{"title":"Two Olea europaea L. Extracts Reduce Harmful Effects in a Model of Neurotoxicity: Involvement of the Endoplasmic Reticulum.","authors":"Jessica Maiuolo, Sonia Bonacci, Francesca Bosco, Lorenza Guarnieri, Stefano Ruga, Antonio Leo, Rita Citraro, Salvatore Ragusa, Ernesto Palma, Vincenzo Mollace, Giovambattista De Sarro","doi":"10.1055/a-2353-1469","DOIUrl":"10.1055/a-2353-1469","url":null,"abstract":"<p><p>Prolonged exposure to lead has been recognized as harmful to human health as it may cause neurotoxic effects including mitochondrial damage, apoptosis, excitotoxicity, and myelin formation alterations, among others. Numerous data have shown that consuming olive oil and its valuable components could reduce neurotoxicity and degenerative conditions. Olive oil is traditionally obtained from olive trees; this plant (<i>Olea europaea</i> L.) is an evergreen fruit tree.In this manuscript, two extracts have been used and compared: the extract from the leaves of <i>Olea europaea</i> L. (OE) and the extract derived from OE but with a further sonication process (s-OE). Therefore, the objectives of this experimental work were as follows: 1) to generate an innovative extract; 2) to test both extracts on a model of neurotoxicity of human neurons induced following lead exposure; and 3) to study the mechanisms behind lead-induced neurotoxicity.The results showed that the mechanism involved in the neurotoxicity of lead included dysfunction of the cellular endoplasmic reticulum, which suffered oxidative damage. In addition, in all experiments, s-OE was more effective than OE, having greater and better effects against lead-induced damage and being dissolved in a smaller amount of EtOH, which promotes its sustainability.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"844-857"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planta medicaPub Date : 2024-09-01Epub Date: 2024-06-10DOI: 10.1055/a-2341-6175
Ying Han, Junli Xi, Puzhao Zhang, Ming Gong, Tao Luo, Feng Shao, Yongxin Li, Lingyun Zhong, Hexiu Quan
{"title":"5(S)-5-Carboxystrictosidine from the Root of Mappianthus iodoides Ameliorates H2O2-induced Apoptosis in H9c2 Cardiomyocytes via PI3K/AKT and ERK Pathways.","authors":"Ying Han, Junli Xi, Puzhao Zhang, Ming Gong, Tao Luo, Feng Shao, Yongxin Li, Lingyun Zhong, Hexiu Quan","doi":"10.1055/a-2341-6175","DOIUrl":"10.1055/a-2341-6175","url":null,"abstract":"<p><p>5(<i>S</i>)-5-carboxystrictosidine (5-CS) is a compound found in the root of <i>Mappianthus iodoides</i>, a traditional Chinese medicine used for the treatment of coronary artery disease. The aim of the present study was to investigate the protective effect of 5-CS against oxidative stress-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms. 5-CS pretreatment significantly protected against H<sub>2</sub>O<sub>2</sub>-induced cell death, LDH leakage, and malondialdehyde (MDA) production, which are indicators for oxidative stress injury. 5-CS also enhanced the activity of SOD and CAT. In addition, 5-CS pretreatment significantly inhibited H<sub>2</sub>O<sub>2</sub>-induced apoptosis, as determined by flow cytometer, suppressed the activity of caspase-3 and caspase-9, and attenuated the activation of cleaved caspase-3 and caspase-9. 5-CS also increased Akt and ERK activation altered by H<sub>2</sub>O<sub>2</sub> using Western blot analysis. The PI3K-specific inhibitor LY294002 abolished 5-CS-induced Akt activation. The ERK-specific inhibitor PD98059 abolished 5-CS-induced ERK activation. Both LY294002 and PD98059 attenuated the protective effect of 5-CS on H9c2 cardiomyocytes against H<sub>2</sub>O<sub>2</sub>-induced apoptosis and cell death. Taken together, these results demonstrate that 5-CS prevents H<sub>2</sub>O<sub>2</sub>-induced oxidative stress injury in H9c2 cells by enhancing the activity of the endogenous antioxidant enzymes, inhibiting apoptosis, and modulating PI3K/Akt and ERK signaling pathways.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"885-895"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301324","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 : 2024-09-01Epub Date: 2024-07-09DOI: 10.1055/a-2363-5033
Jeong In Seo, Young Beom Kwak, Seong Eun Cho, Hye Hyun Yoo
{"title":"An In Silico-Guided Approach for Assessing Herb-Drug Interaction Potential: A Case Study with Cudrania tricuspidata Leaf Extracts.","authors":"Jeong In Seo, Young Beom Kwak, Seong Eun Cho, Hye Hyun Yoo","doi":"10.1055/a-2363-5033","DOIUrl":"10.1055/a-2363-5033","url":null,"abstract":"<p><p><i>Cudrania tricuspidata</i> leaf extracts have long been utilized as traditional oriental medicines across Asian countries like Korea, China, and Japan. These extracts are renowned for their therapeutic benefits in addressing inflammation, tumors, obesity, and diabetes, maintaining their status as a pivotal folk remedy. Given the rising trend of combining medicinal herbs with conventional medications, it is imperative to explore the potential herb-drug interactions. However, there is a dearth of research on evaluating the