Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways.

Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.

Methotrexate-conjugated zinc oxide nanoparticles exert a substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

In the current study, we report the synthesis of methotrexate-conjugated zinc oxide nanoparticles (MTX-ZnONPs) and their high efficacy against lung cancer cells. Conjugation of MTX with ZnONPs was authenticated by UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). This drug-nanoconjugate also showed high drug-loading efficiency. The therapeutic efficacy of MTX-ZnONPs was further tested in vitro against A549 cells, and the results of MTT and LDH release assays showed that MTX-ZnONPs, in addition to free MTX, were efficient in exerting cytotoxic effect on A549 cells; however, the effectiveness of MTX-ZnONPs was found to be considerably enhanced at very low doses compared to that of free MTX. Moreover, ZnONPs alone significantly inhibited the cell viability of A549 cells at a much higher concentration compared to MTX-ZnONPs and MTX. Furthermore, the cytomorphology of A549 cells was characterized by cellular shrinkage and detachment from the surface in all the treatment groups. Similarly, A549 cells, in all the treatment groups, showed fragmented and condensed nuclei, indicating the initiation of apoptosis. Mitochondrial membrane potential (ψm) in A549 cells showed a gradual loss in all the treatment groups. Results of the qualitative and quantitative analyses depicted increased reactive oxygen species (ROS) levels in A549 cells. The results of the caspase activity assay showed that MTX-ZnONPs andfree MTX caused significant activation of caspase-9, -8, and -3 in A549 cells; however, the effect of MTX-ZnONPs was more profound at very low doses compared to that of free MTX. Thus, our results showed high efficacy of MTX-ZnONPs, suggesting efficient intracellular delivery of the drug by ZnONPs as nanocarriers.

Molecular interactions of cucurbitacins A and B with anaplastic lymphoma kinase for lung cancer treatment.

Lung cancer is a major global public health issue and the leading cause of cancer-related deaths. Several medications are commonly used to treat lung cancer, either alone or in combination with other treatments. The anaplastic lymphoma kinase (ALK) protein is one of several target proteins that are thought to be potential therapeutic targets in the context of lung cancer. Several ALK inhibitors have been identified, but many of these have been associated with side effects and toxicity concerns. In this study, we intend to computationally predict the binding potential of cucurbitacins (CBNs), A and B to the active pockets of ALK, in order to estimate their potential ALK inhibitors. Compared to CBN-A, which has a binding energy of -7.9 kcal/mol, CBN B exhibits significantly better binding efficacy with a binding energy of -8.1 kcal/mol. This is closely comparable to the binding energy of Crizotinib, which is -8.2 kcal/mol. The results of the molecular dynamics simulation indicated that the docked complexes remained stable for the duration of the 100 ns simulation period. CBN inhibited the proliferation of both non-small cell lung cancer cell lines, H1299 and A549, in a dose-dependent manner. CBN-B inhibited the proliferation of lung cancer cells, showing IC50 values of 0.08 µM for H1299 cells and 0.10 µM for A549 cells. The computational analyses provide strong evidence that CBN-B has the potential to act as a potent natural inhibitor against ALK, and could prove to be a valuable treatment option for lung cancer.Communicated by Ramaswamy H. Sarma.

Salicylic Acid- and Potassium-Enhanced Resilience of Quinoa (Chenopodium quinoa Willd.) against Salinity and Cadmium Stress through Mitigating Ionic and Oxidative Stress.

Salinity and cadmium (Cd) contamination of soil are serious environmental issues threatening food security. This study investigated the role of salicylic acid (SA) and potassium (K) in enhancing the resilience of quinoa against the combined stress of salinity and Cd. Quinoa plants were grown under NaCl (0, 200 mM) and Cd (0, 100 µM) stress, with the addition of 0.1 mM SA and 10 mM K, separately or in combination. The joint stress of Cd and NaCl caused >50% decrease in plant growth, chlorophyll contents, and stomatal conductance compared to the control plants. The higher accumulation of Na and Cd reduced the uptake of K in quinoa tissues. The joint stress of salinity and Cd caused an 11-fold increase in hydrogen peroxide and 13-fold increase in thiobarbituric acid reactive substances contents, and caused a 61% decrease in membrane stability. An external supply of 0.1 mM SA and 10 mM K helped plants to better adapt to salinity and Cd stress with less of a reduction in plant biomass (shoot 19% and root 24%) and less accumulation of Na and Cd in plant tissues. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) were enhanced by 11-fold, 10-fold, 7.7-fold, and 7-fold, respectively, when SA and K were applied together to the plants subjected to the joint stress of Cd and salinity. Based on the values of the bioconcentration factor (>1), the translocation factor (<1), and the higher tolerance index, it was clear that Cd-contaminated, salty soils could be stabilized with quinoa under the combined supply of SA and K.

