Cytotoxicity, genotoxicity, and gene expression changes induced by methanolic extract of Moringa stenopetala leaf with LC-qTOF-MS metabolic profile, El-Mekkawy, Sahar, Hassan Amal Z., Abdelhafez Mohamed A., Mahmoud Khaled, Mahrous Karima F., Meselhy Meselhy R., Sendker Jandirk, and Abdel-Sattar Essam , Toxicon, Volume 203, p.40–50, (2021) Abstract
Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate, Kohyama, Aki, Kim Min Jo, Yokoyama Rei, Sun Sijia, Omar Ashraf M., Phan Nguyen Duy, Meselhy Meselhy R., Tsuge Kiyoshi, Awale Suresh, and Matsuya Yuji , Bioorganic & medicinal chemistry, p.116563, (2021) Abstract
Chitosan-Coated PLGA Nanoparticles Loaded with Peganum harmala Alkaloids with Promising Antibacterial and Wound Healing Activities, Azzazy, Hassan Mohamed El-Said, Fahmy Sherif Ashraf, Mahdy Noha Khalil, Meselhy Meselhy Ragab, and Bakowsky Udo , Nanomaterials, Volume 11, Number 9, p.2438, (2021) Abstract
The efficacy of Origanum majorana nanocubosomal systems in ameliorating submandibular salivary gland alterations in streptozotocin-induced diabetic rats, Farag, Dina B. E., Yousry Carol, Al-mahallawi Abdulaziz Mohsen, El-Askary Hesham I., Meselhy Meselhy R., and AbuBakr Nermeen , Drug Delivery, Volume 29, Number 1, p.62–74, (2022) Abstract
Evaluation of the Anti-inflammatory and Antioxidant Activities of Selected Resin Exudates, Ali, Dalia E., Abdelrahman Rehab S., Gedaily Rania El A., Ezzat Shahira M., Meselhy Meselhy R., and Abdel-Sattar Essam , Tropical Journal of Natural Product Research, Volume 4, Issue 7, p.255-261, (2020)
Essential oil of cultivated in Egypt: seasonal variation in chemical composition and anticholinesterase activity., Madi, Yasmine F., Choucry Mouchira A., Meselhy Meselhy R., and El-Kashoury El-Sayeda A. , Natural product research, p.1-5, (2020) Abstract

The yield of essential oil obtained by hydrodistillation of fresh leaves ranged from 0.15% to 0.46% w/w; being the highest in spring and the lowest in winter. The oil sample obtained in winter exhibited a moderate acetylcholinesterase inhibitory activity (IC 2.86 ± 0.17 mg/mL), compared to physostigmine (IC 0.012 mg/mL), while other samples were relatively weak (IC values of 2.86-5.40 mg/mL). In all samples, oxygenated monoterpenes were predominating (73.22-89.32%). GC-MS identified a total of 61, 25, 50 and 63 components in oil samples obtained in spring, summer, autumn and winter, respectively. Citral content was the highest in autumn and summer samples (82.02% and 80.01% citral; respectively) and the lowest in winter sample (60.01%). Citral, isolated from the oil demonstrated a relatively potent anticholinesterase activity (IC 0.21 ± 0.01 mg/mL).

UPLC-Orbitrap HRMS metabolic profiling of Cymbopogon citratus cultivated in Egypt; neuroprotective effect against AlCl-induced neurotoxicity in rats., Madi, Yasmine F., Choucry Mouchira A., El-Marasy Salma A., Meselhy Meselhy R., and El-Kashoury El-Sayeda A. , Journal of ethnopharmacology, Volume 259, p.112930, (2020) Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemongrass) is commonly used in teas, soups and treat inflammatory-based ailments, vascular and nervous disorders.

AIM OF THE STUDY: The study aimed to evaluate the neuroprotective effect of Cymbopogon citratus leaves through scientific protocol. The effect of aqueous (AE) and ethanolic (EE) extracts was evaluated against AlCl-induced Alzheimer's disease (AD) in rats. Metabolic profiling of the plant, isolation of bioactive compounds and standardization of the active fraction were investigated.

MATERIALS AND METHODS: AE of Cymbopogon citratus leaves was prepared as per traditional method (infusion), EE was prepared by repeated maceration in 90% ethanol, bioactive fraction (BAEE) was obtained from EE and the active compounds thereof were obtained by column chromatography. Metabolic profiling of Cymbopogon citratus was performed by UPLC-Orbitrap HRMS and HPLC was used for standardization. AlCl-induced Alzheimer's rats were used to assess neuroprotective effect of the extracts. Neuroprotective mechanism(s) of Cymbopogon citratus extracts was clarified through histopathological examination of brain tissues, estimation of AD biochemical markers, oxidative stress and neuroinflammation in brain homogenates. In addition, antioxidant (using DPPH assay) and anticholinesterase (using modified Ellman's method) activities were investigated.

RESULTS: AlCl-treated rats (17 mg/kg/day) showed histopathological alteration in brain tissues together with elevated levels of Aβ, tau proteins, MDA, NF-kB and IL-6. However, treatment with AE and EE of Cymbopogon citratus leaves prevented the pathological changes and maintained the levels of oxidative stress and inflammatory markers. In addition, BAEE significantly inhibited acetylcholinesterase enzyme (2.11 ± 0.11 mg/ml) and exhibited a strong antioxidant activity (24.99 ± 0.00 μg/ml). UPLC-MS of Cymbopogon citratus leaves showed peaks for twenty-eight compounds, twenty-one of them were identified. Three flavonoids; isoorientin, isoschaftoside and luteolin-7-O-neohesperidoside were isolated from BAEE as major constituents. The powdered leaves of Cymbopogon citratus was found to contain remarkable amounts of caffeic acid (3.49 mg/g dry wt.) and isoorientin (7.37 mg/g dry wt.) as determined by HPLC.

