Harmala Seeds Research Articles

Pegaharolines A − I, structurally novel indole alkaloids with anti-HSV-2 virus activities from Peganum harmala L. seeds

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 (IC50 = 0.90 ± 0.10 μM) was much better than that of the positive control (acyclovir, IC50 = 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.

Peganum Harmala seeds extract: A green synthesis route for Mn-doped ZnO nanoparticles as an adsorbent for crystal violet dye removal

Peganum Harmala seeds extract: A green synthesis route for Mn-doped ZnO nanoparticles as an adsorbent for crystal violet dye removal

Alkaloids from the seeds of Peganum harmala and their chemotaxonomic significance

A phytochemical study on the seeds of Peganum harmala led to the separation of 22 alkaloids, including quinazoline alkaloids (1–10), β-carboline alkaloids (11–18), and others alkaloids (19–22). Their structures were identified by comprehensive spectroscopic analysis and comparison with literature data. Compounds 14 and 20–22 were first isolated from Zygophyllaceae family. Compounds 8 and 15 were firstly discovered as natural products. Moreover, the chemotaxonomic significance of the isolated alkaloids is discussed.

Synthesis and Characterization of Novel Biochar Developed from Peganum Harmala Seeds to Adsorb Heavy Metals from Aqueous Solution

Synthesis and Characterization of Novel Biochar Developed from Peganum Harmala Seeds to Adsorb Heavy Metals from Aqueous Solution

Phytochemical Profile, Antioxidant, Anti-Alzheimer, And α-Glucosidase Inhibitory Effect Of Algerian Peganum harmala Seeds Extract.

Peganum harmala seeds crude hydro-methanolic extract and their fractions (obtained with ethyl acetate and butan-1-ol) were analyzed and compared for their chemical profiles of alkaloids and polyphenols content. Moreover, their antioxidant, a-glucosidase, acetylcholinesterase, and butyrylcholinesterase inhibitory activities were evaluated. The butan-1-ol fraction revealed the highest total phenolic content and exhibited the highest antioxidant capacity. From the inhibitory enzyme evaluations, it should be highlighted the butan-1-ol fraction inhibitory potential of ɑ-glucosidase (the IC50= 141.18±4μg/mL), which was better than the acarbose inhibitory effect (IC50= 203.41±1.07 μg/mL). The extracts' chemical profile analysis revealed several compounds, in which quercetin dimethyl ether, harmine and harmaline emerged as the major compounds. The different solvents used impacted Peganum harmala seed contents and biological responses. Statistical analysis showed a significant correlation between bioactive compounds and biological activities. Thus, Peganum harmala seeds could be a promising natural source of bioactive compounds at the crossroads of many human diseases, and its cultivation may be encouraged.

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

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. 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 withflow 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 48h 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. 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.

INVESTIGATION OF POTENTIAL ACTIVITIES OF PEGANUM HARMALA SEEDS: IN SILICO AND IN VITRO ANALYSES

Seeds of Peganum harmala L. have been traditionally used in Algerian medicine. This study investigates whether the antioxidant, antihemolytic, and anti-inflammatory activities of Peganum harmala extracts (PHE) are attributed to polyphenolic compounds, which are abundant in methanol, chloroform, and ethyl acetate extracts. Extraction and fractionation of polyphenols involved solvents with different polarities, resulting in a crude extract (CrE), a chloroform extract (CHE), and an ethyl acetate extract (EAE). The antioxidant potential of CrE and its fractions was assessed using the ferrothiocyanate (FTC) and thiobarbituric acid (TBA) assays. The inhibition of mice erythrocyte hemolysis was evaluated for methanol, chloroform, and ethyl acetate extracts in the presence of the oxidant (AAPH). PMA-induced mouse ear edema was used as an in vivo model for inflammation. The FTC assay demonstrated the strong antioxidant effect of CrE (87.64 ± 0.003%). EAE showed potent antioxidant activity with low MDA absorption levels. Assessment of antihemolytic effects against AAPH-induced oxidative hemolysis revealed significant protective effects of CrE and EAE, with EAE showing the most pronounced effect. In the in vivo model, CrE (100 mg/kg) exhibited substantial anti-inflammatory activity, inhibiting the ear edema. Computational analyses using molecular docking simulations showed that chlorogenic acid, hesperetin, and rutin have promising potential as inhibitors of COX-2 protein, which is a key component in inflammatory pathways. This study highlights the potent antioxidant properties of P. harmala, particularly in CrE, and its anti-inflammatory effects. The bioactive compounds, such as chlorogenic acid, hesperetin, and rutin, exhibit potential as anti-inflammatory agents. P. harmala could be a valuable natural source for potential medical applications, suggesting the need for further exploration in medical treatments.