herb-drug interactions of <i>C. tricuspidata</i> leaf extracts. Also, the intricate chemical composition of medicinal herbs presents methodological hurdles in establishing causal relationships between their constituents and herb-drug interactions. To overcome these challenges, a combined <i>in silico</i> and <i>in vitro</i> workflow was developed and effectively applied to evaluate the potential herb-drug interaction of <i>C. tricuspidata</i> leaf extracts along with the associated chemical factors. In <i>in vitro</i> CYP inhibition assays, <i>C. tricuspidata</i> leaf extracts exhibited potent inhibition of CYP1A2 and CYP2C8, with quercetin, kaempferol, and their glycosides identified as the major constituents. <i>In silico</i> analysis based on the prediction tools (ADMETlab 2.0 and pkCSM) identified key contributors to CYP inhibition, quercetin and kaempferol. Additionally, molecular docking analysis validated the binding of ligands (quercetin and kaempferol) to proteins (CYP1A2 and CYP2C8). These findings suggest that <i>C. tricuspidata</i> leaf extracts could inhibit CYP1A2 and CYP2C8, aiding in understanding the herb-drug interaction potential of <i>C. tricuspidata</i> leaf extracts for safe clinical application. Furthermore, this approach can be broadly applied to study herb-drug interactions of various medicinal herbs, enhancing their therapeutic benefits and reducing adverse reactions by considering chemical profiles relevant to herb-drug interaction potential in herbal preparations.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"858-863"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564036","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":"Fu'cupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster.","authors":"Guoqiong Cao, Zilan Zhu, Dingyi Yang, Wenyu Wu, Fangfang Yang, Yao Liu, Jian Xu, Yongping Zhang","doi":"10.1055/a-2344-8841","DOIUrl":"10.1055/a-2344-8841","url":null,"abstract":"<p><p><i>Corydalis yanhusuo</i>, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of <i>C. yanhusuo</i>. Studies have shown that Fu'cupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of <i>C. yanhusuo</i> was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied <i>in vitro</i>, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fu'cupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing <i>C. yanhusuo</i> extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the <i>C. yanhusuo</i> extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm<sup>2</sup>, respectively. The <i>in vitro</i> diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fu'cupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fu'cupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"876-884"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321396","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 : 2024-09-01Epub Date: 2024-06-29DOI: 10.1055/a-2357-7064
Maima Matin, Farhan Bin Matin, Natalia Ksepka, Kamil Wysocki, Michel-Edwar Mickael, Marek Wieczorek, Jarosław Olav Horbańczuk, Artur Jóźwik, Atanas G Atanasov
{"title":"The Clinical Research on Ginger (Zingiber officinale): Insights from ClinicalTrials.gov analysis.","authors":"Maima Matin, Farhan Bin Matin, Natalia Ksepka, Kamil Wysocki, Michel-Edwar Mickael, Marek Wieczorek, Jarosław Olav Horbańczuk, Artur Jóźwik, Atanas G Atanasov","doi":"10.1055/a-2357-7064","DOIUrl":"10.1055/a-2357-7064","url":null,"abstract":"<p><p>Ginger (<i>Zingiber officinale</i>) has a rich history of traditional medicinal use and has attracted a global interest in its health benefits. This study aims to provide insights into the clinical research landscape on ginger, focusing on its pharmacological effects and studied health-related outcomes. The study design involves systematic analysis of data from clinical trials available on ClinicalTrials.gov and discussion of findings in the context of the existing scientific knowledge. A comprehensive analysis of clinical trials registered on ClinicalTrials.gov related to ginger was first conducted, and the scientific background related to specific ginger clinical research avenues was further evaluated through PubMed searches. A variety of trial designs were identified, including treatment, prevention, and supportive care objectives. A total of 188 studies were identified on ClinicalTrials.gov, of which 89 met the inclusion criteria. Among the 89 trials, treatment objectives were predominant (47.2%), and dietary supplements (40.4%) and drugs (27%) were the most prevalent intervention types. These trials covered various health outcomes, such as antiemetic activity, analgesic function, effects on health-related quality of life, blood pressure variation, energy expenditure, and reduction in xerostomia. This study analysis provides a comprehensive overview of the clinical trials landscape on ginger, focusing on its broad spectrum of potential health benefits. While individual trials show promising results, a significant gap in the available data with a low reporting rate of final results is identified, underscoring the need for further research to establish conclusive evidence of ginger's therapeutic potentials.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"834-843"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470155","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 : 2024-09-01Epub Date: 2024-07-23DOI: 10.1055/a-2359-8097
