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Biology Apr 2022A reliable and science-based taxonomic determination of L. (opium poppy), the illegal species of the genus , may have practical and legal implications for law...
BACKGROUND
A reliable and science-based taxonomic determination of L. (opium poppy), the illegal species of the genus , may have practical and legal implications for law enforcement. is a controlled plant because of its narcotic substances, such as morphine and codeine. As poppy plants have rather similar morphological features, both chemical and genetic analysis are required in order to achieve an accurate characterization of such species. The chemical structures of alkaloids are extremely variable even within the same species, which is why the genetic approach may lead to a more scientific sp. differentiation. The aim of our study was the taxonomic identification of poppy capsules seized by the Italian Police Forces being considered as potential derivatives.
METHODS
The alkaloids detected using gas chromatography/mass-spectrometry (GC/MS) were morphine, codeine, thebaine, noscapine, meconin, hydrocotarnine, and traces of papaverine. Further genetic analysis was carried out simultaneously using three plastid DNA barcoding regions (matK, trnH-psbA, and rbcL) for the samples' identification.
RESULTS
The Random Amplification of Polymorphic DNA (RAPD) method showed that the analysed samples were genetically identical.
CONCLUSIONS
The morphological, toxicological, and genetic profile of the samples revealed that they belonged to species. Furthermore, the alkaloid content of dried poppy capsules might be used to investigate and track their origin.
PubMed: 35625400
DOI: 10.3390/biology11050672 -
Plants (Basel, Switzerland) Apr 2022The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of () in the treatment of hyperactive gut disorders....
The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of () in the treatment of hyperactive gut disorders. The in vivo, castor oil-induced diarrhea model in mice was followed to test its antidiarrheal effect. To test the antispasmodic effect and to explore its pharmacodynamic details, isolated small intestines (ileum) obtained from rats were selected to provide physiological conditions for the ex vivo assays. In the in vivo assays, the orally administered extract of protected mice from diarrheal drops with resultant percent inhibitions of 40% and 80% at the respective doses of 200 mg/kg and 400 mg/kg, while the highest protection (100%) was observed with a positive control drug, loperamide, at 10 mg/kg. In the ileum, produced an antispasmodic effect in a concentration-dependent manner by inhibiting the carbachol (CCh; 1 µM) and high K (80 mM)-evoked spasms with resultant EC values of 1.44 mg/mL (1.08-1.78) and 1.27 mg/mL (0.98-1.66), respectively. Papaverine, a known phosphodiesterase enzyme (PDE) inhibitor and blocker of Ca channels (CCB), also inhibited both CCh and high K induced contractions at comparable EC values of 8.72 µM (7.92-9.24) and 8.14 µM (7.62-8.84), respectively. Contrary to the extract and papaverine, verapamil showed distinctly higher potency in regard to inhibiting high K, compared to CCh-evoked spasms that had EC values of 0.16 µM (0.13-0.261) and 2.54 µM (2.28-2.92), respectively. The inhibitory effects of on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with caused deflection in the Ca CRCs towards the right, constructed in Ca free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of in the treatment of hyperactive gut disorders.
PubMed: 35567184
DOI: 10.3390/plants11091183 -
International Journal of Molecular... Apr 2022Papaverine (PPV) is a benzylisoquinoline alkaloid isolated from that exerts antiproliferative activity. However, several questions remain regarding the biochemical...
Papaverine (PPV) is a benzylisoquinoline alkaloid isolated from that exerts antiproliferative activity. However, several questions remain regarding the biochemical pathways affected by PPV in tumourigenic cells. In this study, the influence of PPV on cell migration (light microscopy), expression of vascular endothelial growth factor (VEGF) B, VEGF R1, VEGF R2, and phosphorylated focal adhesion kinase (pFAK) were investigated using spectrophotometry in MDA-MB-231-, A549- and DU145 cell lines. The migration assay revealed that, after 48 h, PPV (100 µM) reduced cell migration to 81%, 91%, and 71% in MDA-MB-231-, A549-, and DU145 cells, respectively. VEGF B expression was reduced to 0.79-, 0.71-, and 0.73-fold after 48 h of exposure to PPV in MDA-MB-231-, A549- and DU145 cells, while PPV exposure of 48 h increased VEGF R1 expression in MDA-MB-231- and DU145 cells to 1.38 and 1.46. A fold decrease in VEGF R1 expression was observed in A549 cells to 0.90 after exposure to 150 µM. No statistically significant effects were observed on VEGF R2- and FAK expression after exposure to PPV. This study contributes to the understanding of the effects of a phytomedicinal alkaloid compound in cancer cells and may provide novel approaches to the application of non-addictive alkaloids.
Topics: Antineoplastic Agents; Cell Line; Cell Movement; Humans; Neoplasms; Papaverine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 35563045
DOI: 10.3390/ijms23094654 -
Molecules (Basel, Switzerland) Mar 2022This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas...
