Planta medicaPub Date : 2024-08-01Epub Date: 2024-05-15DOI: 10.1055/a-2328-2644
Fábio Alves Aguila, Jairo Kenupp Bastos, Rodrigo C S Veneziani, Glauco Henrique Balthazar Nardotto, Larissa Costa Oliveira, Adriana Rocha, Vera Lucia Lanchote, Sérgio Ricardo Ambrósio
{"title":"Population Pharmacokinetic of the Diterpenes ent-Polyalthic Acid and Dihydro-ent-Agathic Acid from Copaifera Duckei Oil Resin in Rats.","authors":"Fábio Alves Aguila, Jairo Kenupp Bastos, Rodrigo C S Veneziani, Glauco Henrique Balthazar Nardotto, Larissa Costa Oliveira, Adriana Rocha, Vera Lucia Lanchote, Sérgio Ricardo Ambrósio","doi":"10.1055/a-2328-2644","DOIUrl":"10.1055/a-2328-2644","url":null,"abstract":"<p><p>Copaifera duckei oleoresin is a plant product extensively used by the Brazilian population for multiple purposes, such as medicinal and cosmetic. Despite its ethnopharmacological relevance, there is no pharmacokinetic data on this important medicinal plant. Due to this, we determined the pharmacokinetic profile of the major nonvolatile compounds of C. duckei oleoresin. The diterpenes ent-polyalthic acid and dihydro-ent-agathic acid correspond to approximately 40% of the total oleoresin. Quantification was performed using LC-MS/MS, and the validated analytical method showed to be precise, accurate, robust, reliable, and linear between 0.57 and 114.74 µg/mL plasma and 0.09 to 18.85 µg/mL plasma, respectively, for ent-polyalthic acid and dihydro-ent-agathic acid, making it suitable for application in preclinical pharmacokinetic studies. Wistar rats received a single 200 mg/kg oral dose (gavage) of C. duckei oleoresin, and blood was collected from their caudal vein through 48 h. Population pharmacokinetics analysis of <i>ent</i>-polyalthic and dihydro-<i>ent</i>-agathic acids in rats was evaluated using nonlinear mixed-effects modeling conducted in NONMEN software. The pharmacokinetic parameters of ent-polyalthic acid were absorption constant rate = 0.47 h<sup>-1</sup>, central and peripheral apparent volume of distribution = 0.04 L and 2.48 L, respectively, apparent clearance = 0.15 L/h, and elimination half-life = 11.60 h. For dihydro-ent-agathic acid, absorption constant rate = 0.28 h<sup>-1</sup>, central and peripheral apparent volume of distribution = 0.01 L and 0.18 L, respectively, apparent clearance = 0.04 L/h, and elimination half-life = 3.49 h. The apparent clearance, central apparent volume of distribution, and peripheral apparent volume of distribution of <i>ent</i>-polyalthic acid were approximately 3.75, 4.00-, and 13.78-folds higher than those of dihydro-<i>ent</i>-agathic.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"810-820"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-07-16DOI: 10.1055/a-2360-4808
Mariana de Lima Nascimento, Sara Batista do Nascimento, Ednalva de Souza Pereira Lima, Flávio Martins de Oliveira, Rafael Rocha Dos Santos, Isabela da Costa Cesar, Whocely Victor de Castro
{"title":"Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.","authors":"Mariana de Lima Nascimento, Sara Batista do Nascimento, Ednalva de Souza Pereira Lima, Flávio Martins de Oliveira, Rafael Rocha Dos Santos, Isabela da Costa Cesar, Whocely Victor de Castro","doi":"10.1055/a-2360-4808","DOIUrl":"10.1055/a-2360-4808","url":null,"abstract":"<p><p>This work investigated interactions ascribed to the administration of phytomedicines containing <i>Valeriana officinalis</i> and <i>Piper methysticum</i> with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (C<sub>max</sub>) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC<sub>(0-∞)</sub>) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although <i>Valeriana</i> increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing <i>V. officinalis</i> or <i>P. methysticum</i> inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"792-800"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-05-16DOI: 10.1055/a-2309-6298
Klaus Ferdinand Gärditz, Hjördis Czesnick