Effect of iron nanoparticles and conventional sources of Fe on growth, physiology and nutrient accumulation in wheat plants grown on normal and salt-affected soils.

Salt stress is becoming a serious problem for the global environment and agricultural sector. Different sources of iron (Fe) can provide an eco-friendly solution to remediate salt-affected soils. The Fe nanoparticles (FeNPs) and conventional sources of Fe (iron-ethylene diamine tetra acetic acid; Fe-EDTA; and iron sulfate; FeSO4) were used to evaluate their effects on wheat crop grown in normal and salt-affected soils. Application of FeNPs (25 mg/kg) on normal soil increased the dry weights of wheat roots, shoots, and grains by 46%, 59%, and 77%, respectively. In salt-affected soil, FeNPs increased the dry weights of wheat roots, shoots, and grains by 65%, 78%, and 61%, respectively. The application of FeSO4 and Fe-EDTA increased the growth parameters of wheat in both normal and salt-affected soils compared to the respective controls. The photosynthetic parameters, including chlorophyll a (50%), chlorophyll b (67%), carotenoids (62%), and total chlorophyll contents (50%), were increased with the application of FeNPs under salt stress. The FeNPs increased plant-essential nutrients like iron, zinc, calcium, magnesium, and potassium in both normal and salt-affected soils. The experiment revealed that the application of Fe plays a significant role in enhancing the growth of wheat on alkaline normal and salt-affected soils. Maximum growth response was recorded with FeNPs than other Fe sources. The future must be focused on long term field experiments to economize the application of FeNPs on a large scale for commercialization.

Ethanolic Extract of Artemisia vulgaris Leaf Promotes Apoptotic Cell Death in Non-Small-Cell Lung Carcinoma A549 Cells through Inhibition of the Wnt Signaling Pathway.

The Wnt signaling pathway is reported to be associated with lung cancer progression, metastasis and drug resistance, and thus it is an important therapeutic target for lung cancer. Plants have been shown as reservoirs of multiple potential anticancer agents. In the present investigation, the ethanolic leaf extract of Artemisia vulgaris (AvL-EtOH) was initially analyzed by means of gas chromatography-mass spectrometry (GC-MS) to identify the important phytochemical constituents. The GC-MS analysis of AvL-EtOH exhibited 48 peaks of various secondary metabolites such as terpenoids, flavonoids, carbohydrates, coumarins, amino acids, steroids, proteins, phytosterols, and diterpenes. It was found that the treatment with increasing doses of AvL-EtOH suppressed the proliferation and migration of lung cancer cells. Furthermore, AvL-EtOH induced prominent nuclear alteration along with a reduction in mitochondrial membrane potential and increased ROS (reactive oxygen species) generation in lung cancer cells. Moreover, AvL-EtOH-treated cells exhibited increased apoptosis, demonstrated by the activation of caspase cascade. AvL-EtOH also induced downregulation of Wnt3 and ß-catenin expression along with cell cycle protein cyclin D1. Thus, the results of our study elucidated the potential of bioactive components of Artemisia vulgaris in the therapeutic management of lung cancer cells.

Potentiating Biosynthesis of Alkaloids and Polyphenolic Substances in Catharanthus roseus Plant Using ĸ-Carrageenan.