This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography−mass spectrometry (GC−MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC−MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.
Topics: Acacia; Animals; Antidiarrheals; Diarrhea; Gas Chromatography-Mass Spectrometry; Gastrointestinal Agents; Jejunum; Methanol; Mice; Papaverine; Parasympatholytics; Phosphoric Diester Hydrolases; Plant Extracts; Polyphenols; Rats
PubMed: 35408506
DOI: 10.3390/molecules27072107 -
Phytotherapy Research : PTR Jul 2022Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In... (Review)
Review
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In this context, medicinal plants have attracted attention due to the wide availability and variety of therapeutic compounds, such as alkaloids, a vast class with several proven pharmacological effects, like the antiviral and anti-inflammatory activities. Therefore, this scoping review aimed to summarize the current knowledge of the potential applicability of alkaloids for treating COVID-19. A systematic search was performed on PubMed and Scopus, from database inception to August 2021. Among the 63 eligible studies, 65.07% were in silico model, 20.63% in vitro and 14.28% clinical trials and observational studies. According to the in silico assessments, the alkaloids 10-hydroxyusambarensine, cryptospirolepine, crambescidin 826, deoxynortryptoquivaline, ergotamine, michellamine B, nigellidine, norboldine and quinadoline B showed higher binding energy with more than two target proteins. The remaining studies showed potential use of berberine, cephaeline, emetine, homoharringtonine, lycorine, narciclasine, quinine, papaverine and colchicine. The possible ability of alkaloids to inhibit protein targets and to reduce inflammatory markers show the potential for development of new treatment strategies against COVID-19. However, more high quality analyses/reviews in this field are necessary to firmly establish the effectiveness/safety of the alkaloids here described.
Topics: Alkaloids; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35355337
DOI: 10.1002/ptr.7442 -
Molecules (Basel, Switzerland) Feb 2022Fenchone is a bicyclic monoterpene found in a variety of aromatic plants, including and , and is used in the management of airways disorders. This study aimed to...
Fenchone is a bicyclic monoterpene found in a variety of aromatic plants, including and , and is used in the management of airways disorders. This study aimed to explore the bronchodilator effect of fenchone using guinea pig tracheal muscles as an ex vivo model and in silico studies. A concentration-mediated tracheal relaxant effect of fenchone was evaluated using isolated guinea pig trachea mounted in an organ bath provided with physiological conditions. Sustained contractions were achieved using low K (25 mM), high K (80 mM), and carbamylcholine (CCh; 1 µM), and fenchone inhibitory concentration-response curves (CRCs) were obtained against these contractions. Fenchone selectively inhibited with higher potency contractions evoked by low K compared to high K with resultant EC values of 0.62 mg/mL (0.58-0.72; = 5) and 6.44 mg/mL (5.86-7.32; = 5), respectively. Verapamil (VRP) inhibited both low and high K contractions at similar concentrations. Pre-incubation of the tracheal tissues with K channel blockers such as glibenclamide (Gb), 4-aminopyridine (4-AP), and tetraethylammonium (TEA) significantly shifted the inhibitory CRCs of fenchone to the right towards higher doses. Fenchone also inhibited CCh-mediated contractions at comparable potency to its effect against high K [6.28 mg/mL (5.88-6.42, = 4); CCh] and [6.44 mg/mL (5.86-7.32; = 5); high K]. A similar pattern was obtained with papaverine (PPV), a phosphodiesterase (PDE), and Ca inhibitor which inhibited both CCh and high K at similar concentrations [10.46 µM (9.82-11.22, = 4); CCh] and [10.28 µM (9.18-11.36; = 5); high K]. However, verapamil, a standard Ca channel blocker, showed selectively higher potency against high K compared to CCh-mediated contractions with respective EC values of 0.84 mg/mL (0.82-0.96; = 5) 14.46 mg/mL (12.24-16.38, = 4). The PDE-inhibitory action of fenchone was further confirmed when its pre-incubation at 3 and 5 mg/mL potentiated and shifted the isoprenaline inhibitory CRCs towards the left, similar to papaverine, whereas the Ca inhibitory-like action of fenchone pretreated tracheal tissues were authenticated by the rightward shift of Ca CRCs with suppression of maximum response, similar to verapamil, a standard Ca channel blocker. Fenchone showed a spasmolytic effect in isolated trachea mediated predominantly by K channel activation followed by dual inhibition of PDE and Ca channels. Further in silico molecular docking studies provided the insight for binding of fenchone with Ca channel (-5.3 kcal/mol) and K channel (-5.7), which also endorsed the idea of dual inhibition.
Topics: Animals; Calcium Channel Blockers; Camphanes; Chemical Phenomena; Dose-Response Relationship, Drug; Guinea Pigs; In Vitro Techniques; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Norbornanes; Parasympatholytics; Phosphodiesterase Inhibitors; Potassium Channels; Structure-Activity Relationship; Trachea
PubMed: 35209147
DOI: 10.3390/molecules27041360 -
Medicina (Kaunas, Lithuania) Feb 2022: The study aimed to evaluate the effect of the oral administration of drotaverine on maternal and fetal circulation as measured by Doppler sonography in women with a...
