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Asian Pacific Journal of Cancer... Jun 2024Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic...
OBJECTIVE
Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic events within signal transduction pathways governing normal cellular physiology are quantitatively or qualitatively altered. There are various molecular targets like Cyclin D and PI3k- alpha Ras Binding Domain receptor protein involved in the pathogenesis of Oral Squamous Cell Carcinoma. The aim of the study is to demonstrate the computer aided drug design to identify a potent natural molecule for targeting cyclin D4 and PI3K RAS binding protein.
MATERIALS AND METHODS
Target selection (Cyclin D1 and PI3K-alpha Ras Binding Domain receptor) was done and structures were derived from protein data bank. Ligands (Apigenin, Chrysoeriol and Luteolin) selection was done and structure derived. Final docking was performed by Autodock.
RESULTS
From the docking results it can be seen that luteolin has the highest binding energy (-5.45) with the Cyclin D receptor molecule followed by Chrysoeriol (-4.99) and Apigenin (-4.96). The binding energies of the ligands against PI3K-alpha Ras Binding Domain receptors were Apigenin (-4.51), Chrysoeriol (-4.6) and Luteolin (-4.56).
CONCLUSION
The study concludes that all the three selected ligands possess high binding energy with both the target proteins involved in carcinogenesis with highest binding energy possessed by Luteolin against the Cyclin D receptor and by Chrysoeriol against PI3K-RAS binding protein. Thus their activity can be utilized to derive potential Anti-cancer therapeutic drugs.
PubMed: 38918669
DOI: 10.31557/APJCP.2024.25.6.2069 -
Scientific Reports Jun 2024The continuous increase in cancer rates, failure of conventional chemotherapies to control the disease, and excessive toxicity of chemotherapies clearly demand...
The continuous increase in cancer rates, failure of conventional chemotherapies to control the disease, and excessive toxicity of chemotherapies clearly demand alternative approaches. Natural products contain many constituents that can act on various bodily targets to induce pharmacodynamic responses. This study aimed to explore the combined anticancer effects of Rumex obtusifolius (RO) extract and the chemotherapeutic agent 5-fluorouracil (5-FU) on specific molecular targets involved in cancer progression. By focusing on the PI3K/Akt signaling pathway and its related components, such as cytokines, growth factors (TNFa, VEGFa), and enzymes (Arginase, NOS, COX-2, MMP-2), this research sought to elucidate the molecular mechanisms underlying the anticancer effects of RO extract, both independently and in combination with 5-FU, in non-small lung adenocarcinoma A549 cells. The study also investigated the potential interactions of compounds identified by HPLC/MS/MS of RO on PI3K/Akt in the active site pocket through an in silico analysis. The ultimate goal was to identify potent therapeutic combinations that effectively inhibit, prevent or delay cancer development with minimal side effects. The results revealed that the combined treatment of 5-FU and RO demonstrated a significant reduction in TNFa levels, comparable to the effect observed with RO alone. RO modulated the PI3K/Akt pathway, influencing the phosphorylated and total amounts of these proteins during the combined treatment. Notably, COX-2, a key player in inflammatory processes, substantially decreased with the combination treatment. Caspase-3 activity, indicative of apoptosis, increased by 1.8 times in the combined treatment compared to separate treatments. In addition, the in silico analyses explored the binding affinities and interactions of RO's major phytochemicals with intracellular targets, revealing a high affinity for PI3K and Akt. These findings suggest that the combined treatment induces apoptosis in A549 cells by regulating the PI3K/Akt pathway.
Topics: Humans; Fluorouracil; Proto-Oncogene Proteins c-akt; Apoptosis; Plant Extracts; Phosphatidylinositol 3-Kinases; A549 Cells; Rumex; Signal Transduction; Molecular Docking Simulation; Computer Simulation; Lung Neoplasms
PubMed: 38918540
DOI: 10.1038/s41598-024-65816-5 -
Medical Oncology (Northwood, London,... Jun 2024This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The... (Review)
Review
This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies.
