Sleep problems are widely prevalent and associated with various comorbidities including anxiety. Valerian (Valeriana officinalis L.) is a popular herbal medicine used as a sleep aid, however the ...outcomes of previous clinical studies are inconsistent. This study was conducted to update and re-evaluate the available data in order to understand the reason behind the inconsistent outcomes and to provide a broader view of the use of valerian for associated disorders. PubMed, ScienceDirect, and Cochrane Library were searched to retrieve publications relevant to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A total of 60 studies (n=6,894) were included in this review, and meta-analyses were performed to evaluate the effectiveness to improve subjective sleep quality (10 studies, n=1,065) and to reduce anxiety (8 studies, n=535). Results suggested that inconsistent outcomes were possibly due to the variable quality of herbal extracts and that more reliable effects could be expected from the whole root/rhizome. In addition, therapeutic benefits could be optimized when it was combined with appropriate herbal partners. There were no severe adverse events associated with valerian intake in subjects aged between 7 and 80 years. In conclusion, valerian could be a safe and effective herb to promote sleep and prevent associated disorders. However, due to the presence of multiple active constituents and relatively unstable nature of some of the active constituents, it may be necessary to revise the quality control processes, including standardization methods and shelf life.
Metabolic syndromes are frequently associated with dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and cognitive impairment. In addition, ...growing evidence suggests the link between infections and brain disorders, including Alzheimer’s disease. The immune system and energy metabolism are in an intricate relationship. Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced CNS infection susceptibility. Thus, infection and metabolic imbalance can be intertwined to each other in the etiology of brain disorders, including dementia. Insulin and leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and obesity, which are characterized by insulin resistance and leptin signaling deficiency. Examples include human immunodeficiency virus (HIV) infection and periodontal disease caused by an oral pathogen
Porphyromonas gingivalis
. This review explores potential interactions between infectious agents and insulin and leptin signaling pathways, and discuss possible mechanisms underlying the relationship between infection, metabolic dysregulation, and brain disorders, particularly focusing on the roles of insulin and leptin.
As part of the innate immune system, complement plays a critical role in the elimination of pathogens and mobilization of cellular immune responses. In the central nervous system (CNS), many ...complement proteins are locally produced and regulate nervous system development and physiological processes such as neural plasticity. However, aberrant complement activation has been implicated in neurodegeneration, including Alzheimer’s disease. There is a growing list of pathogens that have been shown to interact with the complement system in the brain but the short- and long-term consequences of infection-induced complement activation for neuronal functioning are largely elusive. Available evidence suggests that the infection-induced complement activation could be protective or harmful, depending on the context. Here we summarize how various infectious agents, including bacteria (e.g.,
Streptococcus
spp.), viruses (e.g., HIV and measles virus), fungi (e.g.,
Candida
spp.), parasites (e.g.,
Toxoplasma gondii
and
Plasmodium
spp.), and prion proteins activate and manipulate the complement system in the CNS. We also discuss the potential mechanisms by which the interaction between the infectious agents and the complement system can play a role in neurodegeneration and dementia.
is a neurotropic protozoan parasite, which is linked to neurological manifestations in immunocompromised individuals as well as severe neurodevelopmental sequelae in congenital toxoplasmosis. While ...the complement system is the first line of host defense that plays a significant role in the prevention of parasite dissemination,
artfully evades complement-mediated clearance
recruiting complement regulatory proteins to their surface. On the other hand, the details of
and the complement system interaction in the brain parenchyma remain elusive. In this study, infection-induced changes in the mRNA levels of complement components were analyzed by quantitative PCR using a murine
infection model
and primary glial cells
. In addition to the core components C3 and C1q, anaphylatoxin C3a and C5a receptors (C3aR and C5aR1), as well as alternative complement pathway components properdin (CFP) and factor B (CFB), were significantly upregulated 2 weeks after inoculation. Two months post-infection, CFB, C3, C3aR, and C5aR1 expression remained higher than in controls, while CFP upregulation was transient. Furthermore,
infection induced significant increase in CFP, CFB, C3, and C5aR1 in mixed glial culture, which was abrogated when microglial activation was inhibited by pre-treatment with minocycline. This study sheds new light on the roles for the complement system in the brain parenchyma during
infection, which may lead to the development of novel therapeutic approaches to
infection-induced neurological disorders.
Hypericum perforatum L. has been widely used as a natural antidepressant. However, it is unknown whether it is effective in treating infection-induced neuropsychiatric disorders.
In order to evaluate ...the effectiveness of H. perforatum against infection with neurotropic parasite Toxoplasma gondii, which has been linked to neuropsychiatric disorders, this study investigated the anti-Toxoplasma activity using in vitro models.
Dried alcoholic extracts were prepared from three Hypericum species: H. perforatum, H. erectum, and H. ascyron. H. perforatum extract was further separated by solvent-partitioning. Hyperforin and hypericin levels in the extracts and fractions were analyzed by high resolution LC-MS. Anti-Toxoplasma activities were tested in vitro, using cell lines (Vero and Raw264), murine primary mixed glia, and primary neuron-glia. Toxoplasma proliferation and stage conversion were analyzed by qPCR. Infection-induced damages to the host cells were analyzed by Sulforhodamine B cytotoxicity assay (Vero) and immunofluorescent microscopy (neurons). Infection-induced inflammatory responses in glial cells were analysed by qPCR and immunofluorescent microscopy.