{"title":"Paclitaxel - a Product of Fungal Secondary Metabolism or an Artefact?","authors":"Klaus Ferdinand Gärditz, Hjördis Czesnick","doi":"10.1055/a-2309-6298","DOIUrl":"10.1055/a-2309-6298","url":null,"abstract":"<p><p>Taxol (common name: paclitaxel) is an extremely important component of drugs for the treatment of various cancers. Thirty years after the discovery of its effectiveness, a metabolic precursor of Taxol (10-deacetylbaccatin III) is still primarily extracted from needles of European yew trees. In order to meet the considerable demand, hopes were pinned on the possibilities of biotechnological production from the very beginning. In 1993, as if by chance, Taxol was supposedly discovered in fungi that grow endobiotically in yew trees. This finding aroused hopes of biotechnological use to produce fungal Taxol in large quantities in fermenters. It never came to that. Instead, a confusing flood of publications emerged that claimed to have detected Taxol in more and more eukaryotic and even prokaryotic species. However, researchers never reproduced these rather puzzling results, and they could certainly not be applied on an industrial scale. This paper will show that some of the misguided approaches were apparently based on a seemingly careless handling of sparse evidence and on at least questionable publications. Apparently, the desired gold rush of commercial exploitation was seductive. Scientific skepticism as an indispensable core of good scientific practice was often neglected, and the peer review process has not exerted its corrective effect. Self-critical reflection and more healthy skepticism could help to reduce the risk of such aberrations in drug development. This article uses this case study as a striking example to show what can be learned from the Taxol case in terms of research ethics and the avoidance of questionable research practices.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"726-735"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-06-05DOI: 10.1055/a-2339-2633
Mohammad Al-Amin, Siti Sarah Fazalul Rahiman, Melati Khairuddean, Salizawati Muhamad Salhimi
{"title":"(R)-(-)-Xanthorrhizol Inhibits the Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Matrix Metalloproteinases via the NF-κB Signaling Pathway.","authors":"Mohammad Al-Amin, Siti Sarah Fazalul Rahiman, Melati Khairuddean, Salizawati Muhamad Salhimi","doi":"10.1055/a-2339-2633","DOIUrl":"10.1055/a-2339-2633","url":null,"abstract":"<p><p>(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-<i>κ</i>B signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"785-791"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-03-08DOI: 10.1055/a-2277-4805
Tanmoy Banerjee, Arnab Sarkar, Sk Zeeshan Ali, Rudranil Bhowmik, Sanmoy Karmakar, Amit Kumar Halder, Nilanjan Ghosh
{"title":"Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms.","authors":"Tanmoy Banerjee, Arnab Sarkar, Sk Zeeshan Ali, Rudranil Bhowmik, Sanmoy Karmakar, Amit Kumar Halder, Nilanjan Ghosh","doi":"10.1055/a-2277-4805","DOIUrl":"10.1055/a-2277-4805","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes, leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions. Obeticholic acid is the only approved therapeutic agent for NAFLD. With more scientific enterprise being directed towards the understanding of the underlying mechanisms of NAFLD, novel targets like lipid synthase, farnesoid X receptor signalling, peroxisome proliferator-activated receptors associated with inflammatory signalling, and hepatocellular injury have played a crucial role in the progression of NAFLD to NASH. Phytocompounds have shown promising results in modulating hepatic lipid metabolism and <i>de novo</i> lipogenesis, suggesting their possible role in managing NAFLD. This review discusses the ameliorative role of different classes of phytochemicals with molecular mechanisms in different cell lines and established animal models. These compounds may lead to the development of novel therapeutic strategies for NAFLD progression to NASH. This review also deliberates on phytomolecules undergoing clinical trials for effective management of NAFLD.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"675-707"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-03-08DOI: 10.1055/a-2283-8147
Barbara Tóth, Attila Horváth, Orsolya Jójártné Laczkovich, Zsófia Dalma Biró, Mária Matuz, Dezső Csupor
{"title":"Storage Conditions Influence the Quality of Ginger - A Stability Study Inspired by Clinical Trials.","authors":"Barbara Tóth, Attila Horváth, Orsolya Jójártné Laczkovich, Zsófia Dalma Biró, Mária Matuz, Dezső Csupor","doi":"10.1055/a-2283-8147","DOIUrl":"10.1055/a-2283-8147","url":null,"abstract":"<p><p>Ginger has traditionally been used to treat and prevent nausea and vomiting; however, the results of clinical trials are ambiguous. The efficacy of ginger is attributed to gingerols and their metabolites, shogaols. Since these compounds have different pharmacological profiles, the clinical efficacy of ginger products is largely dependent on their chemical composition. The