Impacts of nutritive and bioactive compounds on cancer development and therapy.

For persons who survive with progressive cancer, nutritional therapy and exercise may be significant factors to improve the health condition and life quality of cancer patients. Nutritional therapy and medications are essential to managing progressive cancer. Cancer survivors, as well as cancer patients, are mostly extremely encouraged to search for knowledge about the selection of diet, exercise, and dietary supplements to recover as well as maintain their treatment consequences, living quality, and survival of patients. A healthy diet plays an important role in cancer treatment. Different articles are studied to collect information and knowledge about the use of nutrients in cancer treatment as well as cancer prevention. The report deliberates nutrition and exercise strategies during the range of cancer care, emphasizing significant concerns during treatment of cancer and for patients of advanced cancer, but concentrating mostly on the requirements of the population of persons who are healthy or who have constant disease following their repossession from management. It also deliberates choice nutrition and exercise problems such as dietary supplements, food care, food selections, and weight; problems interrelated to designated cancer sites, and common questions about diet, and cancer survival. Decrease the side effects of medicines both during and after treatment.

Mineral and Phenolic Composition of Erodium guttatum Extracts and Investigation of Their Antioxidant Properties in Diabetic Mice.

Erodium guttatum is widely used in folk medicine in many countries to treat various ailments such as urinary inflammation, diabetes, constipation, and eczema. The aim of this study is the determination of mineral and phenolic compounds of E. guttatum extracts as well as the investigation of their antidiabetic and antioxidant properties. The mineral composition was determined by the methods of inductively coupled plasma atomic emission spectroscopy analysis. Phytochemical contents of total polyphenols, total flavonoids, and catechic tannins were estimated by colorimetric dosages. The phenolic composition was identified by high-resolution mass spectrometry (HRMS) analysis. The antioxidant activity of E. guttatum extracts was measured in vitro by five methods (DPPH, ABTS, FRAP, H2O2, and xanthine oxidase) and in vivo by assaying the malondialdehyde marker (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The obtained results showed that the root plant material is rich in minerals such as k, Ca, and Mg. The methanolic extract of E. guttatum is the richest in polyphenols (389.20 ± 1.55 mg EAG/gE), tannins (289.70 ± 3.57 mg EC/gE), and flavonoids (432.5 ± 3.21 mg ER/gE). Concerning the ESI-HRMS analysis, it showed the presence of numerous bioactive compounds, including shikimic acid, rottlerine, gallic acid, and vanillic acid. Moreover, the aqueous and alcoholic extracts of E. guttatum exhibited antiradical and antioxidant activity in five tests used, with the best effect of the methanolic extract. Moreover, findings showed that in vivo investigations confirmed those obtained in vitro. On the other hand, E. guttatum showed important antidiabetic effects in vivo. Indeed, diabetic mice treated with extracts of E. guttatum were able to significantly reduce MDA levels and increase the secretion of enzymatic and nonenzymatic antioxidants (SOD, CAT, and GSH, respectively). However, the antioxidant activity of the extracts might be attributed to the abundance of bioactive molecules; as results, this work serves as a foundation for additional pharmacological research.

The Current State of Knowledge in Biological Properties of Cirsimaritin.

The search for natural plant-based products as new pharmacological alternatives to treat various human pathologies has taken on great importance for researchers and research laboratories. In this context, research has intensified to extract and identify natural molecules endowed with biological effects. The objective of this study is to review the source and pharmacological properties of cirsimaritin. The identification and isolation of this flavonoid from various natural sources, including medicinal plants such as Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and Ocimum sanctum, has been carried out and verified using different spectral techniques. Biological effect investigations are carried out with a wide variety of experimental models in vitro and in vivo and laboratory techniques. The results of these research works showed the biological properties of cirsimaritin including anticancer, antimicrobial, antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms involved in the multiple activities of this molecule are diverse and include sub-cellular, cellular, and molecular levels. Indeed, this bioactive induces anti-inflammatory and antiproliferative effects by inhibiting cell membrane receptors, interference with signaling pathways, and inhibiting transcriptional factors such as Nf-κB involved in cell promotion and proliferation. In the light of these results, cirsimaritin appears as a promising and viable alternative natural bioactive drug to treat many pathological conditions.

Antiulcer Effect of Senna multiglandulosa via Increased Secretion of Mucus and Nonprotein Sulfhydryl Groups in an Experimental Murine Model.

