such as ASTM D-6571 and EN-14214. This indicates that the iron-modified clay nano-catalyst can be used as a catalyst for large-scale biodiesel production. This work is important because it could lead to the large-scale production of a novel, non-food feedstock. We may lessen our reliance on fossil fuels and contribute to a more sustainable and ecologically friendly energy future by leveraging the usage of biodiesel produced in this way. The chromatographic assessment of biodiesel production from non-edible seed oil using environmentally benign nano-catalysts holds significant promise in advancing sustainable and eco-friendly biodiesel production methods, contributing to a cleaner and more environmentally responsible energy sector.

Antiseizure Effects of Peganum harmala L. and Lavandula angustifolia.

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for behavioral changes for one hour. In addition, the effects of flumazenil and naloxone on the antiseizure activity of P. harmala and L. angustifolia were assessed. P. harmala showed antiseizure activity at the dose of 10 mg/kg; it prolonged the seizure latency and decreased the seizure duration. The mortality protection rate was 90% for this herbal extract. L. angustifolia (600 mg/kg) prolonged the seizure latency and decreased both seizure duration and mortality. Neither flumazenil nor naloxone significantly reversed the antiseizure activities of P. harmala and L. angustifolia. In mice, the hydroalcoholic extracts of P. harmala and L. angustifolia showed antiseizure activity against PTZ-induced seizures. We could not delineate the exact antiseizure mechanisms of these extracts in the current study.

Innovative spectrofluorometric method for determination of harmaline and harmine in different matrices.

Harmaline and harmine are naturally occurring closely related ß-carboline alkaloids found in Peganum and Banisteriopsis plants. They have historical significance in traditional practices due to their potential psychoactive and therapeutic properties. Herein, a highly sensitive spectrofluorometric method was developed for the quantifying of harmaline and harmine in diverse matrices, including pure forms, seed samples, and spiked plasma. The procedures lie in addressing the challenge of overlapping fluorescence spectra exhibited by harmaline and harmine through the incorporation of hydroxypropyl-ß-cyclodextrin, altering their chemical properties and fluorescence characteristics. Synchronous fluorescence measurements coupled with first derivative mathematical technique make it possible to distinguish between the harmaline and harmine at 419 and 456 nm, respectively. The method effectiveness is demonstrated through spectral analysis, optimization of the measurement conditions, adopting validation parameters and application to the pure form, seed samples and spiked human plasma. This methodology facilitates accurate determination of these alkaloids over the concentration range of 10─200 ng/mL. Thus, the developed approach provides a robust mean for the precise determination of harmaline and harmine, contributing to analytical chemistry's ongoing efforts to address complex challenges in quantification across diverse matrices.

A Novel Aniline Derivative from Peganum harmala L. Promoted Apoptosis via Activating PI3K/AKT/mTOR-Mediated Autophagy in Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is a common clinical malignant tumor with limited therapeutic drugs. Leading by cytotoxicity against NSCLC cell lines (A549 and PC9), bioactivity-guided isolation of components from Peganum harmala seeds led to the isolation of pegaharoline A (PA). PA was elucidated as a structurally novel aniline derivative, originating from tryptamine with a pyrrole ring cleaved and the degradation of carbon. Biological studies showed that PA significantly inhibited NSCLC cell proliferation, suppressed DNA synthesis, arrested the cell cycle, suppressed colony formation and HUVEC angiogenesis, and blocked cell invasion and migration. Molecular docking and surface plasmon resonance (SPR) demonstrated PA could bind with CD133, correspondingly decreased CD133 expression to activate autophagy via inhibiting the PI3K/AKT/mTOR pathway, and increased ROS levels, Bax, and cleaved caspase-3 to promote apoptosis. PA could also decrease p-cyclinD1 and p-Erk1/2 and block the EMT pathway to inhibit NSCLC cell growth, invasion, and migration. According to these results, PA could inhibit NSCLC cell growth by blocking PI3K/AKT/mTOR and EMT pathways. This study provides evidence that PA has a promising future as a candidate for developing drugs for treating NSCLC.

Identification of new modulator of DNA repairing pathways based on natural product (±)-peharmaline A.

The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (±)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (±)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity. ______________________________________________________________________________.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

(±)-Pheharmines A-B, two pairs of racemic alkaloids with a morpholino[4,3,2-hi]ß-carboline core, from the roots of Peganum harmala.