Catharanthus roseus is a medicinal plant that produces indole alkaloids, which are utilized in anticancer therapy. Vinblastine and vincristine, two commercially important antineoplastic alkaloids, are mostly found in the leaves of Catharanthus roseus. ĸ-carrageenan has been proven as plant growth promoting substance for a number of medicinal and agricultural plants. Considering the importance of ĸ-carrageenan as a promoter of plant growth and phytochemical constituents, especially alkaloids production in Catharanthus roseus, an experiment was carried out to explore the effect of ĸ-carrageenan on the plant growth, phytochemicals content, pigments content, and production of antitumor alkaloids in Catharanthus roseus after planting. Foliar application of ĸ-carrageenan (at 0, 400, 600 and 800 ppm) significantly improved the performance of Catharanthus roseus. Phytochemical analysis involved determining the amount of total phenolics (TP), flavonoids (F), free amino acids (FAA), alkaloids (TAC) and pigments contents by spectrophotometer, minerals by ICP, amino acids, phenolic compounds and alkaloids (Vincamine, Catharanthine, Vincracine (Vincristine), and vinblastine) analysis uses HPLC. The results indicated that all examined ĸ-carrageenan treatments led to a significant (p ≤ 0.05) increase in growth parameters compared to the untreated plants. Phytochemical examination indicates that the spray of ĸ-carrageenan at 800 mg L-1 increased the yield of alkaloids (Vincamine, Catharanthine and Vincracine (Vincristine)) by 41.85 µg/g DW, total phenolic compounds by 3948.6 µg gallic/g FW, the content of flavonoids 951.3 µg quercetin /g FW and carotenoids content 32.97 mg/g FW as compared to the control. An amount of 400 ppm ĸ-carrageenan treatment gave the best contents of FAA, Chl a, Chl b and anthocyanin. The element content of K, Ca, Cu, Zn and Se increased by treatments. Amino acids constituents and phenolics compounds contents were altered by ĸ-carrageenan.

Combined effects of zinc oxide nanoparticles and melatonin on wheat growth, chlorophyll contents, cadmium (Cd) and zinc uptake under Cd stress.

Zinc oxide nanoparticles (ZnONPs) and melatonin (MT) have been known to regulate heavy metal toxicities in plants in some studies, the effect of their combined use on cadmium (Cd) uptake by wheat (Triticum aestivum L.) and underlying mechanisms is largely unknown. Thus, plant growth, uptake and translocation of Cd mediated by soil applied ZnONPs and foliar applied MT were investigated in wheat grown in Cd polluted soil under ambient conditions. The results depicted that ZnONPs stimulated the growth, chlorophyll contents, and yield of wheat in a dose additive way and this effect was further increased with foliar application of MT. 100 mg/kg of ZnONPs alone enhanced the grain yield by 60.5 % and this increase was about 177.5 % under combined ZnONPs and 100 µM MT treatment. ZnONPs treatments decreased Cd concentration whereas increased zinc (Zn) concentrations in shoots, roots, husks and grains and the effect was further increased with exogenous MT combined with NPs in a dose-additive way. 50 and 100 mg/kg ZnONPs treatments alone decreased grain Cd by 6.5 %, and 20 % and increased the Zn concentration by 20.1 % and 24 % than control. 100 mg/kg ZnONPs +100 µM MT treatment decreased the grain Cd by 63.5 % and increased grain Zn by 51 % than control treatment. Total Cd uptake (tissues biomass × Cd concentration in respective tissues) in shoots, roots, husks and grains increased with ZnONPs alone or combined with MT than control whereas soil post-harvest bioavailable Cd concentration decreased with treatments than control. The Cd reduction in grains was due to increase in biomass and Zn concentration thereby decreasing bioavailable Cd in soil and its accumulation in plants. This study suggested that combined use of ZnONPs and MT may provide new approaches for minimizing Cd and biofortification of Zn in edible parts of plants.

Effect of soil texture and zinc oxide nanoparticles on growth and accumulation of cadmium by wheat: a life cycle study.

