El-Haleim, E. A. A., and N. A. Sallam, "Vitamin D modulates hepatic microRNAs and mitigates tamoxifen-induced steatohepatitis in female rats", Fundam Clin Pharmacol, vol. 36, issue 2, pp. 338-349, 2022.
Hussein, H. M., M. F. Elyamany, L. A. Rashed, and N. A. Sallam, "Vitamin D mitigates diabetes-associated metabolic and cognitive dysfunction by modulating gut microbiota and colonic cannabinoid receptor 1", Eur J Pharm Sci, vol. 170, pp. 106105, 2022.
Muhammad, R. N., N. Sallam, and H. S. El-Abhar, "Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin", Sci Rep, vol. 10, issue 1, pp. 14693, 2020.
Abdelaziz, A. E., R. H. Sayed, N. A. Sallam, and N. S. El Sayed, "Neuroprotective Effects of Telmisartan and Nifedipine Against Cuprizone-Induced Demyelination and Behavioral Dysfunction in Mice: Roles of NF-κB and Nrf2", Inflammation, vol. 44, issue 4, pp. 1629-1642, 2021.
Sallam, N. A., and S. L. Borgland, "Insulin and endocannabinoids in the mesolimbic system", J Neuroendocrinol, vol. 33, issue 4, pp. e12965, 2021.
Mikolajczak, A., N. A. Sallam, R. D. Singh, T. B. Scheidl, E. J. Walsh, S. Larion, C. Huang, and J. A. Thompson, "Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction", Am J Physiol Endocrinol Metab, vol. 321, issue 5, pp. E581-E591, 2021.
El-Khatib, Y. A., R. H. Sayed, N. A. Sallam, H. F. Zaki, and M. M. Khattab, "17β-Estradiol augments the neuroprotective effect of agomelatine in depressive- and anxiety-like behaviors in ovariectomized rats.", Psychopharmacology, vol. 237, issue 9, pp. 2873-2886, 2020. Abstract

RATIONALE AND OBJECTIVE: Estradiol decline has been associated with depression and anxiety in post-menopausal women. Agomelatine (Ago) is an agonist of the melatonergic MT1/MT2 receptors and an antagonist of the serotonergic 5-HT2c receptors. The present study aimed to evaluate the effects of combining Ago with 17β-estradiol (E2) on ovariectomy (OVX)-induced depressive- and anxiety-like behaviors in young adult female rats.

METHODS: OVX rats were treated with Ago (40 mg/kg/day, p.o.) for 10 days starting 1 week after surgery alone or combined with two doses of E2 (40 μg/kg/day, s.c.) given before behavioral testing.

RESULTS: Co-administration of E2 enhanced the anti-depressant and anxiolytics effects of Ago as evidenced by decreased immobility time in the forced swimming test, as well as increased time spent in the open arms and number of entries to open arms in the elevated plus-maze. In parallel, Ago increased hippocampal norepinephrine, dopamine, melatonin, and brain-derived neurotrophic factor (BDNF). Meanwhile, Ago-treated rats exhibited reduced hippocampal nuclear factor kappa beta (NF-kB) P65 expression and pro-inflammatory cytokine level. Ago upregulated estrogen receptor (ER α and β) mRNA expression in the hippocampus of OVX rats and elevated serum estradiol levels. Co-administration of E2 with Ago synergistically decreased NF-kB P65 expression and pro-inflammatory cytokines, and increased BDNF levels.

CONCLUSION: E2 augmented the neuroprotective effect of Ago in OVX rats via its anti-inflammatory and neurotrophic effects. The combined treatment of E2 and Ago should be further investigated as a treatment of choice for depression, anxiety, and sleep disturbances associated with menopause.

El-Said, Y. A. M., N. A. A. Sallam, A. A. - M. Ain-Shoka, and H. A. - T. Abdel-Latif, "Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats.", Naunyn-Schmiedeberg's archives of pharmacology, vol. 393, issue 12, pp. 2325-2337, 2020. Abstract

Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-β. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.