Two pairs of unprecedented ß-carboline-phenylpropanoid heterogeneous alkaloids, (±)-pheharmines A-B (1-4), characterized by a morpholino[4,3,2-hi]ß-carboline core with two chiral centers, were isolated from the roots of Peganum harmala. The structures, including their absolute configurations, were identified using spectroscopic analyses and electronic circular dichroism (ECD) calculations. The biosynthetic hypothesis for the formation of pheharmines A-B was proposed. Compounds 1-4 exhibited moderate cytotoxic activities against HL-60 cell lines.

Effect of zein and zein-Peganum harmala extract coatings of eggshell on the internal quality of eggs and control of Salmonella enteritidis.

The high nutritional value of egg makes it vital to the human diet. Salmonella enteritidis is one of the major global causes of foodborne enteritis in humans. The chicken intestine is the main source of S. enteritidis. Therefore, eggs play an important role in the transmission of salmonellosis. In this study, we evaluated the effectiveness of coatings made of zein either alone or in combination of hydro-alcoholic extract of Peganum harmala on the quality of eggs and control of S. enteritidis at 7°C during a period of 28 days. Results demonstrated that both types of the coating significantly improved the physicochemical properties of eggs including weight loss, Haugh unit, and yolk index compared to controls during storage. However, neither of coatings resulted in significant changes in yolk color and pH (p < 0.05). Both types of coating caused two log CFU/ml reductions in S. enteritidis population from the first day and eliminated the contamination at the end of the experiment (for 28 days). Salmonella elimination occurred at day 21 for zein-plant extract coating. Our findings demonstrate zein coating can be an appropriate approach for maintaining the quality of eggs during shelf life and an effective and economic strategy for control of S. enteritidis in eggs. PRACTICAL APPLICATION: This study shows that the application of zein coating can preserve the internal quality and freshness of eggs during storage. Moreover, zein coating is a highly effective strategy in the control of Salmonella. This method can be used on a commercial scale for enhancing the safety and quality of eggs.

Antibacterial, Antifungal, Antiviral, and Antiparasitic Activities of Peganum harmala and Its Ingredients: A Review.

Infectious diseases have always been the number one enemy threatening health and well-being. With increasing numbers of infectious diseases, growing resistance of pathogens, and declining roles of antibiotics in the treatment of infectious diseases, it is becoming increasingly difficult to treat new infectious diseases, and there is an urgent need to develop new antibiotics to change the situation. Natural products tend to exhibit many special biological properties. The genus Peganum (Zygophyllaceae) has been used, for a long time, to treat cough, asthma, lumbago, hypertension, diabetes, and Alzheimer's disease. Over the past two decades, a growing number of studies have shown that components from Peganum harmala Linn and its derivatives can inhibit a variety of microorganisms by inducing the accumulation of ROS in microorganisms, damaging cell membranes, thickening cell walls, disturbing cytoplasm, and interfering with DNA synthesis. In this paper, we provide a review on the antibacterial, antifungal, antiviral, and antiparasitic activities of P. harmala, with a view to contribute to research on utilizing P. harmala for medicinal applicaitons and to provide a reference in the field of antimicrobial and a basis for the development of natural antimicrobial agents for the treatment of infectious diseases.

A Possible Synergistic Herbal Solution for COVID-19.

The COVID-19 pandemic has provided an opportunity for repurposing of drugs, including complex, natural drugs, to meet the global need for safe and effective antiviral medicines which do not promote multidrug resistance nor inflate medical costs. The author herein describes his own repurposing of herbal tinctures, previously prepared for oncology, into a possibly synergistic, anti-COVID 41 "herb" formula of extracts derived from 36 different plants and medicinal mushrooms. A method of multi-sample in vitro testing in green monkey kidney vero cells is proposed for testing the Hypothesis that even in such a large combination, antiviral potency may be preserved, along with therapeutic synergy, smoothness, and complexity. The possibility that the formula's potency may improve with age is considered, along with a suitable method for testing it. Collaborative research inquiries are welcome.

Antimicrobial activities of different solvent extracts from stem and seeds of Peganum Harmala L.

