Pomegranate polyphenol punicalin ameliorates lipopolysaccharide-induced memory impairment, behavioral disorders, oxidative stress, and neuroinflammation via inhibition of TLR4-NF-кB pathway.

Neuroinflammation may play an important role in the development of Alzheimer's disease (AD). Previous studies have reported that lipopolysaccharide (LPS)-induced neuroinflammation causes memory impairments and behavioral disorders. We investigated the potential preventive effects of punicalin (PUN), a polyphenolic component of pomegranate, on LPS-induced memory deficiency and anxiety- and depression-like behaviors, along with the underlying mechanisms. LPS-treated cultured microglial BV2 cells and BV2 cell/Neuro-2a (N2a) cell coculture system were investigated for anti-neuroinflammatory effects of PUN in vitro. The in vivo experiments involved mice administered a 4-week course of oral gavage with 1500 mg/kg/d PUN before intraperitoneal LPS (250 mg/kg daily 7 times) injections. The in vitro results demonstrated that PUN inhibited the LPS-induced inflammatory cytokine (IL-18, IL-1ß, TNF-ɑ, and IL-6) production in BV2 cells and protected N2a cells from synaptic damage mediated by BV2 microglia-induced neuroinflammation. In in vivo studies, it was observed that PUN improved memory impairment and anxiety- and depression-like behaviors caused by LPS and reduced the expression of inflammatory proteins such as iNOS, COX-2, IL-1ß, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the LPS-induced production of MDA; increased the activities of CAT, SOD, and GSH-Px, and inhibited LPS-induced Aß1-42 generation through down-regulation of APP and BACE1 expression. Moreover, PUN also suppressed the expression of TLR4, IRAK4, TRAF6, IKK-ß, NF-κB, p65, and HMGB1 in LPS-treated mouse brain and cultured microglial BV-2 cells. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of TLR4-NF-kB activation.

Neuroprotective Potential of Punicalagin, a Natural Component of Pomegranate Polyphenols: A Review.

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD), are major health problems worldwide. To date, available remedies against NDs are limited. In fact, current treatment options include drug intervention and nutritional therapy, which mainly focus on the repair of neuronal damage and functional monitoring. However, these treatments do not completely alleviate disease symptoms. Recently, eliminating harmful molecules, such as reactive oxygen species, and inhibiting neuroinflammation have become potential strategies recommended by many researchers. Accordingly, remarkable interest has been generated in recent years regarding natural products, including polyphenols, that provide neuroprotective effects. In this review, we aimed to provide experimental evidence of the therapeutic potential of punicalagin (PUN), a prevailing compound in pomegranate polyphenols with antioxidant activity. Overall, the chemistry, methods of determination, characteristics of metabolism, transformation mechanisms of action, and neuroprotective effects of PUN on NDs are summarised to provide a scientific basis for elucidating the therapeutic mechanisms and targets of NDs.

Recent advancement in bioeffect, metabolism, stability, and delivery systems of apigenin, a natural flavonoid compound: challenges and perspectives.

Apigenin is a bioflavonoid compound that is widely present in dietary plant foods and possesses biological activities that protect against immune, cardiovascular, and neurodegenerative diseases and cancer. Therefore, apigenin is widely used in food and medicine, and increasing attention has been drawn to developing new delivery systems for apigenin. This review highlights the biological effects, metabolism, stability, and bioactivity of apigenin. In addition, we summarized advancements in the delivery of apigenin, which provides some references for its widespread use in food and medicine. Better stability of apigenin may enhance digestion and absorption and provide health benefits. Constructing delivery systems (such as emulsions, nanostructured lipid carriers, hydrogels, and liposomes) for apigenin is an effective strategy to improve its bioavailability, but more animal and cell experiments are needed to verify these findings. Developing apigenin delivery systems for food commercialization is still challenging, and further research is needed to promote their in-depth development and utilization.

Disease-Associated Oligodendrocyte: New Player in Alzheimer's Disease and CNS Pathologies.

Considerable evidence has shown that the breakdown of myelin has been linked to Alzheimer's disease (AD). Considering the vulnerability of oligodendrocytes to Alzheimer's disease, the myelin sheath breakdown and degeneration are easily induced, suggesting that dysfunction of the oligodendrocytes could be the first step in the progression at the early AD before the occurrence of amyloid and tau pathology. It is considered that amyloid ß-peptide (Aß)-mediated oligodendrocyte dysfunction and demyelination could be manifested through neuroinflammation, oxidative stress, and neuronal ferroptosis. With the development of single-cell sequencing technology, an oligodendrocyte state that increased in association with central nervous system brain pathology (designated as disease-associated oligodendrocytes) has been identified. In the current review, we examine the possible roles of oligodendrocytes in cognitive decline and their molecular characteristics in AD. Altogether, our findings elucidate that targeting oligodendrocytes may be a novel treatment or prevention option for AD.