Ying Hui Loke, Hiu Ching Phang, Najwa Mohamad, Phei Er Kee, Yik-Ling Chew, Siew-Keah Lee, Choon Fu Goh, Chien Ing Yeo, Kai Bin Liew
{"title":"Cocoa Butter: Evolution from Natural Food Ingredient to Pharmaceutical Excipient and Drug Delivery System.","authors":"Ying Hui Loke, Hiu Ching Phang, Najwa Mohamad, Phei Er Kee, Yik-Ling Chew, Siew-Keah Lee, Choon Fu Goh, Chien Ing Yeo, Kai Bin Liew","doi":"10.1055/a-2359-8097","DOIUrl":"10.1055/a-2359-8097","url":null,"abstract":"<p><p>For decades, cocoa butter has been extensively used in food industries, particularly in the production of chocolate confectioneries. The composition of fats within cocoa butter, such as stearic acid, palmitic acid, and oleic acid, determines its properties. Studies have indicated the existence of at least six polymorphic forms of cocoa butter, each possessing distinct characteristics and melting points. Recently, cocoa butter has garnered attention for its potential as a delivery system for pharmaceutical products. This review thoroughly explores cocoa butter, encompassing its production process, composition, properties, and polymorphism. It delves into its diverse applications across various industries including food, cosmetics, and pharmaceuticals. Additionally, the review investigates cocoa butter alternatives aiming to substitute cocoa butter and their roles in different drug delivery systems. The unique properties of cocoa butter have sparked interest in pharmaceutical industries, particularly since its introduction as a drug delivery system and excipient. This has prompted researchers and industry stakeholders to explore novel formulations and delivery methods, thereby expanding the range of options available to consumers in the pharmaceutical market.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"824-833"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752384","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 : 2024-09-01Epub Date: 2024-07-24DOI: 10.1055/a-2360-9639
Leandro Val Sayson, Nicole Bon Campomayor, Darlene Mae Ortiz, Hyun Jun Lee, Sweetie Balataria, Sangsu Park, Jeongin Lim, Heejin Kang, Hee Jin Kim, Mikyung Kim
{"title":"Extracts of Prunella vulgaris Enhanced Pentobarbital-Induced Sleeping Behavior in Mice Potentially via Adenosine A2A Receptor Activity.","authors":"Leandro Val Sayson, Nicole Bon Campomayor, Darlene Mae Ortiz, Hyun Jun Lee, Sweetie Balataria, Sangsu Park, Jeongin Lim, Heejin Kang, Hee Jin Kim, Mikyung Kim","doi":"10.1055/a-2360-9639","DOIUrl":"10.1055/a-2360-9639","url":null,"abstract":"<p><p>The increasing prevalence of sleep dysregulation cases has prompted the search for effective and safe sleep-enhancing agents. Numerous medications used in the treatment of sleep disorders function by enhancing <i>γ</i>-aminobutyric acid neurotransmitter activity. Unfortunately, these substances may induce significant adverse effects in chronic users, such as dependence and motor behavior impairments. Consequently, there is a growing interest in exploring therapeutic sleep-enhancing agents derived from natural sources, with the anticipation of causing less severe side effects. <i>Prunella vulgaris</i> (PV), a perennial plant indigenous to South Korea, exhibits various pharmacological effects, likely attributed to its chemical composition. Rosmarinic acid, one of its components, has previously demonstrated sleep-potentiating properties, suggesting the potential for PV to exhibit similar pharmacological effects. This study aims to investigate the potential effects of repeated administration of PV extract on the sleep behavior, brainwave activity, sleep-wake cycle, and physiological behavior of mice. Findings indicate that PV extracts exhibit sleep-enhancing effects in mice, characterized by prolonged sleep duration and a reduced onset time of pentobarbital-induced sleep. However, PV extracts only reduced alpha wave powers, with minor alterations in wakefulness and rapid-eye-movement sleep duration. In contrast to diazepam, PV extracts lack adverse effects on locomotor activity, motor coordination, or anxiety in mice. Receptor-binding assay and caffeine treatment support the potential involvement of adenosine A<sub>2A</sub> receptors in the effects of PV, suggesting distinct mechanisms of action compared to diazepam, despite both exhibiting sleep-altering effects. Overall, our results suggest that PV holds promise as a potential source of sleep-aiding agents.</p>","PeriodicalId":20127,"journal":{"name":"Planta medica","volume":" ","pages":"864-875"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760329","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: 2024-05-15DOI: 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}