An assessment of the impact of traditional rice cooking practice and eating habits on arsenic and iron transfer into the food chain of smallholders of Indo-Gangetic plain of South-Asia: Using AMMI and Monte-Carlo simulation model.

The current study was designed to investigate the consequences of rice cooking and soaking of cooked rice (CR) with or without arsenic (As) contaminated water on As and Fe (iron) transfer to the human body along with associated health risk assessment using additive main-effects and multiplicative interaction (AMMI) and Monte Carlo Simulation model. In comparison to raw rice, As content in cooked rice (CR) and soaked cooked rice (SCR) enhanced significantly (at p < 0.05 level), regardless of rice cultivars and locations (at p < 0.05 level) due to the use of As-rich water for cooking and soaking purposes. Whereas As content in CR and SCR was reduced significantly due to the use of As-free water for cooking and soaking purposes. The use of As-free water (AFW) also enhanced the Fe content in CR. The overnight soaking of rice invariably enhanced the Fe content despite the use of As-contaminated water in SCR however, comparatively in lesser amount than As-free rice. In the studied area, due to consumption of As-rich CR and SCR children are more vulnerable to health hazards than adults. Consumption of SCR (prepared with AFW) could be an effective method to minimize As transmission and Fe enrichment among consumers.

Biocontrol efficacy of cajeput oil against Anopheles stephensi L. mosquito and its effect on non-target species.

Chemical insecticides are effective at controlling mosquito populations, but their excessive use can pollute the environment and harm non-target organisms. Mosquitoes can also develop resistance to these chemicals over time, which makes long-term mosquito control efforts challenging. In this study, we assessed the phytochemical, biochemical, and insecticidal properties of the chemical constituents of cajeput oil. Results show that Melaleuca cajuputi essential oil may exhibit mosquito larvicidal properties against Anopheles stephensi larvae (second-fourth instar) at 24 h post-treatment. At 24 h post-exposure, the essential oil resulted in a significant decrease in detoxifying enzymes. All of these findings indicate that cajeput oil infects An. stephensi larvae directly affect the immune system, leading to decreased immune function. Cajeput oil significantly affects the second, third, and fourth instar larvae of An. stephensi, according to the bioassay results. Cajeput oil does not induce toxicity in non-target Eudrilus eugeniae earthworm species, as indicated by a histological study of earthworms. Phytochemical screening and GC-MS analysis of the essential oil revealed the presence of several major phytochemicals that contribute to mosquito larvicidal activity. The importance of cajeput oil as an effective candidate for biological control of the malarial vector An. stephensi is supported by this study.

Effects of common dissolved anions on the efficiency of Fe0-based remediation systems.

Quiescent batch experiments were conducted to evaluate the influences of Cl-, F-, HCO3-, HPO42-, and SO42- on the reactivity of metallic iron (Fe0) for water remediation using the methylene blue (MB) method. Strong discoloration of MB indicates high availability of solid iron corrosion products (FeCPs). Tap water was used as an operational reference. Experiments were carried out in graduated test tubes (22 mL) for up to 45 d, using 0.1 g of Fe0 and 0.5 g of sand. Operational parameters investigated were (i) equilibration time (0-45 d), (ii) 4 different types of Fe0, (iii) anion concentration (10 values), and (iv) use of MB and Orange II (O-II). The degree of dye discoloration, the pH, and the iron concentration were monitored in each system. Relative to the reference system, HCO3- enhanced the extent of MB discoloration, while Cl-, F-, HPO42-, and SO42- inhibited it. A different behavior was observed for O-II discoloration: in particular, HCO3- inhibited O-II discoloration. The increased MB discoloration in the HCO3- system was justified by considering the availability of FeCPs as contaminant scavengers, pH increase, and contact time. The addition of any other anion initially delays the availability of FeCPs. Conflicting results in the literature can be attributed to the use of inappropriate experimental conditions. The results indicate that the application of Fe0-based systems for water remediation is a highly site-specific issue which has to include the anion chemistry of the water.

Introducing a novel chemotherapeutic drug formulated with anthraflavic acid for treating human breast carcinoma and type 2 diabetes mellitus.

