Browsing by Author "Saad, Muhammed A"

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Dapagliflozin modulates neuronal injury via instigation of LKB1/p-AMPK/GABAB R2 signaling pathway and suppression of the inflammatory cascade in an essential tremor rat model
(Taylor and Francis Ltd., 2023-04) Kamel, Ahmed S; Farrag, Sama M; Mansour, Heba M; Nassar, Noha N; Saad, Muhammed A
Background Although, disturbances in cellular energy demarcate the neuronal hyperexcitability in essential tremor (ET), nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin’s (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aimed to investigate DAPA’s impact on the GABAB receptor subunit (GABAB R2), notwithstanding the GABA A involvement, in an ET model. Methods ET was induced by a single dose of harmaline (30 mg/kg; i.p.) while DAPA (1mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5th day before ET induction. Results DAPA decreased HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABAB R2 levels. DAPA’s effect was mostly obliterated by DORSO. Conclusion DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems thru LKB1/p-AMPK/GABAB R2 signaling.
A new arsenal of polyphenols to make Parkinson's disease extinct: HPLC-MS/MS profiling, very interesting MAO-B inhibitory activity and antioxidant activity of Otostegia fruticosa
(Taylor and Francis, 16/02/2022) Al-Madhagy, Somaia A; Gad, Sameh S; Mostafa, Eman S; Angelonie, Simone; Saad, Muhammed A; Sabry, Omar M; Caprioli, Giovani; El-Hawary, Seham S
Fifteen compounds belong to phenolic acids, derivatives of phenolic acids, iridoids, xanthones and flavonoids were characterized in the methanolic extract of Otostegia fruticosa leaves using HPLC-MS/MS. Extract has been also investigated for its MAO-B inhibitory activity, antioxidant activity, total phenolic and total flavonoid content. The extract exhibited interesting MAO-B inhibitory activity (IC50; 2.24 ± 0.08) compared to the reference compound selegiline (0.55 ± 0.02 µg/mL). It also showed a potent antioxidant activity proven in both DPPH and ORAC assay methods. The extract showed an IC50 of 3.64 ± 1.22 µg/mL in the DPPH test which was significantly lower than that of the standard ascorbic acid which attained an IC50 of 18.3 ± 1.41 µg/mL. Moreover, in the oxygen radical absorbance capacity assay (ORAC) the extract showed a decline in the IC50 to 3.48 ± 1.16 µg/mL as compared to the standard Trolox which exhibited an IC50 of 27.0 ± 13.41.
A new firewall in the fight against breast cancer: in-vitro and in-silico studies correlating chemistry to apoptotic activity of Otostegia fruticosa
(Taylor and Francis Ltd., 2022-10) Al-Madhagy, Somaia. A; Gad, Sameh S; Mostafa, Eman S; Angelonie, Simone; Saad, Muhammed A; Sabry, Omar M; Caprioli, Giovanni; El-Hawary, Seham S
Breast cancer is the most devastating disease for women. There is a great demand for new sources to treat this disease. Medicinal plants are an indispensable source of bioactive compounds with wide range of pharmacological activities. In-vitro cytotoxic activity of Otostegia fruticosa methanolic extract against human breast cancer was studied using MCF-7 cell line. The extract showed mildly potent activity (IC50 ¼ 51 ± 9.836 mg/mL) in comparison to the standard anticancer doxorubicin (IC50 ¼ 7.467 ± 1.05 mg/mL). Potential compounds responsible for activity have been identified using Molecular Operating Environment (MOE) module on the major compounds detected by HPLC-MS/MS technique against estrogen alpha receptor (ERaþ: PDB ID 2JF9). 3,5-di-O-dicaffeoyl- quinic acid, hyperoside and rutin showed similar binding and antagonistic interaction with the estrogen alpha receptor as tam- oxifen in several poses. The retrieved results confirm that we can add this plant to a powerful arsenal that combats this insidious disease.
Peganum harmala enhanced GLP-1 and restored insulin signaling to alleviate AlCl3-induced Alzheimer-like pathology model
(Springer Nature, 06/08/2021) Saleh, Rofida A; Eissa, Tarek F; Abdallah, Dalaal M; Saad, Muhammed A; El-Abhar, Hanan S
Peganum harmala (P. harmala) is a folk medicinal herb used in the Sinai Peninsula (Egypt) as a remedy for central disorders. The main constituents, harmine and harmaline, have displayed therapeutic efficacy against Alzheimer’s disease (AD); however, the P. harmala potential on sensitizing central insulin to combat AD remains to be clarified. An AD-like rat model was induced by aluminum chloride (AlCl3; 50 mg/kg/day for six consecutive weeks; i.p), whereas a methanolic standardized P. harmala seed extract (187.5 mg/kg; p.o) was given to AD rats starting 2 weeks post AlCl3 exposure. Two additional groups of rats were administered either the vehicle to serve as the normal control or the vehicle + P. harmala seed extract to serve as the P. harmala control group. P. harmala enhanced cognition appraised by Y-maze and Morris water maze tests and improved histopathological structures altered by AlCl3. Additionally, it heightened the hippocampal contents of glucagon-like peptide (GLP)-1 and insulin, but abated insulin receptor substrate-1 phosphorylation at serine 307 (pS307-IRS-1). Besides, P. harmala increased phosphorylated Akt at serine 473 (pS473-Akt) and glucose transporter type (GLUT)4. The extract also curtailed the hippocampal content of beta amyloid (Aβ)42, glycogen synthase (GSK)-3β and phosphorylated tau. It also enhanced Nrf2, while reduced lipid peroxides and replenished glutathione. In conclusion, combating insulin resistance by P. harmala is a novel machinery in attenuating the insidious progression of AD by enhancing both insulin and GLP-1 trajectories in the hippocampus favoring GLUT4 production.