Exploring the potential of Ziziphus nummularia and luteolin-7-O-glucoside as tubulin inhibitors in cancer therapy and survival.

Cancer is responsible for approximately 10 million deaths worldwide, with 70% of the deaths occurring in low- and middle-income countries; as such safer and more effective anti-cancer drugs are required. Therefore, the potential benefits of Ziziphus nummularia and Ziziphus spina-christi as sources of anti-cancer agents were investigated. Z. nummularia and Z. spina-christi extracts were prepared using chloroform, ethanol, ethyl acetate, and water. The extracts' anti-cancer properties were determined using the MTT Cell Viability Assay in four cancer cell lines: breast (KAIMRC2 and MDA-MB-231), colorectal (HCT8), and liver (HepG2). The ApoTox-Glo Triplex Assay and high-content imaging (HCI)-Apoptosis Assay were used to assess KAIMRC2 and HCT8 cells further. In addition, KAIMRC2 cells were tested for microtubule staining, and AKT/mTOR protein expression was determined by western blot analysis. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the secondary metabolites in the ethanol and ethyl acetate extracts, followed by in silico techniques to predict molecular targets and interactions, safety, and pharmacokinetic profile for identified metabolites. Out of the eight extracts, the ethanolic extract of Z. nummularia, exhibited the most potent activity against KAIMRC2 cells with an IC50 value of 29.2 µg/ml. Cancer cell treatment with the ethanolic extract of Z. nummularia resulted in a dose-dependent decrease in cell viability with increased apoptosis and cytotoxic effects. Microtubule staining showed a disrupted microtubular network. The ethanolic extract treatment of KAIMRC2 cells led to upregulated expression of pAKT and pmTOR. In silico studies predicted luteolin-7-O-glucoside to be a ligand for tubulin with the highest docking score (- 7.686) and similar binding interactions relative to the native ligand. Further computational analysis of the metabolites showed acceptable pharmacokinetic and safety profiles, although ethanolic extract metabolites were predicted to have cardiotoxic effects. Ethanolic extraction is optimal for solubilizing active anticancer metabolites from Z. nummularia, which may act by causing M-phase arrest via inhibition of tubulin polymerization. Luteolin-7-O-glucoside is the lead candidate for further research and development as an anti-cancer agent. In addition, this study suggests that herbal treatment could switch on mechanisms of adaptation and survival in cancer cells.

Bimetallic nanoparticles and biochar produced by Adansonia Digitata shell and their effect against tomato pathogenic fungi.

Adansonia digitata L. is a royal tree that is highly valued in Africa for its medicinal and nutritional properties. The objective of this study was to use its fruit shell extract to develop new, powerful mono and bimetallic nanoparticles (NPs) and biochar (BC) using an eco-friendly approach. Silver (Ag), iron oxide (FeO), the bimetallic Ag-FeO NPs, as well as (BC) were fabricated by A. digitata fruit shell extract through a reduction process and biomass pyrolysis, respectively, and their activity against tomato pathogenic fungi Alternaria sp., Sclerotinia sclerotiorum, Fusarium equiseti, and Fusarium venenatum were detected by agar dilution method. The Ag, FeO, Ag-FeONPs, and BC were characterized using a range of powerful analytical techniques such as ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier Transform-Infra Red (FT-IR), dynamic light scatter (DLS), and zeta potential analysis. The fabricated Ag, FeO and Ag-FeO NPs have demonstrated a remarkable level of effectiveness in combating fungal strains. UV-Vis spectra ofAg, FeO, Ag-FeONPs, and BC show broad exhibits peaks at 338, 352, 418, and 480 nm, respectively. The monometallic, bimetallic NPs, and biochar have indicated the presence in various forms mostly in Spherical-shaped. Their size varied from 102.3 to 183.5 nm and the corresponding FTIR spectra suggested that the specific organic functional groups from the plant extract played a significant role in the bio-reduction process. Ag and Ag-FeO NPs exhibited excellent antifungal activity against pathogenic fungi Alternaria sp., S. sclerotiorum, F. equiseti, and F. venenatum. The current study could be a significant achievement in the field of antifungal agents since has the potential to develop new approaches for treating fungal infections.

Bioactive silver nanoparticles fabricated using Lasiurus scindicus and Panicum turgidum seed extracts: anticancer and antibacterial efficiency.