Cadmium (Cd) is getting worldwide attention due to its continuous accumulation in agricultural soils which is due to anthropogenic activities and finally Cd enters in food chain mainly through edible plants. Cadmium free food production on contaminated soils is great challenge which requires some innovative measures for crop production on such soils. The current study evaluated the efficiency of zinc oxide nanoparticles (ZnONPs) (0, 150 and 300 mg/kg) on the growth of wheat in texturally different soils including clay loam (CL), sandy clay loam (SCL), and sandy loam (SL) which were contaminated with were contaminated with 25 mg/kg of Cd before crop growth. Results depicted that doses of ZnONPs and soil textures significantly affected the biological yields, Zn and Cd uptake in wheat plants. The application of 300 mg/kg ZnONPs caused maximum increase in dry weights of shoot (66.6%), roots (58.5%), husk (137.8%) and grains (137.8%) in CL soil. The AB-DTPA extractable Zn was increased while Cd was decreased with doses of NPs depending upon soil textures. The maximum decrease in AB-DTPA extractable Cd was recorded in 300 mg/kg of ZnONPs treatment which was 58.7% in CL, 33.2% in SCL and 12.1% in SL soil as compared to respective controls. Minimum Cd concentrations in roots, shoots, husk and grain were found in 300 mg/kg ZnONPs amended CL soil which was 58%, 76.7%, 58%, and 82.6%, respectively. The minimum bioaccumulation factor (0.14), translocation index (2.46) and health risk index (0.05) was found in CL soil with the highest dose of NPs. The results concluded that use of ZnONPs significantly decreased Cd concentration while increased Zn concentrations in plants depending upon doses of NPs and soil textures.

Preparation and application of nanostructured carbon from oil fly ash for growth promotion and improvement of agricultural crops with different doses.

Application of carbon nanomaterials (CNMs) in agricultural production has piqued the interest of researchers. However, despite the enormous importance of CNMs in plant development, little is known about the effects of carbon nanoparticle (CNP) doses on plant physiological responses. Therefore, the aim of the current study was to check the effects of nanostructured carbon derived from oil fly ash (COFA), which was derived for the first time from high-energy ball-milling followed by a sonication process, on Phaseolus vulgaris L. and Cicer arietinum L. plants. We evaluated the plant physiological and biochemical parameters of the COFA-treated seedlings. Two different doses (4 mg L-1 and 8 mg L-1) of COFA and a control were studied. The results indicated that the germination rate (%), shoot length, root length, pod length, leaf area, fresh weight and dry weight were increased with the addition of COFA. Likewise, COFA increased the contents of chlorophyll pigments (Chla, Chlb, carotenoids), proteins, and carbohydrates in both species compared to the control. Finally, these findings showed that a COFA treatment at 4 mg L-1 after ball milled-sonication in water (BMW4) constituted the best dose for growth and physiology. Our findings reveal that the novel strategy of COFA engineering led to a boost in the growth of Phaseolus vulgaris and Cicer arietinum. Our results have high potential for agricultural research and provide an impact on food security.

Ethanolic extract of Coleus aromaticus leaves impedes the proliferation and instigates apoptotic cell death in liver cancer HepG2 cells through repressing JAK/STAT cascade.

Liver cancer or hepatocellular carcinoma (HCC) has become a leading cause for cancer burden across the globe, and incidences have tripled since the last two decades. Poor diagnosis of primary liver cancer and limited treatment strategies aggravate the challenges. Researchers globally have shown a steep inclination toward the exploration of plant-based compounds for their nutraceutical and anticancer potential to fit into the role of novel chemotherapeutics. Coleus aromaticus is a well-known culinary herb that earlier has been reported for several medicinal attributes. The current investigation deals with exploring the anticancer potential of ethanolic leaf extract of C. aromaticus (CoL-EtOH) against hepatocellular carcinoma HepG2 cell line. The observations made it evident that CoL-EtOH extract impeded the viability of HepG2 at 400 µg/ml (p < .01). Additionally, the extract also succeeded in escalating ROS production (p < .01) which aided dissipation of mitochondrial membrane potential and disruption of nuclear morphology. CoL-EtOH further activated caspase-8, -9, and -3 which was reaffirmed by increase in apoptosis at 400 µg/ml (p < .01). Moreover, post treatment with CaLEt-OH extract significantly reduced the expression of JAK-1 & STAT-3 genes (p < .01) along with regulated expression of Mcl1, Bcl-2, cyclinD1, p21, and p27 within HepG2 cells. This evidence portrays the promising anticancer potential of CoL-EtOH projecting it as a novel chemotherapeutic agent against HCC. PRACTICAL APPLICATIONS: The herb Coleus aromaticus belonging to Lamiaceae family and Coleus genus is known by various names in different regions of the world and several language-specific vernacular names. The herb has been used in therapeutic and medicinal applications as well as in culinary preparations. Various attributes of the nutritional strength and functional characteristics of the leaves in terms of carotenoids, minerals, phenols, dietary fiber, and antioxidant activity have been reported by several researchers. Carvacrol and thymol are majorly found in the plant, while chlorogenic acid and rosmarinic acid etc. as the phenolic components. The herb has been used in therapeutic and medicinal implications as well as in culinary preparations.

