Promising Roles of Phytocompounds and Nutrients in Interventions to Mitigate Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVES: Provide an overview of scientific reports and literature related to the role(s) of phytocompounds and nutrients in neuroprotection. Discuss how these properties may inform nutrition- and dietary interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN), for which there are no effective treatments. METHODS: A literature search (2010-2023) was conducted in PubMed and Google Scholar where search terms-diet, nutrition, neuroprotection, neurodegenerative diseases, and social determinants of health-were used to narrow articles. From this search, manuscripts were reviewed to provide an overview of the neuroprotective properties of various phytocompounds and nutrients and their observed effects in neurodegenerative conditions and CIPN. Social determinant of health factors (SDOH) related to economic stability and access to nutritious foods were also reviewed as potential barriers to dietary interventions. RESULTS: Twenty-eight publications were included in this literature review. Phytocompounds found in green tea (EGCG), turmeric (curcumin), cruciferous vegetables (sulforaphane), as well as certain vitamins, are promising, targeted interventions to mitigate CIPN. SDOH factors such as economic instability and limited access to nutritious foods may act as barriers to dietary interventions and limit their generalizability. CONCLUSION: Dietary interventions focused on the use of phytocompounds and vitamins with known antioxidant, anti-inflammatory, and neuroprotective properties, hold promise and may provide patients with natural, non-pharmacological therapeutics for the management and/or prevention of CIPN. However, rigorous clinical trial research is needed to explore these effects in humans. IMPLICATIONS FOR NURSING PRACTICE: Nurses support cancer survivors at the point-of-care, particularly during and after neurotoxic chemotherapy treatments. If future research supports dietary interventions to mitigate CIPN, nurses will ultimately be positioned to help translate this knowledge into clinical practice through educating patients on how to infuse nutrient-rich foods into their diets. Further, nurses will need to be conscious of SDOH factors that may impede access to these foods.

Profiling of antioxidant properties and identification of potential analgesic inhibitory activities of Allophylus villosus and Mycetia sinensis employing in vivo, in vitro, and computational techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of plants for medicinal purposes, called phytomedicine, has been known to provide relief from pain. In Bangladesh, the Chakma indigenous community has been using Allophylus villosus and Mycetia sinensis to treat various types of pain and inflammation. AIM OF THE STUDY: The object of this research is to evaluate the effectiveness of these plants in relieving pain and their antioxidant properties using various approaches such as in vitro, in vivo, and computational techniques. Additionally, the investigation will also analyse the phytochemicals present in these plants. MATERIALS AND METHODS: We conducted in vivo analgesic experiment on Swiss albino mice and in-silico inhibitory activities on COX-2 & 15-LOX-2 enzymes. Assessment of DPPH, Anti Radical Activities (ARA), FRAP, H2O2 Free Radical Scavenging, Reducing the power of both plants performed significant % inhibition with tolerable IC50. Qualitative screening of functional groups of phytochemicals was précised by FTIR and GC-MS analysis demonstrated phytochemical investigations. RESULTS: The ethyl acetate (EtOAc) fractioned Mycetia sinensis extract as well as the ethanoic extract and all fractioned extracts of Allophylus villosus have reported a significant percentage (%) of writhing inhibition (p < 0.05) with the concentrated doses 250 mg as well as 500 mg among the Swiss albino mice for writhing observation of analgesic effect. In the silico observation, a molecular-docking investigation has performed according to GC-MS generated 43 phyto-compounds of both plants to screen their binding affinity by targeting COX-2 and 15-LOX-2 enzymes. Consequently, in order to assess and ascertain the effectiveness of the sorted phytocompounds, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) investigation, DFT (Density-functional theory) by QM (Quantum mechanics), and MDS (Molecular dynamics simulation) were carried out. As the outcome, compounds like 5-(2,4-ditert-butylphenoxy)-5-oxopentanoic acid; 2,4-ditert-butylphenyl 5-hydroxypentanoate; 3,3-diphenyl-5-methyl-3H-pyrazole; 2-O-(6-methylheptan-2-yl) 1-O-octyl benzene-1,2-dicarboxylate and dioctan-3-yl benzene-1,2-dicarboxylate derived from the ethnic plant A. villosus and another ethnic plant M. sinensis extracts enchants magnificent analgesic inhibitions and performed more significant drug like activities with the targeted enzymes. CONCLUSIONS: Phytocompounds from A. villosus & M. sinensis exhibited potential antagonist activity against human 15-lipoxygenase-2 and cyclooxygenase-2 proteins. The effective ester compounds from these plants performed more potential anti-nociceptive activity which could be used as a drug in future.