Applying extracts from plants is considered a safe approach in biomedicine and bio-nanotechnology. The present report is considered the first study that evaluated the seeds of Lasiurus scindicus and Panicum turgidum as biogenic agents in the synthesis of silver nanoparticles (AgNPs) which had bioactivity against cancer cells and bacteria. Assessment of NPs activity against varied cell lines (colorectal cancer HCT116 and breast cancer MDA MBA 231 and MCF 10A used as control) was performed beside the antibacterial efficiency. Different techniques (DLS, TEM, EDX and FTIR) were applied to characterize the biosynthesized AgNPs. The phytochemicals from both L. scindicus and Panicum turgidum were identified by GC-MS analysis. Spherical monodisperse NPs at average diameters of 149.6 and 100.4 nm were obtained from seed extract of L. scindicus (L-AgNPs) and P. turgidum, (P-AgNPs) respectively. A strong absorption peak at 3 keV is observed by the EDX spectrum in the tested NPs. Our study provided effective NPs in mitigating the tested cell lines and the lowest IC50 were 7.8 and 10.30 for MDA MB231 treated by L-AgNPs and P-AgNPs, respectively. Both fabricated NPs might differentially target the MDA MB231 cells compared to HCT116 and MCF10A. Ultrastructural changes and damage for the NPs-treated MDA MB231 cells were studied using TEM and LSM analysis. Antibacterial activity was also observed. About 200 compounds were identified in L. scindicus and P. turgidum by GC-MS analysis might be responsible for the NPs reduction and capping abilities. Efficient NPs against cancer cells and microbes were obtained, however large-scale screening is needed to validate our findings.

Exploring in vitro and in silico Biological Activities of Calligonum Comosum and Rumex Vesicarius: Implications on Anticancer and Antibacterial Therapeutics.

Introduction: The adverse effects of clinically used anti-cancer medication and the rise in resistive micro-organisms have limited therapeutic options. Multiple anti-cancer drugs are derived from medicinal herbs which also have shown anti-bacterial effects. This study aimed to identify the optimal extraction solvent for detecting the cytotoxic and anti-bacterial effects of Calligonum comosum (C. Comosum) and Rumex vesicarius (R. Vesicarius) extracts. Additionally, the study aimed to identify active metabolites and assess their potential as future drug candidates for anti-cancer and anti-bacterial therapeutics. Methods: Leaves from both plants were extracted using ethanol, ethyl acetate, chloroform, and water. The cytotoxic effects of the extracts were tested on liver, colon, and breast cancer cell lines. Apoptosis was assessed using High Content Imaging (HCI) and the ApoTox triplex Glo assay. The anti-bacterial effects were determined using agar-well diffusion. Liquid chromatography-mass spectrometry (LC-MS) was used to tentatively identify the secondary metabolites. In silico computational studies were conducted to determine the metabolites' mode of action, safety, and pharmacokinetic properties. Results: The ethanolic extract of C. Comosum exhibited potent cytotoxicity on breast cancer cell lines, with IC50 values of 54.97 µg/mL and 58 µg/mL for KAIMRC2 and MDA-MB-231, respectively. It also induced apoptosis in colon and breast cancer cell lines. All tested extracts of C. Comosum and R. Vesicarius demonstrated anti-bacterial activity against Staphylococcus aureus and Escherichia coli. Seven active metabolites were identified, one of which is Kaempferol 3-O-Glucoside-7-O-Rhamnoside, which showed strong (predicted) anti-cancer activity. Kaempferol 3-O-Glucoside-7-O-Rhamnoside and Quercetin-3-O-Glucuronide also exhibited potential anti-bacterial effects on gram-positive and negative bacteria. Conclusion: Ethanol extraction of C. Comosum solubilizes active metabolites with potential therapeutic applications in cancer treatment and bacterial infections. Kaempferol 3-O-Glucoside-7-O-Rhamnoside, in particular, shows promise as a dual therapeutic drug candidate for further research and development to improve its efficacy, safety, and pharmacokinetic profile.

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles - Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine.

Introduction: Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC50=29.5 µg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

Proteomic Profiling Reveals Cytotoxic Mechanisms of Action and Adaptive Mechanisms of Resistance in Porphyromonas gingivalis: Treatment with Juglans regia and Melaleuca alternifolia.

