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Prenatal stress is a significant risk factor that can lead to neurobehavioral deficits in offspring. In the present study, we examined the effects of a probiotic mixture on anxiety, memory, and underlying possible molecular pathways in prenatally stressed rats. Male offspring exposed to chronic unpredictable stress (CUS) during fetal life were received either saline (CUS+SAL) or a probiotic mixture (CUS+PRO) for 30 days post-weaning. Non-stressed controls were also given either saline (CON+SAL) or probiotics (CON+PRO). The passive avoidance test and the elevated zero maze test were used to assess avoidance memory and anxiety-like behavior, respectively. In comparison to the CON+SAL controls, the CUS+SAL group exhibited significant anxiety-like behavior and impaired avoidance memory. At a molecular level, the behavioral impairments were accompanied by increased serum levels of the oxidant, MDA, and decreased serum levels of antioxidants, TAC, GSH, and SOD, upregulation of the hippocampal serotonin receptor Htr1a gene, while downregulation of microRNAs miR-26a and miR-320-3p, reduced BDNF, and increased Bax/Bcl-2 ratio apoptosis in the duodenum. Probiotics effectively mitigated these alterations. The intervention improved behavioral functions, normalized oxidative and antioxidative stress markers, and restored the expression of Htr1a and miR-320-3p to near-normal levels, while miR-26a expression remained unaffected by the treatment. It also enhanced the Bax/Bcl-2 ratio and increased BDNF content. Interestingly, unstressed control rats were unresponsive to the probiotic treatment. Conclusively, probiotic supplementation sufficiently alleviates the adverse effects of fetal life stress, possibly by affecting the gut-brain axis, highlighting the importance of beneficial bacteria in neurobehavioral development and maintenance. Show less

In this study, we investigated the effects and molecular mechanisms by which Scutellaria barbata flavonoids (SBFs) enhance neurogenesis and ameliorate memory impairment mediated by CREB phosphorylation in rats, using a network pharmacology approach. The active ingredients of SBFs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology platform. An Alzheimer's disease (AD) model was established by intracerebroventricular injection of Aβ25-35 combined with AlCl₃ and RHTGF-β1 (composited Aβ) in rats. The Morris water maze was used to confirm the successful establishment of the AD rat model. Successfully modeled rats were randomly divided into three groups: a model group and two treatment groups receiving either 140 mg/kg SBFs or 0.5 mg/kg Rolipram (positive control). After 38 days, the Morris water maze test was performed to assess learning and memory abilities. Hematoxylin-eosin (HE) staining, immunohistochemistry, quantitative PCR (qPCR), and Western blotting (WB) were conducted to evaluate neuronal morphology, NeuN protein expression, the mRNA levels of TrkB, RSK, CREB, and BDNF, and the protein expression of NeuN, TrkB, RSK, P-CREB-Ser133, and BDNF in the hippocampus and cerebral cortex of the rats. These results indicate that SBFs and Rolipram ameliorate learning and memory impairment, reduce neuropathological changes, promote neurogenesis, and upregulate the BDNF- RSK-CREB signaling pathway through the activation of CREB phosphorylation. The findings suggest that the effects of SBFs are similar to those of Rolipram and that SBFs may also act as activators of CREB phosphorylation. Overall, SBFs promote neurogenesis and improve learning and memory deficits, possibly by enhancing CREB phosphorylation. This study identified the key targets and signaling pathways of SBFs in AD, indicating that SBFs represent a promising multitarget therapeutic candidate for the treatment of AD. However, our research has some limitations. Further studies are needed to determine the absorption route, major active components, and metabolic forms of the bioactive substances in SBFs. In future work, we aim to clarify the potential mechanisms of SBFs in AD by integrating multiple omics approaches and to evaluate the safety and efficacy of SBFs in AD treatment. Thirty-seven targets were identified based on the intersection between AD-related targets and the components of SBFs. SBFs were involved in anti-AD activity through the MAPK signaling pathway, including the BDNF-RSK-CREB pathway. SBFs attenuated memory impairment, ameliorated neuropathological changes, increased NeuN protein expression, and regulated the mRNA expression of TrkB, RSK, CREB, and BDNF, as well as the protein expression of NeuN, TrkB, RSK, P-CREB-Ser133, and BDNF. Rolipram produced similar effects to SBFs. Network pharmacology analysis and animal experiments confirmed that SBFs promote neurogenesis and ameliorate learning and memory impairment in AD model rats, primarily by facilitating CREB phosphorylation, similar to Rolipram. This study indicates that SBFs may be a promising therapeutic candidate for the treatment of AD. Show less