Insight into the role of adult hippocampal neurogenesis in aging and Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia and seriously affects the quality of life of the elderly. Neurodegeneration is closely related to hippocampal dysfunction in AD patients. The hippocampus is key to creating new memories and is also one of the first areas of the brain to deteriorate with age. Mammalian neurogenesis occurs mainly in the hippocampus. Recent studies have confirmed that neurogenesis in the hippocampus is sustainable but decreases with age, which seriously affects the learning and memory function of AD patients. At present, our understanding of neurogenesis is still relatively shallow, especially pertaining to the influence and role of neurogenesis during aging and cognitive deficits in AD patients. Interestingly, many recent studies have described the characteristics of neurogenesis in animal models. This article reviews the progress of neurogenesis research in the context of aging and AD to provide new insights into neurogenesis.

Physical compatibility and chemical stability of dezocine and ramosetron in 0.9% sodium chloride injection for patient-controlled analgesia administration.

As an antiemetic, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist (ramosetron) is generally administered to prevent and treat postoperative nausea and vomiting induced by intravenous dezocine for patient-controlled analgesia. To date, the physicochemical stability of dezocine-ramosetron admixtures has not been assessed. The primary objective of this study was to evaluate the physicochemical stability of a combination of dezocine and ramosetron in 0.9% sodium chloride (normal saline [NS]) injections. Dezocine-ramosetron admixtures were prepared and stored in glass bottles and polyvinyl chloride (PVC) bags refrigerated at 4°C or stored at ambient temperatures (25°C) for up to 14 days. Initial concentrations were 5.0 mg/100 mL for dezocine and 0.3 mg/100 mL for ramosetron used as the diluents. Stability parameters (drug concentrations and pH values) were determined using high-performance liquid chromatography and pH measurements, respectively. Compatibility (cloudiness, discoloration, and precipitation) was assessed visually. After 14 days at 4 °C or 25 °C, the concentration losses of dezocine and ramosetron were both < 4%. Furthermore, there were no significant changes in color, turbidity, or pH values were observed in any of the batches. The results indicated that mixtures of dezocine and ramosetron in NS injections were continuously physically and chemically stable for 14 days in glass bottles or PVC bags stored at 4 °C or 25 °C.

Plasmatic trimethylamine N-oxide and its relation to stroke: A systematic review and dose-response meta-analysis.

BACKGROUND: Elevated circulating concentrations of the gut metabolite, trimethylamine N-oxide (TMAO), were found in patients who experienced stroke. However, it has not been reported whether a high level of TMAO is associated with a significantly increased risk of stroke. This study aimed to review the available scientific evidence about the relationship between TMAO levels and the risk of stroke in a dose-response meta-analysis. METHODS: The PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure databases were searched for studies starting from September 1996 to December 2020. Nine studies including 4402 subjects were reviewed in this study. RESULTS: The results of meta-analysis showed that high levels of circulating TMAO were associated with an increased risk of stroke in patients in the random-effects model (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12-2.41; P = 0.047). The OR for the prevalence of stroke increased by 48% per 5-µmol/L increment (OR, 1.05; 95% CI, 1.16-1.78; P < 0.001) and by 132% per 10-µmol/L increment (OR, 2.32; 95% CI, 1.38-3.86; P < 0.001) in circulating TMAO concentration according to the dose-response meta-analysis. CONCLUSION: There was a significant association between higher plasma TMAO concentrations and the risk of stroke. Further in-depth studies are warranted to validate this interaction and explore potential mechanisms.

Compatibility and stability of methylprednisolone sodium succinate and granisetron hydrochloride in 0.9% sodium chloride solution.

A combination of methylprednisolone sodium succinate (MSS) and granisetron hydrochloride (GH) is generally devoted to treating the chemotherapy-induced nausea and vomiting. To date, none of these novel mixtures have been commercially available. The present study was aimed at investigating physical and chemical compatibility and stability of a combination of MSS with GH in 0.9% sodium chloride injection for 72 hours at 4°C and 25°C. A mixture of MSS (0.4-0.8 mg/mL) with GH (0.03 mg/mL) was prepared and stored in both polyvinyl chloride bags and glass bottles using 0.9% sodium chloride injection as a diluent. The study was performed using a validated and stability-indicating high-performance liquid chromatography method. The physical compatibility was assessed by a spectrometer. Furthermore, the pH measurement of each sample was measured electronically. All test solutions stored at 4°C or 25°C had a no >2% loss of the initial concentration throughout the 72-hour study period. All solutions remained clear and colorless throughout the study and were without precipitation or turbidity in any of the batches. The drug mixtures of MSS (0.4-0.8 mg/mL) and GH (0.03 mg/mL) in 0.9% sodium chloride injections were physically and chemically stable for at least 72 hours when stored at 4°C or 25°C in polyvinyl chloride bags or glass bottles.

