Sulforaphane protects against LPS-induced liver injury in mice by antagonizing oxidative stress and apoptosis through AMPK activation.

Objectives: Given the adverse effect of liver injury on a multitude of body functions, it is vital to understand its underlying mechanism and how to overcome it. In this study, lipopolysaccharide (LPS) was used to induce liver injury, while sulforaphane (SFN), a natural phytochemical, was used as the antagonist to overcome the deleterious effect. Methods: Twenty-four mice were divided into three groups: Control group (0.9% saline), LPS induction group (0.75 mg/kg), and SFN treatment (25 mg/kg) followed by LPS induction group (0.75 mg/kg), all with access to food and water ad libitum. Blood samples from retro-orbital sinus were used to measure liver function through two aminotransferases (i.e., alanine transaminase [ALT] and aspartate transaminase [AST]) whereas liver homogenate was used to measure glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) (antioxidant activity markers); caspase-3 (apoptosis marker); malondialdehyde (MDA) (lipid peroxidation marker); and NO. AMP-activated protein kinase (AMPK), a cellular energy homeostasis and lipid metabolism sensor, was also measured. Statistical analysis including normalization, analysis of variance, Kruskal-Wallis test, and significance of P < 0.05 were applied to all collected data. Results: SFN treatment significantly attenuated all tests compared to the induced liver injury by LPS where significant reduction was observed in the levels of hepatic function markers (AST and ALT), lipid peroxidation marker (MDA) as well as apoptosis marker (caspase-3) whereas a marked increase was observed for antioxidant activity markers (SOD, CAT, and GSH) and AMPK. Conclusion: These results indicate the protective effect of SFN as it re-instated the levels of antioxidation while decreasing the level of the biomarkers, which were significantly increased during liver injury induction by LPS.

Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.

BACKGROUND: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally. OBJECTIVE: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers. METHODS: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1ß (IL-1ß), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets. RESULTS: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1ß, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol. CONCLUSION: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

6-Shogaol improves sorafenib efficacy in colorectal cancer cells by modulating its cellular accumulation and metabolism.

Carcinoma of the colon and rectum, also known as colorectal cancer, ranks as the third most frequently diagnosed malignancy globally. Sorafenib exhibits broad-spectrum antitumor activity against Raf, VEGF, and PDGF pathways in hepatocellular, thyroid, and renal cancers, but faces resistance in colorectal malignancies. 6-Shogaol, a prominent natural compound found in Zingiberaceae, exhibits antioxidant, anti-inflammatory, anticancer, and antiemetic properties. We investigated the influence of 6-shogaol on sorafenib's cytotoxic profile against colorectal cancer cell lines (HT-29, HCT-116, CaCo-2, and LS174T) through its effects on cellular accumulation and metabolism. Cytotoxicity was assessed using the sulpharodamine B assay, caspase-3 and c-PARP cleavage, cell cycle distribution analysis, and P-gp efflux activity. 6-Shogoal showed considerable cytotoxicity with decreased IC50 in colorectal cancer cell lines. Combining sorafenib and 6-shogaol increased c-PARP and pro-caspase-3 concentrations in HCT-116 cells compared to sorafenib alone. In combination, pro-caspase-3 concentrations were decreased in CaCo-2 cells compared to alone. Sorafenib combinations with 6-shogaol showed a significant drop in cell cycle distribution from 16.96±1.10 % to 9.16±1.85 %, respectively. At 100 µM, sorafenib and 6-shogaol showed potent and significant activity with intra-cellular rhodamine concentration on P-gp efflux activity in CRC cell lines. In conclusion, 6-shogaol substantially improved the cytotoxic profile of sorafenib by affecting its cellular uptake and metabolism. Future research should focus on dosage optimization and formulation and evaluate the efficacy and safety of the combination in animal models with colorectal cancer.

In vivo and computational investigation of butin against alloxan-induced diabetes via biochemical, histopathological, and molecular interactions.

Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1ß, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of - 7.4, - 6.5, and - 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.