Utilization of Fruit Seed-Based Bioactive Compounds for Formulating the Nutraceuticals and Functional Food: A Review.

Fruit seeds include a large number of bioactive substances with potential applications in the culinary and pharmaceutical industries, satisfying current demands for natural ingredients, which are generally preferred since they have fewer adverse effects than artificial components. Researchers have long been interested in the functional features, as well as the proximate and mineral compositions, of diverse fruit seeds such as tomato, apple, guava, and dates, among others. Bioactive components such as proteins (bioactive peptides), carotenoids (lycopene), polysaccharides (pectin), phytochemicals (flavonoids), and vitamins (-tocopherol) are abundant in fruit by-products and have significant health benefits, making them a viable alternative for the formulation of a wide range of food products with significant functional and nutraceutical potential. This article discusses the role and activities of bioactive chemicals found in tomato, apple, dates, and guava seeds, which can be used in a variety of food forms to cure a variety of cardiovascular and neurological disorders, as well as act as an antioxidant, anticancer, and antibacterial agent. The extraction of diverse bioactive components from by-products could pave the path for the creation of value-added products from the fruit industry, making it more commercially viable while also reducing environmental pollution caused by by-products from the fruit industry.

Investigation of antidiabetic properties of shikonin by targeting aldose reductase enzyme: In silico and in vitro studies.

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase.

Exogenous Paclobutrazol Reinforces the Antioxidant and Antimicrobial Properties of Lavender (Lavandula officinalis L.) Oil through Modulating Its Composition of Oxygenated Terpenes.

Plant growth regulators can affect the primary and secondary metabolites of various plant species. However, the effect of paclobutrazol (PBZ) on the composition of lavender oil, especially related to the terpenoid pathway, is still unclear in literatures. In this study, the effect of PBZ as a foliar spray (0.200, 400 and 600 ppm) on the vegetative growth, phytochemical content, and both antioxidant and antimicrobial properties of lavender oil were investigated. The results indicated that all examined PBZ treatments led to a significant (p ≤ 0.05) decrease in growth parameters compared to the untreated plants. Meanwhile, the yield of essential oil was significantly decreased by the treatment of PBZ at 200 ppm compared to the control. In contrast, applied-PBZ significantly enhanced the chlorophyll content and displayed a marked change in the composition of the essential oil. This change included an obvious and significant increase in 3-carene, eucalyptol, γ-terpinene, α-pinocarvone, caryophyllene, ß-vetivenene, ß-santalol, ledol, geranyl isovalerate, farnesol, caryophyllene oxide, and phytol percentage. Generally, the highest significant values were achieved by the treatment of 400 ppm compared to the other treatments. Furthermore, this treatment showed the highest free radical scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) by 13% over the control. Additionally, to determine the antimicrobial activities of the extracted oil, each treatment was examined against two strains of Gram positive bacteria (S. aureus and B. cereus), two strains of Gram negative bacteria (S. enteritidis and E. coli), and two fungal species (C. albicans and A. niger) represent the yeast modal and filamentous fungus, respectively. The findings demonstrated that all examined species were more sensitive to the oil that was extracted from lavender plants, treated with 400 ppm PBZ, compared to the other concentrations.

Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan: A Comprehensive Review on Traditional Uses, Phytochemistry and Pharmacology.