The increasing trend in the rise of antibiotic-resistant bacteria pushes research to discover new efficacious antibacterial agents from natural and synthetic sources. Porphyromonas gingivalis is a well-known bacterium commonly known for causing periodontal disease, and it is associated with the pathogenesis of life-changing systemic conditions such as Alzheimer's. Proteomic research can be utilized to test new antibacterial drugs and understand the adaptive resistive mechanisms of bacteria; hence, it is important in the drug discovery process. The current study focuses on identifying the antibacterial effects of Juglans regia (JR) and Melaleuca alternifolia (MA) on P. gingivalis and uses proteomics to identify modes of action while exploring its adaptive mechanisms. JR and MA extracts were tested for antibacterial efficacy using the agar well diffusion assay. A proteomic study was conducted identifying upregulated and downregulated proteins compared to control by 2D-DIGE analysis, and proteins were identified using MADLI-TOF/MS. The bacterial inhibition for JR was 20.14 ± 0.2, and that for MA was 19.72 ± 0.5 mm. Out of 88 differentially expressed proteins, there were 17 common differentially expressed proteins: 10 were upregulated and 7 were downregulated in both treatments. Among the upregulated proteins were Arginine-tRNA ligase, ATP-dependent Clp protease proteolytic, and flavodoxins. In contrast, down-regulated proteins were ATP synthase subunit alpha and quinone, among others, which are known antibacterial targets. STRING analysis indicated a strong network of interactions between differentially expressed proteins, mainly involved in protein translation, post-translational modification, energy production, metabolic pathways, and protein repair and degradation. Both extracts were equi-efficacious at inhibiting P. gingivalis and displayed some overlapping proteomic profiles. However, the MR extract had a greater fold change in its profile than the JA extract. Downregulated proteins indicated similarity in the mode of action, and upregulated proteins appear to be related to adaptive mechanisms important in promoting repair, growth, survival, virulence, and resistance. Hence, both extracts may be useful in preventing P. gingivalis-associated conditions. Furthermore, our results may be helpful to researchers in identifying new antibiotics which may offset these mechanisms of resistance.

Limoniastrum monopetalum-Mediated Nanoparticles and Biomedicines: In Silico Study and Molecular Prediction of Biomolecules.

An in silico approach applying computer-simulated models helps enhance biomedicines by sightseeing the pharmacology of potential therapeutics. Currently, an in silico study combined with in vitro assays investigated the antimicrobial ability of Limoniastrum monopetalum and silver nanoparticles (AgNPs) fabricated by its aid. AgNPs mediated by L. monopetalum were characterized using FTIR, TEM, SEM, and DLS. L. monopetalum metabolites were detected by QTOF-LCMS and assessed using an in silico study for pharmacological properties. The antibacterial ability of an L. monopetalum extract and AgNPs was investigated. PASS Online predictions and the swissADME web server were used for antibacterial activity and potential molecular target metabolites, respectively. Spherical AgNPs with a 68.79 nm average size diameter were obtained. Twelve biomolecules (ferulic acid, trihydroxy-octadecenoic acid, catechin, pinoresinol, gallic acid, myricetin, 6-hydroxyluteolin, 6,7-dihydroxy-5-methoxy 7-O-ß-d-glucopyranoside, methyl gallate, isorhamnetin, chlorogenic acid, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-ß-l-mannopyranosyl)-ß-d-glucopyranoside) were identified. The L. monopetalum extract and AgNPs displayed antibacterial effects. The computational study suggested that L. Monopetalum metabolites could hold promising antibacterial activity with minimal toxicity and an acceptable pharmaceutical profile. The in silico approach indicated that metabolites 8 and 12 have the highest antibacterial activity, and swissADME web server results suggested the CA II enzyme as a potential molecular target for both metabolites. Novel therapeutic agents could be discovered using in silico molecular target prediction combined with in vitro studies. Among L. Monopetalum metabolites, metabolite 12 could serve as a starting point for potential antibacterial treatment for several human bacterial infections.

In-silico predicting as a tool to develop plant-based biomedicines and nanoparticles: Lycium shawii metabolites.

