Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

To investigate the N-containing compounds in the seeds of Paganum harmala,fourteen compounds were finally isolated from the 95% Et OH extract of P. harmala seeds by using various chromatographic techniques including silica gel,MCI resin,and ODS column chromatography as well as the semi-preparative HPLC. Depending on spectroscopic techniques and comparison with the reported data in the literatures,the structures of all compounds were identified as N-[3-(2-amino-4-methoxyphenyl)-3-oxopropyl]acetamide(1),dehydroharmalacidine(2),harmalacidine(3),harmine N-oxide(4),harmine(5),tetrahydroharmine(6),demethylharmalacidine(7),harmol(8),tetrahydroharmol(9),harmindol β-D-glucopyranoside(10),tryptophyl β-D-glucopyranoside(11),pegamineβ-D-glucopyranoside(12),vasicol(13) and vasicinone(14). Among them,1 was a new compound,and 2 and 10 were obtained as natural products for the first time.
Chromatography, High Pressure Liquid ; Nitrogen ; analysis ; Peganum ; chemistry ; Phytochemicals ; analysis ; Plant Extracts ; chemistry ; Seeds ; chemistry

The optic-fiber sensor technology combined with near-infrared diffuse reflection spectroscopy was applied to directly analyze Peganum harmala and identify different origin of P. harmala on the basis of principal component analysis, clustering analysis, SIMCA method, which resulted in the establishment of a new method to rapidly and nondestructively identify the origin of P. harmala. The original full wavelength spectrum for principal component analysis and the score of first two principal components can distinguish four origins of P. harmala basically. In the wavelength range of 866-2,507 nm, MSC as pretreatment method to establish the best model of clustering analysis to forecast the samples with the accuracy of 91.67%, can distinguish the four origins of P. harmala while in the wavelength of 1,085-2,507 nm, normalization method as pretreatment methods to establish a best model of SIMCA to forecast the sample, all the samples except for the changji sample have been identified with a total recognition rate of 97.22%. The results show that using near infrared diffuse reflectance spectroscopy combined with SIMCA is the best method that can be effectively used to identify the P. harmala.
Cluster Analysis ; Models, Theoretical ; Peganum ; chemistry ; Principal Component Analysis ; Spectroscopy, Near-Infrared ; methods

OBJECTIVETo establish the quality standards of the herbs of Peganum harmala.

METHODAccording to the Chinese Pharmacopoeia (2010 version, volume 1) and its appendix method, the water, total ash, acid insoluble ash, water-soluble extractives, and heavy metal were analyzed for herbs of P. harmala. TLC method was used to separate harmaline, harmine and vasicine from the herb samples by mixture of ethyl acetate-methanol-ammonia (10: 1.5: 0.5) as a developing solvent on high performance silica gel precoated plate (HSGF254) and to identify them inspected under UV 366 nm, visualized by spraying with both Dragendorff reagent, and by bioautographic assay. In the HPLC method, vasicine was separated on a C18 (4.6 mm x 250 mm, 5 microm) column with metnanol-0.1% trifluoroacetic acid (15:85) as the mobile phase and detected at at 280 nm.

RESULTIn the TLC procedures, 254 nm fluorescent and bioautographic assay for the detection of acetylcholinesterase inhibitor can be used for the qualitative identification of the active ingredients. For the HPLC quantitation method, the calibration curve of vasicine displayed ideal linearity over the range of 0.7923-792.3 mg x L(-1) with the regression equation of Y = 18,227X - 24.879 (r = 0.9999). The average recovery of vasicine was 101.6% with a RSD of 1.9%. The RSD values of intra-day and inter-day precision were less than 2%. The content of vasicine in 10 batches of herbs of P. harmala fluctuates between 0.23% and 1.47%.

CONCLUSIONThe results indicated that the limit of vasicine was not lower than 0.6%, and the water, total ash, acid insoluble ash, and water-soluble extractives were not more than 10.0%, 20.0%, 1.7%, and 30.0%, respectively. The heavy metal of plumbum, cadmium, arsenic, mercury, and copper were not more than 5, 3, 2, 2, and 20 mg x kg(-1), respectively. The qualitative and quantitative method established was suitable for the quality evaluation and assessment of herbs of P. harmala.

Alkaloids ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; standards ; Humans ; Metals, Heavy ; chemistry ; Peganum ; chemistry ; Quality Control ; Quinazolines ; chemistry

OBJECTIVETo investigate the representation methods of dissolubility property of total alkaloid extract from Peganum hamala in different solvents, and to investigate the evaluation method of the dissolubility property of extracts from traditional Chinese medicine.

METHODThe dissolubility property of the whole extract and markers of harmaline and harmine, as well as the particle diameter distribution of the extract in different solvents were evaluated by precipitation method, solubility test, and the particle diameter test.

RESULTBoth the alkaloid extract and it's index ingredients had good solubility in absolute ethanol, 95% ethanol, and 80% ethanol, while the solubility in 60% ethanol was poor, and worst in water. The sequence of particle diameter of extract in solvents was in the following order water > 95% ethanol > 60% ethanol > 60% ethanol > 80% ethanol.

CONCLUSIONThe extract has good solubility in the ethanol solution whose concentration is over 80%. The results between precipitation method and index components method have certain correlation. The particle diameter method can provide distribution information of the extract in different solvents. Combination of those three methods could reflect the dissolubility property of extracts from traditional Chinese medicine more comprehensively.

Alkaloids ; chemistry ; isolation & purification ; Chemical Fractionation ; methods ; Particle Size ; Peganum ; chemistry ; Plant Extracts ; chemistry ; isolation & purification ; Solubility ; Solvents ; chemistry

OBJECTIVETo investigate the protective effect of 17beta-estradiol (E2), peganum harmala extract (PHE) administration and calorie restriction (CR) treatment (60%) on oxidative stress and hepato-toxicity in aged rats.

METHODSEighteen months old animals that were treated at the age of 12 months were divided into 4 groups: normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group.

RESULTSAging significantly decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and increased lactate deshydrogenase (LDH), gamma-glytamyl transferase (GGT), phosphatase alkalines (PAL), aspartate and lactate transaminase (AST and ALT) activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17beta-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats.

CONCLUSIONThe antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.

Aging ; physiology ; Animals ; Body Weight ; Caloric Restriction ; Catalase ; metabolism ; Estradiol ; blood ; pharmacology ; Female ; Glutathione Peroxidase ; metabolism ; Liver ; anatomy & histology ; drug effects ; Male ; Organ Size ; Oxidative Stress ; drug effects ; Peganum ; chemistry ; Phytoestrogens ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Rats ; Superoxide Dismutase ; metabolism ; Thiobarbituric Acid Reactive Substances

AIMTo investigate the effects of 17beta-estradiol (E2), Peganum harmala extract (PHE) and caloric restriction (CR) on various testis parameters during aging.

METHODSTwelve month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR (40%).

RESULTSOur results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes: gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats.

CONCLUSIONBesides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species (ROS) produced in large quantities in the aged testis.

Aging ; physiology ; Animals ; Antioxidants ; metabolism ; Aromatase ; biosynthesis ; genetics ; Caloric Restriction ; Estradiol ; metabolism ; pharmacology ; Estrogens ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Oxidative Stress ; drug effects ; Peganum ; chemistry ; Plant Extracts ; pharmacology ; RNA ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Receptors, Estrogen ; biosynthesis ; genetics ; Testis ; drug effects ; enzymology ; growth & development ; Testosterone ; metabolism ; Thiobarbituric Acid Reactive Substances ; metabolism