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.

ERADICATION OF HETEROGENEOUS VANCOMYCIN ITERMEDIATED STAPHYLOCOCCUS AUREUS (hVISA) USING PEGANUM HARMALA L. SEEDS EXTRACTS

The main purpose of this research is to evaluate the antibacterial essential oil of Peganum harmala L. seeds against locally isolated heterogeneous vancomycin intermediated Staphylococcus aureus (hVISA) at doses ranging from 0.03 to 200 mg/ml. The filtered essential oil of P. harmala, after extract by the 96% ethanol in a Soxhlet extraction device, was analyzed by GC/MS (gas chromatography-mass spectroscopy). The results showed that the P. harmala seeds oils contained several compounds, such as Harmine (58.26%), followed by 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (28.55%) and Hexadecanoic acid, methyl ester (4.30%), It is highly effective against targeted bacteria. The MIC method was used to investigate antibacterial activity by measuring the lowest inhibitory concentration of the extract and observed that the inhibition concentration against hVISA isolates was 0.3 mg/ml. The gene expression was detected after RNA extract from hVISA (untreated and treated) with P. harmala essential oil using the Quantitative Real-Time PCR method the results revealed that gene expression was low after bacterial with plant extract treatment. Finally, the ethanolic extract of p. harmala seeds appears to be a potential therapy choice for hVISA infection.

STUDY THE EFFECT OF THE AQUATIC AND ALCOHOLIC EXTRACTS OF Peganum harmala SEEDS ON Entamoeba histolytica IN VITRO

In vitro test has been made to find out the efficacy of aqueous and ethanolic extract of Peganum harmala seeds against Entamoeba histolytica in three concentrations (1000, 1500, 2000 μg/ml) in an exposure time of 2hrs, preliminary chemical analysis has been performed for some chemical groups which may exist in the seeds.Results showed that all concentrations of alcohol extracts caused high mortality against parasite by using the alcohol extract in all used concentrations, this may due to the high containing of alkaloids. The highest mortality percentage achieved by alcohol extract was 97.5% while it was 90.1% by aqueous extract at 2000 μg/ml.

Peganum Harmala L. plant as green non-toxic adsorbent for iron removal from water

The present work focuses on examining the batch removal of Fe (III) from water using powdered Peganum Harmala seeds, characterized as FT-IR. In this work, several parameters are measured, including contact time, pH, Fe (III) concentration, reaction temperature effect, and adsorbent dose effect. Fe (III) adsorption was assessed using a UV-vis spectrophotometer at a wavelength of 620 nm. The findings demonstrated a positive correlation between the dosage of adsorbent and Fe (III) ions removal, with an increase in the adsorbent dose corresponding to higher elimination of Fe (III) ions. Therefore, the Langmuir isotherm model yielded more accurate equilibrium data compared to the Frendulich model. The kinetic data were mostly analyzed using a pseudo-second-order model rather than a pseudo-first-order model. Thermodynamic parameters, including enthalpy (ΔH◦), entropy (ΔS◦), and free energy (ΔG◦), were calculated. The adsorption process was found to be exothermic. Overall, Peganum Harmala was a favorable adsorbent for removing Fe (III) from aqueous solutions.

Effect of Peganum harmala seeds extract on the hepatic tissue structure and fetus of mice

Peganum harmala is one of the most used plants for the treatment of many diseases. Its effective compounds have pharmaceutical and medicinal properties. This study aims to determine the effect of aqueous extract of harmala plant seeds on body and liver weight, aspartate aminotransferase (AST), alanine transaminase (ALT), and the histological structure of liver of mice, as well as the size of the fetuses sired by treated mice. Sixteen adult male mice were divided into two groups of eight. The first group (control) was given distilled water orally, while the second group received the aqueous extract of harmala seeds at a dose of 300 mg/kg bw for three weeks. three untreated females were housed with one treated male for mating. At the end of the treatment, six male mice of each group were weighed and killed. Liver was extracted, weighed and its enzymes were measured. Also, sections of the liver were prepared for histological examination. The results showed a decrease in the body weight of the treated mice and a significant increase in the average weight of the fetuses compared with the control group, as well as marked changes in the hepatic tissue structure. There was no impact of the extract on fetal body length, liver weight and hepatic enzymes (AST and ALT) of treated mice. Further studies should be conducted to determine a safe dose that does not affect any organ in the body, so that it can be used for the treatment of many diseases.

