Polyalthia longifolia-mediated green synthesis of zinc oxide nanoparticles: characterization, photocatalytic and antifungal activities.

The biological synthesis of zinc oxide nanoparticles (ZnO NPs) from plant extracts has emerged as a novel method for producing NPs with great scalability and biocompatibility. The present study is focused on bio-fabricated zinc oxide nanomaterial characterization and investigation of its photocatalytic and antifungal activities. ZnO NPs were biosynthesized using the leaf extract of Polyalthia longifolia without using harmful reducing or capping chemicals, which demonstrated fungicidal activity against Fusarium oxysporum f. sp. ciceris. The results showed that the inhibition of the radial growth of F. oxysporum f. sp. ciceris was enhanced as the concentration increased from 100 ppm to 300 ppm. The effectiveness of the photocatalytic activity of biosynthesized ZnO NPs was analyzed using MB dye degradation in aqueous medium under ultraviolet (UV) radiation and natural sunlight. After four consecutive cycles, the photocatalytic degradation of MB was stable and was 84%, 83%, 83%, and 83%, respectively, during natural sunlight exposure. Under the UV sources, degradation reached 92%, 89%, 88%, and 87%, respectively, in 90 minutes. This study suggests that the ZnO NPs obtained from plant extract have outstanding photocatalytic and antifungal activities against F. oxysporum f. sp. ciceris and have the potential for application as a natural pest control agent to reduce pathogenesis.

Molecular Insight into Prostate Cancer: Preventive Role of Selective Bioactive Molecules.

Prostate cancer (CaP) is one of the most prevalent male malignancies, accounting for a considerable number of annual mortalities. However, the prompt identification of early-stage CaP often faces delays due to diverse factors, including socioeconomic inequalities. The androgen receptor (AR), in conjunction with various other signaling pathways, exerts a central influence on the genesis, progression, and metastasis of CaP, with androgen deprivation therapy (ADT) serving as the primary therapeutic strategy. Therapeutic modalities encompassing surgery, chemotherapy, hormonal intervention, and radiotherapy have been formulated for addressing early and metastatic CaP. Nonetheless, the heterogeneous tumor microenvironment frequently triggers the activation of signaling pathways, culminating in the emergence of chemoresistance, an aspect to which cancer stem cells (CSCs) notably contribute. Phytochemicals emerge as reservoirs of bioactive agents conferring manifold advantages against human morbidity. Several of these phytochemicals demonstrate potential chemoprotective and chemosensitizing properties against CaP, with selectivity exhibited towards malignant cells while sparing their normal counterparts. In this context, the present review aims to elucidate the intricate molecular underpinnings associated with metastatic CaP development and the acquisition of chemoresistance. Moreover, the contributions of phytochemicals to ameliorating CaP initiation, progression, and chemoresistance are also discussed.

Lupeol, an androgen receptor inhibitor, enhances the chemosensitivity of prostate cancer stem cells to antiandrogen enzalutamide-based therapy.

Enzalutamide is an androgen receptor (AR) antagonist commonly used in the treatment of prostate cancer (CaP). However, due to the potential toxicity and development of resistance associated with Enzalutamide-based therapy, there is a need to explore additional compounds that can enhance its therapeutic effectiveness while minimizing toxicity. Lupeol is a pharmacologically active triterpene having anticancer effects. The objective of this study was to explore Lupeol's potential in enhancing the chemosensitivity of chemoresistant CaP cells to Enzalutamide in vitro and in a mouse model. To test our hypothesis, we performed cell viability and luciferase reporter gene assay, flow cytometry, animal studies, and histopathological analysis. Finally, we analyzed the change in selective metabolites in the prostate tissue by LCMS. Results demonstrated that a combination of Lupeol and Enzalutamide could better (i) suppress the Cancer Stem Cells (CSCs) and chemoresistant cells (PTEN-CaP8 and PC3) viability and migration, (ii) increase cell cycle arrest, (iii) inhibit the transcriptional activity of AR, c-MYC, c-FLIP, and TCF (iv) inhibit tumor growth in a mouse model (v) protect Enzalutamide-induced adverse effects in prostate glands and gut tissue (vi) decrease levels of testosterone and methionine metabolites. In conclusion, Lupeol enhances the pharmacological efficacy of Enzalutamide and reduces the adverse effects. Thus, Lupeol could be a promising adjuvant for improving Enzalutamide-based treatment outcomes and warrant further research.

Flubendiamide induced genetic and cellular damages directly influence the life cycle of the oriental leaf worm, Spodoptera litura.