goal of our study was to examine the stability of ginger, determining the 6-gingerol contents in order to assess the effects of different storage conditions. We have performed a 6-month stability test with dry ginger rhizome samples stored in a constant climate chamber in three different storage containers (uncovered glass container, glass container sealed with rubber stopper, and plastic container). The 6-gingerol contents were measured by HPLC method. The concentration of 6-gingerol decreased in all samples. In the sealed glass container, the decrease in 6-gingerol content was significantly lower than in the unsealed glass container and in the plastic container. These results demonstrate that storage conditions have a significant impact on the quality of ginger, which may also affect efficacy.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"736-740"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Estrogenic Activity of Derris scandens Stem Extract and its Major Compounds Using MCF-7 Cell Proliferation Assay and Estrogen-Related Gene Expression.","authors":"Worapol Sae-Foo, Gorawit Yusakul, Natsajee Nualkaew, Waraporn Putalun","doi":"10.1055/a-2328-2750","DOIUrl":"10.1055/a-2328-2750","url":null,"abstract":"<p><p><i>Derris scandens</i>, which contains isoflavones and prenylated derivatives, has analgesic and anti-inflammatory properties and is an ingredient in traditional Thai medicine for perimenopause and menopause. However, the estrogenic activity of <i>D. scandens</i> has not yet been explored. Therefore, this study aimed to examine the estrogenic activity of the stem extract of <i>D. scandens</i> and its isoflavone derivatives. In this study, we conducted a proliferation assay in MCF-7 cells, and used quantitative reverse transcription polymerase chain reaction to assess gene expression. We found that the relative cell proliferation of the compounds (1 µM) was ranked in the following order as compared to 0.1 nM 17<i>β</i>-estradiol (100%): genistein (97.84%) > derrisisoflavone A (83.17%) > genistein-7-<i>O</i>-[<i>α</i>-rhamnopyranosyl-(1 → 6)-glucopyranoside] (69.55%) > 6,8-diprenylgenistein (51.91%) > lupalbigenin (18.72%). Furthermore, cotreatment with 1 µM lupalbigenin and 0.1 nM 17<i>β</i>-estradiol was performed, which decreased cell proliferation to 80.38%. <i>In vitro</i> results suggest that lupalbigenin has an estrogen-antagonistic effect. At a dose of 1 µM, genistein had the strongest efficacy in increasing the expression of human estrogen receptor <i>β</i> by 4.0-fold compared to the control. Furthermore, genistein-7-<i>O</i>-[<i>α</i>-rhamnopyranosyl-(1 → 6)]-<i>β</i>-glucopyranoside augmented the gene expression of human estrogen receptor <i>α</i> and human estrogen receptor <i>β</i> by 1.5- and 3.4-fold, respectively. Prenylated derivatives of genistein (derrisisoflavone A, 6,8-diprenylgenistein, and lupalbigenin) significantly suppressed the gene expression of the human androgen receptor. The administration of the crude extract at 10 µg/mL significantly suppressed human androgen receptor (0.6-fold) and transmembrane protease serine 2 (0.1-fold) expression but did not significantly affect human estrogen receptor <i>α</i> and human estrogen receptor <i>β</i> gene expression. This herbal medicine may be safe for estrogen-exposed breast cancer patients.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"766-773"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery and Characterization of Panaxatriol as a Novel Thrombin Inhibitor from Panax notoginseng Using a Combination of Computational and Experimental Approaches.","authors":"Xing Wang, Yuqing Ma, Chunfang Zuo, Zixi Zhao, Ruonan Ma, Lele Wang, Yuzhen Fang, Yuxin Zhang, Xia Wu","doi":"10.1055/a-2339-2720","DOIUrl":"10.1055/a-2339-2720","url":null,"abstract":"<p><p>Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from <i>Panax notoginseng</i> and evaluate their biological activity <i>in vitro</i> and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assays, surface plasmon resonance, and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that panaxatriol directly inhibits thrombin, with an IC<sub>50</sub> of 10.3 µM. Binding studies using surface plasmon resonance revealed that panaxatriol interacts with thrombin, with a K<sub>D</sub> value of 7.8 µM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was - 23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitors.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"801-809"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-08-01Epub Date: 2024-06-17DOI: 10.1055/a-2320-8822