Effect of Peganum harmala seeds extract on the hepatic tissue structure and fetus of mice

Peganum harmala is one of the most used plants for the treatment of many diseases. Its effective compounds have pharmaceutical and medicinal properties. This study aims to determine the effect of aqueous extract of harmala plant seeds on body and liver weight, aspartate aminotransferase (AST), alanine transaminase (ALT), and the histological structure of liver of mice, as well as the size of the fetuses sired by treated mice. Sixteen adult male mice were divided into two groups of eight. The first group (control) was given distilled water orally, while the second group received the aqueous extract of harmala seeds at a dose of 300 mg/kg bw for three weeks. three untreated females were housed with one treated male for mating. At the end of the treatment, six male mice of each group were weighed and killed. Liver was extracted, weighed and its enzymes were measured. Also, sections of the liver were prepared for histological examination. The results showed a decrease in the body weight of the treated mice and a significant increase in the average weight of the fetuses compared with the control group, as well as marked changes in the hepatic tissue structure. There was no impact of the extract on fetal body length, liver weight and hepatic enzymes (AST and ALT) of treated mice. Further studies should be conducted to determine a safe dose that does not affect any organ in the body, so that it can be used for the treatment of many diseases.

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.

Effect of Peganum harmala Total Alkaloid Extract on Sexual Behavior and Sperm Parameters in Male Mice.

The study was designed to evaluate the effects of the total alkaloid extract of Algerian Peganum harmala seeds on sexual behavior and male reproductive function. After two weeks of acclimatization, the male mice were randomly divided into four groups (seven mice in each group). For 35 days, the extract was administered orally at dose levels of 6.25, 12.5, and 25 mg/kg body weight per day to the respective groups of male mice (n = 7) and normal saline daily to the control group. On day 28, sexual behavior parameters were recorded. At the end of the trial, reproductive organ weights, sperm quality, seminal fructose, and testosterone hormone levels were evaluated. The three treated groups were compared with the control using statistical variance analysis (one-way ANOVA, p < 0.05), followed by Tukey's test. The results of the groups treated with 12.5 and 6.25 mg/kg of P. harmala alkaloid revealed the MF and IF parameters to be the lowest compared to the control group (p < 0.05). However, the male mice treated with 25 mg/kg recorded the highest values. A low significant value of ML was observed in the group treated with 25 mg/kg of the total alkaloid extract of P. harmala compared to the control group (p < 0.01), while a rise was observed in the concentration group treated with 6.25 mg/kg. Regarding IL, the male mice treated with different concentrations of the total alkaloid extract of P. harmala recorded a higher time than the control group. Moreover, an increase in the gonadosomatic index was noticed in all groups compared to the control group. However, there was a significant (p < 0.01) decrease in the sperm counts of the groups treated with 12.5 mg/kg and 6.25 mg/kg. However, there was no significant difference in the motility, membrane integrity, and total antioxidant capacity of sperm cells compared to the control. The extract treatment also brought about a non-significant increase in fructose content of the seminal vesicle and serum testosterone level. The findings of this study demonstrate that the extract acts in a dose-dependent manner, and it has varying effects on the reproductive parameters of male mice.

Peganutonin A, a novel melatonin analogue from the seeds of Peganum harmala

Peganutonin A, a novel melatonin analogue from the seeds of Peganum harmala

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.______________________________________________________________________________

Lethal and Sublethal Toxicity of Beta-Carboline Alkaloids from Peganum harmala (L.) against Aedes albopictus Larvae (Diptera: Culicidae).