The influence of medicinal plants on humanity spans time immemorial. These plants are also used at present with local and tribal peoples for the cures of various illnesses. Nature has produced an immense number of medicinal plants, which directly or indirectly help to treat various ailments and have numerous applications in the fields of pharmaceuticals, agriculture, food flavors and preservatives, aromas, and cosmetics. Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan (synonym: Bergenia ligulate Engl.), is an important medicinal plant belonging to the Saxifragaceae family, and not to be confused with Bergenia ciliata (Haw.) Sternb., and is popularly known as Pashanbheda (meaning to dissolve the kidney stone). This plant is a rich source of secondary metabolites (SMs) such as coumarins, flavonoids, benzenoids, lactones, tannins, phenols, and sterols, which make this plant a highly valued medicinal herb with a broad spectrum of pharmacological activities such as anti-urolithic, antioxidant, anti-viral, free radical scavenging, antidiabetic, anti-hepatotoxic, diuretic, antipyretic, anti-oxaluria, anti-tumour, antibacterial, antifungal, anti-inflammatory, antimicrobial, and cardioprotective. This review summarizes traditional uses and offers up to date data for future research on B. pacumbis.

Doxorubicin-Conjugated Zinc Oxide Nanoparticles, Biogenically Synthesised Using a Fungus Aspergillus niger, Exhibit High Therapeutic Efficacy against Lung Cancer Cells.

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. Molecular analysis based on 18S rRNA gene sequencing led to its identification as Aspergillus niger with the NCBI accession no. OL636020. The fungus was found to produce ZnONPs via the reduction of zinc ions from zinc sulphate. The ZnONPs were characterised by various biophysical techniques. ZnONPs were further bioconjugated with the anti-cancer drug doxorubicin (DOX), which was further confirmed by different physical techniques. Furthermore, we examined the cytotoxic efficacy of Doxorubicin-bioconjugated-ZnONPs (DOX-ZnONPs) against lung cancer A549 cells in comparison to ZnONPs and DOX alone. The cytotoxicity caused due to ZnONPs, DOX and DOX-ZnONPs in lung cancer A549 cells was assessed by MTT assay. DOX-ZnONPs strongly inhibited the proliferation of A549 with IC50 value of 0.34 µg/mL, which is lower than IC50 of DOX alone (0.56 µg/mL). Moreover, DOX-ZnONPs treated cells also showed increased nuclear condensation, enhanced ROS generation in cytosol and reduced mitochondrial membrane potential. To investigate the induction of apoptosis, caspase-3 activity was measured in all the treated groups. Conclusively, results of our study have established that DOX-ZnONPs have strong therapeutic efficacy to inhibit the growth of lung cancer cells in comparison to DOX alone. Our study also offers substantial evidence for the biogenically synthesised zinc oxide nanoparticle as a promising candidate for a drug delivery system.

A Comparative Antibacterial, Antioxidant, and Antineoplastic Potential of Rauwolfia serpentina (L.) Leaf Extract with Its Biologically Synthesized Gold Nanoparticles (R-AuNPs).

