Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TaxonomyFunctional Disorder, Traditional Medicine, Herbal Medicine

Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 μg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 μM and melphalan at CC50 = 36.3 μM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 μg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera’s potential as an affordable source of therapeutic agents for a range of oral malignancies

A Single DC Source Nine-Level Switched-Capacitor Boost Inverter Topology with Reduced Switch Count

This paper presents a new boost inverter topology with nine level output voltage waveform using a single dc source and two switched capacitors. The capacitor voltages are self-balancing and thus is devoid of any sensors and auxiliary circuitry. The output voltage is twice higher than the input voltage, which eliminates the need for an input dc boost converter especially when the inverter is powered from a renewable source. The merits of the proposed topology in terms of the number of devices and cost are highlighted by comparing the recent and conventional inverter topologies. In addition to this, the total voltage stress of the proposed topology is lower and have a maximum efficiency of 98.25%. The operation and dynamic performance of the proposed topology have been simulated using PLECS software and are validated using an experimental setup considering a different dynamic operation.This work was supported in part by the Scientific Research Deanship, Taif University, Saudi Arabia, under Grant 1-439 - 6072.Scopu

Computational investigation of the structure and antioxidant activity of some pyrazole and pyrazolone derivatives

Pyrazoles and pyrazolones constitute a group of organic compounds that have various medical applications such as antimicrobial, antipyretic, anti-inflammatory, antitumor and antioxidants. Pyrazolones can exist in different isomeric forms (CH, NH, OH) due to keto-enol, lactam-lactim and imine-enamine tautomerism. Determination of the most stable tautomeric form is thus important for understanding their biological roles at the molecular level. We performed a theoretical investigation of the structural and antioxidant properties of three synthetic pyrazolones (1–3), one synthetic pyrazole (4), one natural pyrazole (5) and two engineered hydroxyl derivatives of 1 (7, 8) and of 5 (9, 10) using the density functional theory at the B3LYP/6-311++G(d,p) level of theory in gas phase and in methanol (using the polarizable continuum model). It is found that substituents and solvents may influence the relative stability of pyrazolone isomers and that the CH tautomer is typically the least stable. Vertical ionization potentials, vertical electron affinities and X–H bond dissociation energies (X = C, N, O, S) are calculated for the global minimum structures and compared with those of the standard antioxidant flavonoid quercetin (6). Calculations predict that compounds 1 and 5 have antioxidant activity similar to 6 and that their mono and dihydroxyl derivatives (7–10) are more efficient antioxidants. Results also indicate that compounds 1–10 preferably interact with free radicals adopting the H atom transfer rather than the sequential electron transfer proton transfer mechanism. The study gives insight into the structural requirements for the design of highly efficient antioxidants. Keywords: Pyrazoles, Pyrazolones, Natural pyrazole, Tautomerism, DFT calculations, Antioxidants, Structural desig

Control of a Stand-Alone Variable Speed Wind Energy Supply System †

applied science

Real-time mode of operation data analysis to catch the thread-tip denotes the failure cause of the grid-tie PV central inverter

Abstract The inverter is considered the core of the PV power plant. The inverter’s failure leads to generation loss and decreases plant availability. So, it is required to investigate a clear Root Cause Analysis (RCA) to deduce the failure causes and implement the required corrective action in addition to the preventive action to avoid more inverter failure, hereby maintaining the plant available to a certain value. This paper discusses real-time mode operation data analysis of the PV grid-connected inverter due to real central inverter incidents in Benban solar park located in Egypt.The central inverter plays an important role in the Mega-Scale PV power plant. The main function of this inverter is to convert the DC power produced by the PV modules to AC power to be injected into the utility grid by considering specific characteristics based on the grid code. The availability of any PV power plant directly depends on the healthy inverter’s operation. The more increases for the installed inverters, the less availability loss in the case of inverter partial or catastrophic failures. So, it is required to focus on the failure causes of the central inverter by implementing a technical analysis using the available operational data. The monitored data of the central inverter in the PV power plant is classified into two types. The first type is the continuous time data stored in the memory. It represents the waveforms of inverter outputs like voltage, current, frequency, …. etc. Unfortunately, in case of a catastrophic failure, the central inverter is completely charred, and the continuous time data is lost due to storage memory damage. The second type is the operation data that is recorded by the SCADA system (per one-minute interval). Hereby, the operation data is the sole data in the case of the completely charred inverter. The representation of the operational data in curves indicates symptoms that can be used for the RCA processes. The investigation outcomes include three results. The first result is detecting the signature of the IGBT thermal stress on the voltage balance of the DC link capacitor. The second result is verifying a scenario for the cause of the IGBT failure by implementing a technical mathematical model based on the detected symptoms that denote the fault signature which is considered the thread-tip for detecting the failure cause. The third result is the simulating scenario for the interpretation of a DC link capacitors explosion due to the short circuit fault that occurred due to IGBT failure. The investigation in this paper is performed based on operation data analysis of the PV grid-connected inverter (central type) due to a real incident. The analysis methodology is based on mathematical calculation for the IGBT junction temperature using the measured heatsink temperature. The study concludes that after the IGBT failure occurred, it was a short circuit for a while and closed the terminals of the DC link capacitors. So, the DC link capacitors exploded and produced heavy sparks that led to enough fire to burn the inverter container completely

Common-Ground Photovoltaic Inverters for Leakage Current Mitigation: Comparative Review

In photovoltaic systems, parasitic capacitance is often formed between PV panels and the ground. Because of the switching nature of PV converters, a high-frequency voltage is usually generated over these parasitic capacitances; this, in turn, can result in a common-mode current known as leakage current. This current can badly reach a high value if a resonance circuit is excited through the PV’s parasitic capacitance and the converter’s inductive components. Transformers are usually used for leakage current mitigation. However, this decreases the efficiency and increases the cost, size, and weight of the PV systems. Number of strategies have been introduced to mitigate the leakage current in transformer-less converters. Among these strategies, using common-ground converters is considered the most effective solution as it offers a solid connection between the negative terminal of PV modules and the neutral of the grid side; thus, complete mitigation of the leakage current is achieved. Number of common-ground inverters have been recently presented. These inverters are different in their size, cost, boosting capability, the possibility of producing DC currents, and their capability to offer multilevel shaping of output voltage. This work introduces a comprehensive review and classification for various common-ground PV inverters. Therefore, a clear picture of the advantages and disadvantages of these inverters is clarified. This provides a useful indication for a trade-off between gaining some of the advantages and losing others in PV systems. In addition, the potentials for optimization based on different performance indicators are identified

Structures of Two New Flavonoids and Effects of Licorice Phenolics on Vancomycin-Resistant Enterococcus Species

Since our previous study revealed that several licorice phenolics have antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA), and suppressive effects on the oxacillin resistance of MRSA, we further investigated effectiveness of licorice constituents on vancomycin-resistant Enterococcus (VRE) bacteria, and purified 32 phenolic compounds. Two flavonoids among them were characterized structurally, and identified their structures as demethylglycyrol (31) and 5,7-di-O-methylluteone (32), respectively. Examination of antibacterial effects of licorice phenolics showed that 3-arylcoumarins such as licoarylcoumarin (9) and glycycoumarin (26), and 2-arylcoumarones such as gancaonin I (17), have moderate to potent antibacterial effects on the VRE strains used in this study