ABSTRACT
Modulation of in vivo adult neurogenesis (AN) is an evolving concept in managing neurodegenerative diseases. CDRI-08, a bacoside-enriched fraction of Bacopa monnieri, has been demonstrated for its neuroprotective actions, but its effect on AN remains unexplored. This article describes the status of AN by monitoring neuronal stem cells (NSCs) proliferation, differentiation/maturation markers and BDNF-TrkB levels (NSCs signalling players) vs. the level of neurodegeneration and their modulations by CDRI-08 in the hippocampal dentate gyrus (DG) of male rats with moderate grade hepatic encephalopathy (MoHE). For NSC proliferation, 10 mg/kg b.w. 5-bromo-2'-deoxyuridine (BrdU) was administered i.p. during the last 3 days, and for the NSC differentiation study, it was given during the first 3 days to the control, the MoHE (developed by 100 mg/kg b.w. of thioacetamide i.p. up to 10 days) and to the MoHE male rats co-treated with 350 mg/kg b.w. CDRI-08. Compared with the control rats, the hippocampus DG region of MoHE rats showed significant decreases in the number of Nestin+/BrdU+ and SOX2+/BrdU+ (proliferating) and DCX+/BrdU+ and NeuN+/BrdU+ (differentiating) NSCs. This was consistent with a similar decline in BDNF+/TrkB+ NSCs. However, all these NSC marker positive cells were observed to be recovered to their control levels, with a concordant restoration of total cell numbers in the DG of the CDRI-08-treated MoHE rats. The findings suggest that the restoration of hippocampal AN by CDRI-08 is consistent with the recovery of BDNF-TrkB-expressing NSCs in the MoHE rat model of neurodegeneration.
ABSTRACT
Background: Inorganic biomaterials are biologically active and are used as implants and drug delivery system. They have therapeutically active elements present in their framework that are released in the physiological milieu. Release of these dopants above the supraphysiological limit may produce adverse effects and physicochemical interactions with the loaded drugs. Therefore, this necessitates evaluating the in vivo release kinetics, biodistribution, and excretion profiles of dopants from barium-doped bioglass (BaBG) that has potential anti-inflammatory, antiulcer, and regenerative properties. Methods: In vitro leaching of Ca, Si, and Ba from BaBG was analyzed in simulated body fluid. Release kinetics post single-dose oral administration (1, 5, and 10 mg/kg) was performed in rats. Blood was collected at different time points, and pharmacokinetic parameters of released elements were calculated. The routes of excretion and biodistribution in major organs were evaluated using ICP-MS. Results: Elements were released after the oral administration of BaBG into the plasma. They showed dose-dependent release kinetics and mean residence time. Cmax was observed at 24 h for all elements, followed by a downhill fall. There was also a dose-dependent increase in the volume of distribution, and the clearance of dopants was mostly through feces. Ba and Si were biodistributed significantly in the liver, spleen, and kidneys. However, by the end of day 7, there was a leveling-off effect observed for all elements. Conclusion: All of the dopants exhibited a dose-dependent increase in release kinetics and biodistribution in vital organs. This study will help in dose optimization and understanding of various physicochemical and pharmacokinetic interactions when BaBG is used for future pharmacological studies.