: The study aimed to evaluate the effect of the oral administration of drotaverine on maternal and fetal circulation as measured by Doppler sonography in women with a risk of preterm birth. : The present prospective study was conducted on 34 women with singleton pregnancy at 26-36 weeks of gestation. Doppler flow and pulsatility index (PI) assessments of the umbilical artery, fetal middle cerebral artery, and uterine arteries were performed before and 90-120 min after oral drotaverine administration. : There were no statistically significant differences between the Doppler assessment (PI Uma-umbilical artery, MCA-middle cerebral artery, and ltUta-left uterine artery) before drotaverine administration and 90-120 min after oral intake, but there were statistically significant differences between the PI assessment of the rtUta (right uterine artery, 0.55 vs. 0.75, = 0.05) and the mean of the Uta (0.66 vs. 0.74, = 0.03). For changes in the CUR (cerebro-umbilical ratio) and % changes in the CUR and mean PI of the Uta, there was no correlation with obstetric history, AFI (amniotic fluid index), gestation week, infertility history, systolic pressure, or diastolic pressure. There was a statistically positive correlation between changes in the CUR and % change in the CUR and body weight and in height. : Drotaverine has no statistically significant influence on the MCA and Uma PI. The oral administration of drotaverine has an impact on PI rtUta and the mean PI Uta.
Topics: Administration, Oral; Female; Humans; Infant, Newborn; Papaverine; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Premature Birth; Prospective Studies; Ultrasonography, Prenatal
PubMed: 35208558
DOI: 10.3390/medicina58020235 -
International Journal of Environmental... Feb 2022Obesity is associated with endothelial dysfunction and this relationship is probably mediated in part by inflammation. The current study evaluated the effects of...
Obesity is associated with endothelial dysfunction and this relationship is probably mediated in part by inflammation. The current study evaluated the effects of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, on endothelial and vascular reactivity, endothelial nitric oxide synthase (eNOS) immunoreactivity, and serum and aortic concentrations of TNF-α in a diet-induced rat model. Male weanling Wistar rats were exposed to a standard diet and cafeteria diet (CD) for 12 weeks and etanercept was administered during CD treatment. Isolated aortas of the rats were used for isometric tension recording. Carbachol-induced relaxant responses were impaired in CD-fed rats, while etanercept treatment improved these endothelium-dependent relaxations. No significant change was observed in papaverine- and sodium nitroprusside (SNP)-induced relaxant responses. eNOS expression decreased in CD-fed rats, but no change was observed between etanercept-treated CD-fed rats and control rats. CD significantly increased both the serum and the aortic levels of TNF-α, while etanercept treatment suppressed these elevated levels. CD resulted in a significant increase in the body weight of the rats. Etanercept-treated (ETA) CD-fed rats gained less weight than both CD-fed and control rats.
Topics: Animals; Diet; Endothelium, Vascular; Etanercept; Male; Nitric Oxide; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vascular Diseases
PubMed: 35206342
DOI: 10.3390/ijerph19042138 -
Evidence-based Complementary and... 2022Angiogenesis plays a critical role in tumorigenesis as it provides the necessary blood supply to the newly grown solid tumor. It helps maintain the tumor...
Angiogenesis plays a critical role in tumorigenesis as it provides the necessary blood supply to the newly grown solid tumor. It helps maintain the tumor microenvironment, promotes tumor development, progression, and metastasis. The vascular epithelial growth factor (VEGF), interacting with the tyrosine kinase receptor VEGFR-2 on endothelial cells, exerts its proangiogenic activity. Hence, targeting the VEGFR-2 signaling is considered a promising strategy to inhibit angiogenesis and thus cancer treatment. This study aims to identify the bioactive compounds derived from the medicinal herb that effectively binds with VEGFR-2. The bioactive compounds of were first screened for their physicochemical properties using the DataWarrior program (version 5.5.0). Finally, 17 compounds that obeyed Lipinski's rule of five and showed good drug-likeness were selected for molecular docking studies. Molecular docking results showed that the ligands ajmalicidine, 1, 2-dihydrovomilenine, rauwolscine, yohimbine, ajmaline, and papaverine interact strongly with the target VEGFR-2 receptor. Hydrogen bonds and hydrophobic interactions stabilized the interactions of these compounds with VEGFR-2. These compounds showed favourable drug-like properties and possess no significant toxicity. Therefore, the findings of this study indicate that the compounds derived from can be considered for the development of antiangiogenic drug candidates by targeting VEGFR-2.
PubMed: 35198035
DOI: 10.1155/2022/6224666 -
European Cardiology Feb 2021
Review
PubMed: 35106076
DOI: 10.15420/ecr.2021.16.PO4