Topics: Humans; Iridoids; Neoplasms; Phytochemicals; Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Apoptosis
PubMed: 38918260
DOI: 10.1007/s12032-024-02429-y -
Nutrition Reviews Jun 2024The elderly population is increasing worldwide every day. Age is a significant factor in the progression of neurological diseases, which can also cause cognitive decline...
The elderly population is increasing worldwide every day. Age is a significant factor in the progression of neurological diseases, which can also cause cognitive decline and memory disorders. Inflammation and oxidative stress are primary drivers of senescence and disorders, particularly those associated with aging and neurodegenerative diseases. Bioactive phytochemicals are considered a promising therapeutic strategy in combating aging and age-related pathological conditions. One of the phytochemicals with diverse biological properties encompassing antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, antifungal, antidepressant, anti-allergic, and anti-aging properties is curcumin. Curcumin, a polyphenolic structure with a distinct orange hue and unique chemical properties, is derived from the roots of Curcuma longa, a member of the Zingiberaceae family, commonly known as turmeric. It has been noted that the incidence of neurodegenerative diseases is low in societies that consume curcumin widely. Therefore, this review investigates the effect of curcumin on aging and Alzheimer and Parkinson disease, which are the most prevalent age-related neurodegenerative diseases.
PubMed: 38916925
DOI: 10.1093/nutrit/nuae079 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Our study focused on enhancing the production of anthraquinone derivatives in Oldenlandia umbellata using fungal elicitors. Aspergillus niger, Mucor prayagensis, and...
Our study focused on enhancing the production of anthraquinone derivatives in Oldenlandia umbellata using fungal elicitors. Aspergillus niger, Mucor prayagensis, and Trichoderma viride were used to elicit the anthraquinone derivatives in root cultures. The elicitation process led to an increase in the production of phytochemicals and secondary metabolites, with the highest total protein content observed in A. niger-elicited plants. We performed qualitative and quantitative phytochemical screening of the 80% methanol extract of the plants. Using reverse phase-ultra-fast liquid chromatography, we identified and quantified five anthraquinone compounds: aloe-emodin, rhein, emodin, chrysophanol, and alizarin. The in vitro root samples elicited with A. niger and M. prayagensis exhibited four and three anthraquinone derivatives, respectively, whereas those elicited with T. viride showed only two derivatives. Interestingly, chrysophanol content was the highest in A. niger-elicited root samples. We constructed a system pharmacology framework consisting of 40 nodes and 45 edges with 34 interacting genes. We also identified human proteins that interact with these derivatives, and inferred their roles in cancer-associated pathways. These anthraquinone derivatives interact with various proteins in multiple pathways, including apoptosis, human cytomegalovirus infection, proteoglycans in cancer, MAPK signaling, and hepatitis C, highlighting their potential therapeutic applications in cancer treatment.
PubMed: 38916834
DOI: 10.1007/s00210-024-03239-9 -
Current Nutrition Reports Jun 2024The Amazon region has a high biodiversity of flora, with an elevated variety of fruits, such as Camu-Camu (Myrciaria dúbia), Açaí (Euterpe oleracea Mart.), Tucumã... (Review)
Review
PURPOSE OF REVIEW
The Amazon region has a high biodiversity of flora, with an elevated variety of fruits, such as Camu-Camu (Myrciaria dúbia), Açaí (Euterpe oleracea Mart.), Tucumã (Astrocaryum aculeatum and Astrocaryum vulgare), Fruta-do-conde (Annona squamosa L.), Cupuaçu (Theobroma grandiflorum), Graviola (Annona muricata L.), Guarana (Paullinia cupana Kunth var. sorbilis), and Pitanga (Eugenia uniflora), among many others, that are rich in phytochemicals, minerals and vitamins with prominent antioxidant and anti-inflammatory potential.
RECENT FINDINGS
Studies evaluating the chemical composition of these fruits have observed a high content of nutrients and bioactive compounds. Such components are associated with significant biological effects in treating various non-communicable diseases (NCDs) and related complications. Regular intake of these fruits from Amazonas emerges as a potential therapeutic approach to preventing and treating NCDs as a nutritional strategy to reduce the incidence or mitigate common complications in these patients, which are the leading global causes of death. As studies remain largely unexplored, this narrative review discusses the possible health-beneficial effects for patients with NCDs.