INTRODUCTION AND PURPOSE: In silico approach helps develop biomedicines and is useful for exploring the pharmacology of potential therapeutics using computer-simulated models. In vitro assays were used to determine the anti-microbial and cytotoxic efficacies of silver nanoparticles (AgNPs) synthesized with the shrub Lycium shawii. METHODS: In silico predicting was performed to assess the L. shawii metabolites identified using QTOF-LCMS for their pharmacological properties. L. shawii mediated AgNPs were synthesized and characterized (FTIR, TEM, SEM, DLS and EDX). The anti-bacterial efficacies of L. shawii extract, AgNPs, and penicillin-conjugated AgNPs (pen-AgNPs) were determined. The cytotoxicity of the AgNPs was measured against colorectal cancer cell line (HCT116), normal breast epithelium (MCF 10 A), and breast cancer cell line (MDA MB 231). RESULTS AND DISCUSSION: Five molecules (costunolide, catechin, emodin, lyciumaside, and aloe emodin 11-O-rhamnoside) were detected in the L. shawii extract. AgNPs (69 nm) were spherical with crystallographic structure. All three agents prepared showed inhibitory activity against the tested bacteria, the most efficacious being pen-AgNPs. High cytotoxicity of AgNPs (IC50 62 µg/ml) was observed against HCT116, IC50 was 78 µg/ml for MCF 10 A, and 250 µg/ml for MDA MB 231, of which cells showed apoptotic features under TEM examination. The in silico approach indicated that the carbonic anhydrase IX enzyme was the target molecule mediating anti-cancer and anti-bacterial activities and that emodin was the metabolite in action. CONCLUSIONS: Combining in vitro studies and in silico molecular target prediction helps find novel therapeutic agents. Among L. shawii metabolites, emodin is suggested for further studies as an agent for drug development against pathogenic bacteria and cancer.

Phytoproduct, Arabic Gum and Opophytum forsskalii Seeds for Bio-Fabrication of Silver Nanoparticles: Antimicrobial and Cytotoxic Capabilities.

The application of biological materials in synthesizing nanoparticles has become significant issue in nanotechnology. This research was designed to assess biogenic silver nanoparticles (AgNPs) fabricated using two aqueous extracts of Acacia arabica (Arabic Gum) (A-AgNPs) and Opophytum forsskalii (Samh) seed (O-AgNPs), which were used as reducing and capping agents in the NPs development, respectively. The current study is considered as the first report for AgNP preparation using Opophytum forsskalii extract. The dynamic light scattering, transmission electron microscopy, and scanning electron microscopy were employed to analyze the size and morphology of the biogenic AgNPs. Fourier transform infrared (FTIR) spectroscopy and chromatography/mass spectrometry (GC-MS) techniques were used to identify the possible phyto-components of plant extracts. The phyto-fabricated NPs were assessed for their antibacterial activity and also when combined with some antibiotics against Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa and Escherichia coli (Gram-negative) and their anticandidal ability against Candida albicans using an agar well diffusion test. Furthermore, cytotoxicity against LoVo cancer cell lines was studied. The results demonstrated the capability of the investigated plant extracts to change Ag+ ions into spherical AgNPs with average size diameters of 91 nm for the prepared O-AgNPs and 75 nm for A-AgNPs. The phyto-fabricated AgNPs presented substantial antimicrobial capabilities with a zone diameter in the range of 10-29.3 mm. Synergistic effects against all tested strains were observed when the antibiotic and phyto-fabricated AgNPs were combined and assessed. The IC50 of the fabricated O-AgNPs against LoVo cancer cell lines was 28.32 µg/mL. Ten and four chemical components were identified in Acacia arabica (Arabic Gum) and Opophytum forsskalii seed extracts, respectively, by GC-MS that are expected as NPs reducing and capping agents. Current results could lead to options for further research, such as investigating the internal mechanism of AgNPs in bacteria, Candida spp., and LoVo cancer cell lines as well as identifying specific molecules with a substantial impact as metal-reducing agents and biological activities.

Biological Potential of Silver Nanoparticles Mediated by Leucophyllum frutescens and Russelia equisetiformis Extracts.

