Innovative spectrofluorometric method for determination of harmaline and harmine in different matrices.

Harmaline and harmine are naturally occurring closely related ß-carboline alkaloids found in Peganum and Banisteriopsis plants. They have historical significance in traditional practices due to their potential psychoactive and therapeutic properties. Herein, a highly sensitive spectrofluorometric method was developed for the quantifying of harmaline and harmine in diverse matrices, including pure forms, seed samples, and spiked plasma. The procedures lie in addressing the challenge of overlapping fluorescence spectra exhibited by harmaline and harmine through the incorporation of hydroxypropyl-ß-cyclodextrin, altering their chemical properties and fluorescence characteristics. Synchronous fluorescence measurements coupled with first derivative mathematical technique make it possible to distinguish between the harmaline and harmine at 419 and 456 nm, respectively. The method effectiveness is demonstrated through spectral analysis, optimization of the measurement conditions, adopting validation parameters and application to the pure form, seed samples and spiked human plasma. This methodology facilitates accurate determination of these alkaloids over the concentration range of 10─200 ng/mL. Thus, the developed approach provides a robust mean for the precise determination of harmaline and harmine, contributing to analytical chemistry's ongoing efforts to address complex challenges in quantification across diverse matrices.

Antioxidant, cytotoxic and apoptotic activities of the rhizome of Zingiber zerumbet Linn. in Ehrlich ascites carcinoma bearing Swiss albino mice.

Due to having a long history of traditional uses as a functional food, Zingiber zerumbet was selected here to explore the inherent antioxidant and antineoplastic activities of methanolic extract of its rhizome (MEZZR) against Ehrlich ascites carcinoma (EAC) cells. The rich polyphenol containing MEZZR showed a marked DPPH, ABTS, nitric oxide radicals and lipid peroxidation inhibition activity with an IC50 of 3.43 ± 1.25, 11.38 ± 1.39, 23.12 ± 3.39 and 16.47 ± 1.47 µg/ml, respectively, when compared to the standard catechin. In vivo, MEZZR significantly inhibited EAC cell growth, decreased body weight gain, increased life span and restored the altered hematological characteristics of EAC-bearing mice. Moreover, MEZZR induced nuclear condensation and fragmentation, which are notable features of apoptosis as observed by fluorescence microscopy after staining EAC cells of MEZZR-treated mice with Hoechst 33342. Additionally, in vitro, the cell growth inhibition caused by the MEZZR in MTT assay, was remarkably decreased in the presence of caspase-3, -8 and -9 inhibitors. This study thus suggests that MEZZR may possess promising antiproliferative efficacy against EAC cells by inducing cell apoptosis.

Functional microbiome strategies for the bioremediation of petroleum-hydrocarbon and heavy metal contaminated soils: A review.

Petroleum hydrocarbons and heavy metals are the two major soil contaminants that are released into the environment in the forms of industrial effluents. These contaminants exert serious impacts on human health and the sustainability of the environment. In this context, remediation of these pollutants via a biological approach can be effective, low-cost, and eco-friendly approach. The implementation of microorganisms and metagenomics are regarded as the advanced solution for remediating such pollutants. Further, microbiomes can overcome this issue via adopting specific structural, functional and metabolic pathways involved in the microbial community to degrade these pollutants. Genomic sequencing and library can effectively channelize the degradation of these pollutants via microbiomes. Nevertheless, more advanced technology and reliable strategies are required to develop. The present review provides insights into the role of microbiomes to effectively remediate/degrade petroleum hydrocarbons and heavy metals in contaminated soil. The possible degradation mechanisms of these pollutants have also been discussed in detail along with their existing limitations. Finally, prospects of the bioremediation strategies using microbiomes are discussed.

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

INTRODUCTION: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance. METHODS: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities. RESULTS: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites. DISCUSSION: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.

Effects of sequential ethanol exposure and repeated high-dose methamphetamine on striatal and hippocampal dopamine, serotonin and glutamate tissue content in Wistar rats.

Alcohol (ethanol) and methamphetamine (METH) co-abuse is a major public health issue. Ethanol or METH exposure has been associated with changes in neurotransmitter levels in several central brain regions. However, little is known about the effect of sequential exposure to ethanol and METH on glutamate, dopamine and serotonin tissue content in striatum and hippocampus. In this study, we investigated the effects of sequential exposure to ethanol and METH on tissue content of these neurotransmitters. Male Wistar rats were orally gavaged with either ethanol (6g/kg) or water for seven days. Rats were administered with high dose of METH (10mg/kg, i.p. every 2h×4) or saline on Day 8 and euthanized 48h of last METH or saline i.p. injection. In the striatum, sequential exposure to ethanol and METH increased glutamate tissue content while reducing dopamine and serotonin tissue content as compared to the group exposed to ethanol alone. In the hippocampus, sequential exposure to ethanol and METH decreased serotonin tissue content as compared to the group that was exposed to ethanol alone. However, this study showed that ethanol has no additive effect to METH on tissue content of dopamine and serotonin as compared to METH in the striatum and hippocampus. This study demonstrated that sequential exposure of ethanol and METH has an additive effect on tissue content of certain neurotransmitters in the brain.

Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on tissue content of dopamine and serotonin as well as glutamate and glutamine.

Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a ß-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every 2h×4) followed by either saline or CEF (200mg/kg, i.p, every day×3) post-treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc and PFC. Importantly, dopamine tissue content was completely restored in the NAc following CEF post-treatment. Additionally, METH caused a significant decrease in glutamate and glutamine tissue content in PFC, and this effect was attenuated by CEF post-treatment. These findings demonstrate for the first time the attenuating effects of CEF post-treatment on METH induced alterations in the tissue contents of dopamine, glutamate, and glutamine.