A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum

Li, Shuping; Cheng, Xuemei; Wang, Changhong

doi:10.1016/j.jep.2017.03.049

Cited by 101 publications

(89 citation statements)

References 148 publications

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“…Therefore, there is a need to find new strategies against ACV-resistant HSV viruses, to prevent resistance and improve efficacy and pharmacokinetics of actual treatments [2,4]. β-carbolines (βCs) alkaloids are widely distributed in nature; they can be found in mammals [5], plants [6] and other organisms. Depending on their intrinsic chemical structure, βCs show a broad pharmacological spectrum [6,7] as promising anti-tumor [7], antimicrobial [8][9][10][11] and antiviral agents [12].…”

Section: Introductionmentioning

confidence: 99%

β-Carboline derivatives as novel antivirals for herpes simplex virus

Gonzalez

Cabrerizo

Baiker³

et al. 2018

International Journal of Antimicrobial Agents

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Several commercial and novel synthetic β-carbolines (βCs) were evaluated for their antiviral activity against herpes simplex virus type 1 (HSV-1) using an adapted MTS assay. Of 21 drugs tested, although 11 exerted antiviral activity at non-cytotoxic concentrations, only 3 of them [9-methyl-norharmane (9-Me-nHo), 9-methyl-harmane (9-Me-Ho) and 6-methoxy-harmane (6-MeO-Ho)] completely avoided virus-driven cytopathic effects. Half-maximal effective concentrations (EC values) (4.9 ± 0.4, 5.9 ± 0.8 and 19.5 ± 0.3 µM, respectively) and selectivity indexes (88.8, 40.2 and 7.0, respectively) of the latter three βCs against HSV-1 were determined by MTS, flow cytometry and plaque reduction assays. The mode of action of these drugs was also evaluated. According to time-of-addition assays, the selected compounds were not virucidal and did not interfere with attachment or penetration of HSV-1, but interfered with later events of virus infection. Western blot studies showed that early and late protein expression was significantly delayed or even suppressed. Herpes simplex virus type 2 (HSV-2) was also inhibited by the selected substances in a similar manner. Interestingly, 6-MeO-Ho, 9-Me-Ho and 9-Me-nHo restricted HSV-1 ICP0 localisation to the nucleus during later stages of infection, possibly affecting its functionality in the cytoplasm where ICP0 normally inhibits antiviral signalling and promotes viral replication. In silico prediction of ADME (Absorption, Distribution, Metabolism and Excretion) properties showed that all compounds fulfilled Lipinski's rule and their calculated absorptions were >95%.

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Section: Introductionmentioning

confidence: 99%

β-Carboline derivatives as novel antivirals for herpes simplex virus

Gonzalez

Cabrerizo

Baiker³

et al. 2018

International Journal of Antimicrobial Agents

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“…Die Alkaloide der Steppenraute beeinflussen sowohl das periphere als auch das zentrale Nervensystem, dazu zählen eine Analgesie, bedingt u. a. durch Interaktion mit Opioid-Rezeptoren [10] und dem GABAergen System [11] sowie eine antidepressive Wirkung, bedingt durch die starke Hemmung der Monoamin-Oxidasen A / B und der Catecholamin-O-Methyl-Transferase, wodurch die Konzentrationen der Neurotransmitter Serotonin, Dopamin und Noradrenalin steigen [8]. Auch die Auslösung von Halluzinationen sowie eine gewisse Antiparkinson-Aktivität lassen sich teilweise durch diese pharmakologischen Wirkungen erklären [12].…”

Section: Wirkungen Auf Das Nervensystemunclassified

“…PPARγ wird u. a. durch Harmin moduliert und könnte damit zu einer Verbesserung der Insulinwirkung beitragen [22]. In tierexperimentellen Untersuchungen wurden eine signifikante Veränderung der Blutlipide als auch eine Senkung des HbA 1c -Wertes bei diabetischen Ratten durch die Gabe von hydroalkoholischen Samenextrakten beobachtet [8].…”

