scholarly journals Flavonoids Synergistically Enhance the Anti-Glioblastoma Effects of Chemotherapeutic Drugs

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1841
Author(s):  
Kevin Zhai ◽  
Alena Mazurakova ◽  
Lenka Koklesova ◽  
Peter Kubatka ◽  
Dietrich Büsselberg
Keyword(s):  
Intracellular Signaling ◽  
Tumor Resection ◽  
Plant Secondary Metabolites ◽  
Biological Properties ◽  
Treatment Modalities ◽  
Central Nervous System Tumor ◽  
Chemotherapeutic Drugs ◽  
Preclinical Research ◽  
Beneficial Effects ◽  
Synergistic Enhancement

Flavonoids are polyphenolic plant secondary metabolites with pleiotropic biological properties, including anti-cancer activities. These natural compounds have potential utility in glioblastoma (GBM), a malignant central nervous system tumor derived from astrocytes. Conventional GBM treatment modalities such as chemotherapy, radiation therapy, and surgical tumor resection are beneficial but limited by extensive tumor invasion and drug/radiation resistance. Therefore, dietary flavonoids—with demonstrated anti-GBM properties in preclinical research—are potential alternative therapies. This review explores the synergistic enhancement of the anti-GBM effects of conventional chemotherapeutic drugs by flavonoids. Primary studies published between 2011 and 2021 on flavonoid–chemotherapeutic synergy in GBM were obtained from PubMed. These studies demonstrate that flavonoids such as chrysin, epigallocatechin-3-gallate (EGCG), formononetin, hispidulin, icariin, quercetin, rutin, and silibinin synergistically enhance the effects of canonical chemotherapeutics. These beneficial effects are mediated by the modulation of intracellular signaling mechanisms related to apoptosis, proliferation, autophagy, motility, and chemoresistance. In this light, flavonoids hold promise in improving current therapeutic strategies and ultimately overcoming GBM drug resistance. However, despite positive preclinical results, further investigations are necessary before the commencement of clinical trials. Key considerations include the bioavailability, blood–brain barrier (BBB) permeability, and safety of flavonoids; optimal dosages of flavonoids and chemotherapeutics; drug delivery platforms; and the potential for adverse interactions.

Plant Extracts and their Secondary Metabolites as Modulators of Kinases

2020 ◽  
Vol 20 (12) ◽  
pp. 1093-1104 ◽  
Author(s):  
Muhammad Shoaib Ali Gill ◽  
Hammad Saleem ◽  
Nafees Ahemad
Keyword(s):  
Signal Transduction ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Cell Biology ◽  
Kinase Inhibitor ◽  
Plant Secondary Metabolites ◽  
Biological Properties ◽  
Drug Candidate ◽  
New Chemical Entities ◽  
Natural Flora

Natural Products (NP), specifically from medicinal plants or herbs, have been extensively utilized to analyze the fundamental mechanisms of ultimate natural sciences as well as therapeutics. Isolation of secondary metabolites from these sources and their respective biological properties, along with their lower toxicities and cost-effectiveness, make them a significant research focus for drug discovery. In recent times, there has been a considerable focus on isolating new chemical entities from natural flora to meet the immense demand for kinase modulators, and also to overcome major unmet medical challenges in relation to signal transduction pathways. The signal transduction systems are amongst the foremost pathways involved in the maintenance of life and protein kinases play an imperative part in these signaling pathways. It is important to find a kinase inhibitor, as it can be used not only to study cell biology but can also be used as a drug candidate for cancer and metabolic disorders. A number of plant extracts and their isolated secondary metabolites such as flavonoids, phenolics, terpenoids, and alkaloids have exhibited activities against various kinases. In the current review, we have presented a brief overview of some important classes of plant secondary metabolites as kinase modulators. Moreover, a number of phytocompounds with kinase inhibition potential, isolated from different plant species, are also discussed.