Introduction: Molecular docking as a versatile theoretical method was used to investigate the biological activities of anthraflavic acid in the presence of α-amylase. The outcomes revealed that anthraflavic acid has a considerable binding affinity to the enzyme with a docking score of -7.913 kcal/mol. These outcomes were further evaluated with free binding energy calculations, and it was concluded that anthraflavic acid could be a potential inhibitor for α-amylase. Material and methods: Anthraflavic acid was explored in anti-human breast carcinoma tests. The in vitro cytotoxic and anti-breast carcinoma effects of biologically synthesized anthraflavic acid against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines were assessed. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the anti-breast carcinoma properties of anthraflavic acid could significantly kill the MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines in a time- and concentration-dependent manner. Also, we used human umbilical vein endothelial cells (HUVECs) to determine the cytotoxicity potentials of anthraflavic acid using MTT assay. Results: The IC50 values of anthraflavic acid were 159, 193, 253, 156, 241, and 218 µg/ml against MCF-7, CAMA-1, SK-BR-3, MDA-MB-231, AU565 [AU-565], and Hs 281.T cancer cell lines. Conclusions: It seems the anti-human breast carcinoma effect of recent nanoparticles is due to their antioxidant effects.

Comparing the Positive Impacts and Stress Induction by Polyethylene Glycol (PEG 6000) Variable Levels on Canola (Brassica napus L.) Growth, Yield, and Oil Contents.

Seed quality (i.e., emergence energy, viability, physical purity, size, weight) is a critical factor that influences the yield of crops. Poor seed quality can lead to reduced germination rates, lower plant populations, and, ultimately, lower crop yields. On the other hand, seed priming is suggested to be an effective technique for improving seeds germination and plant population. In this study, we investigated the effect of seed priming with polyethylene glycol (PEG) on the germination, growth, and yield of two varieties of canola, super canola, and sandal canola. The treatment plan includes five concentrations of PEG (i.e., 5, 10, 15, 20%), distilled water priming, and control (no priming). All of the treatments were applied in 3 replications following a completely randomized design. Our results showed that seed priming with 5%PEG (T2) significantly improved radicle length (50 and 36%), plant height (43 and 34%), chlorophyll a (44 and 43%), chlorophyll b (120 and 208%), and total chlorophyll (83 and 111%) compared to control in super canola and sandal canola, respectively. In particular, seed priming with 5%PEG resulted in the highest increase in protein contents (25 and 1.40%), oleic acid (26 and 40%), and linolenic acid (6 and 6%) compared to control in super canola and sandal canola, respectively. It is concluded that seed priming with 5%PEG is an effective treatment to improve the performance of canola crops in terms of seedling growth, yield, chlorophyll, protein, and oil content. More investigations are recommended as future perspectives using other canola varieties to declare 5% PEG as an effective treatment for canola for improvement in growth, oil, protein, and chlorophyll contents.

Antioxidant and anticancer potential of ethyl acetate extract of bark and flower of Tecoma stans (Linn) and In Silico studies on phytoligands against Bcl 2 and VEGFR2 factors.

This study was designed to appraise the antioxidant and anticancer competence of solvent extracts of Tecoma stans (Linn) and analyze the phytoligands interaction against Bcl 2 VEGFR2 through in silico studies. The phytochemical analysis revealed that the ethyl acetate extract contains more number of pharmaceutically valuable phytochemicals than other solvent extracts. Among the various phytochemicals, flavonoid was found as a predominant component, and UV-Vis- spectrophotometer analysis initially confirmed it. Hence, the column chromatogram was performed to purify the flavonoid, and High-performance liquid chromatography (HPLC) was performed. It revealed that the flavonoid enriched fraction by compared with standard flavonoid molecules. About 84.69% and 80.43% of antioxidant activity were found from ethyl acetate extract of bark and flower at the dosage of 80 µg mL-1 with the IC50 value of 47.24 and 43.40 µg mL-1, respectively. In a dose-dependent mode, the ethyl acetate extract of bark and flower showed cytotoxicity against breast cancer cell line MCF 7 (Michigan Cancer Foundation-7) as up to 81.38% and 80.94% of cytotoxicity respectively. Furthermore, the IC50 was found as 208.507 µg mL-1 and 207.38 µg mL-1 for bark and flower extract correspondingly. About 10 medicinal valued flavonoid components were identified from bark (6) and flower (4) ethyl acetate extract through LC-MS analysis. Out of 10 components, the 3,5-O-dicaffeoylquinic acid (ΔG -8.8) and Isorhamnetin-3-O-rutinoside (ΔG -8.3) had the competence to interact with Bcl 2 (B-Cell Lymphoma 2) and VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) respectively with more energy. Hence, these results confirm that the ethyl acetate extract of bark and flower of T. stans has significant medicinal potential and could be used as antioxidant and anticancer agent after some animal performance study.

