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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.

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
Synthetic E-guggulsterone derivative GSD-1 inhibits NF-κB signaling and suppresses the metastatic potential of breast cancer cells., Abdellatef, Amira A., Zhou Yue, Yamada Akane, Elmekkawy Sahar A., Kohyama Aki, Yokoyama Satoru, Meselhy Meselhy R., Matsuya Yuji, Sakurai Hiroaki, and Hayakawa Yoshihiro , Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Volume 140, p.111737, (2021) Abstract

Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione], is the main active phytosterol constituent in guggul, the gum resin of Commiphora wightii (Arnott.) Bhand./Commiphora mukul Engl. tree, and is known for its medicinal effects. In this study, we report that GSD-1, a structurally-related synthetic GS derivative, strongly inhibits NF-κB activation induced by TNF-α. GSD-1 prevented the nuclear translocation of p65 through the blockade of IκBα degradation and p65 phosphorylation, and further inhibited the activation of upstream kinases, including transforming growth factor-β activated kinase 1 (TAK1), IκB kinase (IKK) α, and IKKβ. Furthermore, GSD-1 inhibited the cell-intrinsic activation of NF-κB, and exerted its direct anti-cancer and anti-metastatic effects in both murine and human breast cancer cell lines. This study demonstrated GSD-1 to be an attractive compound to target NF-κB activation that has potential for treating breast cancer growth and metastasis.

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.

Comparative Antioxidant Activities of Selected Apiaceous Plants, Emad, Ayat M., Ali Sherifa F., Meselhy Meselhy R., and Sattar Essam A. , Pharmacognosy Journal, Volume 11, Issue 6, p.1-6, (2019)
Neuroprotective effect of Salvia splendens extract and its constituents against AlCl3‑induced Alzheimer’s disease in rats, Salma Ahmed El‑Sawi, Shahira Mohamed Ezzat, Hanan Farouk Aly, Rana Merghany Merghany, and Meselhy Meselhy Ragab , Advances in Traditional Medicine, Volume Online version, (2019)
Chemical and biological study of Manilkara zapota (L.) Van Royen leaves (Sapotaceae) cultivated in Egypt, m Fayek, Nesrin, Monem Azza Abdel R., Mossa Mohamed Y., Meselhy Meselhy R., and Shazly Amani H. , Pharmacognosy research, Volume 4, Issue 2, p.85, (2012) Abstract
In vivo Antiviral Activity of Stephania cepharantha against Herpes Simplex Virus Type‐1, ari Nawawi, As', Nakamura Norio, Meselhy Meselhy R., Hattori Masao, Kurokawa Masahiko, Shiraki Kimiyasu, Kashiwaba Noriaki, and Ono Minoru , Phytotherapy research, Volume 15, Issue 6, p.497-500, (2001) Abstract
Pharmacokinetic study of paeoniflorin, paeonimetabolin-I and glycyrrhetic acid in humans after oral administration of paeony root, Glycyrrhiza and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang)., Bando, Miyuki, Shibahara Naotoshi, Shimada Yutaka, Meselhy Meselhy R., Akao Teruaki, Itoh Takashi, and Terasawa Katsutoshi , Journal of Traditional Medicines, Volume 17, Issue 1, p.26-33, (2000) Abstract
Conversion of aconitine to lipoaconitine by human intestinal bacteria and their antinociceptive effects in mice, Kawata, Yukio, Cho-mei MA, Nakamura Norio, WANG Hong, NAMBA Tsuneo, SATOH Kazuya, and KURAISHI Yasushi , 和漢医薬学雑誌= Journal of traditional medicines, Volume 16, Issue 1, p.15-23, (1999) Abstract
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
Disposition of paeoniflorin and paeonimetabolin I in rats after oral administration of Toki-Shakuyaku-San (TS) and Shakuyaku-Kanzo-To (SK), Meselhy, Meselhy R., Heikal Ola A., Akao Teruaki, KHOJIMATOV OLIM, Hattori Masao, ONO HIROMASA, and SADAKANE CHIHARU , Natural medicines= 生薬學雜誌, Volume 52, Issue 3, p.265-268, (1998) Abstract