Diosgenin: Therapeutic Action, Pharmacology and Applications

2017 ◽  
Vol 5 (1) ◽  
pp. 7-15
Author(s):  
Sanasam Sanjeev ◽  
◽  
Maibam Sunita Devi ◽  
Khushboo Maurya ◽  
Vikas Kumar Roy ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Drug Development ◽  
Liver Diseases ◽  
Potential Role ◽  
Wide Spectrum ◽  
Herbal Product ◽  
Biological Properties ◽  
Therapeutic Action ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Beneficial Effects

Diosgenin [25R-spriost-5-en-3þ-ol], is an important steroidal metabolite found in various plant species. The discovery of diosgenin has made it one of the most researched and studied herbal product. Moreover, there is excellent opportunity to address whether diosgenin plays a role in chemoprevention versus therapy, or both. However, rigorous experimental based evidence in support of ethnomedicine-derived notions would lead to the development of products relevant to drug development. The health beneficial effects of diosgenin are further extended to its potential role to treat other ailments such as HIV and hepatitis-C infections as well as liver diseases. There is little information regarding the bioavailability, pharmacokinetics and pharmacodynamics of diosgenin in relation to its health beneficial effects. It has been reported to have wide spectrum of biological properties that contributes to several diseases in its role as a health beneficial phytochemical by citing new studies.

scholarly journals Melatonin in Wine and Beer: Beneficial Effects

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 343
Author(s):  
Javier Marhuenda ◽  
Débora Villaño ◽  
Raúl Arcusa ◽  
Pilar Zafrilla
Keyword(s):  
Intracellular Signaling ◽  
Plasma Concentrations ◽  
Radical Scavenging ◽  
Direct Interaction ◽  
Melatonin Receptors ◽  
Current Evidence ◽  
Sleep Cycle ◽  
Beneficial Effects ◽  
Neuroprotective Actions ◽  
Radical Scavenging Properties

Melatonin is a hormone secreted in the pineal gland with several functions, especially regulation of circadian sleep cycle and the biological processes related to it. This review evaluates the bioavailability of melatonin and resulting metabolites, the presence of melatonin in wine and beer and factors that influence it, and finally the different benefits related to treatment with melatonin. When administered orally, melatonin is mainly absorbed in the rectum and the ileum; it has a half-life of about 0.45–1 h and is extensively inactivated in the liver by phase 2 enzymes. Melatonin (MEL) concentration varies from picograms to ng/mL in fermented beverages such as wine and beer, depending on the fermentation process. These low quantities, within a dietary intake, are enough to reach significant plasma concentrations of melatonin, and are thus able to exert beneficial effects. Melatonin has demonstrated antioxidant, anticarcinogenic, immunomodulatory and neuroprotective actions. These benefits are related to its free radical scavenging properties as well and the direct interaction with melatonin receptors, which are involved in complex intracellular signaling pathways, including inhibition of angiogenesis and cell proliferation, among others. In the present review, the current evidence on the effects of melatonin on different pathophysiological conditions is also discussed.

scholarly journals Evaluation of Leaf Litter Mulching and Incorporation on Skid Trails for the Recovery of Soil Physico-Chemical and Biological Properties of Mixed Broadleaved Forests

Land ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 625
Author(s):  
Meghdad Jourgholami ◽  
Azadeh Khoramizadeh ◽  
Angela Lo Monaco ◽  
Rachele Venanzi ◽  
Francesco Latterini ◽  
...  
Keyword(s):  
Soil Properties ◽  
Soil Compaction ◽  
Biological Properties ◽  
Soil Protection ◽  
Natural Soil ◽  
Compacted Soils ◽  
Beneficial Effects ◽  
Physico Chemical ◽  
Forest Logging ◽  
Soil Recovery

Engineering applications can be used to mitigate the adverse effects of soil compaction and amend compacted soils. Previous literature has highlighted the beneficial effects of interventions such as litter mulching and incorporation on skid trails. However, little is known about the effectiveness of these alternatives in restoring forest soil quality after forest logging. The objective of this study was to properly elucidate the effects of the above mentioned soil protection methods, litter incorporation before skidding (LI) and litter mulching after skidding (LM), on the recovery of compacted soil’s physico-chemical and biological properties on skid trails over a 2-year period in the Hyrcanian forests of Iran to identify the best option for restoration intervention. The litter used in both methods consisted of dried leaves of the hornbeam and maple tree in three intensities of 3, 6, and 9 Mg ha−1. The results showed that the application of both methods (LI and LM) significantly improved the soil properties when compared to the untreated skid trail. Results showed that the recovery values of soil properties in the LI treatments were significantly higher than those of the LM. The recovery values of soil properties by 6 and 9 Mg ha−1 were significantly higher than those of 3 Mg ha−1, while the differences were not significant between 6 and 9 Mg ha−1. Our findings showed that soil properties were partially recovered (70–80%) over a 2-year period from treatment, compared to untreated, but the full recovery of soil properties required more time to return to the pre-harvest value. Overall, the results of this study demonstrated that the application of soil protection methods accelerates the process of recovering soil properties much faster than natural soil recovery, which can take more than 20 years in these forests.