Indiscriminate uses of insecticide greatly damage the environment as well as non-target organisms. Thus, multiple levels of bioassays can help better management of our environment. Flubendiamide is a phthalic acid diamide insecticide that ceases the function of insect muscle leading to paralysis and death. Here, we aimed to explore the effects of Flubendiamide on the life cycle of Spodoptera litura vis-a-vis the mode of action. Fourth instar larvae of the same age (120 ± 2 h) and size were fed with different concentrations (20-80 µg/mL) of Flubendiamide for 12-72 h. We performed a pharmacokinetics study, different biochemical assays, p450, Ecdysone receptor (EcR) and other genes expression analyses by Real-Time PCR and gross damages by Dye exclusion assay and histopathology. Our results demonstrate that the mean concentration of Flubendiamide after 48 h is 9.907 µg/mL and (i) altered the molting, metamorphosis, and reproduction at 80 µg/mL (24 h) (ii) increases all oxidative stress parameters (ROS/RNS, MDA, 8OHdG), decreases oxidative defense mechanisms (SOD, CAT, GST) at 80 µg/mL (48 h) and p450 in a time and concentration-dependent manner, (iii) activates CncC/Maf apoptotic pathways at 80 µg/mL concentration at 24 h while the expression declined from 48 h onwards, (iii) downregulates the EcR expression in a time and concentration-dependent manner, which might be responsible for disturbed molting, metamorphosis, and reproduction, and (iv) increase the expression of apoptotic genes (Caspase 1, -3, and - 5), in time and concentration-dependent manner causing gross morphological and histological damages. In conclusion, indiscriminate use of this insecticide can affect the ecosystem and have the capacity to cause multiple hazardous effects on experimental organisms. Thus, it warrants further investigations to improve and optimize the integrated pest management packages, including Flubendiamide for better management.

Grass-Shaped Zinc Oxide Nanoparticles Synthesized by the Sol-Gel Process and Their Antagonistic Properties towards the Biotrophic Parasite, Meloidogyne incognita.

The presence of Meloidogyne spp., also known as root-knot nematodes, presents a significant danger to global agricultural progress. Since chemical nematicides have high levels of toxicity, it is imperative to develop environmentally friendly methods to manage root-knot nematodes. Nanotechnology is now the most progressive way to attract researchers due to its innovative quality in combating plant diseases. Our study focused on the sol-gel process to synthesize grass-shaped zinc oxide nanoparticles (G-ZnO NPs) and assess its nematicidal behavior against Meloidogyne incognita. Various concentrations (250, 500, 750, and 1000 ppm) of G-ZnO NPs were utilized to expose both the infectious stage (J2s) and egg masses of M. incognita. Laboratory results revealed that G-ZnO NPs showed toxicity to J2s with LC50 values of 1352.96, 969.64, and 621.53 ppm at 12, 24, and 36 hours, respectively, and the result was the inhibition of egg hatching in M. incognita. All three exposure periods were reported linked with the concentration strength of G-ZnO NPs. The pot experiment results exhibited that G-ZnO NPs significantly reduced the root-gall infection of chickpea plants under M. incognita attack. Compared with the untreated control, there was a significant improvement in plant growth attributes and physiological parameters as well, when distinct G-ZnO NP doses (250, 500, 750, and 1000 ppm) were applied. In the pot study, we noticed a reduction in the root-gall index with an increase in the concentration of G-ZnO NPs. The results confirmed that G-ZnO NPs have enormous potential in sustainable agriculture for controlling the root-knot nematode, M. incognita, in chickpea production.

Implication of Lupeol in compensating Sorafenib-induced perturbations of redox homeostasis: A preclinical study in mouse model.

AIMS: Cancer chemotherapeutic drugs can potentially cause several adverse effects that influence a patient's general well-being. Sorafenib, an approved drug used in clinics against multiple cancers whose overall efficacy suffered a serious setback due to various side effects, leading to its frequent discontinuation. Lupeol has recently been considered an important prospective therapeutic agent due to its low toxicity and enhanced biological efficacy. Hence, our study aimed to evaluate whether Lupeol can perturb the Sorafenib-induced toxicity. MAIN METHODS: To test our hypothesis, we studied DNA interaction, level of cytokines, LFT/RFT, oxidant/antioxidant status, and their influences on genetic, cellular, and histopathological changes using both in vitro and in vivo models. KEY FINDINGS: The Sorafenib-treated group showed a marked increase in reactive oxygen and nitrogen species (ROS/RNS), an increase in liver and renal function marker enzymes, serum cytokines (IL-6, TNF-α, IL-1ß) macromolecular damages (protein, lipid, and DNA), and a decrease in antioxidant enzymes (SOD, CAT, TrxR, GPx, GST). Moreover, Sorafenib-induced oxidative stress caused marked cytoarchitectural damage in the liver and kidney and increased p53 and BAX expression. Interestingly, combining Lupeol with Sorafenib improves all the examined toxic insults caused by Sorafenib. In conclusion, our findings suggest that Lupeol can be used in combination with Sorafenib to reduce ROS/RNS-induced macromolecule damage, which might result in hepato-renal toxicity. SIGNIFICANCE: This study presents the possible protective effect of Lupeol against Sorafenib-induced adverse effects by perturbing redox homeostasis imbalance and apoptosis leading to tissue damage. This study is a fascinating finding that warrants further in-depth preclinical and clinical studies.