Hyperforin was identified only in H. perforatum among the three tested species, whereas hypericin was present in H. perforatum and H. erectum. H. perforatum extract and hyperforin-enriched fraction, as well as hyperforin, exhibited significant anti-Toxoplasma property as well as inhibitory activity against infection-induced inflammatory responses in glial cells. In addition, H. perforatum-derived hyperforin-enriched fraction restored neuro-supportive environment in mixed neuron-glia culture.
H. perforatum and its major constituent hyperforin are promising anti-Toxoplasma agents that could potentially protect neurons and glial cells against infection-induced damages. Further study is warranted to establish in vivo efficacy.
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Hypericum erectum
is an important ethnobotanical medicine in East Asian tradition. To explore the anti-parasitic potential of
H. erectum
, inhibitory effects on the growth of intracellular parasite
...Toxoplasma
and on the encystation of intestinal parasite
Entamoeba
were examined. The constituents in
H. erectum
alcoholic extracts and fractions separated by solvent-partitioning were analysed by high resolution LC–MS.
Toxoplasma gondii
growth inhibition assay was performed using GFP-labelled
T. gondii
strain PTG-GFP by measuring the fluorescence intensity. Anti-
Toxoplasma
drug pyrimethamine was used as a positive control.
T. gondii
-induced immune reaction was assessed by quantitative PCR and fluorescence microscopy, using co-culture of PTG-GFP and monocyte-macrophage cell line Raw264. The inhibitory effect on the encystation of
Entamoeba invadens
was measured by flow-cytometry, where paromomycin was used as a positive control.
H. erectum
methanol (MeOH) extract (50 µg/mL) and ethyl acetate (EtOAc) fraction (50 µg/mL) inhibited the growth of
T. gondii
, while 50%MeOH extract and hydrophilic fractions were ineffective. Co-culture with
T. gondii
reduced the viability of macrophages, however macrophages were protected in the presence of
H. erectum
MeOH extract or EtOAc fraction (above 10 µg/mL). The MeOH extract and EtOAc fraction also effectively suppressed the encystation of
E. invadens
at 1 mg/mL. Hypericine, a major constituent in MeOH extract and EtOAc fraction, inhibited
T. gondii
growth and
E. invadens
encystation. Our results demonstrated that
H. erectum
effectively inhibited
Toxoplasma
growth and
Entamoeba
encystation. These activities are partly mediated by hypericin. In addition, it was suggested the extract and fraction may protect innate immune cells from
Toxoplasma
-induced damages, thereby enhancing parasite clearance. Further investigation is warranted to address the in vivo effectiveness of
H. erectum
as an anti-protozoal medicine.
Anaphylatoxin C3a is a third complement component (C3)-derived peptide, the multiple functions of which range from stimulation of inflammation to neuroprotection. In a previous study, we have shown ...that signaling through C3a receptor positively regulates in vivo neurogenesis in adult mouse brain. Here, we studied the direct effects of C3a on adult mouse whole brain-derived neural progenitor cells (NPCs) in vitro. Our results demonstrate that NPCs bind C3a in a specific and reversible manner and that C3a stimulates neuronal differentiation of NPCs. Furthermore, C3a stimulated the migration of NPCs induced by low concentrations of stromal cell-derived factor (SDF)-1alpha, whereas it inhibited NPC migration at high concentration of SDF-1alpha. In the same manner, C3a modulated SDF-1alpha-induced extracellular-signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in these cells. In addition, C3a had inhibitory effect on SDF-1alpha-induced neuronal differentiation of NPCs. These data show that C3a modulates SDF-1alpha-induced differentiation and migration of these cells, conceivably through the regulation of ERK1/2 phosphorylation. Our results provide the first evidence that C3a regulates neurogenesis by directly affecting the fate and properties of NPCs.
Several molecular mechanisms potentially leading to neuronal cell death are explained, including direct neurotoxic effects of bacterial products and indirect routes mediated by microglial activation ...and neuroinflammation. Alzheimer's disease and age-related macular degeneration are neurodegenerative disorders with distinct pathologies, but the two diseases share a number of common risk factors. ...they consider the possible significance of these processes in the insidious development of neurodegeneration and dementia, pointing out that the outcomes of complement system activation in the CNS may be context-dependent and influenced by numerous regulatory factors. Taking advantage of advances in high-throughput research technologies in the last few decades, multiple research groups have progressively explored the composition of the microbial fauna within the human body system that is associated with health and disease.
The root of
Angelica acutiloba
Kitagawa is an important crude drug in Kampo medicines (traditional Japanese medicine). Chemical evaluation of crude drugs is crucial to ensuring the safety and ...efficacy of herbal medicine; however, there is currently no chemical standard for the
A. acutiloba
crude drug in Japanese pharmacopoeia. (
E
)-ferulic acid (FA) is an important active ingredient of
Angelica
spp., including
A. sinensis
(Oliv.) Diels, and has been suggested as a marker for quality evaluation of those crude drugs. However, it has been controversial whether FA is a reliable marker constituent of
A. acutiloba.
To achieve effective extraction of FA from
A. acutiloba
, we compared three different extraction methods: alkaline hydrolysis, ethanol extraction, and hexane extraction. FA levels in these extracts were assessed using high performance liquid chromatography (HPLC), and alkaline hydrolysis was found to be the most effective. Furthermore, in the hydrolysate, FA was distinctly identified by thin layer chromatography (TLC) analysis. These results provide useful information for the quality control of the
A. acutiloba
crude drug.
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