Wild medicinal herbs have been used as folk and traditional medicines all across the world since well before recorded history. This present study was designed to test the antimicrobial activities of five different solvent extracted samples (n-hexane, n-butanol, ethyl acetate, methanol, and water) of Peganum harmala using stems and seeds. Two different strains of Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacteria (Bacillus subtilus and Staphylococcus aureus), and one fungal strain (Candida albicans) were used. The antimicrobial activities were measured using a disc diffusion assay. Two concentrations of the extracts (1 and 2mgDisc-1) were used. Ethyl acetate fraction was found more affective among the tested solvents and showed maximum activity (zone of inhibition) against S. aureus (65.53 and 81.10%), E. coli (46.22 and 61.29%) while n-butanol and water fractions gave maximum activity against S. aureus (78.86 and 70.00%) and K. pneumonia (57.00 and 61.39%) respectively. Water fraction showed maximum activity against C. albicans (60.00 and 81.88%). In the case of the stem, Ethyl acetate again showed more activity against B. subtilus (38.57 and 42.10%) and S. aureus (36.66 and 46.66%) while n-butanol showed maximum activity against K. pneumonia (24.55 and 32.44%) and E. coli (27.93 and 37.61%). Methanol was found more effective against C. albicans (25.71 and 43.80%). Seed extracted samples were found more effective compared to the stem. Ethyl acetate, butanol, and aqueous extracted samples showed good activity against the tested microbes, so these fractions are recommended for study their mechanism of actions and isolation of bioactive metabolites responsible for antimicrobial activities. The P. harmala should be evaluated for their bioactive compounds to be used in future studies. Our objective is to provide the framework for future study on the roles of P. harmala as traditional medicines.

Ruta graveolens, Peganum harmala, and Citrullus colocynthis methanolic extracts have in vitro protoscolocidal effects and act against bacteria isolated from echinococcal hydatid cyst fluid.

Echinococcosis is a common and endemic disease that affects both humans and animals. In this study, the in vitro activities of methanolic extracts of Ruta graveolens, Peganum harmala aerial parts, and Citrullus colocynthis seeds against protoscolosis and isolated bacterial strains from hydatid cysts were assessed using disc diffusion methods and Minimum Inhibitory Concentration (MIC). The chemical composition of three methanolic extracts was studied using LC-MS. After 3 h of exposure to 40 mg/mL R. graveolens extract, a tenfold protoscolocidal effect was seen when compared to the convintional medication (ABZ) for the same duration (P < 0.05). The bacteria listed below were isolated from hydatid cyst fluid collected from a variety of sick locations, including the lung and liver. Micrococcus spp., E. coli, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter amnigenus, Pseudomonas aeruginosa, Staphylococcus xylosus, and Achromobacter xylosoxidans are among the bacteria that have been identified. The most effective extract was R. graveolens, followed by P. harmala and C. colocynthis, according to the results of antibacterial activity using the disc diffusion method. R. graveolens extract had the lowest MIC values (less than 2 mg/mL) against all microorganisms tested. This shows that the R. graveolens extract has additional properties, such as the ability to be both scolocidal and bactericidal. Because these bacteria are among the most prevalent pathogenic bacteria that increase the risk of secondary infection during hydatid cysts, the results of inhibitory zones and MICs of the R. graveolens methanol extract are considered highly promising.

In vitro Eradication of Pseudomonas aeruginosa Persister Cell Producers by Peganum harmala.

BACKGROUND: Because of increasing antibiotic failure and recurrence of infections in patients with P. aeruginosa, the present study was designed to determine the antibiotic resistance status, presence of persister cells and investigate the antipersister effect of Peganum harmala in P. aeruginosa clinical isolates in vitro in Ilam, Iran. METHODS: Thirty P. aeruginosa urinary clinical isolates were collected from hospitals in Ilam, Iran and identified by common microbiological and biochemical tests. Afterward, antibiotic susceptibility assay, persister cell assay, P. harmala extraction, cell culture, and cell viability assays were performed. RESULTS: A high rate of antibiotic resistance was observed. All isolates were resistant to co-amoxiclav. Also, 83.3% (n = 25), 90% (n = 27), and 36.6% (n = 11) of isolates showed resistance to ceftazidime, kanamycin, and tobramycin, respectively. The MIC and MBC values for imipenem were ≤ 2 and 2 µg/mL for susceptible isolates, respectively. In addition, 6.66% (n = 2) of isolates were persister cells and were also sensitive to imipenem by MIC but did not show any MBC. IC50 for P. harmala was 35 µg/mL. Eventually, MIC value of P. harmala against two P. aeruginosa persister cell producer isolates was 3 µg/mL and 1 µg/mL, and the value of MBC was 10 µg/mL and 30 µl/mL. CONCLUSIONS: Our findings demonstrated that P. harmala may be a suitable antipersister herbal medicine against P. aeruginosa clinical isolates. In this regard, comprehensive research is needed in the future to gain more information in this area.