Peganum Harmala Seeds Research Articles

A comparative study of total phenolic contents and antioxidant potential of seeds of Peganum harmala

A comparative study of total phenolic contents and antioxidant potential of seeds of Peganum harmala

A comparative study of total phenolic contents and antioxidant potential of seeds of Peganum harmala

A comparative study of total phenolic contents and antioxidant potential of seeds of Peganum harmala

Comparison of zero valent iron and zinc oxide green nanoparticles loaded on activated carbon for efficient removal of Methylene blue

In this study, iron nanoparticles (GnZVI) and zinc oxide nanoparticles (GnZnO) were synthesized by Peganum harmala seeds extract using green method, and were loaded on activated carbon derived from P. harmala seed (AC). TEM analysis showed that the nanoparticle size was smaller than 100 nm, while EDAX analysis confirmed that GnZVI and GnZnO were stabilized on AC. BET analysis showed that GnZnO/AC and GnZVI/AC special surface areas were 208 and 107 m(2)/g, respectively. Moreover, the FTIR analysis showed the role of polyphenolic groups in the synthesis of nanoparticles. It was generally found that GnZnO/AC showed higher efficiency in the adsorption of methylene blue as compared with GnZVI/AC.

Effect of Alkaloids Extract of Peganum Harmala Seeds on Histo-Function of Rat’s Testes

Effect of Alkaloids Extract of Peganum Harmala Seeds on Histo-Function of Rat’s Testes

Extracts of compound Muniziqi granule suppressed uterus contraction and ameliorated oxytocin-induced primary dysmenorrhea

Ethnopharmacological relevanceCompound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM. Aim of the studyThis work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. Materials and methodsIn vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), thromboxane B2 (TXB2), and nitric oxide (NO) levels in uterine tissues and PGF2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. ResultsIn contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF2α, 6-k-PGF1α, TXB2, NO and MDA in uterine tissues and PGF2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. ConclusionsCMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.

Effects of Spinal-Z in Patients with Gastroesophageal Cancer.

ObjectiveThe purpose of this study was to investigate the efficacy and safety of spinal-Z, derived from Peganum harmala seeds and Dracocephalum Kotschyi Boiss leaves, in patients with esophageal and stomach adenocarcinoma, and squamous cell carcinoma of the esophagus.MethodsSixty-one patients with malignancies of the upper gastrointestinal tract were randomly assigned to one of two groups (treatment or control) in a double-blind fashion. Six capsules of Spinal-Z were prescribed to the patients with the regimen of 600 mg/m2/day, and placebo to the control group, for six months.ResultsThere were no significant differences between the two groups with regard to age, sex, duration of cancer, type of cancer and family history of cancer. There were significant differences in abdominal pain, heartburn, constipation and vomiting between the two groups, following spinal-Z therapy. Evaluation of drug side effects showed no difference in cough or other respiratory symptoms, itching, headache or dizziness between the two groups, both before and after treatment.ConclusionThis study indicates that Spinal-Z is safe and efficacious in the management of patients with upper gastrointestinal tract cancers.

Racemic indole alkaloids from the seeds of Peganum harmala

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.

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC50 value of 15.41 μM.

HPLC and GC–MS Analysis of Tunisian Peganum harmala Seeds Oil and Evaluation of Some Biological Activities

In this work, we characterized by high-performance liquid chromatography, the γ-tocopherol (573.66 μg/g), and by gas chromatography-mass spectrometry, the linoleic acid (62.05%) as major components from Peganum harmala L. seeds oil and evaluated their potential in vivo acute antiinflammatory, analgesic activities, and in vitro antioxidative capacity. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay showed an important antioxidant activity (62.50% with an IC50 of 4.8 mg/mL). In addition, the antiinflammatory effect of the formulation cream at 20% caused a reduction in inflammation at 5 hours after carrageenan application compared with diclofenac at 1% (60.4%; 45.65%; respectively). A slight potential peripheral analgesia was noted in plantar test in treated rats with cream (20 s). Therefore, our findings demonstrate that formulation cream of P. harmala seeds oil has an interesting antiinflammatory activity with a slight peripheral analgesic effect due mainly to its richness on linoleic acid, γ-tocopherol, and polyphenols and to its important antioxidant capacity.

Abstract 3253: Targeting G-quadruplex nucleic acids: a series of β-carboline alkaloids with new skeletons from the seeds of Peganum harmala