Section: Antidiabetische Wirkungunclassified

“…Extrakte der Droge konnten in vitro die Proliferation unterschiedlicher Bakterien [23], Pilze [24] und Protozoen [25] hemmen. Dies lässt sich durchaus mit der traditionellen Anwendung der Droge bei Bronchitis, Dermatosen, Augenerkrankungen sowie Fieber in Verbindung bringen [8]. Da β-Carboline die Freisetzung proinflammatorischer Mediatoren, wie Tumor-Nekrose-Faktor-α (TNF-α) und Prostaglandin E 2 (PGE 2 ) in vitro zu hemmen vermögen, verweisen einige Autoren auf eine immunmodulatorische Aktivität der Droge [26].…”

Section: Antimikrobielle Und Entzündungshemmende Wirkungenunclassified

“…Mutagenität bzw. Teratogenität [8,29] der Droge lassen sich auf einzelne Alkaloide zurückführen und wurden sowohl in vitro als auch im Tierversuch nachgewiesen.…”

Section: Toxikologieunclassified

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Die Steppenraute, Peganum harmala L. – eine alte Unbekannte

Baroud¹,

Kermani²,

Melzig³

2019

Z Phytother

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ZusammenfassungDie Steppenraute Peganum harmala L. ist eine Pflanze der Trockengebiete Zentralasiens bis in den Mittelmeerraum aus der Familie der Nitrariaceae. Besonders die Samen (Semen Harmalae) werden seit der Antike zu rituellen Zwecken als Halluzinogen und in der traditionellen Heilkunde verwendet. Inhaltsstoffe sind v. a. Indolalkaloide, wie β-Carboline und Chinazolinalkaloide mit ausgeprägten Wirkungen auf das ZNS und das Herz-Kreislauf-System. Trotz einer großen Anzahl von Berichten zu vielfältigen pharmakologischen Effekten besitzt die Droge gegenwärtig keine therapeutische Bedeutung.

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GZ17‐6.02 initiates DNA damage causing autophagosome‐dependent HDAC degradation resulting in enhanced anti‐PD1 checkpoint inhibitory antibody efficacy

Booth

Roberts

West

et al. 2020

Journal Cellular Physiology

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Our studies examined the molecular mechanisms by which the novel cancer therapeutic GZ17‐6.02 (NCT03775525) killed GI tumor cells. TZ17‐6.02 activated ATM which was responsible for increased phosphorylation of nuclear γH2AX and AMPKα T172. ATM‐AMPK signaling was responsible for the subsequent inactivation of mTORC1 and mTORC2, dephosphorylation of ULK1 S757, and increased phosphorylation of ULK1 S317 and of ATG13 S318, which collectively caused enhanced autophagosome formation. GZ17‐6.02 interacted with 5‐fluorouracil in an additive to greater than additive fashion to kill all of the tested GI tumor cell types. This was associated with greater ATM activation and a greater mammalian target of rapamycin inactivation and autophagosome induction. As a result, autophagy‐dependent degradation of multiple histone deacetylase (HDAC) proteins and chaperone proteins occurred. Loss of HDAC expression was causal in reduced expression of programed death ligand 1 (PD‐L1), ornithine decarboxylase, and indole amine 2,3‐dioxygenase (IDO1) and in the elevated expression of major histocompatibility complex Class IA (MHCA). Treatment with GZ17‐6.02 also resulted in enhanced efficacy of a subsequently administered anti‐PD1 checkpoint inhibitory antibody. Thus, the primary mode of GZ17‐6.02 action is to induce a DNA damage response concomitant with ATM activation, that triggers a series of interconnected molecular events that result in tumor cell death and enhanced immunogenicity.

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A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum

Cited by 101 publications

References 148 publications

β-Carboline derivatives as novel antivirals for herpes simplex virus

β-Carboline derivatives as novel antivirals for herpes simplex virus

Die Steppenraute, Peganum harmala L. – eine alte Unbekannte

GZ17‐6.02 initiates DNA damage causing autophagosome‐dependent HDAC degradation resulting in enhanced anti‐PD1 checkpoint inhibitory antibody efficacy

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