Chemical characterization of the polyphenolic rich fraction of Thunbergia erecta and its therapeutic potential against doxorubicin and cyclophosphamide-induced cognitive impairment in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Thunbergia erecta (Benth.) was traditionally used as anxiolytic, sedative and antidepressant. AIM OF THE STUDY: The study aimed to characterize T. erecta leaf ethyl acetate fraction of alcohol extract (TEAF) and evaluate its neuroprotective effect on doxorubicin and cyclophosphamide-induced chemobrain. MATERIALS AND METHODS: Chemical profiling of TEAF was done using (Liquid chromatography coupled with mass (LC-ESI-MS/MS). In vivo chemobrain model was performed by cognitive impairment induced by doxorubicin and cyclophosphamide. Behavioral assessments included moris water maze, y maze, novel object recognition task and passive avoidance tests. Histological examination and oxidative stress markers were investigated. Protein expression of HMDGB1/RAGE/pNF-κB pathway markers was done using western blotting. All results were applied to hippocampus and prefrontal cortex of rats. Molecular docking was done within the active sites of Human Receptor for Advanced Glycation Endproducts (RAGE) using Discovery studio software. RESULTS: Twenty-one phytoconstituents, mostly polyphenolics, were characterized in TEAF of which eleven compounds were tentatively identified for the first time from T. erecta leaves where rosmarinic acid (11) represents the most prevailing compound. TEAF resulted in a marked dose-dependent amelioration of the histopathological changes evidenced by normal histological structure demonstrated in the hypocampal gesture of rats. TEAF demonstrated an enhanced memory and learning functioning in the different behavioral tests assessed especially at 200 mg/kg. It showed significant long-term spatial memory enhancement manifested by 50.32% increase in probe trial relative to chemobrain-induced group. It showed pronounced antioxidant activity evidenced by the significant elevation of prefrontal cortical and hippocampal reduced glutathione levels by 2.45 and 2.65 folds, respectively relative to the chemobrain-induced group. The pronounced reduction in hydrogen peroxide (1.24-1.93 folds) and malondialdehyde levels (1.42-2.60 folds) with significant elevation of catalase activity (12.65-31.47%) induced by TEAF supported its potent antioxidant activity. TEAF reversed the inflammatory cytokines release induced by chemotherapy via its interference with HMGB1/RAGE pathway suppressing the expression of HMBG1, RAGE, p65 (NF-kB), and IL-1ß. In silico studies showed that rosmarinic acid displayed the best fitting at the active site of RAGE (ΔG = -40.39 kcal/mol). CONCLUSIONS: Thunbergia erecta can act as a promising remedy for chemobrain that further consolidates its traditional importance.

Chemical constituents and gastro-protective potential of Pachira glabra leaves against ethanol-induced gastric ulcer in experimental rat model.

Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)-ß -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3'-O-ß-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)- ß -Dgalactoside (4), quercetin-3- O-ß -D-galactoside (5), 7-hydroxy maltol-3-O-ß-D-glucoside (6), maltol-3- O-ß -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.