Ginsenoside Rd, a protopanaxadiol abundant in Panax ginseng and Panax notoginseng, possesses well-documented neuroprotective properties but suffers from low bioavailability. Here, we engineered nanoparticles from zein, chitosan-α-lipoic acid copolymer, and sodium alginate for the delivery of ginsenoside Rd (Rd) and evaluated their efficacy in alleviating scopolamine-induced memory impairment in a mouse model. The results demonstrated that the nanoparticles successfully encapsulated Rd, with an encapsulation efficiency of approximately 73.23 %, and exhibited a hollow spherical morphology. Additionally, the carrier exhibited exceptional stability under varying temperature and salt ion conditions, along with the ability to be readily redispersed. The incorporation of Rd into nanoparticles significantly improved its antioxidant efficacy, as well as its stability and sustained release profile in the gastrointestinal environment. In vivo experiments demonstrated that Rd-loaded nanoparticles significantly improved scopolamine-induced memory deficits, oxidative stress, cholinergic system dysfunction, and neuronal damage in the hippocampal region of mice, outperforming the effects of ginsenoside Rd alone. Western blot results indicated that Rd-loaded nanoparticles improved memory-impaired mice by upregulating p-CaMKII, p-CREB, and BDNF protein expression through modulating the long-term potentiation pathway. We further found that Rd-loaded nanoparticles treatment increased the richness and diversity of gut microbiota. This study provides a promising strategy for the effective treatment of improving learning memory. Show less

Enhancing memory and alleviating amnesia are among the conditions that Ganoderma lucidum has historically been used to treat. However, there are relatively few studies on the potential therapeutic effects of active ingredients derived from Ganoderma lucidum in the treatment of memory impairment. This study investigated the ameliorative effect of Lucidenic acid A (LAA) on memory impairment via in vivo and in vitro experiments using experimental pharmacology approaches. In vivo, behavioral tests were used to evaluate memory impairment in mice. Transmission electron microscopy, Hematoxylin-Eosin (HE) staining, and Nissl staining were employed to observe pathological changes in mice. Western blotting (WB) was used for protein expression analysis. In vitro, CCK-8 assay and cell scratch test were used to evaluate changes in cell viability. Reactive oxygen species (ROS) immunofluorescence staining was used to assess intracellular oxidative stress changes. WB was also used for protein expression analysis. The results show that LAA can not only improve spatial learning and memory abilities and alleviate cholinergic system impairments in mice with memory impairment, but also mitigate oxidative stress and inflammatory responses, and reduce pathological changes in brain tissue. In addition to improving memory impairment in mice, LAA can also alleviate inflammation, oxidative stress, and neuronal apoptosis induced in cells. LAA can induce the activation of the PI3K/AKT/BDNF pathway, thereby alleviating inflammation, oxidative stress, and cholinergic system impairments caused by scopolamine (SCOP) administration, and improving memory impairment. Show less

Lead (Pb) accumulation in the hippocampus and the resulting oxidative stress contribute to memory impairments, highlighting the hippocampus as a primary target for Pb neurotoxicity. Selenium-containing peptides TSeMMM and SeMDPGQQ are able to alleviate Pb-induced oxidative neurological damage and the specific microRNAs involved in the memory protection by the two peptides need to be explored. In this study, mouse memory impairment models were constructed through the administration of 20 mg kg Show less