Plant-derived agents are powerful bio-pesticides for the eco-friendly control of mosquito vectors and other blood-sucking arthropods. The larval toxicity of beta-carboline alkaloids against the Asian tiger mosquito, Aedes albopictus (Skuse) (Diptera: Culicidae), was investigated under laboratory conditions. The total alkaloid extracts (TAEs) and beta-carboline alkaloids (harmaline, harmine, harmalol, and harman) from Peganum harmala seeds were isolated and tested in this bioassay. All alkaloids were tested either individually or as binary mixtures, using the co-toxicity coefficient (CTC) and Abbott's formula analysis. The results revealed considerable toxicity of the tested alkaloids against A. albopictus larvae. When all larval instars were exposed to the TAEs at 48 h post-treatment, the mortality of all larval instars varied in a concentration-dependent manner. The second-instar larvae were the most susceptible to different concentrations of TAEs, and the fourth-instar larvae were more tolerant to TAEs than the second-instar larvae. Especially, the third-instar larvae exposed to all alkaloids also showed that all doses resulted in an increased mortality of the third-instar larvae at 48 h post-treatment, and the toxicities of the tested alkaloids in a descending order were TAEs > harmaline > harmine > harmalol, with the LC50 values of 44.54 ± 2.56, 55.51 ± 3.01, 93.67 ± 4.53, and 117.87 ± 5.61 μg/mL at 48 h post-treatment, respectively. In addition, all compounds were also tested individually or in a 1:1 ratio (dose LC25/LC25) as binary mixtures to assess the synergistic toxicity of these binary combinations against the third-instar larvae at 24 and 48 h post-treatment, respectively. The results demonstrated that when tested as a binary mixture, all compounds (especially TAEs, harmaline, and harmine) showed their synergistic effects, exceeding the toxicity of each compound alone. Interestingly, the obtained data further revealed that the TAEs at sublethal doses (LC10 and LC25) could significantly delay the larval development and decrease the pupation and emergence rates of A. albopictus. This phenomenon could be helpful in order to develop more effective control strategies for different notorious vector mosquitoes.

Harmaline exerts potentially anti-cancer effects on U-87 human malignant glioblastoma cells in vitro

Harmaline is a β-carboline alkaloid that can be extracted from the seeds of Peganum harmala. Harmaline has been shown to exhibit a potent cytotoxic effect against tumor cells. In this study, the anti-glioblastoma activity of harmaline was investigated in vitro. Cell viability, apoptosis, and cell cycle arrest were assessed in U-87 cells treated with harmaline at different doses. Reactive oxygen species (ROS) generation and the mRNA expression of apoptosis-associated genes were assessed. The anti-metastatic effect of harmaline on U-87 cells was evaluated by gelatin zymography assay where matrix metalloproteinase [MMP]-2/-9 enzymatic activity was measured, and the scratch assay was used to assess migratory responses. Flow cytometry demonstrated that harmaline could suppress the proliferation and induce sub-G1 cell cycle arrest and apoptotic cell death in glioblastoma cells. Harmaline treatment was also associated with an upregulation of the cell cycle-related genes, p21 and p53, and pro-apoptotic Bax, as well as the induction of ROS. The zymography assay indicated that the essential steps of metastasis were potently suppressed by harmaline through inhibiting the expression of MMP-2 and - 9. In addition, the migration of U-87 cells was significantly reduced after harmaline treatment. Our data suggest a basis for further research of harmaline which has potential cytotoxic activities in glioblastoma cells; inducing cell cycle arrest and apoptosis, repression of migration, possibly invasion, and metastasis.

Systematic and Toxicological Study with Synergy of the Mosquitoes in EL Kantara Region (Biskra, Southern Algeria)

Abstract Recent years have seen the re-emergence of vector-borne diseases, representing more than 17% of infectious diseases globally. Most of these diseases can be prevented by vector control measures. Series of difficulties which are linked to the fight. Plant insecticides can present interesting alternatives to the chemical insecticides currently used in the fight against these pests. In the first part, we have inventoried the vector species in the region of El Kantara, Biskra, by conducting surveys of three sites. The second part focuses on the biological control of the larvae of the most abundant species in the region, that is, Culiseta longiareolata. The faunal inventory of the species of Culicidae in the three sites of El Kantara showed seven species belonging to three genera. The genus Culiseta was the best represented, particularly with the species C. longiareolata (89.91%). The toxicological activity of the ethanoic extracts of the seeds of Peganum harmala and Citrullus colocynthis was studied in synergy against the larvae of Culiseta longiareolata at different concentrations. The mortality rate increased over time to reach more than 70% after 5 days.