Development of Anti-Inflammatory Drug from Crataeva Nurvala: In Silico and In Vitro Approach.

Background: Crataeva nurvala, a medicinal plant with potential therapeutic properties, offers a promising avenue for the development of novel anti-inflammatory drugs. This study adopted a combined in silico and in vitro approach to investigate the anti-inflammatory potential of compounds derived from Crataeva nurvala. Materials and Methods: In the in silico phase, virtual screening and molecular docking analyses were conducted to identify bioactive compounds from Crataeva nurvala that could interact with key inflammatory targets. Subsequently, selected compounds were synthesized and subjected to in vitro experimentation. Cellular models were employed to assess the anti-inflammatory effects of Crataeva nurvala-derived compounds, focusing on the modulation of pro-inflammatory cytokine levels and the underlying signaling pathways. Results: Virtual screening and molecular docking led to the identification of several bioactive compounds with favorable interactions with inflammatory targets. In the in vitro experiments, treatment with Crataeva nurvala-derived compounds resulted in a significant reduction in pro-inflammatory cytokine production. Moreover, the compounds exhibited the ability to modulate inflammatory signaling pathways, further substantiating their anti-inflammatory potential. Conclusions: This study not only contributes to the development of effective anti-inflammatory drugs but also underscores the value of harnessing natural sources such as Crataeva nurvala for therapeutic interventions in inflammatory disorders. The dual-phase strategy presented here provides a robust framework for anti-inflammatory drug discovery and validation.

Exploring the Therapeutic Potential of Petiveria alliacea L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2's Main Protease (Mpro).

The outbreak of SARS-CoV-2, also known as the COVID-19 pandemic, is still a critical risk factor for both human life and the global economy. Although, several promising therapies have been introduced in the literature to inhibit SARS-CoV-2, most of them are synthetic drugs that may have some adverse effects on the human body. Therefore, the main objective of this study was to carry out an in-silico investigation into the medicinal properties of Petiveria alliacea L. (P. alliacea L.)-mediated phytocompounds for the treatment of SARS-CoV-2 infections since phytochemicals have fewer adverse effects compared to synthetic drugs. To explore potential phytocompounds from P. alliacea L. as candidate drug molecules, we selected the infection-causing main protease (Mpro) of SARS-CoV-2 as the receptor protein. The molecular docking analysis of these receptor proteins with the different phytocompounds of P. alliacea L. was performed using AutoDock Vina. Then, we selected the three top-ranked phytocompounds (myricitrin, engeletin, and astilbin) as the candidate drug molecules based on their highest binding affinity scores of -8.9, -8.7 and -8.3 (Kcal/mol), respectively. Then, a 100 ns molecular dynamics (MD) simulation study was performed for their complexes with Mpro using YASARA software, computed RMSD, RMSF, PCA, DCCM, MM/PBSA, and free energy landscape (FEL), and found their almost stable binding performance. In addition, biological activity, ADME/T, DFT, and drug-likeness analyses exhibited the suitable pharmacokinetics properties of the selected phytocompounds. Therefore, the results of this study might be a useful resource for formulating a safe treatment plan for SARS-CoV-2 infections after experimental validation in wet-lab and clinical trials.

A mechanistic review of the pharmacological potential of narirutin: a dietary flavonoid.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Phytochemical characterisation and toxicity effect of Tithonia diversifolia (Hemls.) A. Gray leaf extract on fall army worm Spodoptera frugiperda (JE Smith) larvae.