ICTs and the challenge of health system transition in low and middle-income countries.

The aim of this paper is to contribute to debates about how governments and other stakeholders can influence the application of ICTs to increase access to safe, effective and affordable treatment of common illnesses, especially by the poor. First, it argues that the health sector is best conceptualized as a 'knowledge economy'. This supports a broadened view of health service provision that includes formal and informal arrangements for the provision of medical advice and drugs. This is particularly important in countries with a pluralistic health system, with relatively underdeveloped institutional arrangements. It then argues that reframing the health sector as a knowledge economy allows us to circumvent the blind spots associated with donor-driven ICT-interventions and consider more broadly the forces that are driving e-health innovations. It draws on small case studies in Bangladesh and China to illustrate new types of organization and new kinds of relationship between organizations that are emerging. It argues that several factors have impeded the rapid diffusion of ICT innovations at scale including: the limited capacity of innovations to meet health service needs, the time it takes to build new kinds of partnership between public and private actors and participants in the health and communications sectors and the lack of a supportive regulatory environment. It emphasises the need to understand the political economy of the digital health knowledge economy and the new regulatory challenges likely to emerge. It concludes that governments will need to play a more active role to facilitate the diffusion of beneficial ICT innovations at scale and ensure that the overall pattern of health system development meets the needs of the population, including the poor.

The direct asymmetric alkylation of α-amino aldehydes with 3-indolylmethanols by enamine catalysis.

This work describes an efficient α-alkylation reaction of α-amino aldehydes with 3-indolylmethanols. In the promotion of catalyst 3f, the target products were obtained in high yields (up to 99%), good diastereoselectivities (up to 88:12), and excellent enantioselectivities (up to 96% ee). The direct alkylation products can be readily converted into other tryptophan derivatives without the loss of stereoselectivities.

[Effect of active site of Xiangsha Liujunzitang on behavior and injury of hippocampal neurons in depression model mice].

OBJECTIVE: To observe the effect of the active site of Xiangshia Liujunzitang on behavior, injury of hippocampal neurons and Ca2+ ion in hippocampal synaptic in the depression model mice. METHOD: Sixty male Kunming mice were randomly divided into 5 group, the control group, the model group and the active site of Xiangshia Liujunzitang groups (400, 600, 800 mg x kg(-1) body weight). The model was established by separation and chronic unpredictable mild stimulation. The increased weight and crossing scores, rearing scores were measured by open-field and sweet water consumption of mice. Cone cell and configuration of neuron in CA1, CA3 region of hippocampus were observed by Nissl. The concentration of Hippocampal synaptic Ca2+ was detected by fluorimetry. RESULT: Comparing with the mice of control, the increased weight was slowed (P < 0.001), the scores of rearing and crossing were decreased (P < 0.001), sweet water consumption were decreased, too. Numbers of cone cells in CA3 region of hippocampus were decreased obviously (P < 0.001), and Ca2+ ion in hippocampal synaptic was increased obviously. Comparing with the mice of model, the active site of Xiangshia Liujunzitang could increase the increased weight on the 14 th and 21 st day obviously. The active site of Xiangshia Liujunzitang could increase the scores of crossing obviously (P < 0.05), with no dose-effect relationship. The active site of Xiangshia Liujunzitang (800 mg x kg(-1)) could increase the scores of rearing obviously (P < 0.001); The active site of Xiangshia Liujunzitang (400, 600, 800 mg x kg(-1)) could increase sweet water consumption obviously (P < 0.01, P < 0.01, P < 0.001); The active site of Xiangshia Liujunzitang (600, 800 mg x kg(-1)) could increase numbers of cone cell in CA3 region of hippocampus obviously (P < 0.001); The active site of Xiangshia Liujunzitang (600, 800 mg x kg(-1)) could decreased Ca2+ in hippocampal synaptic with dose-effect relationship (P < 0.01, P < 0.001). CONCLUSION: The active site of Xiangshia Liujunzitang can improve all the symptoms of the depression model mice and protect the injury of hippocampal neurons in the depression model mice. The possible mechanism of action is to restrict Ca2+ ion overfreight.