Antimicrobial, antioxidant, anticancer, and antithrombotic, competency of saponins from the root of Decalepis hamiltonii.

The goal of this study was to extract saponins from the tuberous root of Decalepis hamiltonii and assess their potential clinical applications, which included antioxidant, antibacterial, antithrombotic, and anticancer properties. Surprisingly, the results of this study revealed that the extracted saponins have excellent antioxidant activities, as demonstrated by 2,2-diphenylpicrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Hydrogen peroxide (H2O2), and Nitric oxide (NO) scavenging assays. Nonetheless, at a concentration of 100 g/mL, crude saponin had excellent antibacterial activity, particularly against gramme positive bacteria (Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, and Micrococcus luteus), followed by gramme negative bacteria (Escherichia coli, Salmonella typhi, Proteus mirabilis, and Klebsiella pneumonia). Despite this, the crude saponin had no effect on Aspergillus niger and Candida albicans. The crude saponin also possesses outstanding in vitro antithrombotic activity on blood clot. Interestingly, the crude saponins have an outstanding anticancer activity of 89.26%, with an IC50 value of 58.41 µg/mL. Overall, the findings conclude that crude saponin derived from D. hamiltonii tuberous root could be used in pharmaceutical formulations.

Anti-diabetic efficacy and selective inhibition of methyl glyoxal, intervention with biogenic Zinc oxide nanoparticle.

Non-enzymatic glycation of biomolecules results in advanced glycation end products (AGEs), which are responsible for secondary complications in diabetes. Inhibiting methyl glyoxal (MGO) induced advanced glycation end product (AGE) formation is the only way to alleviate diabetic complications. This study aimed to look into the abilities of herbal extract Kigelia africana and K. africana synthesized zinc oxide nanoparticles (ZnONPs) to inhibit the emergence of MG-derived AGEs. The study intended to determine antioxidant and AGE inhibition of the plant extract and ZnONPs. ZnONPs were tested for the efficiency of anti-diabetic activity in streptozotocin-induced diabetic Wister rats. We discovered that the MGO-trapping effects on the prevention of AGE production were mediated by the downregulation of the amplification of MGO-trapping impacts on the hypoglycemic and antihyperlipidemic mechanisms of ZnONPs. According to histological findings, the treatment with ZnONPs also successfully lowers inflammation in the hepatic and renal tissues. Overall, future mechanistic research could establish ZnONPs potential anti-diabetic properties.

An Insight into Biochemical Characterization and Explorations of Antioxidant, Antibacterial, Cytotoxic, and Antidiabetic Activities by Trachyspermum ammi Nanosuspensions.

BACKGROUND: Trachyspermum ammi is a frequently utilized traditional medicinal plant renowned for its pharmacological attributes, particularly in the realm of treating infectious diseases. This current study aims to comprehensively assess the in vitro properties of freshly prepared nanosuspensions derived from Trachyspermum ammi extracts, with a focus on their cost-effective potential in various areas, including antioxidant, antibacterial, cytotoxic, and antidiabetic activities. METHODS: Biochemical characterization of T. ammi nanosuspensions by high-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR) analyses. RESULTS: HPLC analysis revealed the presence of kaempferol and sinapic acid in various amounts at 11.5 ppm and 12.3 ppm, respectively. FTIR analysis of T. ammi powder revealed the presence of alcohols and amines. The assessment of antioxidant activity was conducted using a DPPH scavenging assay, indicating that the nanosuspensions exhibited their highest free radical scavenging activity, reaching 14.9%. Nanosuspensions showed 3.75 ± 3.529.5% biofilm inhibition activity against Escherichia coli. The antidiabetic activity was accessed through antiglycation and α- amylase inhibition assays, while nanosuspension showed the maximum inhibition activity at 25.35 ± 0.912133% and 34.6 ± 1.3675%. Hemolytic activity was also evaluated, and T. ammi nanosuspension showed 22.73 ± 1.539% hemolysis. CONCLUSIONS: This nanotechnology approach has established a foundation to produce plant-based nanosuspensions, offering a promising avenue for the biopharmaceutical production of herbal nanomedicines. These nanosuspensions have the potential to enhance bioavailability and can serve as a viable alternative to synthetic formulations.

