QBT improved cognitive dysfunction in rats with vascular dementia by regulating the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD pathways to inhibit ferroptosis and pyroptosis of neurons.

Background: The novel phthalein component QBT, extracted from Ligusticum chuanxiong, shows promising biological activity against cerebrovascular diseases. This study focused on ferroptosis and pyroptosis to explore the effects of QBT on nerve injury, cognitive dysfunction, and related mechanisms in a rat model of vascular dementia (VaD).

Methods: We established a rat model of VaD and administered QBT as a treatment.

A novel phthalein component ameliorates neuroinflammation and cognitive dysfunction by suppressing the CXCL12/CXCR4 axis in rats with vascular dementia.

Ethnopharmacological Relevance: Chuanxiong, a plant of the Umbelliferae family, is a genuine medicinal herb from Sichuan Province. Phthalides are one of its main active components and exhibit good protective effect against cerebrovascular diseases. However, the mechanism by which phthalides exert neuroprotective effects is still largely unclear.

Modulation of Xiongdanjiuxin pills on the gut-liver axis in high-fat diet rats.

Aim: Xiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications.

Main Methods: We used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP.

Probiotics Improve Cognitive Impairment by Decreasing Bacteria-Related Pattern Recognition Receptor-Mediated Inflammation in the Gut-Brain Axis of Mice.

Introduction: Some studies have found that probiotics can improve cognitive impairment in Alzheimer's disease, although the specific molecular mechanism by which this occurs has not been reported. Our previous research found that probiotics inhibited bacteria-related Toll-like receptor 4- and retinoic-acid-inducible gene-I-mediated nuclear factor-κB signaling pathways to improve cognitive impairment. However, it is unclear whether probiotics have similar effects on other pattern recognition receptors that respond to bacteria.

Phthalide derivative CD21 regulates the platelet- neutrophil extracellular trap-thrombin axis and protects against ischemic brain injury in rodents.

Prothrombotic and proinflammatory properties of neutrophil extracellular traps (NETs) contribute to brain damage after ischemic stroke. CD21 is a novel phthalide neuroprotectant against cerebral ischemia in rodents. This study investigated effects of CD21 on the platelet-NET-thrombin axis and ischemic brain injury and the underlying mechanism.

Neuroprotective effect of alpha-kinase 1 knockdown against cerebral ischemia through inhibition of the NF-κB pathway and neuroinflammation.

Background: Activation of the nuclear factor B (NF-κB) signaling pathway by pattern recognition receptors (PRRs) is regarded as a crucial mechanism of neuroinflammation and brain injury after acute ischemic stroke. The stimulation of alpha-kinase 1 (ALPK1), a newly identified PRR, triggers NF-κB activation and an inflammatory response. Longitudinal population-based genetic epidemiological studies suggest that the ALPK1 gene is a susceptible site to ischemic stroke.

Far beyond anti-angiogenesis: Benefits for anti-basicFGF therapy in cancer.

Basic FGF (bFGF) was discovered as a typical inducer of angiogenesis and has already been studied for 3 decades. Recent evidence indicates that bFGF plays different roles and controls signaling pathways that participate in the hallmarks of cancer, underscoring bFGF an appealing target for anti-cancer therapy. However, the early clinical trials designed to block bFGF signaling showed safety without satisfiable benefits for cancer patients.

Phthalide derivative CD21 attenuates tissue plasminogen activator-induced hemorrhagic transformation in ischemic stroke by enhancing macrophage scavenger receptor 1-mediated DAMP (peroxiredoxin 1) clearance.

Background: Hemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke.

Nrf2 signalling pathway and autophagy impact on the preventive effect of green tea extract against alcohol-induced liver injury.

Objectives: To explore the potential molecular mechanism underlying the effect of green tea extract (TE), rich in tea polyphenols (TPs), on improving alcohol-induced liver injury.