Peptic ulcer is a universal condition that is a public health problem due to its prevalence, risk of complications and socioeconomic impact. This study aimed to determine the antiulcer effect of the hydroalcoholic extract from Senna multiglandulosa leaves against ethanol-induced gastric ulcer in rats. Thirty-six male albino Holtzman rats were assigned to six groups. Group I received physiological saline (PS) at doses of 10 mL/kg; group II: ethanol (PS + ethanol 5 mL/kg); group III; omeprazole 100 mg/kg/day (gold standard); groups IV, V and VI received doses of 100, 250 and 500 mg/kg/day of S. multiglandulosa extract, respectively. The stomach was removed to determine the ulcerative lesions and two sections of the glandular zone to carry out the analysis of the gastric mucus and sulfhydryl groups content. As result, S. multiglandulosa at doses of 250 and 500 mg/kg produced a significant decrease of the injured area, with values of 46.28 ± 7.95 mm2 and 6.91 ± 2.48 mm2, respectively (P < 0.001). The protective effect was showed at dose of 500 mg/kg (92.27%) and a significant increase in the production of mucus with a value of 83.13 ± 13.09 mg/mL/g of tissue (61.14%). The production of nonprotein sulfhydryl groups (NP-SG) also increased significantly at the three evaluated doses, being 250.34 ± 21.16 µg/g tissue at dose of 500 mg/kg (119.94%). It is concluded that S. multiglandulosa extract protected against ethanol-induced gastric ulcer due to increased gastric mucus secretion and its antioxidant activity due to the generation of nonprotein sulfhydryl groups.

Singular and Combined Effects of Essential Oil and Honey of Eucalyptus Globulus on Anti-Inflammatory, Antioxidant, Dermatoprotective, and Antimicrobial Properties: In Vitro and In Vivo Findings.

Eucalyptus globulus is a plant widely used by the world population, including Morocco, in the treatment of several pathologies. The aim of this work is to evaluate the antioxidant, anti-inflammatory, dermatoprotective, and antimicrobial effects of essential oil and honey from E. globulus, as well as their combination. Chemical composition was determined by GC-MS analysis. The antioxidant activity was evaluated by three tests, namely, DPPH, reducing power, and the ß-carotene/linoleic acid assay. The anti-inflammatory activity was investigated in vitro (5-lipoxygenase inhibition) and in vivo (carrageenan-induced paw edema model), while the dermatoprotective activity was tested in vitro (tyrosinase inhibition). Moreover, the antibacterial activity was assessed using agar well diffusion and microdilution methods. The results showed that eucalyptol presents the main compound of the essential oil of E. globulus (90.14%). The mixture of essential oil with honey showed the best antioxidant effects for all the tests used (0.07 < IC50 < 0.19 mg/mL), while the essential oil was the most active against tyrosinase (IC50 = 38.21 ± 0.13 µg/mL) and 5-lipoxygenase (IC50 = 0.88 ± 0.01 µg/mL), which corroborated the in vivo test. Additionally, the essential oil showed the best bactericidal effects against all strains tested, with inhibition diameter values ranging from 12.8 to 21.6 mm. The findings of this work showed that the combination of the essential oil with honey showed important results in terms of biological activity, but the determination of the underlying mechanisms of action remains a major prospect to be determined.

Inhibition of α-Amylase, α-Glucosidase, and Lipase, Intestinal Glucose Absorption, and Antidiabetic Properties by Extracts of Erodium guttatum.

Erodium guttatum is widely used in traditional medicine to treat various diseases, including diabetes. In this study, we evaluated in vitro inhibitory activity of extracts of E. guttatum on α-amylase, α-glucosidase, and lipase and then studied in vivo using different animal models. The results showed that the aqueous and alcoholic extracts of E. guttatum significantly inhibited digestive enzymes. The extracts of E. guttatum significantly reduced postprandial hyperglycemia after starch loading in normal rats. Additionally, extracts of E. guttatum significantly decrease the intestinal absorption of D-glucose. However, the methanolic extract of E. guttatum showed remarkable antidiabetic activity compared to the aqueous and ethanolic extracts of E. guttatum. In addition, the extracts significantly reduced blood sugar levels in albino mice and hematological and biochemical profiles. Therefore, the results of this study show that the extracts of E. guttatum have antidiabetic effects and could therefore be suggested in the management of type 2 diabetes.

Determination of Volatile Compounds of Mentha piperita and Lavandula multifida and Investigation of Their Antibacterial, Antioxidant, and Antidiabetic Properties.