Abstract G-quadruplexes are DNA secondary structures implicated in essential physiological and pathological processes, such as tumorgenesis. Small molecules which can stabilize or induce G-quadruplex formation have potential as antitumor agents through the alteration of oncogene expression levels or the disruption of telomere maintenance. Targeting G-quadruplex nucleic acids, we screened 17 medicinal plants for binding activity to a model G-quadruplex d(TTGGGTT)4 system by 1H NMR experiment. We found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity and specific cytotoxicity against the PC-3 cancer cell line with an IC50 value of 13.65 μg/mL. Subsequently, 1H NMR and bioassay co-guided isolation of the extract of P. harmala L. was performed and obtained 21 new alkaloids, including 10 novel β-carboline alkaloids with unprecedented carbon skeletons, and 12 known analogues. Their structures including the absolute configurations were determined by extensive analysis of spectroscopic data, X-ray crystallography, ECD calculations, and ECD exciton chirality approaches. The antiproliferative activities and G-quadruplex binding activities were evaluated for these newly discovered and previously reported alkaloids. Some of the isolates showed pronounced cytotoxic effects with IC50 values below 10 µM and significant G-quadruplex binding activities. More interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against HL-60, PC-3 and SGC-7901 cell lines, with IC50 values of 3.81 ± 0.32, 11.52 ± 0.62, and 15.16 ± 0.42 µM, respectively. The G-quadruplex interactions positively correlated with antiproliferative activities suggesting these β-carboline alkaloids may exert their anti-cancer effects through G-quadruplex interactions. This work contributed a practical strategy at first time for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes. Citation Format: Kaibo wang, Huiming Hua, Danzhou Yang. Targeting G-quadruplex nucleic acids: a series of β-carboline alkaloids with new skeletons from the seeds of Peganum harmala [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3253. doi:10.1158/1538-7445.AM2017-3253

(±)‐Peharmaline A: A Pair of Rare β‐Carboline–Vasicinone Hybrid Alkaloid Enantiomers from Peganum harmala

(±)‐Peharmaline A (1), a pair of rare β‐carboline–vasicinone hybrid alkaloid enantiomers with the hitherto unknown hybrid dimeric system, was isolated from the seeds of Peganum harmala L. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Plausible biogenetic pathways involving Mannich/Pictet–Spengler‐type and intermolecular Michael addition reactions are briefly discussed. Compound 1 exhibited significant cytotoxic activities against HL‐60, PC‐3, and SGC‐7901 cancer cell lines with median inhibitory concentration values of 9.2, 21.6, and 25.4 µm, respectively. However, two biosynthetically related precursors, harmaline and vasicinone, were inactive. This cytotoxic β‐carboline–vasicinone hybrid dimeric alkaloid may give some insight into the discovery of new lead compounds for cancer therapy.

Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new β-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,β-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 μM.

Optimization of Continuous Flow Adsorption of Heavy Metal Ions on Continuous System Column by Peganum Harmala Seeds

Optimization of Continuous Flow Adsorption of Heavy Metal Ions on Continuous System Column by Peganum Harmala Seeds

Peganum harmala seeds: evaluation of antiasthmatic effect by using clonidine induced mast cell degranulation

Aim of study: The aim of study was to evaluate antiasthmatic activity of various extracts of Peganum harmala seeds to validate its traditional use. Materials and methods: In the present study petroleum ether, ethanol and water extract of Peganum harmala seeds at the doses of 25-100 mg/kg i. p. was evaluated for antiasthmatic activity using clonidine induced mast cells degranulation in mice. Results: Treatment group of PEEE (Peganum harmala ethanol extract) exhibited significant mast cell stabilizing potential at 100 mg/kg i.p 68.85±1.30 as compared to control group. Percent protection offered by PHEE at 100 mg/kg was 20.28% and was of statistical significance as compared to PHPEE and PHWE. Conclusion: It can be concluded that the ethanol extract of Peganum harmala (PHEE) may be useful in management of asthma.

Impact of oral capsule of Peganum harmala on alleviating urinary symptoms in men with benign prostatic hyperplasia; a randomized clinical trial.

Introduction: Benign prostatic hyperplasia (BPH) is considered as a major cause of lower urinary tract symptoms (LUTS) in older men and its most common sign is nocturia. Objectives: This study aimed to determine the effect of the seeds of Peganum harmala compared with tamsulosin on alleviating urinary symptoms in patients with BPH. Patients and Methods: In this single blind clinical trial study, 90 patients diagnosed with BPH and LUTS, based on international prostate standard survey (IPSS) were divided into three groups. The first group was received oral capsule of P. harmala, the second group was administered tamsulosin with oral P. harmala seed and the third group was received tamsulosin drug and they were evaluated after 4 weeks. Results: The results showed that the difference between mean scores of IPSS was significant after the intervention (P=0.001). Besides, the mean of IPSS in the three groups was significantly different (P=0.001) (the first group 41.9±5.3, the second group 21.0±4.4 ,the third group 16.5±3.7 respectively). However, after the intervention, patients in the second group had the lowest average on most indicators of IPSS but the difference was only significant about urinary frequency, nocturia and intermittency(P<0.05). Conclusion: Application of Peganum harmala seed can be useful in reducing urinary symptoms in patients with BPH.

In vitro ovicidal activity of Peganum harmala seeds extract on the eggs of Fasciola hepatica.