Awareness about environmental concerns is increasing, specially the pollution resulting from nanoparticles (NPs) production, which has led to great interest in the usage of biogenic agents for their fabrication. The current investigation used eco-friendly organic phytomolecules from Leucophyllum frutescens and Russelia equisetiformis leaves extract for the first time in the fabrication of silver NPs from silver ions and further an assessment of their biological activities was performed. The leaves extract from both plant sources were used as capping and reducing agents and added to AgNO3. The mixtures were observed for colour changes, and after a stable dark brown colour was obtained, the NPs were separated and further investigated using dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy. The Fourier transform infrared spectroscopy technique was employed to determine the active organic ingredients in the plant extracts. The prepared NPs were tested against three cell lines (two cancer ones and one normal control) and the effects observed using TEM and confocal laser scanning microscopy (LSM). Antibacterial activity against two Gram positive and two Gram negative species was examined and the synergistic effect of the ampicillin-NPs conjugate was studied. Findings showed successful conversion of Ag ions into L-AgNPs and R-AgNPs achieved using L.frutescens and R. equisetiformis extracts, respectively. A mean size of 112.9 nm for L-AgNPs and 151.7 nm for R-AgNPs and negative zeta potentials were noted. TEM analysis showed spherical NPs and EDS indicated Ag at 3 keV. Reduction in cancer cell viability with low half-maximal inhibitory concentrations was noted for both tested NPs. Structural changes and apoptotic features in the treated cancer cell lines were noted by TEM and cell death was confirmed by LSM. Furthermore, higher antibacterial activity was noticed against Gram positive compared with Gram negative bacteria as well as high synergistic effect was noted for the Amp-NPs conjugate, specially against Gram positive bacteria. The current investigation has thus developed an eco-friendly NPs synthesis route by applying plant extracts to efficiently produce NPs endowed with potential cytotoxic and antibacterial capacity, which therefore could be recommended as new approaches to overcome human diseases with minimal environmental impact.

Lepidium sativum Sprouts Grown under Elevated CO2 Hyperaccumulate Glucosinolates and Antioxidants and Exhibit Enhanced Biological and Reduced Antinutritional Properties.

The nutritional and health-promoting properties of plants are largely determined by their tissue chemistry. Tuning growth conditions could affect the accumulation of phytochemicals and, therefore, enhance the biological activities. Herein, the impact of elevated CO2 (eCO2; 620 µmol CO2 mol-1 air) on growth and chemical composition of sprouts of three Lepidium sativum cultivars (Haraz, Khider and Rajab) was investigated. Changes in the sprout actions against some human chronic diseases were evaluated. eCO2 induced biomass accumulation (1.46-, 1.47- and 2-fold in Haraz, Khider and Rajab, respectively) and pigment accumulation and reduced the level of antinutrients in L. sativum cultivars. Compared to the control, eCO2 induced total glucosinolate accumulation (0.40-, 0.90- and 1.29-fold in Khider, Haraz and Rajab, respectively), possibly through increased amino acid production, and their hydrolysis by myrosinase. In line with increased polyphenol production, improved phenylalanine ammonia lyase activity was observed. The antioxidant, anti-inflammatory, hypocholesterolemic, antibacterial and anticancer activities of the produced sprouts were significantly improved by sprouting and eCO2 exposure. PCA indicated that the cultivars showed interspecific responses. Thus, the present study confirms the synergistic effect of sprouting with eCO2 exposure as a promising approach to produce more bioactive L. sativum sprouts.

Synergistic and Antagonistic Effects of Biogenic Silver Nanoparticles in Combination With Antibiotics Against Some Pathogenic Microbes.

The latest advances in green nanoparticle synthesis have preserved natural and non-renewable resources and decreased environmental pollution. The current study was designed to evaluate silver nanoparticles (AgNPs) fabricated using aqueous extracts of two medicinal plants, Anastatica hierochuntica L. (Kaff Maryam) and Artemisia absinthium. The phytochemicals were detected by Fourier-transform infrared spectroscopy (FTIR) and Chromatography/Mass Spectrometry (GC-MS). The effects of the AgNPs on Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans as well as the cytotoxicity against MDA-MB-231 cells were examined. The synergistic and antagonistic effects of the biogenic AgNPs in combination with standard antibiotics against several microbes were also investigated. The ability of the plant extracts to transfer silver ions to AgNPs was measured via dynamic light scattering, zeta potential measurement, and transmission electron microscopy. The most sensitive microbes to AgNP treatment were examined via scanning electron microscopy to assess morphological changes. Biogenic AgNPs showed significant antibacterial effects against most of the tested microbes and significant cytotoxicity was noted. Polysaccharides, proteins and Phenolic compounds are likely involved in AgNP biosynthesis since hydroxyl groups and amides were detected via FTIR as well as GC-MS. This study confirmed that plant-based AgNP fabrication with AgNO3 as the Ag (I) delivering salt can be an economical and practical approach for large-scale production of particles with antimicrobial and cytotoxic potential. The synergistic effects of biogenic AgNPs in combination with some antibiotics support their potential as a safe therapeutic for bacterial infections because they are capped with organic biomolecules.