Ingestion and effects of green synthesized cadmium sulphide nanoparticle on Spodoptera Litura as an insecticidal and their antimicrobial and anticancer activities.

The current study investigated the multifunctional properties of Cadmium Sulphide Nanoparticles synthesized using a green synthesis method (CdS NPs) using a green feedstock, Nopal Cactus fruit extract. The biological activities of the CdS NPs were thoroughly investigated, including their insecticidal, antibacterial, and anticancer activities. The different concentrations (0.005-0.04%) of CdS NPs were fed to the larvae of Spodoptera litura, and their ingestion effects were observed on the different biological, biochemical, and oxidative stress markers. There are significant dose-dependent changes in the biochemical parameters like superoxide dismutase (SOD), Catalase (CAT), Glutathione-S-transferase (GST), and MDA level as a marker of lipid peroxidation in the treated larvae were studied. In the highest concentration (0.04%), significant larval mortality (46.66%), malformation (pupae and adult) (27.78%), inhibition of adult emergence (43.87%), as well as reduced fecundity (25.28%), and fertility (22.74%) as compared to control was observed. CdS NPs have been investigated for antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus bacterial strains. In vitro anticancer activities were carried out to decrease the viability of the Pancreatic cancer cell line. The cells showed 18% and 12% viability at a 200 µg/ml concentration when incubated with CdS NPs for 24 and 48 h, respectively, confirming its potent anticancer property. The lack of cytotoxicity against the (RBC) endorses the biocompatible nature of synthesized CdS NPs. It was observed that green synthesized CdS NPs could be used as a promising insecticidal, antibacterial, and anticancer agent.

Anti-quorum Sensing and Anti-biofilm Activity of Zinc Oxide Nanospikes.

This study evaluates the impact of two separate incubation periods (4 and 6 weeks) on the morphology of sol-gel-fabricated ZnO nanospikes (ZNs), that is, ZN1 and ZN2, respectively. We further analyzed the inhibitory effects of ZN1 and ZN2 on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa (PAO1) and Chromobacterium violaceum (strains 12472 and CVO26). The size of the synthesized ZNs was in the range of 40-130 nm, and finer nanoparticles were synthesized after an incubation period of 6 weeks. Treatment with ZNs decreased the production of violacein in the pathogen without affecting the bacterial growth, which indicated that ZNs inhibited the QS signaling regulated by N-acyl homoserine lactone. ZN2 had a higher inhibitory action on the virulence factor productivity than ZN1. Furthermore, ZN2-treated cells displayed a substantial decrease in azocasein-degrading protease activity (80%), elastase activity (83%), and pyocyanin production (85%) relative to untreated P. aeruginosa PAO1 cells. Treatment with ZN2 decreased swarming motility and exopolysaccharide production by 89 and 85%, respectively. ZN2 was effective against both the las & pqs systems of P. aeruginosa and exhibited broad-spectrum activity. Additionally, ZN2 was more efficient in inhibiting the biofilm formation at the attachment stage than ZN1. These findings revealed that in P. aeruginosa, ZN2 demonstrated inhibitory effects on QS as well as on the development of biofilms. Thus, ZN2 can be potentially used to treat drug-resistant P. aeruginosa infections.

Interaction of thiamethoxam with DNA: Hazardous effect on biochemical and biological parameters of the exposed organism.

In the present scenario, insecticides/pesticides are used intensively to control the various insect pests. Indiscriminate use of these insecticides/pesticides affects the structure and function of the ecosystem. In this context, a thorough toxicological study of each insecticide/pesticide is a must to understand the hazardous effect of these chemicals on the target and non-target organisms. The present study was aimed to understand the hazardous effect of thiamethoxam against the Spodoptera litura. Different concentrations (20-80 µg/mL) of thiamethoxam were prepared, and fourth instar larvae of S. litura were allowed to feed for 12-72 h. We first examined the interaction of thiamethoxam with DNA. Next, treated and non-treated larvae were assessed for different biological parameters such as mortality, emergence, fecundity, fertility, longevities, and biochemical parameters. Our result showed that thiamethoxam directly interacts with the DNA and significantly influenced the different biological and biochemical parameters of exposed the organisms. We observed a significant change in stress enzymes such as SOD, CAT, and GST. A similar observation was also made with the oxidative marker for lipid damage, MDA and DNA damage, 8-OHdG, respectively. In conclusion, our results suggest that improper use of synthetic chemical insecticides influenced both biological and biochemical parameters through oxidative stress and probably damage the genetic material.