OBJECTIVES: To mitigate the losses due to fall armyworm (FAW) infestation in maize, chemical pesticides had been the first choice and widely used as an emergency response. However, it comes with attendant health effect. This necessitates the development of plant based effective and safer pesticides. This research investigate response of fall armyworm larvae when they are exposed to crude and partially purified Tithonia diversifolia leaf extract. METHODS: Chemical constituent of the extract was identified using NIST08.LIB library spectra provided by the software on a GC-MS system and FTIR analysis was done using KBr pellet technique with a resolution and scanning speed of 4 cm-1 and 2 mm/s. Dose dependent toxicity assay of T. diversifolia extracts on FAW at different growth stages under controlled environment in laboratory, followed by its effect under phytotron were examined against control and azadirachtin from neem. RESULTS: The GC-MS of the butanol eluent revealed 20 compounds out of which the major ones being beta-d-glucopyranoside, methyl (15.225 %) palmitic acid, TMS derivative (10.98 %) and hexadecanoic acid, 2-[(trimethylsily)oxy]-, methyl ester (8.75 %). The FT-IR spectroscopic analysis of the butanol eluent of T. diversifolia leaf extract revealed the presence of alcohols, phenols, aldehydes, ketones, alkanes and primary amines. The butanol eluent and crude extract caused 96 % mortality at neonate and first instar FAW larvae. CONCLUSIONS: The toxic and repellant effects revealed by diet bioassay and phytotron experiment respectively suggest that butanol eluent of T. diversifolia leaf extract could be a good and effective target for biopesticide production against FAW.

Network pharmacology-integrated molecular docking analysis of phytocompounds of Caesalpinia pulcherrima (peacock flower) as potential anti-metastatic agents.

Caesalpinia pulcherrima, or peacock flower, has been a subject of cancer therapeutics research, showing promising anti-cancer and anti-metastatic properties. The present research aims to investigate the anti-metastatic potential of the flower, through bioinformatics approaches. Metastasis targets numbering 471 were identified through overlap analysis following NCBI gene, Gene Card and OMIM query. Phytocompounds of the flower were retrieved from PubChem and their protein interactions predicted using Super-PRED and TargetNet. The 28 targets that overlapped with the predicted proteins were used to generate STRING >0.7. Enrichment analysis revealed that C. pulcherrima may inhibit metastasis through angiogenesis-related and leukocyte migration-related pathways. HSP90AA1, ESR1, PIK3CA, ERBB2, KDR and MMP9 were identified as potential core targets while and 6 compounds (3-[(4-Hydroxyphenyl)methylidene]-7,8-dimethoxychromen-4-one (163076213), clotrimazole (2812), Isovouacapenol A (636673), [(4aR,5R,6aS,7R,11aS,11bR)-4a-hydroxy-4,4,7,11b-tetramethyl-9-oxo-1,2,3,5,6,6a,7,11a-octahydronaphtho[2,1-f][1]benzofuran-5-yl] benzoate (163104827), Stigmast-5-en-3beta-ol (86821) and 4,2'-dihydroxy-4'-methoxychalcone (592216)) were identified as potential core compounds. Molecular docking analysis and molecular dynamics simulations investigations revealed that ERBB2, HSP90AA1 and KDR, along with the newly discovered 163076213 compound to be the most significant metastasis targets and bioactive compound, respectively. These three core targets demonstrated interactions consistent with angiogenesis and leukocyte migration pathways. Furthermore, potentially novel interactions, such as KDR-MMP9, KDR-PIK3CA, ERBB2-HSP90AA1, ERBB2-ESR1, ERBB2-PIK3CA and ERBB2-MMP9 interactions were identified and may play a role in crosslinking the aforementioned metastatic pathways. Therefore, the present study revealed the main mechanisms behind the anti-metastatic effects of C. pulcherrima, paving the path for further research on these compounds and proteins to accelerate the research of cancer therapeutics and application of C. pulcherrima.Communicated by Ramaswamy H. Sarma.

The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phytocompound as a Novel Approach to the Elimination of Pathogens.

Due to the wide applications of silver nanoparticles (AgNPs), research on their ecological synthesis has been extensive in recent years. In our study, biogenic silver nanoparticles were synthesized extracellularly using the white rot fungus Trametes versicolor via two cultivation methods: static and shaking. The cell filtrate of the fungus was used as a reducing agent in the process of nanoparticle synthesis. Characterization of the obtained nanoparticles was carried out using UV-VIS spectroscopy and scanning electron microscopy. The biosynthesized nanoparticles have antimicrobial potential against pathogenic bacteria, particularly in Gram-negative strains. The bactericidal effect was obtained for E. coli at a concentration of 7 µg/mL. The use of higher concentrations of compounds was necessary for Gram-positive bacteria. Taking into account the problem of the risk of cytotoxicity of AgNPs, combined therapy using a phytochemical was used for the first time, which was aimed at reducing the doses of nanoparticles. The most representative synergistic effect was observed in the treatment of 5 µg/mL silver nanoparticles in combination with 15 µg/mL ursolic acid against E. coli and P. aeruginosa with a bactericidal effect. Moreover, the coadministration of nanoparticles considerably reduced the growth of both Staphylococcus strains, with a bactericidal effect against S. aureus. The viability test confirmed the strong synergistic effect of both tested compounds. Silver nanoparticles synthesized using the T. versicolor showed excellent antibacterial potential, which opens perspectives for future investigations concerning the use of the nanoparticles as antimicrobials in the areas of health.