Chemical Diversity and Bioactivities of Monoterpene Indole Alkaloids (MIAs) from Six Apocynaceae Genera.

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.

Kefir: A protective dietary supplementation against viral infection.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a recently discovered coronavirus termed 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2). Several scholars have tested antiviral drugs and compounds to overcome COVID-19. 'Kefir' is a fermented milk drink similar to a thin yogurt that is made from kefir grains. Kefir and its probiotic contents can modulate the immune system to suppress infections from viruses (e.g., Zika, hepatitis C, influenza, rotaviruses). The antiviral mechanisms of kefir involve enhancement of macrophage production, increasing phagocytosis, boosting production of cluster of differentiation-positive (CD4+), CD8+, immunoglobulin (Ig)G+ and IgA+ B cells, T cells, neutrophils, as well as cytokines (e.g., interleukin (IL)-2, IL-12, interferon gamma-γ). Kefir can act as an anti-inflammatory agent by reducing expression of IL-6, IL-1, TNF-α, and interferon-γ. Hence, kefir might be a significant inhibitor of the 'cytokine storm' that contributes to COVID-19. Here, we review several studies with a particular emphasis on the effect of kefir consumption and their microbial composition against viral infection, as well as discussing the further development of kefir as a protective supplementary dietary against SARS-CoV-2 infection via modulating the immune response.

Antimicrobial Mechanism and Identification of the Proteins Mediated by Extracts from Asphaltum punjabianum and Myrtus communis.

Myrtus communis ("myrtle") and Asphaltum punjabianum ("shilajeet") are a medicinal plant and a long-term-humified dead plant material, respectively. We studied their antibacterial and anticandidal activities against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. The activities of the aqueous extracts of the studied materials were measured using agar-well diffusion methods. Furthermore, proteomic analysis of treated microbial cells was conducted to identify affected proteins. The results showed both antibacterial and anticandidal activities for the myrtle extract (ME), while the shilajeet extract (SE) showed antibacterial activity only. The highest antimicrobial activity was observed against E. coli among the microbes tested; therefore, it was taken as the model for the proteomic analysis to identify the antimicrobial mechanism of ME and SE using two-dimensional electrophoresis. Upregulation of expression of 42 proteins and downregulation of expression of 6 proteins were observed in E. coli treated with ME, whereas 12 upregulated and 104 downregulated proteins were detected in E. coli treated with SE, in comparison with the control. About 85% of identified expressed proteins were from the cytoplasm and 15% from microbial cell walls, indicating the penetration of extracts inside cells. A higher percentage of expressed proteins was recorded for enzymatic activity. Our findings suggest that the major targets of the antibacterial action were proteins involved in the outer membrane, oxidative stress, and metabolism. Our data might reveal new targets for antimicrobial agents.

Antibacterial and Cytotoxic Potential of Biosynthesized Silver Nanoparticles by Some Plant Extracts.

The provision of nanoparticles using biogenic material as a part of green chemistry is an attractive nanotechnology. The current research aimed to test the antimicrobial and cytotoxic efficacy of silver nanoparticles synthesized by extracts of Phoenix dactylifera, Ferula asafetida, and Acacia nilotica as reductant and stabilizing agents in silver nanoparticle formation. Synthesized nanoparticles were evaluated for their antimicrobial activity against Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa and Escherichia coli (Gram-negative) using an agar well diffusion assay. Furthermore, cytotoxic ability was investigated against LoVo cells. The potential phyto-constituents of plant extracts were identified by Fourier-transform infrared spectroscopy (FT-IR) techniques. Field emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), and zeta potential analyzed the size and morphology of the biogenic nanoparticles. The current study revealed the ability of the tested plant extract to convert silver ions to silver nanoparticles with an average size that ranged between 67.8 ± 0.3 and 155.7 ± 1.5 nm in diameter. Biogenic AgNPs showed significant antibacterial ability (10 to 32 mm diameter) and anticancer ability against a LoVo cell with IC50 ranged between 35.15⁻56.73 µg/mL. The innovation of the present study is that the green synthesis of NPs, which is simple and cost effective, provides stable nano-materials and can be an alternative for the large-scale synthesis of silver nanoparticles.