The current study focused on the antioxidant potential, α-amylase inhibitory activity, and hypoglycemic, hypolipidemic, and histoprotective (pancreas and kidney) effects of polyherbal emulsion on the alloxan-induced diabetic rats. Polyherbal formulations were prepared from extracts and oils of Nigella sativa (N. sativa), Citrullus colocynthis (C. colocynthis), and Silybum marianum (S. marianum). Out of nine stable formulations, one formulation named F6-SMONSECCE was found to be the best after its evaluation using antioxidant and in vitro α-amylase inhibition assay. The prepared herbal formulations showed significant (p < 0.05) antioxidant activity in terms of radical scavenging as 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assays and also revealed the presence of a significant amount of total phenolic and flavonoid contents. "F6- SMONSECCE" (prepared with composition; Silybum marianum oil (SMO) + Nigella sativa extract (NSE) + Citrullus colocynthis extract CCE) was selected for an in vivo trial to ascertain its antidiabetic potential. The treatment dose was determined by using an acute toxicity trial on rats. Administration of alloxan (150 mg/kg b.w., i.p.) significantly (P < 0.05) augmented the blood glucose levels and lipid contents as total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-c), and very-low-density lipoproteins (VLDL-c). However, the levels of insulin and high-density lipoproteins (HDL-c) were found to be decreased, and the histopathological alterations were also found in the pancreas and kidney. The administration of the polyherbal formulation (F6-SMONSECCE) significantly attenuated the blood glucose levels (22.94%), TC (29.10%), TG (38.15%), LDL-c (27.58%), and VLDL-c (71.52%), whereas on the other side, the insulin (-149.15%) and HDL-c levels (-22.22%) were significantly increased. A significant histopathological normalization was observed in the pancreas and kidney tissues of the F6-SMONSECCE-treated rats. The current findings proposed that the prepared polyherbal formulation "F6-SMONSECCE" exhibited significant antioxidant, antilipidemic, and hypoglycemic potential and hence might be suggested as a remedy against diabetes or as a coadjuvant to synthetic medicines to maintain normal physiology.

Myocardial infarction is irreversible cardiac tissue necrosis due to the blockage of one of the arteries. It leads to an insufficient supply of oxygen and nutrients, creating muscular damage in the affected regions. In the present study, aqueous methanolic extract of Thymus linearis was prepared to evaluate its activity against ischemic stress due to free radical production. GC-MS analysis was performed to evaluate the phytochemicals present in the plant extract. A chemical database of 30 compounds was virtually screened against NF-κB, COX2, and MCL, where γ-cadinene, β-bisabolene, and β-caryophyllene were found to be the best interacting ligands. To systematically assess cardioprotective activity against ischemia, isoproterenol and doxorubicin were used to induce cardiotoxicity in rats. The prepared extract of T. linearis (100 mg/kg) was given daily to animals for 21 days before injecting isoproterenol (85 mg/kg of animal weight) subcutaneously in two doses on the 20th and 21st days. In the case of doxorubicin, cardiotoxicity was induced in rats by a single injection (15 mg/kg) on the seventh day, and the extract was given to animals for 10 consecutive days. Animals' blood samples were used to monitor cardiac, liver, and other marker enzymes, including LDH, CPK, and AST. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were also assayed in blood plasma to determine the degree of oxidative stress. H&E staining was performed to evaluate cardioprotection by plant extract, showing significant preventive effects in reducing cardiac injury induced by isoproterenol and doxorubicin.

Riboswitches are regulatory noncoding RNAs found in bacteria, fungi and plants, that modulate gene expressions through structural changes in response to ligand binding. Understanding how ligands interact with riboswitches in solution can shed light on the molecular mechanisms of this ancient regulators. Previous studies showed that riboswitches undergo global conformation changes in response to ligand binding to relay information. Here, we report conformation switching models of the recently discovered tetrahydrofolic acid-responsive second class of tetrahydrofolate (THF-II) riboswitches in response to ligand binding. Using a combination of selective 2′-hydroxyl acylation, analyzed by primer extension (SHAPE) assay, 3D modeling and small-angle X-ray scattering (SAXS), we found that the ligand specifically recognizes and reshapes the THF-II riboswitch loop regions, but does not affect the stability of the P3 helix. Our results show that the THF-II riboswitch undergoes only local conformation changes in response to ligand binding, rearranging the Loop1-P3-Loop2 region and rotating Loop1 from a ~120° angle to a ~75° angle. This distinct conformation changes suggest a unique regulatory mechanism of the THF-II riboswitch, previously unseen in other riboswitches. Our findings may contribute to the fields of RNA sensors and drug design.

The design and development of fluorescent materials for detecting cancer-related enzymes are crucial for cancer diagnosis and treatment. Herein, we present a substituted rhodamine derivative for the chromogenic and fluorogenic detection of the cancer-relevant enzyme γ-glutamyltranspeptidase (GGT). Initially, the probe is non-chromic and non-emissive due to its spirolactam form, which hinders extensive electronic delocalization over broader pathway. However, selective enzymatic cleavage of the side-coupled group triggers spirolactam ring opening, resulting in electronic flow across the rhodamine skeleton, and reduces the band gap for low-energy electronic transitions. This transformation turns the reaction mixture from colorless to intense pink, with prominent UV and fluorescence bands. The sensor’s selectivity was tested against various human enzymes, including urease, alkaline phosphatase, acetylcholinesterase, tyrosinase, and cyclooxygenase, and showed no response. Absorption and fluorescence titration analyses of the probe upon incremental addition of GGT into the probe solution revealed a consistent increase in both absorption and emission spectra, along with intensified pink coloration. The cellular toxicity of the receptor was evaluated using the MTT assay, and bioimaging analysis was performed on BHK-21 cells, which produced bright red fluorescence, demonstrating the probe’s excellent cell penetration and digestion capabilities for intracellular analytical detection. Molecular docking results supported the fact that probe-4 made stable interactions with the GGT active site residues.