Mentha piperita and Lavandula multifida are widely used in Moroccan traditional medicine for the treatment of diabetes and infectious diseases. The aims of this work were the determination of the chemical composition of Mentha piperita (MPEO) and Lavandula multifida (LMEO) essential oils and the evaluation of their antibacterial, antioxidant, and antidiabetic activities. The chemical composition was determined by GC-MS analysis. The antibacterial effects were evaluated against several bacterial strains using disc diffusion, MIC, and MBC methods. The antioxidant activity was evaluated in vitro using DPPH, H2O2, and xanthine oxidase, and the antidiabetic activity was estimated by the inhibitory effects of α-amylase, α-glucosidase, and lipase activities. GC-MS results showed that the main compounds of MPEO were menthone (29.24%), levomenthol (38.73%), and eucalyptol (6.75%). However, eucalyptol (28.11%), 2-bornanone (11.57%), endo-borneol (7.82%), and linalyl acetate (5.22%) are the major compounds of LMEO. The results exhibited important inhibitory effects against some bacterial strains with MIC = MBC = 0.39 mg/mL for MPEO against Staphylococcus aureus ATCC. However, LMEO exhibited remarkable antioxidant and antidiabetic activities compared to MPEO. Indeed, LMEO inhibited DPPH, H2O2, and xanthine oxidase with concentrations of 15.23, 21.52, and 8.89 µg/mL, respectively. Moreover, LMEO exhibited α-amylase and α-glucosidase at IC50 = 85.34 and IC50 = 59.36 µg/mL, respectively. The findings showed that both MPEO and LMEO exhibit promising biological properties. However, the application of these species or their main bioactive compounds requires further investigation.

phytochemdb: a platform for virtual screening and computer-aided drug designing.

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed 'phytochemdb', a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood-Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. 'phytochemdb' is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. 'phytochemdb' is available for free at https://phytochemdb.com/.

Computational screening and biochemical analysis of Pistacia integerrima and Pandanus odorifer plants to find effective inhibitors against Receptor-Binding domain (RBD) of the spike protein of SARS-Cov-2.

Although World Health Organization-approved emergency vaccines are available in many countries, the mortality rate from COVID-19 remains high due to the fourth or fifth wave and the delta variant of the coronavirus. Thus, an effective mechanistic investigation in treating this disease is urgently needed. In this work, we extracted phytochemicals from two mangrove plants, Pistacia integerrima and Pandanus odorifer, assessing their potential actions against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. The antioxidant activities of Pistacia integerrima leaves and fruits were 142.10 and 97.13 µg/mL, respectively, whereas Pandanus odorifer leaves and fruits were 112.50 and 292.71 µg/mL, respectively. Furthermore, leaf extracts from both plants had lower cytotoxicity against Artemia salina than fruit extracts. Gas chromatography-mass spectrometry analysis revealed a total of 145 potential phytochemicals from these extracts. Three phytochemicals, 28-demethyl-beta-amyrone, 24-Noroleana-3,12-diene, and stigmasterol, displayed binding free energy values of - 8.3, -7.5, and - 8.1 Kcal/mol, respectively, in complexes with the spike protein of SARS-CoV-2. The root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, wet-lab validations are necessary to support these findings.

Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach.

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (-10.1 kcal/mol), kuwanon S (-9.6 kcal/mol), manuifolin H (-9.5 kcal/mol), and kuwanon F (-9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.

An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants.

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation.

BACKGROUND: SYK gene regulates the expression of SYK kinase (Spleen tyrosine kinase), an important non-receptor protein-tyrosine kinase for immunological receptor-mediated signaling, which is also considered a tumor growth metastasis initiator. An onco-informatics analysis was adopted to evaluate the expression and prognostic value of the SYK gene in colorectal cancer (CRC), the third most fatal cancer type; of late, it may be a biomarker as another targeted site for CRC. In addition, identify the potential phytochemicals that may inhibit the overexpression of the SYK kinase protein and minimize the human CRC. MATERIALS & METHODS: The differential expression of the SYK gene was analyzed using several transcriptomic databases, including Oncomine, UALCAN, GENT2, and GEPIA2. The server cBioPortal was used to analyze the mutations and copy number alterations, whereas GENT2, Gene Expression Profiling Interactive Analysis (GEPIA), Onco-Lnc, and PrognoScan were used to examine the survival rate. The protein-protein interaction network of SYK kinase and its co-expressed genes was conducted via Gene-MANIA. Considering the SYK kinase may be the targeted site, the selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. Molecular interactions were also observed by following the Ligplot+ version 2.2. YASARA molecular dynamics simulator was applied for the post-validation of the selected phytochemicals. RESULTS: Our result reveals an increased level of mRNA expression of the SYK gene in colorectal adenocarcinoma (COAD) samples compared to those in normal tissues. A significant methylation level and various genetic alterations recurrence of the SYK gene were analyzed where the fluctuation of the SYK alteration frequency was detected across different CRC studies. As a result, a lower level of SYK expression was related to higher chances of survival. This was evidenced by multiple bioinformatics platforms and web resources, which demonstrated that the SYK gene can be a potential biomarker for CRC. In this study, aromatic phytochemicals, such as kaempferol and glabridin that target the macromolecule (SYK kinase), showed higher stability than the controls, and we have estimated that these bioactive potential phytochemicals might be a useful option for CRC patients after the clinical trial. CONCLUSIONS: Our onco-informatics investigation suggests that the SYK gene can be a potential prognostic biomarker of CRC. On the contrary, SYK kinase would be a major target, and all selected compounds were validated against the protein using in-silico drug design approaches. Here, more in vitro and in vivo analysis is required for targeting SYK protein in CRC.