Deep Learning Mechanism for Predicting the Axillary Lymph Node Metastasis in Patients with Primary Breast Cancer.

The second largest cause of mortality worldwide is breast cancer, and it mostly occurs in women. Early diagnosis has improved further treatments and reduced the level of mortality. A unique deep learning algorithm is presented for predicting breast cancer in its early stages. This method utilizes numerous layers to retrieve significantly greater amounts of information from the source inputs. It could perform automatic quantitative evaluation of complicated image properties in the medical field and give greater precision and reliability during the diagnosis. The dataset of axillary lymph nodes from the breast cancer patients was collected from Erasmus Medical Center. A total of 1050 images were studied from the 850 patients during the years 2018 to 2021. For the independent test, data samples were collected for 100 images from 95 patients at national cancer institute. The existence of axillary lymph nodes was confirmed by pathologic examination. The feed forward, radial basis function, and Kohonen self-organizing are the artificial neural networks (ANNs) which are used to train 84% of the Erasmus Medical Center dataset and test the remaining 16% of the independent dataset. The proposed model performance was determined in terms of accuracy (Ac), sensitivity (Sn), specificity (Sf), and the outcome of the receiver operating curve (Roc), which was compared to the other four radiologists' mechanism. The result of the study shows that the proposed mechanism achieves 95% sensitivity, 96% specificity, and 98% accuracy, which is higher than the radiologists' models (90% sensitivity, 92% specificity, and 94% accuracy). Deep learning algorithms could accurately predict the clinical negativity of axillary lymph node metastases by utilizing images of initial breast cancer patients. This method provides an earlier diagnostic technique for axillary lymph node metastases in patients with medically negative changes in axillary lymph nodes.

Anticancer effect of selenium/chitosan/polyethylene glycol/allyl isothiocyanate nanocomposites against diethylnitrosamine-induced liver cancer in rats.

Background: Nano-based drug delivery systems have shown several advantages in cancer treatment like specific targeting of cancer cells, good pharmacokinetics, and lesser adverse effects. Liver cancer is a fifth most common cancer and third leading cause of cancer-related mortalities worldwide. Objective: The present study focusses to formulate the selenium (S)/chitosan (C)/polyethylene glycol (Pg)/allyl isothiocyanate (AI) nanocomposites (SCPg-AI-NCs) and assess its therapeutic properties against the diethylnitrosamine (DEN)-induced liver cancer in rats via inhibition of oxidative stress and tumor markers. Methodology: The SCPg-AI-NCs were synthesized by ionic gelation technique and characterized by various characterization techniques. The liver cancer was induced to the rats by injecting a DEN (200 mg/kg) on the 8th day of experiment. Then DEN-induced rats treated with 10 mg/kg of formulated SCPg-AI-NCs an hour before DEN administration for 16 weeks. The 8-hydroxy-2' -deoxyguanosine (8-OHdG) content, albumin, globulin, and total protein were examined by standard methods. The level of glutathione (GSH), vitamin-C & -E, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were examined using assay kits. The liver marker enzymes i.e., alanine transaminase (ALT), aspartate tansaminase (AST), γ-glutamyl transaminase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), Bax, and Bcl-2 levels, and caspase-3&9 activities was examined using assay kits and the liver histopathology was assessed microscopically by hematoxylin and eosin staining method. The effect of formulated SCPg-AI-NCs on the viability and apoptotic cell death on the HepG2 cells were examined using MTT and dual staining assays, respectively. Results: The results of different characterization studies demonstrated the formation of SCPg-AI-NCs with tetragonal shape, narrowed distribution, and size ranging from 390 to 450 nm. The formulated SCPg-AI-NCs treated liver cancer rats indicated the reduced levels of 8-OHdG, albumin, globulin, and total protein. The SCPg-AI-NCs treatment appreciably improved the GSH, vitamin-C & -E contents, and SOD, CAT, GPx, and GR activities in the serum of liver cancer rats. The SCPg-AI-NCs treatment remarkably reduced the liver marker enzyme activities in the DEN-induced rats. The SCPg-AI-NCs treatment decreased the AFP and CEA contents and enhanced the Bax and caspase 3&9 activities in the DEN-induced rats. The SCPg-AI-NCs effectively decreased the cell viability and induced apoptosis in the HepG2 cells. Conclusion: The present findings suggested that the formulated SCPg-AI-NCs remarkably inhibited the DEN-induced liver carcinogenesis in rats. These findings provide an evidence that SCPg-AI-NCs can be a promising anticancer nano-drug in the future to treat the liver carcinogenesis.

