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Journal Article
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.

Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum, El-Mekkawy, Sahar, Meselhy Meselhy R., Nakamura Norio, Tezuka Yasuhiro, Hattori Masao, Kakiuchi Nobuko, Shimotohno Kunitada, Kawahata Takuya, and Otake Toru , Phytochemistry, Volume 49, Issue 6, p.1651-1657, (1998) Abstract
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Anti-HIV-1 phorbol esters from the seeds of Croton tiglium, El-Mekkawy, Sahar, Meselhy Meselhy R., Nakamura Norio, Hattori Masao, Kawahata Takuya, and Otake Toru , Phytochemistry, Volume 53, Issue 4, p.457-464, (2000) Abstract
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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.

Anticonvulsant activity of paeonimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis, Abdel-Hafez, Atef A., Meselhy Meselhy R., Nakamura Norio, Hattori Masao, WATANABE Hiroshi, MURAKAMI Yukihisa, EL-GENDY Mahmoud A., MAHFOUZ Nadia M., and MOHAMED Tarek A. , Biological and Pharmaceutical Bulletin, Volume 22, Issue 5, p.491-497, (1999) Abstract
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Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng drugs in SK-N-SH cells, Tohda, Chihiro, Matsumoto Noriaki, Zou Kun, Meselhy Meselhy R., and Komatsu Katsuko , The Japanese Journal of Pharmacology, Volume 90, Issue 3, p.254-262, (2002) Abstract
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Aβ (25–35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins, Tohda, Chihiro, Matsumoto Noriaki, Zou Kun, Meselhy Meselhy R., and Komatsu Katsuko , Neuropsychopharmacology, Volume 29, Issue 5, p.860, (2004) Abstract
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