Rauwolfia serpentina (R. serpentina), belonging to the family Apocynaceae, is a renowned medicinal herb for its different pharmacological activities such as antibacterial, antifungal, anti-inflammatory, and antiproliferative characteristics. This study has done a comparative assessment of the antibacterial, antioxidant, and anti-cancer activity of R. serpentina aqueous leaf extract (RSALE) with encapsulated gold nanoparticles (R-AuNPs). The R-AuNPs are prepared so that they are significant in size, monodispersed, and extremely stable. Their characterization was done by numerous parameters, including UV-visible spectroscopy (528 nm), transmission electron microscopy (~17 d. nm), dynamic light scattering (~68 d. nm), and zeta-potential (~-17 mV). Subsequently, a potent antibacterial activity was depicted via RSALE and R-AuNPs when examined by disc diffusion against various Gram-positive and Gram-negative bacterial strains. The obtained zones of inhibition of RSALE (100 mg/mL) were 34 ± 0.1, 35 ± 0.1, 28.4 ± 0.01, and 18 ± 0.01, although those of R-AuNPs (15 mg/mL) were 24.4 ± 0.12, 22 ± 0.07, 20 ± 0.16, and 17 ± 0.3 against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (MTCC 8114), and Streptococcus pyogenes (ATCC 19615), respectively. However, no zone of inhibition was obtained when tested against Proteus vulgaris (MTCC 1771). Furthermore, the obtained MIC values for Staphylococcus aureus were 0.91, 0.61, and 1.15 mg/mL; for Escherichia coli, 0.79, 0.36, and 1.02 mg/mL; for Bacillus subtilis 0.42, 0.27, and 0.474 mg/mL; and for Streptococcus pyogenes, 7.67, 3.86, and 8.5 mg/mL of pure RSALE, R-AuNPs, and Amoxicillin (control), respectively, incorporating that R-AuNPs have been shown to have a 1.4-fold, 2.1-fold, 1.5-fold, and 1.9-fold enhanced antibacterial activity in contrast to pure RSALE tested against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Proteus vulgaris, respectively. Additionally, an enhanced antioxidant potential was detected in R-AuNPs compared to RSALE evaluated by the 2,2-Diphenyl-1-Picryl Hydrazyl Radical Scavenging (DPPH) Ferric reducing antioxidant power (FRAP) assay. The determined IC 50 values of RSALE and R-AuNPs were 0.131 ± 0.05 and 0.184 ± 0.02 mg/mL, and 0.110 ± 0.1 and 0.106 ± 0.24 mg/mL via the FRAP and DPPH assays, respectively. In addition, the anti-cancer activity against the human cervical cancer (Hela) cell line was evaluated, and the MTT assay results revealed that R-AuNPs (IC50 88.3 µg/mL) had an enhanced anti-cancer potential in contrast to RSALE (171.5 µg/mL). Subsequently, the findings of this study indicated that R. serpentina leaves and their nanoformulation can be used as a potent source for the treatment of the above-mentioned complications and can be used as a possible agent for novel target-based therapies for the management of different ailments.

Computational Screening of Natural Compounds for Identification of Potential Anti-Cancer Agents Targeting MCM7 Protein.

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of -9.95, -8.92, and -8.71 kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (-6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics.

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

Mass propagation of Juniperus procera Hoechst. Ex Endl. From seedling and screening of bioactive compounds in shoot and callus extract.

BACKGROUND: Juniperus procera Hoechst. ex Endl. is a medicinal tree in Saudi Arabia, primarily in the Enemas region, but it is locally threatened due to die-back disease and difficulties regarding seed reproduction (seed dormancy and underdeveloped embryonic anatomy, and germination rate < 40%). Hence, the alternative methods for reproduction of Juniperus procera are really needed for conservation and getting mass propagation for pharmaceutical uses. RESULTS: In this manuscript, we articulated the successful in vitro shoot multiplication and callus induction of J. procera by using young seedling as explants and detected an important antibacterial and antitumor product. Explants were grown on different types of media with the supplement of different combinations of Plant Growth Regulators (PGRs) at different concentrations. The best media for shoot multiplication was Woody Plant Media (WPM) supplemented with PGRs (0.5 µM of IAA and 0.5 µM BAP or 0.5 µM IBA and 0.5 µM BAP). Whereas for callus induction and formation Woody Plant Media (WPM) with the addition of PGRs (0.5 µM 2,4-D and 0.5 µM BAP) was better than the Chu Basal Salt Mixture (N6), Gamborg's B-5 Basal Medium (B5), and Murashige and Skoog media. The possibility of multiplication of J. procera in vitro creates significant advantages to overcome the difficulties of seeds dormancy for the reproduction of plants, conservation of trees, and getting mass propagation material for pharmaceutical studies. The shoot and callus extract of J. procera was detected using gas chromatography-mass spectrometry analysis and revealed more than 20 compounds related to secondary metabolites, which contained antibacterial and antitumor agents, such as ferruginol, Retinol, and Quinolone as well as confirmed by Direct Analysis in Real Time, Time of Flight Mass Spectrometry (DART-ToF-MS). Podophyllotoxin (PTOX) was detected in callus material by HPLC with sigma standard and confirmed by DART-ToF-MS and UV spectra. CONCLUSION: We successfully conducted in vitro shoot multiplication and callus induction from J. procera seedlings using WPM and a different combination of PGRs and, detected an important antibacterial and antitumor product such as ferruginol and podophyllotoxin. According to our findings, J. procera has become a new natural source of novel bioactive compounds.