CONCLUSION: Cymbopogon citratus ethanolic extract attenuates AlCl-induced neurotoxicity in rats through inhibition of oxidative stress and inflammatory markers. This effect could possibly attributed, in part to its high content of phenolic acids and flavonoids. Accordingly, we recommend Cymbopogon citratus leaves for protection against AD.

Anti-inflammatory and antioxidant effects of Apium graveolens L. extracts mitigate against fatal acetaminophen-induced acute liver toxicity., Emad, Ayat M., Ali Sherifa F., Abdel-Rahman Engy A., Meselhy Meselhy R., Farag Mohamed A., Ali Sameh S., and Abdel-Sattar Essam A. , Journal of food biochemistry, p.e13399, (2020) Abstract

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC-MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hydroxyl radical quenching effect using electron paramagnetic resonance spin trapping technique. Treatment of Acetaminophen-induced hepatotoxicity (AAH) rats with MCRE lowered serum levels of AST, ALT, ALP, TNF-α, and IL-1β significantly. Additionally, MCRE significantly increased total antioxidant capacity (TAC) and glutathione (GSH) levels relative to AAH rats. Strikingly, Kaplan-Meier survival analysis of all groups revealed a 100% prevention of acetaminophen-induced mortality of rats by MCRE pretreatment (100 mg/kg/day). MCRE prevented AAH-associated severe weight loss and elicited normal behavior in the rescued rats. Our results suggest that pretreatment with MCRE can mitigate against overdosed acetaminophen-induced acute liver failure and warrant further investigations on the potential of postinjury intervention. PRACTICAL APPLICATIONS: Acetaminophen-induced hepatotoxicity (AAH) accounts for alerting numbers of overdose-related acute liver failure and liver transplant cases with increased morbidity and mortality rates. Currently proposed mechanisms implicate mitochondria-mediated oxidative stress and inflammation in the pathogenesis of AAH, which underline current interventions employing antioxidants to combat liver damage by over-dosed acetaminophen. The present work uncovers potent protective effects of some celery extracts (and their fractions) against acetaminophen-induced oxidative stress and inflammation. Treatment of rats with fatal liver injury with methanol extract of celery root significantly reduced secretion of liver enzymes and markedly decreased inflammatory as well as oxidative stress markers in these animals. This, in turn, rescued challenged rats exposed to fatal doses of acetaminophen completely, which establishes methanol extracts of celery roots as effective therapeutic intervention against AAH. The antioxidant capacity of the extracts was determined using EPR technique, and the secondary metabolites related to antioxidant activity were characterized via UPLC-MS.

UPLC-PDA-ESI/MS metabolic profiling of dill shoots bioactive fraction; evidence of its antioxidant and hepatoprotective effects in vitro and in vivo., Rasheed, Dalia M., Emad Ayat M., Ali Sherifa F., Ali Sameh S., Farag Mohamed A., Meselhy Meselhy R., and Sattar Essam A. , Journal of food biochemistry, p.e13741, (2021) Abstract

Hydroxyl radical ( OH) scavenging capacity of aqueous dill (Anethum graveolens L.) shoot (ADSh) extract was assessed using electron paramagnetic resonance (EPR) spectroscopy. ADSh extract (at concentrations of 0.5 and 10 mg/ml) exerted high (OH) radical scavenging power. ADSh extract was further fractionated on Diaion HP-20 column to yield five fractions. EPR spin-trapping assay revealed fraction 4 (eluted with 75% aq. MeOH) to possess ( OH) radical scavenging capacity over a concentration range (0.01-10 mg/ml), whereas fraction 2 (eluted with 25% aq. MeOH) appeared to be pro-oxidant at concentration 0.01 mg/ml. UPLC-PDA-ESI-MS metabolite profiling of ADSh extract revealed 87 metabolites, of which 64 compounds were identified in fraction 4, the most active fraction. Furthermore, ADSh extract demonstrated a hepatoprotective effect against acetaminophen (APAP)-induced hepatotoxicity in rats. Pretreatment of rats with ADSh extract (200 mg/kg b.wt) markedly attenuated the increased in the serum hepatic enzyme levels. It also increased free glutathione level and total antioxidant capacity in the serum of treated rats. [Correction added on May 3, 2021, after first online publication: "rates" has been changed to "rats" in the previous sentence.] Additionally, levels of (TNF-α and IL-1β) were back to almost normal levels compared to the control group. The above findings suggest that ADSh extract has a protective effect against APAP-induced liver damage.

Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities., Fahmy, Sherif Ashraf, Issa Marwa Y., Saleh Basma M., Meselhy Meselhy Ragab, and Azzazy Hassan Mohamed El-Said , ACS omega, Volume 6, Issue 18, p.11954-11963, (2021) Abstract

Amphiphilic macrocycles, such as -sulfonatocalix[6]arenes (-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from . seeds. Ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in -SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of -30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC values of HARF encapsulated in -SC6 (H/-SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC of the H/-SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of alkaloid-rich fraction into self-assembled -SC6 significantly increases its antioxidant and cytotoxic activities.