Enhanced Insecticidal Activity of Thiamethoxam by Zinc Oxide Nanoparticles: A Novel Nanotechnology Approach for Pest Control.

Indiscriminate and unregulated application of pesticides produces deleterious effect in various groups of organisms including humans and the environment. To solve these issues, it has been reported that the residue-free green nanocomposite synergistically enhances the pesticide efficacy. In this study, ZnO nanoparticles (NPs) with a thiamethoxam nanocomposite were synthesized and we investigated their synergistic effect on 4th instar larvae of Spodoptera litura (Lepidoptera: Noctuidae). These larvae were allowed to feed on the composite of ZnO NPs with thiamethoxam (10-90 mg/L) and thiamethoxam-impregnated castor leaves. Observations showed an increased larval mortality (27% increased mortality), a malformation in pupae and adults, overdue emergence, and reduced fecundity and fertility. A significant dose-dependent variation in the biochemical parameters such as superoxide dismutase (SOD), glutathione-S-transferase (GST), and thiobarbituric acid-reactive substances (TBARS) in the treated larvae was also observed. A decline of 72.42 and 33.82% in SOD and GST activity ,respectively, was observed at higher concentration as compared to the control. On the contrary, it enhanced the TBARS level up to 56.7%. The synthesized nanocomposite was characterized by different biophysical techniques such as X-ray diffraction (average crystalline size 34 nm), scanning electron microscopy, transmission electron microscopy (average particle size 30 nm), and Fourier transform infrared spectroscopy (Zn-O stretching peaks at 432 cm-1 and 503 cm-1). The observation of the present study suggests that ZnO NPs pave the way for developing cost-effective, eco-friendly, and capable nanomaterial for its applications in the field of biological sciences.

Hazardous sub-cellular effects of Fipronil directly influence the organismal parameters of Spodoptera litura.

Indiscriminate use of insecticides/pesticides affects the structure and function of the ecosystems. The present study was aimed to investigate the toxic potential of Fipronil (a second generation phenylpyrazole) using Spodoptera litura larvae (Lepidoptera: Noctuidae) as an experimental model. Commercial grade of Fipronil, an insecticide was fed (20-80 mg/L) to the 4th instar larvae of S. litura for 12-72 h and examined different molecular, biochemical and organismal parameters. We observed a significant dose- and time-dependent changes in the biochemical parameters such as Superoxide dismutase (SOD), Glutathione-S-transferase (GST), Catalase (CAT), level of 8-hydroxy 2'-deoxyguanosine (8-OHdG) and Thiobarbituric Acid Reactive Substances (TBARS) [Malondialdehyde (MDA) equivalent] in the exposed larvae. We also observed that Fipronil interacts with DNA. Next, we examined the influence of sub-cellular damages at the organismal level. The alterations in the parameter such as the delayed emergence of larvae, reduced fecundity, fertility and increased rate of malformation in pupae and adults indicate the sub-organismal damages influence at the organismal level. The findings of the present study suggest that discriminatory non-scientific use of insecticide/pesticide might influence the population dynamics of insects and in large ecosystem too and needs further thorough investigations.

New withanolide, acyl and menthyl glucosides from fruits of Withania coagulans Dunal.

The fruits of Withania coagulans Dunal (family: Solanaceae) are sweet, sedative, emetic, alterative and diuretic; used to treat asthma, biliousness, strangury, wounds, dyspepsia, flatulent colic, liver complaints and intestinal infections. Phytochemical investigation of the fruits yielded a withanolide tetraglucoside identified as (20S, 22R)-5alpha, 20alpha-diacetoxy-6beta-hydroxy- 1-oxowitha-2,24-dienolide-6-beta-D-glucopyranosyl-(6' --> 1")-beta-D-glucopyranosyl-(6" --> 1''')-beta-D-glucopyranosyl-(6''' --> 1''''-beta-D-glucopyranoside), a capryloyl hexaglucoside formulated as n-octanoyl-beta-D-glucopyranosyl-(6a --> 1b)-beta-D-glucopyranosyl-(6b --> c)-beta-D-glucopyranosyl-(6c --> 1d)-beta-D-glucopyranosyl-(6d --> 1e)-glucopyranosyl-(6e --> 1f)-glucopyranoside and a menthyl tetraglucoside characterized as menthol-O-alpha-L-glucopyranosyl-(2a --> 1b)-O-alpha-L-glucopyranosyl-(2b --> 1c)-O-alpha-L-glucopyranosyl-(2c --> 1d)-O-alpha-L-glucopyranoside along with three fatty acid esters, n-nonacosanyl linolenate, n-octacosanyl linolenate and n-heptacosanyl linolenate. The structures of the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical means.