Bioactive phytoconstituents of ethanolic extract from Chromolaena odorata leaves interact with vascular endothelial growth factor and cyclooxygenase-2: A molecular docking study.

Chromolaena odorata is an invasive plant with a broad spectrum of medicinal properties, including wound healing. This study aimed to evaluate the interaction of the already identified bioactive phytoconstituents from ethanolic extracts of C. odorata leaves with two angiogenesis-related proteins - vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in silico. A molecular docking protocol was performed on AutoDock Vina employing the molecular structure of VEGF (3HNG) and COX-2 (3LN1) downloaded from the Protein Data Bank. The results reveal that most of the phytoconstituents possess strong binding affinity, where ß-tocopherol and squalene have the highest values. In conclusion, it is highly possible that the phytoconstituents of C. odorata from the ethanolic leaf extract perform an interaction with VEGF and COX-2 and affect their activities.

Ethanolic Extract from Limonia acidissima L. Fruit Attenuates Serum Uric Acid Level via URAT1 in Potassium Oxonate-Induced Hyperuricemic Rats.

A high prevalence of hyperuricemia among adult and older adult populations has intrigued the development of its therapy based on natural products. Our objective was to investigate the antihyperuricemic activity of the natural product from Limonia acidissima L. in vivo. The extract was obtained through the maceration of L. acidissima fruits using an ethanolic solvent and was tested for its antihyperuricemic activity against potassium oxonate-induced hyperuricemic rats. Serum uric acid, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) were observed before and after the treatment. Expression of urate transporter 1 (URAT1) was also measured using a quantitative polymerase chain reaction. Antioxidant activity based on a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, along with total phenolic content (TPC) and total flavonoid content (TFC), were measured. Herein, we present the evidence of the serum uric acid lowering effect of the L. acidissima fruit extract along with improved AST and ALT (p < 0.01). The reduction of serum uric acid was in accordance with the decreasing trend of URAT1 (1.02 ± 0.05-fold change in the 200 mg group), except in a group treated with 400 mg/kg body weight extract. At the same time, BUN increased significantly in the 400 mg group (from 17.60 ± 3.286 to 22.80 ± 3.564 mg/dL, p = 0.007), suggesting the renal toxicity of the concentration. The IC50 for DPPH inhibition was 0.14 ± 0.02 mg/L with TPC and TFC of 143.9 ± 5.24 mg GAE/g extract and 390.2 ± 3.66 mg QE/g extract, respectively. Further studies should be carried out to prove this correlation along with the safe concentration range of the extract.

Cell death regulation: A new way for natural products to treat osteoporosis.

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.

Novel Eubacterium rectale inhibitor from Coriandrum sativum L. for possible prevention of colorectal cancer: a computational approach.

This research aims to screen out the effective bioactive compounds from Coriander (Coriandrum sativum L.), which may be novel potential inhibitors of Eubacterium rectale for the prevention of colorectal cancer (CRC). A series of 8 coriander-derived chemical compounds previously assessed for their anti-inflammatory, antioxidant, and antidiabetic activities were tested against Carbohydrate ABC transporter substrate-binding protein and compared to the standard inhibitor Acarbose, to support their use as novel Eubacterium rectale inhibitors. Herein, these derivatives were submitted to a thorough analysis of docking studies, in which detailed interactions of the selected phytocompounds with carbohydrate ABC transporter substrate-binding protein were revealed. Molecular docking analysis recommends Rutin, Gallocatechin, and Epigallocatechin as the most potential Eubacterium rectale inhibitors among the eight selected phytochemical compounds. Subsequently, the stability of the three selected phytochemical complexes was checked using molecular dynamics (MD) simulation at 100 ns and Molecular Mechanics combined with Poisson-Boltzmann Surface Area (MM-PBSA). The results show quite good stability for Rutin and Gallocatechin. In silico ADMET prediction was performed on the selected compounds, and the findings revealed a reasonably good ADMET profile for both Rutin and Gallocatechin. The current findings predict that Gallocatechin could be a better CRC preventive natural compound, and, further in vitro, in vivo and clinical studies may confirm its therapeutic potential.Communicated by Ramaswamy H. Sarma.