Peganum harmala seeds extract has been previously reported to have antimicrobial and other medicinal properties. The aim of this study was to evaluate the ovicidal activity of the methanolic extract of P. harmala seeds against the eggs of F. hepatica. The phenolic compounds of the methanolic extract of P. harmala seeds were identified by HPLC analysis. Catechin, rutin, p-Coumaric acid, chloregenic acid and hesperetin were found to be the major phenolic compounds. F. hepatica eggs were collected from the gall bladder of naturally infected sheep. The eggs were exposed to two concentrations of P. harmala seeds extract (1 and 3mg/mL) for 24 and 48h. To investigate the effect of the P. harmala seeds extract on the miracidial formation, the treated eggs were incubated at 28°C for 14days. The results indicated that F. hepatica eggs were susceptible to the methanolic extract of P. harmala seeds. Following 24h exposure of the eggs to P. harmala seeds extract with concentrations of 1 and 3mg/mL, the miracidial formation reduced to 5 and 2.2% respectively (compared with 60% for the control group). Following 48h of exposure of the eggs to P. harmala seeds extract with 1mg/mL concentration, the miracidial formation reduced to 0.5%. In this exposure time, no miracidial formation was observed in the eggs exposed to P. harmala seeds extract with concentration of 3mg/mL. Therefore, the results of this study indicated that P. harmala seeds extract has high ovicidal activity against the eggs of F. hepatica. Accordingly, this extract may have the potential flukicidal activity against the immature and mature F. hepatica.

Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats.

The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200–230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin (HbA1C) were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and HbA1C levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes.

Harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways.

Harmine, a β-carboline alkaloid isolated from the seeds of Peganum harmala, possesses both antitumor and anti‑nociceptive effects and inhibits human DNA topoisomerase. However, no detailed data are available concerning the mechanisms of harmine in human colorectal carcinoma SW620 cells. In the present study, we demonstrated that harmine inhibited the proliferation of SW620 cells in a dose-dependent manner using MTT and clone formation assays, and the IC50 value of harmine on the growth inhibition of SW620 cells for 48h was 5.13µg/ml. PI staining showed that harmine altered the cell cycle distribution by decreasing the proportion of cells in the G0-G1phase and increasing the proportion in the Sand G2-Mphase. The expression level of cyclinD1 was decreased, while the expression of cyclinA, E2andB1, CDK1/cdc2, Myt-1 and p-cdc2(Tyr15) were increased, which was in accordance with the S and G2/Mphase arrest. Hoechst33258 staining revealed nuclear fragmentation, chromosomal condensation and cell shrinkage in the SW620 cells treated with harmine. Flow cytometry revealed that the percentage of apoptotic sub-G1 cells increased from 7.19 to 26.58%, while in the control group, sub-G1 cells only increased from 1.53 to 1.60%. Furthermore, early and late apoptotic cells were increased from 11.96 to 26.38% when incubated with the indicated concentration of harmine for 48h, while in the control group, <8% of cells underwent apoptosis. JC-1 staining revealed that harmine decreased mitochondrial transmembrane potential (ΔΨm). The apoptosis of SW620 cells was also detected by western blot analysis, showing caspase-3and-9, and PARP activation; the downregulation of Bcl-2, Mcl-1, Bcl-xL; and the upregulation of Bax. The expression of p-ERK, p-Akt (Ser473) and p-Akt (Thr308) was inhibited, and phosphorylation of downstream targets of Akt, such as p-FoxO3a and p-GSK‑3β were also attenuated. In conclusion, harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways.

Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities.

Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3 ± 1.9% at 100 µM). Compound 2 exhibited the best anti-AChE activity (IC50=1.9 ± 1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0 ± 0.3 µM (3a) and IC50=6.3 ± 0.4 µM (3b) against HCT 116 cells, IC50=5.0 ± 1.0 µM (3d) against MCF7 cells).

Peganum Harmala L. Extract Reduces Oxidative Stress and Improves Symptoms in 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

Parkinson's disease is one of the most common neurodegenerative disorders. There are many documents about the effects of oxidative stress in Parkinson's disease etiology. Angiotensin II activates NADPH dependent oxidases and causes superoxides formation. Peganum harmala L. extract, which has angiotensin converting enzyme (ACE) inhibitory effect, is considered to evaluate oxidative stress inhibition and Parkinson's disease improvement. Male rats weighting 200-250 g were divided into 5 groups: Control, Neurotoxin (injection of 6-hydroxydopamine into left hemisphere substantia nigra), Peganum harmala's seeds aqueous extract (10 mg/kg) and captopril (5 mg/kg). Peganum harmala and captopril were injected intraperitonealy -144, -120, -96, -72, -48, -24, -2, 4 and 24 h relative to 6-hydroxydopamine injection time. Muscle stiffness, apomorphine induced unilateral rotation, amount of brain's protein oxidation and lipid peroxidation, ACE activity and histology of substantia nigra were assayed in all groups. Peganum harmala improved Muscle stiffness and one-direction rotation behavior significantly. It also reduced brain's lipid and protein oxidation levels in neurotoxin-injected rats significantly. In Peganum harmala group compared to control group, brain's ACE activity was significantly inhibited. In histological study, Peganum harmala prevented degeneration of dopaminergic neurons, too. In conclusion, aqueous extract of Peganum harmala could prevent symptoms and reduced oxidative stress markers in rats with Parkinson's disease induced by 6-hydroxydopamine.