Fault Kinematics Along the Coastal Plain of South Louisiana: Implications for Tectono-Climatic-Induced Deformation Along a Passive Continental Margin

Kinematic analysis of faults along the northern coastal plain of the Gulf of Mexico shows a correlation between pulses of faulting during the late Cenozoic and changes in the tectonic and climatic settings acting on the source areas which provide sediments to the Gulf. Pulses of faulting during the Oligocene-Early Miocene, Late Miocene, Pliocene, and Pleistocene correlate to major tectonic and climatic changes in the source region of sediments. Slip rates of faulting increase with younger events. The increase in slip rates is likely related to a combination of increase in sedimentation rates and pre-weakened Oligocene –Miocene rock that resulted from earlier faulting activity. The observations in this study also suggest that during the Pliocene and Pleistocene, crustal failure accompanying lithospheric flexure better explains the reactivation of faults on the coastal plain

UPLC-HR-ESI-MS ANALYSIS AND ANTIPROLIFERATIVE AND ANTI-DIABESITY SCREENING OF FLOWERS, ROOTS, AND AERIAL PARTS OF SOLANUM ELAEAGNIFOLIUM

Objective: Solanum elaeagnifolium Cav. is an invasive summer-growing wild perennial herb but is traditionally used to treat some health conditions, including toothache and constipation. This study aimed to identify the chemical composition of various parts of this herb (flowers, roots, and aerial parts) and explore its biological properties. Methods: Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) was used for the first time for the root to analyze the hydro-alcoholic extract besides flowers and aerial parts of S. elaeagnifolium. Sulforhodamine B (SRB) assay was used to assess the antiproliferative effects of the same extracts on the colorectal cancer cell lines (CACO2, SW620, HT29, and HCT116). The aqueous extracts of the plant’s three parts were evaluated in vitro for their anti-diabesity properties. Results: For the first time, other compounds in three plant parts were identified using UPLC-MS: hyperoside and apigenin (flavonoids), in flowers and roots, naringin (flavonoid) in the roots, and apigenin (flavonoid) in aerial parts, diosgenin (steroids sapogenin) solamargine, and solasodine (alkaloids) in the three parts. In addition to the previously identified compounds; chlorogenic acid and kaempferol were in the aerial part, and flowers; and luteolin (flavonoids) were in the aerial parts. Pharmacologically, the aqueous extracts of flowers and roots proved anti-diabesity activity, and no anti-proliferative effect was detected for their hydro-alcoholic extracts. Neither anti-obesity nor anti-proliferative activities were detected in the aerial part extracts.  Conclusion: Further in-vivo and in-vitro investigations are required for the different parts of S. elaeagnifolium to explore more biological activities and evaluate the plant’s toxicity

Combinatorial Regimen of Carbamazepine and Imipramine Exhibits Synergism against Grandmal Epilepsy in Rats: Inhibition of Pro-Inflammatory Cytokines and PI3K/Akt/mTOR Signaling Pathway

Epilepsy is a neurodegenerative disorder that causes recurring seizures. Thirty-five percent of patients remain refractory, with a higher prevalence of depression. We investigated the anticonvulsant efficacy of carbamazepine (CBZ; 20 and 50 mg/kg), imipramine (IMI; 10 and 20 mg/kg) alone, and as a low dose combination. This preclinical investigation included dosing of rats for 14 days followed by elicitation of electroshock on the last day of treatment. Along with behavioral monitoring, the rat hippocampus was processed for quantification of mTOR, IL-1β, IL-6 and TNF-α levels. The histopathological analysis of rat hippocampus was performed to ascertain neuroprotection. In vitro studies and in silico studies were also conducted. We found that the low dose combinatorial therapy of CBZ (20 mg/kg) + IMI (10 mg/kg) exhibits synergism (p < 0.001) in abrogation of maximal electroshock (MES) induced convulsions/tonic hind limb extension (THLE), by reducing levels of pro-inflammatory cytokines, and weakening of the PI3K/Akt/mTOR signal. The combination also exhibits cooperative binding at the Akt. As far as neuroprotection is concerned, the said combination increased cell viability by 166.37% compared to Pentylenetetrazol (PTZ) treated HEK-293 cells. Thus, the combination of CBZ (20 mg/kg) + IMI (10 mg/kg) is a fruitful combination therapy to elevate seizure threshold and provide neuroprotection

Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitro and Computational Studies

Epilepsy is a chronic neurodegenerative disease characterized by multiple seizures, hereto 35% of patients remain poor responders. Phenytoin (PHT; 20 and 40 mg/kg) and thymoquinone (THQ; 40 and 80 mg/kg) were given alone and as a low dose combination for 14 days (p.o), prior to challenge with maximal electroshock (MES; 180 mA, 220 V, 0.2 s). Apart from observing convulsions, hippocampal mTOR, IL-1β, IL-6 and TNF-α levels were measured. Hippocampal histomorphological analysis was also conducted. In vitro cell line studies and molecular docking studies were run in parallel. The results revealed the synergistic potential of the novel duo-drug combination regimen: PHT (20 mg/kg) and THQ (40 mg/kg) against MES-induced convulsions. MES amplified signaling through mTOR, and inflated the levels of proinflammatory markers (IL-1β, IL-6 and TNF-α), which was significantly averted (p < 0.001) with the said drug combination. The computational studies revealed that PHT and THQ cooperatively bind the active site on Akt (upstream target of m-TOR) and establish a good network of intermolecular interactions, which indicates the sequential inhibition of PI3K/Akt/m-TOR signaling with the combination. The combination also increased cell viability by 242.81% compared to 85.66% viability from the the toxic control. The results suggest that the PHT and THQ in combination possesses excellent anticonvulsant and neuroprotective effects