Cranberry Pomace Extract Exerts Antiviral Activity against Zika and Dengue Virus at Safe Doses for Adult Zebrafish.

Mosquito-borne dengue virus (DENV) and zika virus (ZIKV) infections constitute a global health emergency. Antivirals directly targeting the virus infectious cycle are still needed to prevent dengue hemorrhagic fever and congenital zika syndrome. In the present study, we demonstrated that Cranberry Pomace (CP) extract, a polyphenol-rich agrifood byproduct recovered following cranberry juice extraction, blocks DENV and ZIKV infection in human Huh7.5 and A549 cell lines, respectively, in non-cytotoxic concentrations. Our virological assays identified CP extract as a potential inhibitor of virus entry into the host-cell by acting directly on viral particles, thus preventing their attachment to the cell surface. At effective antiviral doses, CP extract proved safe and tolerable in a zebrafish model. In conclusion, polyphenol-rich agrifood byproducts such as berry extracts are a promising source of safe and naturally derived nutraceutical antivirals that target medically important pathogens.

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19.

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNß and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of -5.752 and Glide gscore of -5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging.

Over thousands of years, natural bioactive compounds derived from plants (bioactive phytocompounds, BPCs) have been used worldwide to address human health issues. Today, they are a significant resource for drug discovery in the development of modern medicines. Although many BPCs have promising biological activities, most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility, structural instability, short half-life, poor bioavailability, and non-specific distribution to organs. Researchers have utilized emerging nanoformulation (NF) technologies to overcome these limitations as they have demonstrated great potential to improve the solubility, stability, and pharmacokinetic and pharmacodynamic characteristics of BPCs. This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy. This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications. Finally, this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.

Potential of phytocompounds from Brassica oleracea targeting S2-domain of SARS-CoV-2 spike glycoproteins: Structural and molecular insights.

By 24th Sep. 2021, there are more than 229 million COVID-19 cases worldwide, the researchers are tirelessly working to discover and develop an efficient drug molecule against this devastative viral infection. This study aims to evaluate the inhibitory efficiency of the organic acids and phenolic compounds present in Brassica oleracea (Tronchuda Cabbage) against spike glycoprotein in SARS-CoV-2. Thirty-seven phytocompounds are screened on the basis of their molecular weight (<500 g/mol) and 14 ligands are docked using Autodock Vina and Autodock4 (version 4.2.6). The stability of the top five docked complexes was analyzed using classical molecular dynamics (MD) simulation. ADMET analysis is performed for the top five compounds and their targets are identified using SwissTargetPrediction. Phytoactives from B. oleracea namely Astragalin, 3-p-coumaroylquinic acid, 4-p-coumaroylquinic acid and sinapoyl-D-glucoside showed high binding affinities and free energy of binding during molecular docking and MD simulation studies (∼ 8.5-9.0 kcal/mol) for the spike glycoprotein trimer of SARS-CoV2. The ADMET analysis revealed that these phytocompounds have good solubility in the aqueous phase and that they don't penetrate the blood brain barrier. Moreover, there is no P-gp substrate inhibition, CYP1A2 inhibition, CYP2C19 inhibition, CYP2C9 inhibition, CYP2D6 inhibition and CYP3A4 inhibition observed for these compounds. Additionally, zero PAINS alerts were reported. These findings from molecular docking and MD simulation studies suggest that astragalin and coumaroylquinic acids from Tronchuda cabbage possess potential inhibitory capacity against spike glycoprotein trimer of SARS-CoV-2 and could be further taken up as lead targets for drug discovery.

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells.

Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer.

An Overview of Phytotherapy Used in the Management of Type II Diabetes.