Methods: Mice were intragastrically treated with 50% (v/v) alcohol administration (15 ml/kg BW) with or without three doses of TE (50, 120 and 300 mg TPs/kg BW) daily for 4 weeks, and biological changes were tested.

Key Findings: The TE improved the functional and histological situations in the liver of the mice accepted alcohol administration, including enzymes for alcohol metabolism, oxidative stress and lipid accumulation.

Gut Microbiota in Tumor Microenvironment: A Critical Regulator in Cancer Initiation and Development as Potential Targets for Chinese Medicine.

Cancer is a disease with a high mortality and disability rate. Cancer consists not only of cancer cells, but also of the surrounding microenvironment and tumor microenvironment (TME) constantly interacting with tumor cells to support tumor development and progression. Over the last decade, accumulating evidence has implicated that microbiota profoundly influences cancer initiation and progression.

Age-related cognitive decline is associated with microbiota-gut-brain axis disorders and neuroinflammation in mice.

Age-related cognitive decline is associated with chronic low grade neuroinflammation that may result from a complex interplay among many factors, such as bidirectional communication between the central nervous system (CNS) and gut microbiota. The present study used 2-month-old (young group) and 15-month-old (aged group) male C57BL/6 mice to explore the potential association between age-related cognitive decline and the microbiota-gut-brain axis disorder. We observed that aged mice exhibited significant deficits in learning and memory, neuronal and synaptic function compared with young mice.

Klotho overexpression improves amyloid-β clearance and cognition in the APP/PS1 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by the presence of amyloid-β (Aβ) plaques. We previously reported that Klotho lowered Aβ levels in the brain and protected against cognitive deficits in amyloid precursor protein/presenilin 1(APP/PS1) mice. However, the underlying mechanism remains unclear.

Phthalide derivative CD21 alleviates cerebral ischemia-induced neuroinflammation: Involvement of microglial M2 polarization via AMPK activation.

Microglia can be activated to become the classic phenotype (M1) or alternative phenotype (M2), which play an important role in regulating neuroinflammatory response and tissue repair after ischemic stroke. CD21, a novel phthalide derivative, is a potential neuroprotectant against ischemic brain injury. The present study further investigated the effects of CD21 on post-ischemic microglial polarization and the underlying mechanisms.

Phthalide derivative CD21 ameliorates ischemic brain injury in a mouse model of global cerebral ischemia: involvement of inhibition of NLRP3.

The activation of NLRP3 inflammasome is closely related to ischemic brain injury and inhibition of NLRP3 inflammasome activation may be a new therapeutic strategy for ischemic stroke. Our previous studies showed that ligustilide (LIG) had a dose-dependent neuroprotective effect on various models of cerebral ischemia and dementia in vivo and in vitro. CD21, a kind of phthalide derivative, was modified from LIG.

Neuroprotective Effect of Phthalide Derivative CD21 against Ischemic Brain Injury:Involvement of MSR1 Mediated DAMP peroxiredoxin1 Clearance and TLR4 Signaling Inhibition.

The macrophage scavenger receptor 1 (MSR1)-induced resolution of neuroinflammation may be a novel therapeutic strategy for ischemic stroke. Our previous study showed that the neuroprotective and anti-inflammatory effects of phthalide are associated with the inhibition of the post-ischemic damage-associated molecular pattern (DAMP)/Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of the phthalide derivative CD21 on ischemic brain injury and the mechanism underlying MSR1-induced resolution of neuroinflammation.

[Effects of Low Concentration Hydrogen Inhalation on Asthma and Sleep Function in Mice].

Objective: This study was designed to investigate the effects of low concentration hydrogen inhalation on asthma and sleep function in mice and the potential mechanism.

Methods: In the asthma experiment, BALB/c mice were randomly divided into normal control group, asthma model group and hydrogen treatment group. After establishing ovalbumin (OVA)-induced asthma model, the hydrogen treatment group mice were treated by inhalation of hydrogen (24-26 mL/L per day) for 7 consecutive days, and the normal control group and asthma model group mice received similar treatment by inhalation of air.

Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice.

Epidemiological studies suggest that chronic periodontitis (CP) is closely associated with the incidence and progression of cognitive impairment. The present study investigated the causal relationship between CP and cognitive decline and the underlying mechanism in mice. Long-term ligature around the left second maxillary molar tooth was used to induce CP in mice.

Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer's disease-like pathology and cognitive deficits in mice.

Alzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. However, the role of Klotho in the progression of AD remains elusive.

The neuroprotective effects and probable mechanisms of Ligustilide and its degradative products on intracerebral hemorrhage in mice.

Background: Intracerebral hemorrhage (ICH) is a common neurological emergency with higher mortality and disability rate than cerebral ischemia. Although diverse therapeutic interventions have been explored for potential neuroprotection from ICH, no effective drugs until now are available for improvement of survival rate or the life quality of survivors after ICH. Just like cerebral ischemia, inflammatory mechanism is highly thought to play a vital role in hemorrhagic brain injury.

Lentivirus-mediated klotho up-regulation improves aging-related memory deficits and oxidative stress in senescence-accelerated mouse prone-8 mice.

Aims: Oxidative stress caused by aging aggravates neuropathological changes and cognitive deficits. Klotho, an anti-aging protein, shows an anti-oxidative effect. The aims of the present study were to determine the potential therapeutic effect of klotho in aging-related neuropathological changes and memory impairments in senescence-accelerated mouse prone-8 (SAMP8) mice, and identify the potential mechanism of these neuroprotective effects.

Protective Effect of Klotho against Ischemic Brain Injury Is Associated with Inhibition of RIG-I/NF-κB Signaling.

Aging is the greatest independent risk factor for the occurrence of stroke and poor outcomes, at least partially through progressive increases in oxidative stress and inflammation with advanced age. Klotho is an antiaging gene, the expression of which declines with age. Klotho may protect against neuronal oxidative damage that is induced by glutamate.

Klotho upregulation contributes to the neuroprotection of ligustilide against cerebral ischemic injury in mice.

Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice.

Neuroprotective effect of a novel gastrodin derivative against ischemic brain injury: involvement of peroxiredoxin and TLR4 signaling inhibition.

The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling appears to be a potential therapeutic strategy for neuroinflammatory injury after acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for the treatment of cerebral ischemia, accompanied by regulation of the autoimmune inflammatory response. The present study investigated the neuroprotective effects of Gas and its derivative, Gas-D, with a focus on the potential mechanism associated with inflammatory Prx-Toll-like receptor 4 (TLR4) signaling.

Neuroprotective Effect of Ligustilide through Induction of α-Secretase Processing of Both APP and Klotho in a Mouse Model of Alzheimer's Disease.

Emerging evidence suggests that alpha-processing single transmembrane proteins, amyloid precursor protein (APP) and anti-aging protein Klotho, are likely to be involved in the progression of Alzheimer's disease (AD). The natural phthalide Ligustilide (LIG) has been demonstrated to protect against aging- and amyloid-β (Aβ)-induced brain dysfunction in animal models. The present study is to investigate the effects of LIG on cognitive deficits and metabolism of both APP and Klotho and its underlying mechanism in AD double-transgenic (APP/PS1) mice and cultured human cells.

Peroxiredoxin 1-mediated activation of TLR4/NF-κB pathway contributes to neuroinflammatory injury in intracerebral hemorrhage.

The proinflammatory properties of extracellular peroxiredoxins (Prxs) via induction of Toll-like receptor 4 (TLR4) activation have been gradually revealed under diverse stress conditions, including cerebral ischemia but not hemorrhage. Prx1 is proposed to be a major hemorrhagic stress-inducible isoform of Prxs during acute and subacute phases of intracerebral hemorrhage (ICH). However, the potential of Prx1 in the neuroinflammatory injury after ICH remains unclear.