scholarly journals Orchestration of Primary Hemostasis by Platelet and Endothelial Lysosome-Related Organelles

2020 ◽  
Vol 40 (6) ◽  
pp. 1441-1453 ◽  
Author(s):  
Ellie Karampini ◽  
Ruben Bierings ◽  
Jan Voorberg
Keyword(s):  
Endothelial Cells ◽  
Intracellular Signaling ◽  
Protein Complexes ◽  
Biological Properties ◽  
Bleeding Disorders ◽  
Granule Formation ◽  
Primary Hemostasis ◽  
Granule Maturation ◽  
Lysosome Related Organelles ◽  
Von Willebrand

Megakaryocyte-derived platelets and endothelial cells store their hemostatic cargo in α- and δ-granules and Weibel-Palade bodies, respectively. These storage granules belong to the lysosome-related organelles (LROs), a heterogeneous group of organelles that are rapidly released following agonist-induced triggering of intracellular signaling pathways. Following vascular injury, endothelial Weibel-Palade bodies release their content into the vascular lumen and promote the formation of long VWF (von Willebrand factor) strings that form an adhesive platform for platelets. Binding to VWF strings as well as exposed subendothelial collagen activates platelets resulting in the release of α- and δ-granules, which are crucial events in formation of a primary hemostatic plug. Biogenesis and secretion of these LROs are pivotal for the maintenance of proper hemostasis. Several bleeding disorders have been linked to abnormal generation of LROs in megakaryocytes and endothelial cells. Recent reviews have emphasized common pathways in the biogenesis and biological properties of LROs, focusing mainly on melanosomes. Despite many similarities, LROs in platelet and endothelial cells clearly possess distinct properties that allow them to provide a highly coordinated and synergistic contribution to primary hemostasis by sequentially releasing hemostatic cargo. In this brief review, we discuss in depth the known regulators of α- and δ-granules in megakaryocytes/platelets and Weibel-Palade bodies in endothelial cells, starting from transcription factors that have been associated with granule formation to protein complexes that promote granule maturation. In addition, we provide a detailed view on the interplay between platelet and endothelial LROs in controlling hemostasis as well as their dysfunction in LRO related bleeding disorders.

scholarly journals Phytochemical Screening, Antioxidant and Antibacterial Activities of the Root Extract of Cyphostemma adenocaule (Steud. ex A. Rich.) Wild & R.B.Drumm

2021 ◽  
Vol 10 (2) ◽  
pp. 105-110
Author(s):  
Abdulbasit Haliru Yakubu ◽  
Mohammed Mustapha Mohammed ◽  
Abdulqadir Bukar Bababe ◽  
Hassan Yesufu Braimah
Keyword(s):  
Scientific Evidence ◽  
Antibacterial Properties ◽  
Plant Secondary Metabolites ◽  
Biological Properties ◽  
Chloroform Extract ◽  
Chemical Diversity ◽  
Root Extract ◽  
Moderate Activity ◽  
Phytochemical Screening ◽  
Test Organisms

Plant secondary metabolites have provided important bioactive principles for developing new lead compounds. Within their confinement, they exhibit unique chemical diversity, which influences their diverse biological properties. The Vitaceae family is known for its potent antioxidant and antibacterial phytoconstituents, among other biological properties. Cyphostemma adenocaule is one of the family members explored for its ethnomedicinal properties. This study undertook the evaluation of the phytochemical, antioxidant, and antibacterial properties of the root extract of Cyphostemma adenocaule. Preliminary phytochemical screening revealed the presence of flavonoids, alkaloids, carbohydrates & glycoside, saponins, and tannins. The methanol root extract had the highest activity in the DPPH assay, providing IC50 (50% inhibition) of 10.87µg/ml, followed by n-Hexane (IC50 74.10µg/ml) and chloroform (IC50 74.31µg/ml) extract. In the antibacterial assay, the chloroform extract was active against E. coli (24.00±0.15) and had moderate activity against Staph. aureus (12.5±0.18). The n-Hexane extract was completely inactive against the test organisms while the methanol extract showed poor activity against the test organisms. The present study adds to the existing literature on Cyphostemma adenocaule with scientific evidence into its biological properties.