Biological Activities of Some Natural Compounds and Their Cytotoxicity Studies against Breast and Prostate Cancer Cell Lines and Anti-COVID19 Studies.

In this study, we investigated the inhibition effects of matairesinol, pregnanolone, hamamelitannin, secoisolariciresinol, and secoisolariciresinol diglicoside compounds on HMG-CoA reductase and urease enzymes. We have obtained results for the HMG-CoA reductase enzyme at the millimolar level, and for the urease enzyme at the micromolar level. Molecular docking calculations were made for their biological activities were compared. In docking calculations, proteins of experimentally used enzymes, activities of SARS-CoV-2 virus against RNA-dependent RNA polymerase (RdRp) protein, and anti-oxidant protein were compared. Then, ADME/T calculations were made to use the molecules as drugs. Cytotoxicity potential of these complexes against human breast and prostate cancers demonstrated that these compounds had good cytotoxic effects. There is growing attention to phenolic molecules and their presumed role in avoiding diverse degenerative diseases, such as cardiovascular and cancer diseases.

Loss of TIPE3 reduced the proliferation, survival and migration of lung cancer cells through inactivation of Akt/mTOR, NF-κB, and STAT-3 signaling cascades.

Lung cancer is the foremost cause of cancer related mortality among men and one of the most fatal cancers among women. Notably, the 5-year survival rate of lung cancer is very low; 5% in developing countries. This low survival rate can be attributed to factors like late stage diagnosis, rapid postoperative recurrences in the patients undergoing treatment and development of chemoresistance against different agents used for treating lung cancer. Therefore, in this study we evaluated the potential of a recently identified protein namely TIPE3 which is known as a transfer protein of lipid second messengers as a lung cancer biomarker. TIPE3 was found to be significantly upregulated in lung cancer tissues indicating its role in the positive regulation of lung cancer. Supporting this finding, knockout of TIPE3 was also found to reduce the proliferation, survival and migration of lung cancer cells and arrested the G2 phase of cell cycle through inactivation of Akt/mTOR, NF-κB, STAT-3 signaling. It is well evinced that tobacco is the major risk factor of lung cancer which affects both males and females. Therefore, this study also evaluated the involvement of TIPE3 in tobacco mediated lung carcinogenesis. Notably, this study shows for the first time that TIPE3 positively regulates tobacco induced proliferation, survival and migration of lung cancer through modulation of Akt/mTOR signaling. Thus, TIPE3 plays critical role in the pathogenesis of lung cancer and hence it can be specifically targeted to develop novel therapeutic strategies.

Spectral and structure characterization of Ferula assafoetida fabricated silver nanoparticles and evaluation of its cytotoxic, and photocatalytic competence.

This study aims to develop an eco-friendly method for rapidly synthesizing silver nanoparticles (AgNPs) using Asafoetida ethanol extracts and to validate AgNPs synthesis using UV-vis spectroscopy (absorption spectrum), FTIR (functional groups), XRD (crystallinity), FE-SEM (size of the particles) and SEM-EDAX (Purity). Furthermore, to evaluate the anti-proliferative effect of Ag NPs against grown cultured L6 cell lines, studies have shown that AgNPs biosynthesis inhibits cancer cell growth compared to control cell lines. UV-vis absorption verified the existence of Ag NPs, and the spectrum was observed at 480 nm. Functional groups are present in the synthesized Ag NPs were shifted on 528.48 cm-1 confirmed using an FT-IR spectrum. Consequently, anti-cancer efficacy observed the IC50 value of As Ag NPs against L6 cells was 1.0 µg/mL for 48 h. Finally, using a halogen lamp, studies explored the photocatalytic degradation of AgNPs against the methylene blue radioactive dye and achieved a 96 percent degradation rate in 90 min. Asafoetida mediated silver nanoparticles show grater photodegradation for methylene blue dye, which is present in textile industries, when exposed to solar light, and it has a wide range of potential applications in wastewater treatment. As a whole, biosynthesized silver nanoparticles showed excellent cytotoxic, antioxidant, and photocatalytic dye degradation effects.