PubMed: 38916807
DOI: 10.1007/s13668-024-00553-9 -
Ibrain 2024Neurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts...
Neurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts focus on implementing diverse strategies to mitigate the adverse effects of neurodegeneration, with the goal of decelerating the pathology progression. Notably, in recent years, it has emerged that the use of nanoparticles (NPs), particularly those obtained through green chemical processes, could constitute a promising therapeutic approach. Green NPs, exclusively sourced from phytochemicals, are deemed safer compared to NPs synthetized through conventional chemical route. In this study, the effects of green chemistry-derived silver NPs (AgNPs) were assessed in neuroblastoma cells, SHSY-5Y, which are considered a pivotal model for investigating neurodegenerative diseases. Specifically, we used two different concentrations (0.5 and 1 µM) of AgNPs and two time points (24 and 48 h) to evaluate the impact on neuroblastoma cells by observing viability reduction and intracellular calcium production, especially using 1 µM at 48 h. Furthermore, investigation using atomic force microscopy (AFM) unveiled an alteration in Young's modulus due to the reorganization of cortical actin following exposure to green AgNPs. This evidence was further corroborated by confocal microscopy acquisitions as well as coherency and density analyses on actin fibers. Our in vitro findings suggest the potential efficacy of green AgNPs against neurodegeneration; therefore, further in vivo studies are imperative to optimize possible therapeutic protocols.
PubMed: 38915951
DOI: 10.1002/ibra.12157 -
Frontiers in Immunology 2024Garlic ( L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to... (Review)
Review
Garlic ( L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many and studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, β-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and β-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
Topics: Garlic; Humans; Animals; Plant Extracts; Antioxidants; Phytochemicals; Sulfinic Acids; Disulfides
PubMed: 38915405
DOI: 10.3389/fimmu.2024.1277074 -
Journal of AOAC International Jun 2024Glucosinolates play important role in providing defense to plants and helps them in coping against various biotic as well as abiotic stress. Many living beings including...
BACKGROUND
Glucosinolates play important role in providing defense to plants and helps them in coping against various biotic as well as abiotic stress. Many living beings including humans, animals, and even some herbivores have adapted themselves to use this defense mechanism for their own use. More than 120 glucosinolates are distributed within a large number of plants. Many factors are known to influence the GSL composition in a plant. Among these, cofactors, myrosinase isozymes, heavy metals and the environmental conditions such as light, CO2 and temperature are important in the regulation. These factors ensure that different glucosinolate composition could be produced by the plants, thus impacting the defense mechanism.
OBJECTIVE
The objective of the current review is to highlight the importance of factors responsible for affecting glucosinolate composition and concentration.
METHODS
The review has been compiled using accessible literature from Pubmed, Scopus, and Google scholar. Efforts have been made to restrict the literature to the last 5 years (2018-2023), with some exceptions.
RESULTS
The current critical review acts as a resource for all the researchers working on this essential compound. It provides information on the factors that may influence the glucosinolate production. It also gives them an opportunity to modify the glucosinolate composition of a plant using the given information.
CONCLUSION
Glucosinolates have long been an ignored class of biomolecule. The plethora of biological activities of the compounds can be useful. Though there are some harmful components such as goitrin and progoitrin, these can be easily removed by modulating some of the factors highlighted in the review.
HIGHLIGHTS
The current review has touched base on almost all the factors that have the ability to modify glucosinolate composition and concentration. The mechanistic action of these factors have also been discussed using the current available literature.
PubMed: 38913875
DOI: 10.1093/jaoacint/qsae049 -
Archives of Microbiology Jun 2024Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly...
Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.
Topics: Pseudomonas aeruginosa; Quorum Sensing; Triclosan; Biofilms; Acyclic Monoterpenes; Drug Synergism; Molecular Docking Simulation; Anti-Bacterial Agents; Virulence; Bacterial Proteins; Pyocyanine
PubMed: 38913239
DOI: 10.1007/s00203-024-04059-4