In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in Wuhan, China, in December 2019. Elderly individuals and those with comorbid conditions may be more vulnerable to this disease. Consequently, several research laboratories continue to focus on developing drugs to treat this infection because this disease has developed into a global pandemic with an extremely limited number of specific treatments available. Natural herbal remedies have long been used to treat illnesses in a variety of cultures. Modern medicine has achieved success due to the effectiveness of traditional medicines, which are derived from medicinal plants. The objective of this study was to determine whether components of natural origin from Iranian medicinal plants have an antiviral effect that can prevent humans from this coronavirus infection using the most reliable molecular docking method; in our case, we focused on the main protease (Mpro) and a receptor-binding domain (RBD). The results of molecular docking showed that among 169 molecules of natural origin from common Iranian medicinal plants, 20 molecules (chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, etc.) can be proposed as inhibitors against this coronavirus based on the binding free energy and type of interactions between these molecules and the studied proteins. Moreover, a molecular dynamics simulation study revealed that the chelidimerine-Mpro and somniferine-RBD complexes were stable for up to 50 ns below 0.5 nm. Our results provide valuable insights into this mechanism, which sheds light on future structure-based designs of high-potency inhibitors for SARS-CoV-2.

Efficacy of Phytochemicals Derived from Avicennia officinalis for the Management of COVID-19: A Combined In Silico and Biochemical Study.

The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 µg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina. The gas chromatography-mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of -6.75, -6.7, -6.3, and -6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes' binding rigidity in the atomistic simulated environment. However, this study's findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.

A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.

Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd.

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

Methanolic Bark Extract of Abroma augusta (L.) Induces Apoptosis in EAC Cells through Altered Expression of Apoptosis Regulatory Genes.

Abroma augusta (L.), one of the herbal medicinal plants, is widely used for treatment of various maladies. The present study was initiated to determine the antioxidant, hemolytic, cytotoxicity, and anticancer activities of methanolic extract from the bark of the plant. The phytochemical screening was done by analyzing different phytochemicals present in the extract. We observed the presence of alkaloids, steroids, terpenoids, flavonoids, reducing sugars, and glycosides in the bark extract which showed the highest antioxidant capacity. Antioxidant potential of the methanolic extract was evaluated in vitro by DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay method. This extract showed prominent scavenging activity with IC50 value of 38.65 µg/ml. The hemolytic activity of the extract was evaluated at concentrations ranging from 250 to 1000 µg/ml. It was observed that the extract induced hemolysis percentage of 9.41% to 4.1%, which implies that the extract has no potent hemolytic activity. Cytotoxicity and anticancer activities were observed on Ehrlich ascites carcinoma (EAC) cells. In addition, the bark showed promising cytotoxicity with IC50 value of 329.41 µg/ml, and the study indicated that the extract was capable of inhibiting EAC cell growth by 75.5% when administered at 100 mg/kg/day body weight intraperitoneally for five consecutive days to Swiss albino mice. Morphological change of apoptotic cell was determined by fluorescence and optical microscopy. DNA fragmentation is another marker for apoptosis, and the bark extract-treated EAC cells showed smeared and fragmented DNA bands. Apoptosis correlated well with the upregulation of p53 and Bax and also with the downregulation of NF-κB and Bcl-2. Furthermore, activity and interaction of two A. augusta compounds were tested through molecular docking simulation study. In conclusion, our results suggest that A. augusta bark has the potential to be considered as an anticancer agent.