Diabetes mellitus is related to unconstrained high blood sugar and linked with long-term impairment, dysfunction and failure of several organs. Since 1980, the global frequency of diabetes has almost doubled in the adult population. In very rare cases due to poor prevention and management programs, diabetes causes worsening of health and reduced lifespan of the world population, thus impacting on the world's economy. Supplements, however, help in the improvement of nutritional deficiencies. Phytotherapeutics has the advantage of being economical and easy to access with marginal side effects. So, it is a preferred candidate for the management of diabetes. Currently, a multitude of pharmaceuticals are used which are obtained from natural sources having medicinal properties. The mechanistic approaches are based on the regulation of insulin signaling pathways, translocation of GLUT-4 receptors and/or activation of PPAR γ. These natural compounds include numerous flavonoids which help in preventing glucose absorption by preventing the absorption of α-amylase and α-glucosidase. But to validate the efficacy and safety profile of these compounds, detailed validatory clinical studies are required. This review majorly focuses on the mechanistic approaches of various naturally derived compounds relevant for the condition of Diabetes Mellitus.

A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits.

Hesperidin, a phytoactive compound, is an abundant and economical dietary bioflavonoid possessing numerous biological and medicinal benefits. Several studies have strongly proven the significant chemotherapeutic potential of hesperidin. Therefore, this review aims to bring together the existing studies demonstrating hesperidin as a potential anticancer agent with its mode of action reported in the therapeutic strategies for numerous cancer types. Hesperidin acts via modulating multiple pathways involving cell cycle arrest, apoptosis, antiangiogenic, antimetastatic and DNA repair in various cancer cells. Hesperidin has been reported to alter several molecular targets related to carcinogenesis, such as reactive nitrogen species, cellular kinases, transcription factors, reactive oxygen species, drug transporters, cell cycle mediators and inflammatory cytokines. Collectively, this review provides significant insights for the potential of hesperidin to be a strong and promising candidate for pharmaceuticals, functional foods, dietary supplements, nutraceuticals and geared toward the better management of carcinoma.

Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications.

The skin is the primordial barrier that protects the human body against environmental factors. Due to the arise of dermatological pathologies, the development of efficient delivery systems for topical applications has received increased interest. The highest challenge consists of increasing the penetration of the active ingredients through the skin barrier, alongside to the need of obtaining enough skin retention to achieve therapeutic concentrations. Metals, specially noble metals, have been used for years to treat and prevent health issues, among them dermatological disorders. Nanoparticles have been extensively used for topical applications given their advantages, namely by enhancing solubility of apolar drugs, the possibility of controlled release, the higher stability and the capability to target specific areas and delivery of high concentrations of active ingredients. In order to take advantage of the before mentioned unique properties of nanoparticles and the biological activities of metals, various metal-based nanoparticles (MNPs) have been synthesized in the past few years, such as silver (AgNPs), gold (AuNPs), zinc (ZnNPs), zinc oxide (ZnONPs), copper (CuNPs) and copper oxide (CuONPs) nanoparticles. These MNPs are flexible structures that allow the control of physical characteristics, with enhanced surface properties, which provides a high applicability in dermopharmacy and cosmetics. The conventional methods for synthesizing nanoparticles (physical and chemical approaches) are associated with major drawbacks, being the most concerning the high cost (in resources, energy, time and space) and human/environmental toxicity. Hence, the need to develop an alternative synthesis pathway was imposed, giving rise to the green synthesis methodology. In general, green synthesis consist of using biological sources (plants, bacteria or fungi) to synthesize ecological benign, non-hazard and biocompatible nanoparticles. With the development of green synthesis, starting materials have been used more frequently, among them plants. Plant-mediated green synthesis of nanoparticles is based on the use of plant extracts to synthesize nanoparticles, and their outstanding advantages have paved the way for exciting developments on nanoparticle synthesis to the detriment of complex and toxicity-associated chemical and physical synthesis. MNPs produced by plant-mediated synthesis also demonstrate notorious biological activities, i.e., anticancer, antioxidant, anti-inflammatory, antimicrobial, wound healing and antiaging activities. However, safety assessment of phyto MNPs (phyto-MNPs) holds significant importance due to the lack of toxicological studies and the conception issues that some of the available studies show. In general, current studies suggest the biocompatibility and safety of phyto-MNPs, together with significantly improved and relevant biological activities towards dermopharmaceutical and cosmetic applications. Against this backdrop, there is still a long way to run until the application of phyto-MNPs in the medical, pharmaceutical and cosmetic fields, but studies so far show a very high potential towards their clinical translation for dermopharmaceutical and cosmetics applications. This review focuses on phyto-MNPs synthesized resorting to various plant extracts, including their production, characterization and the biological activities that support their topical application for dermopharmaceutical and cosmetic purposes.