Lung cancer induced by Benzo(A)Pyrene: ChemoProtective effect of sinapic acid in swiss albino mice.

Cancer of lung is the utmost typical cause of death and the number of cases is increasing rapidly, which has emerged as a major leading health problem. A large amount of reports suggested that Benzo(a)pyrene [B(a)P] in cigarette smoke plays the major function in an initiation of cancer of lung. Cancer prevention or chemoprevention has become a compelling approach recently for treatment of lung cancer. So, discovering a fresh candidate with reduced toxicity for targeting lung cancer is vital and urgent. Sinapic acid which is a widely extracted in various vegetables and fruit exhibits rich anti-oxidant content, anti-inflammatory and anti-tumor activity. But, the chemopreventive action of sinapic acid against lung cancer initiated by B[a]P remain unclear. Following, an in-vivo B[a]P-stimulated lung cancer in swiss albino mice and an in-vitro human lung cancer cell (A549) model were established to examine the chemopreventive activities of sinapic acid. The levels of immunoglobulins (IgG and IgM), oxidative and inflammatory markers, and tumor markers level was studied using kits and standard methods. The results showed administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice by a decline in IgG and IgM level, leukocyte count, neutrophil function tests, soluble immune complex, lipid peroxidation, pro-inflammatory cytokines, tumor markers (AHH, LDH, GGT, 5'NT and CEA) and enhanced phagocytic index, activity index and antioxidant defense enzymes. In addition, in-vitro studies showed potential cytotoxicity against human lung cancer and exhibited a potential cytotoxic (MTT assay) and apoptotic activity by elevation of ROS production and caspase activity (caspase-3 and caspase-9). Collectively, the results, clearly specifies sinapic acid can be utilized as an effective chemo preventative agent against lung carcinogenesis.

Tris(dibenzylideneacetone)dipalladium(0) (Tris DBA) Abrogates Tumor Progression in Hepatocellular Carcinoma and Multiple Myeloma Preclinical Models by Regulating the STAT3 Signaling Pathway.

STAT3 is an oncogenic transcription factor that controls the expression of genes associated with oncogenesis and malignant progression. Persistent activation of STAT3 is observed in human malignancies, including hepatocellular carcinoma (HCC) and multiple myeloma (MM). Here, we have investigated the action of Tris(dibenzylideneacetone) dipalladium 0 (Tris DBA) on STAT3 signaling in HCC and MM cells. Tris DBA decreased cell viability, increased apoptosis, and inhibited IL-6 induced/constitutive activation of STAT3, JAK1, JAK2, and Src in HCC and MM cells. Tris DBA downmodulated the nuclear translocation of STAT3 and reduced its DNA binding ability. It upregulated the expression of SHP2 (protein and mRNA) to induce STAT3 dephosphorylation, and the inhibition of SHP2 reversed this effect. Tris DBA downregulated the expression of STAT3-driven genes, suppressed cell migration/invasion. Tris DBA significantly inhibited tumor growth in xenograft MM and orthotopic HCC preclinical mice models with a reduction in the expression of various prosurvival biomarkers in MM tumor tissues without displaying significant toxicity. Overall, Tris DBA functions as a good inhibitor of STAT3 signaling in preclinical HCC and MM models.

Diosgenin attenuates tumor growth and metastasis in transgenic prostate cancer mouse model by negatively regulating both NF-κB/STAT3 signaling cascades.