Nica Classen, Thanet Pitakbut, Michael Schöfbänker, Joachim Kühn, Eike R Hrincius, Stephan Ludwig, Andreas Hensel, Oliver Kayser
{"title":"Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion.","authors":"Nica Classen, Thanet Pitakbut, Michael Schöfbänker, Joachim Kühn, Eike R Hrincius, Stephan Ludwig, Andreas Hensel, Oliver Kayser","doi":"10.1055/a-2320-8822","DOIUrl":"10.1055/a-2320-8822","url":null,"abstract":"<p><p>The search for new active substances against SARS-CoV-2 is still a central challenge after the COVID-19 pandemic. Antiviral agents to complement vaccination are an important pillar in the clinical situation. Selected cannabinoids such as cannabigerol, cannabicyclol, cannabichromene, and cannabicitran from <i>Cannabis sativa</i> and synthetic homologues of cannabigerol and cannabicyclol were evaluated for effects on the cell viability of Vero cells (CC<sub>50</sub> of cannabigerol and cannabicyclol 40 resp. 38 µM) and reduced virus entry of vesicular stomatitis pseudotyped viruses with surface-expressed SARS-CoV-2 spike protein at 20 µM. In addition to a reduction of pseudotyped virus entry, a titer reduction assay on Vero cells after preincubation of Wuhan SARS-CoV-2 significantly confirmed antiviral activity. Investigations on the molecular targets addressed by cannabigerol and cannabicyclol indicated that both compounds are inhibitors of SARS-CoV-2 spike protein-mediated membrane fusion, as could be shown by a virus-free reporter fusion inhibition assay (EC<sub>50</sub> for cannabigerol 5.5 µM and for cannabicyclol 10.8 µM) and by monitoring syncytia formation in Vero reporter cells. Selectivity indices were calculated as 7.4 for cannabigerol and 3.5 for cannabicyclol. Systematic semisynthetic alterations of cannabigerol and cannabicyclol indicated that the side chains of both compounds do not contribute to the observed anti-membrane fusion activity.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"717-725"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evidence of Urtica dioica Agglutinin's Antiproliferative and Anti-migratory Potentials on the Hyaluronic Acid-Overexpressing Prostate Cancer Cells.","authors":"Mohammadkazem Heydari, Abasalt Hosseinzadeh Colagar, Davood Sabour, Hamid Reza Khorasani","doi":"10.1055/a-2324-2250","DOIUrl":"10.1055/a-2324-2250","url":null,"abstract":"<p><p>Hyaluronic acid is composed of repeating sugar units, glucuronic acid and N-acetylglucosamine, which are often associated with increased tumor progression. <i>Urtica dioica</i> agglutinin is a potential component that exhibits a high affinity for binding to N-acetylglucosamine. This study aimed to investigate <i>U. dioica</i> Agglutinin's potential to inhibit the proliferation and migration of prostate cancer cells with high expression of hyaluronic acid through molecular docking and <i>in vitro</i> studies. The expression of hyaluronan synthase genes in prostate tissue and cell lines was checked by an <i>in silico</i> study, and the interaction between hyaluronic acid with both CD44 transmembrane glycoprotein and <i>U. dioica</i> agglutinin was analyzed through molecular docking. <i>U. dioica</i> Agglutinin's effect on cell viability (neutral red uptake assay), migration (scratch wound healing assays), and both <i>CD44</i> and <i>Nanog</i> expression (quantitative real-time polymerase chain reaction) were assessed <i>in vitro</i>. The results showed that in prostate cancer cell lines, the PC3 cell line has the highest expression of hyaluronan synthase genes. <i>U. dioica</i> agglutinin exhibits an interaction of six specific residues on CD44 compared to hyaluronic acid's singular residue. While <i>U. dioica</i> agglutinin alone effectively reduced cell viability and wound closer (≥ 150 µg/mL), combining it with hyaluronic acid significantly shifted the effective concentration to a higher dose (≥ 350 µg/mL). These results, together with low <i>Nanog</i> and high <i>CD44</i> gene expression, suggest that <i>U. dioica</i> agglutinin may impair the CD44-HA pathway in PC3 cells. This possibility is supported by <i>U. dioica</i> Agglutinin's ability to compete with hyaluronic acid for binding to CD44. Based on this, <i>U. dioica</i> agglutinin as a plant lectin shows promise in inhibiting cancer proliferation and migration by targeting its dependence on hyaluronic acid.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"774-784"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}