Craniopharyngioma: a comparison of tumor control with various treatment strategies

2010 ◽  
Vol 28 (4) ◽  
pp. E5 ◽  
Author(s):  
Isaac Yang ◽  
Michael E. Sughrue ◽  
Martin J. Rutkowski ◽  
Rajwant Kaur ◽  
Michael E. Ivan ◽  
...  
Keyword(s):  
Tumor Resection ◽  
Treatment Strategies ◽  
Group Versus ◽  
Outcome Data ◽  
Treatment Modalities ◽  
Rank Test ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Log Rank Test ◽  
Significant Difference

Object Craniopharyngiomas have a propensity to recur after resection, potentially causing death through their aggressive local behavior in their critical site of origin. Recent data suggest that subtotal resection (STR) followed by adjuvant radiotherapy (XRT) may be an appealing substitute for gross-total resection (GTR), providing similar rates of tumor control without the morbidity associated with aggressive resection. Here, the authors summarize the published literature regarding rates of tumor control with various treatment modalities for craniopharyngiomas. Methods The authors performed a comprehensive search of the English language literature to identify studies publishing outcome data on patients undergoing surgery for craniopharyngioma. Rates of progression-free survival (PFS) and overall survival (OS) were determined through Kaplan-Meier analysis. Results There were 442 patients who underwent tumor resection. Among these patients, GTR was achieved in 256 cases (58%), STR in 101 cases (23%), and STR+XRT in 85 cases (19%). The 2- and 5-year PFS rates for the GTR group versus the STR+XRT group were 88 versus 91%, and 67 versus 69%, respectively. The 5- and 10-year OS rates for the GTR group versus the STR+XRT group were 98 versus 99%, and 98 versus 95%, respectively. There was no significant difference in PFS (log-rank test) or OS with GTR (log-rank test). Conclusions Given the relative rarity of craniopharyngioma, this study provides estimates of outcome for a variety of treatment combinations, as not all treatments are an option for all patients with these tumors.

Diffuse Pigmented Villonodular Synovitis Around the Ankle

2018 ◽  
Vol 108 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Keiichi Muramatsu ◽  
Ryuta Iwanaga ◽  
Yasuhiro Tominaga ◽  
Takahiro Hashimoto ◽  
Toshihiko Taguchi
Keyword(s):  
Ankle Joint ◽  
Tumor Resection ◽  
Tumor Location ◽  
Pigmented Villonodular Synovitis ◽  
Growth Patterns ◽  
Treatment Modalities ◽  
Villonodular Synovitis ◽  
Lateral Incision ◽  
Pigmented Villonodular

Background: Pigmented villonodular synovitis (PVNS) is a rare disorder around the ankle joint. The optimal treatment for diffuse-type PVNS is still controversial because of the high incidence of recurrence. We present the clinical features of our patients and review the current diagnostic and treatment modalities. Methods: Five patients with PVNS located around the ankle were surgically treated. In three patients, diffuse PVNS arose from the ankle joint, and in the other two it arose from the calcaneocuboid and intercuneiform joints. The average follow-up time after surgery was 2.9 years (range, 2–4.6 years). Results: The average time between onset of pain and diagnosis of PVNS was 6.4 years (range, 4–10 years). Arthrotomic tumor resection was performed in all of the patients. In the three patients with ankle joint PVNS, both medial and lateral approaches were used. One patient experienced mild infection at the surgical site, but this healed conservatively. No tumor recurrences had occurred after minimum follow-up of 2 years, although mild pain persisted in the three patients with ankle PVNS. Conclusions: Diagnosis of diffuse PVNS is frequently delayed due to vague symptoms and variable growth patterns. Orthopedic clinicians should be aware of the existence of this lesion, and it should be suspected in patients with persistent ankle swelling. To prevent tumor recurrence, accurate evaluation of tumor location and careful operative planning are mandatory. A combined surgical approach involving medial and lateral incision is necessary to expose the entire joint cavity.

scholarly journals The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress, and Inflammation in Protective and Adaptive Responses

2020 ◽  
Vol 21 (23) ◽  
pp. 9262
Author(s):  
Luc Rochette ◽  
Loubna Mazini ◽  
Gabriel Malka ◽  
Marianne Zeller ◽  
Yves Cottin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intracellular Signaling ◽  
Adipose Derived Stem Cells ◽  
Adaptive Responses ◽  
Complex Signals ◽  
Beneficial Effects ◽  
Secondary Messenger ◽  
Secreted Factors ◽  
Oxidation Reduction ◽  
Therapeutic Properties

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.

scholarly journals Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 170 ◽  
Author(s):  
Gabriele Serreli ◽  
Monica Deiana
Keyword(s):  
Olive Oil ◽  
Intracellular Signaling ◽  
Cellular Response ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Main Concern ◽  
Beneficial Effects ◽  
Positive Effects

Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds.

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