Prostate cancer (PCa) is a common disease among men especially in the old age. The deregulated activation of oncogenic and pro-survival transcription factors has been linked with tumor progression in PCa patients. The consequence of diosgenin treatment on NF-κB/STAT3 activation in PCa cells as well as transgenic mouse model was determined. We also validated the hypothesis of targeting these transcription factors using in silico proteomics simulation model. Diosgenin abrogated NF-κB/STAT3 activation and this action was caused as a result of suppression of protein kinases and reporter gene activity that led to a substantial reduction in the expression of various tumorigenic gene products. In vivo, diosgenin (2% w/w) when mixed in diet and fed to mice abrogated tumor progression in transgenic mice. Diosgenin was also detected in serum and was well absorbed orally. Overall, our data highlights the promising efficacy of diosgenin in PCa therapy.

Hepatoprotective potential of kirenol on ethanol-induced liver toxicity in albino rats and acetaminophen-induced oxidative stress-mediated apoptosis in hepatic HepG2 cells.

Liver diseases are a major health issue in both men and women and cause significant mortality worldwide. The hepatoprotective effects of kirenol were evaluated in acetaminophen (APAP)-induced toxicity in HepG2 cells and ethanol (EtOH)- induced hepatotoxicity in rats. The cytotoxicity of kirenol (IC50 , 25 µM/ml) and APAP (20 µg/ml) with sylimarin (IC50 , 15 µg/ml) was observed in HepG2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, reactive oxygen species formation, mitochondrial membrane potential, and oxidative stress markers such as thiobarbituric acid-reactive substance, suproxide dismutase, and catalase were assayed. Rats were administered a different dose (10, 20, and 30 mg/kg/day) for a period of 4 weeks before a single dose of EtOH (40% vol/vol) 3 g/kg/day. EtOH administered rats appeared to have lower body weight gain, severe hepatic and kidney damage as proved by elevated aspartate transaminase, alanine transaminase, alkaline phosphatase, uric acid, increased malondialdehyde (MDA), and inflammatory markers, and reduced glutathione (GSH) levels. Results showed that the kirenol treatment enhanced the GSH and reduced MDA in the liver and renal tissues and restored TNF-α and IL-6. Histoanalysis proved the protective effects of kirenol. In conclusion, it was proved that the kirenol demonstrated a hepato-protective effect in APAP- and EtOH-induced liver toxicity in HepG2 cells and rats, respectively.

Phyllanthin inhibits MOLT-4 leukemic cancer cell growth and induces apoptosis through the inhibition of AKT and JNK signaling pathway.

Among cancers, leukemia is a multistep progression that involves genetic modifications of normal hematopoietic progenitor cells to cancerous cells. In recent times, leukemia cases and their mortality rate have increased rapidly. Therefore, the immense need for a therapeutic approach is crucial that can control this type of cancer. Phyllanthin is a lignan compound constituent from the Phyllanthus species and has numerous beneficial effects as a dietary component. The present study aims to determine the impact of phyllanthin on the MOLT-4 cytotoxic effect. MOLT-4 cells and MS-5 cells were cultured at different concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 µM/ml), and the viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The level of reactive oxygen species, the membrane potential of mitochondria, apoptosis by 2',7'-dichlorofluorescin-diacetate (DCF-DA), rhodamine, acridine orange (AO)/ethidium bromide (EB), 4',6-diamidino-2-phenylindole (DAPI)/propidium iodide (PI) staining, gene expression of signaling molecules, and protein levels were assessed by reverse-transcription polymerase chain reaction and western blot analysis. Phyllanthin did not show toxicity toward MS-5 cells and significantly decreased the cell viability of MOLT-4 cells with an IC50 value of 25 µM/ml. Also, phyllanthin induced the production of reactive oxygen species and led to the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, antiapoptotic gene Bcl-2, NF-κB, and TNF-α decreased, but the proapoptotic Bax mRNA expression was increased. The phosphorylated protein levels of p-PI3K1/2, p-ERK1/2, and p-AKT were decreased, whereas the levels of p-p38 and p-JNKT1/2 increased. Our results confirmed that phyllanthin inhibits the MOLT-4 cells, increases apoptosis, and inhibits MOLT-4 migration and cell invasion. Therefore, phyllanthin can be used as a potential target for leukemia treatment.

Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells.

Liver cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver cancer often initiates as fibrosis, develops as cirrhosis, and results in cancer. For centuries, medicinal plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.