PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

Effects of Peganum harmala L. Seed Extract on Culex pipiens (Diptera: Culicidae)

Mosquito-borne diseases result in the loss of life and economy, primarily in subtropical and tropical countries, and the emerging resistance to insecticides is increasing this threat. Botanical insecticides are promising substitutes for synthetic insecticides. This study evaluated the larvicidal and growth index of Culex pipiens of four solvent extracts of Terminalia chebula, Aloe perryi, and Peganum harmala against Cx. pipiens. None of the 12 extracts exhibited larvicidal potential against third instars except the ethyl acetate extract of P. harmala. After 24 h of exposure, the LC50 value was 314.88 ppm, and the LC90 value was 464.19 ppm. At 320 ppm, the hatchability was 25.83%, and it resulted in 100% mortality. In addition, the eggs treated with the EtOAc extract of P. Harmala exhibited a long larval period compared with the control. The larval period continued for 12 days, and the pupal period took three days in the treatment groups. The growth index data also exhibited a decrease (0.00–7.53) in the treated groups compare with 8.5 in the control. The transformation of eggs into adults decreased with increasing concentrations. This paper is the first report on the development and growth index of Cx. pipiens potential using P. harmala seeds.

Synthesis and Structural Confirmation of the Thiazole Alkaloids Derived from Peganum harmala L.

Peganumal A and B are thiazole alkaloids isolated from the seeds of Peganum harmala L. Thiazole moieties are rarely found in natural products, but diverse compounds possessing thiazole moieties have attracted attention owing to their broad range of biological activities. Peganumals are the first natural thiazole compounds isolated from the genus Peganum. It was difficult to define the exact structure of peganumal A via spectroscopic analysis. In this paper, we report the first total synthesis of peganumal A and B. The 5-benzylthiazole skeleton possessing methyl or hydrogen at the 2-position of the peganumals was efficiently constructed via the Hantzsch thiazole synthesis of the α-bromoaldehyde intermediate. Moreover, the spectral data of the synthetic 2H–thiazole compound were identical to those previously reported for peganumal A. The synthesis allowed the confirmation of the structure of peganumal A.

Additional resource for diabetes diagnostics in animals and humans

Veterinary doctors often observe cases of unexplained elevated glucose and ketones in urine of domestic animals without any other signs of diabetes. We studies these effects from the standpoint of the phenomenon of interdependent conditions in animals and humans, described by T.V.Novosadyuk in 2000. She was the first to provide a theoretical and practical foundation for clinical cases of simultaneously developing similar diseases in domestic animals and their owners. During the last 5 years we studied health of humans in families where domestic animals are affected by the laboratory abnormalities described above. In vast majority of cases it has been found out that animal owners have diabetes mellitus of variable severity. At the same time there were no disorders of carbohydrate metabolism in animal owners in 11 cases. We recommended members of these families to undergo a specialized examination. In all of these cases latent diabetes mellitus was found in humans who had especially close relationships with animals. These findings led to initiation of treatment in humans. At the same time animals were treated with a collar with a linen sack attached containing Peganum Harmala 30 globules. Repeated laboratory tests were performed after one month of such treatment. Normalization of laboratory variables was observed in all of the cases. Based on the study results we developed an algorhythm of activities that helps to diagnose early and latent forms of diabetes mellitus in domestic animals and their owners. This algorhythm includes: - test for glucose and/or ketones in animal urine after correction of feeding and care defects. - blood and urine glucose tests in family members of animal owners. In cases of deviations from normal values we recommended them to consult appropriate specialists and begin treatment immediately. - animals are given collars with Peganum Harmala 30 globules in a linen sack attached. - granules are removed when laboratory values normalize in animals. Control urinalysis is performed every three months durign a year. This approach is especially useful in latent early forms of diabetes mellitus when abnormal findings in animals or their owners enable us to suspect a similar disease in another. In such a way, the suggested algorithm is effective for organization of preclinical diagnostics in both domestic animals and their owners. In the future it is possible to enrich not only veterinary but also medical practice with new options for effective patient aid by practical development of the use of animal and human interdependent conditions.