Study on the molecular mechanisms of Liuwei Dihuang decoction against aging-related cognitive impairment based on network pharmacology and experimental verification.

Objective: Based on network pharmacology and experimental validation, this study aimed to screen the potential targets of Liuwei Dihuang decoction (LW) against mild cognitive impairment (MCI). Methods: Based on network pharmacology, this study preliminarily explored the targets and molecular mechanisms of LW in the treatment of MCI. The results showed that the mechanism of action of LW against MCI may be related to the cAMP pathway. Then, an aging cell and animal model was established to further verify its molecular mechanism. Results: A total of 23 active ingredients were identified in LW. In addition, through network pharmacological analysis, we found 22 anti-MCI active ingredients in LW, of which alisol B had the most significant effect, and predicted the potential mechanism pathway by which LW may improve MCI through the cAMP signaling pathway. Further in vivo and in vitro experiments confirmed that LW can alleviate cognitive dysfunction in aging mice and reduce D-galactose-induced senescent cells, which may be through activation of the cAMP/PKA/CREB signaling pathway. Conclusion: This study found that the traditional Chinese medicine formula LW may play a role in improving MCI by regulating the cAMP/PKA/CREB signaling pathway, which provides a reference for further clinical research on the anti-MCI effect of LW and its molecular mechanism.

Polygonatum polysaccharide ameliorates D-galactose-induced cognitive dysfunction in aging rats by inhibiting ferroptosis through activation of Nrf2.

CONTEXT: Aging is a major risk factor for various neurodegenerative diseases, and ferroptosis has been identified as an important mode of cell death during accelerated aging. As the main component of the edible plant YuZhu in China, Polygonatum polysaccharide (POP) is an important natural compound with anti-aging properties. OBJECTIVE: To evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved and to evaluate the overall anti-aging effects of POP on cognitive impairment due to accelerated aging. MATERIALS AND METHODS: A D-galactose (D-gal)-induced accelerated aging rat model was established to evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved. In turn, Morris water maze and open field experiments were used to evaluate the anti-aging effects of POP on cognitive impairment due to accelerated aging. RESULTS: The mechanism by which POP affects nuclear factor E2-related factor 2 (Nrf2), an essential transcription factor, was confirmed. POP significantly improved d-gal-induced cognitive dysfunction in treated model rats, which exhibited reduced pathological changes in the hippocampus, reduced latency of the water maze platform, and increased exploration time in the central area in the open field experiment compared to those of untreated model rats. Furthermore, POP intervention downregulated ferroptosis-related proteins and upregulated Nrf2 expression, and selective inhibition of Nrf2 eliminated the ability of POP to reduce ferroptosis. CONCLUSIONS: POP is a natural ingredient with therapeutic potential due to its ability to alleviate aging by activating Nrf2, inhibiting ferroptosis, and alleviating cognitive dysfunction.

Effect of different oral anticoagulants on cognitive function in patients with atrial fibrillation: A Bayesian network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is 1 of the most common types of arrhythmias. At present, the treatment for patients with AF mainly includes oral anticoagulants (OACs). Studies have shown that OACs are associated with cognitive decline in patients with atrial fibrillation; however, there is a lack of relevant evidence. This study used Bayesian network meta-analysis (NMA) to investigate the effects of different oral anticoagulants on cognitive decline in patients with AF. METHODS: We systematically searched for clinical studies on oral anticoagulants in patients with AF in PubMed, Web of Science, Embase, and the Cochrane Library as of July 3, 2023. Cochrane's randomized controlled trial bias risk assessment tool and the Newcastle-Ottawa Scale were used to assess the bias risk of the included studies. The main outcome measure was decreased cognitive functioning. RESULTS: Ten studies were included, including 2 RCTs and 7 RCSs, including 882,847 patients with AF. Five oral anticoagulants and 2 anticoagulants were included: VKAs (especially warfarin), Dabigatran, Edoxaban, Rivaroxaban, Apixaban, and Aspirin, Clopidogrel. The results of the mesh meta-analysis showed that VKAs were superior to warfarin in reducing the risk of cognitive decline in patients with AF (OR = -1.19, 95% CI (-2.35, -0.06), P < .05) (Table 5). The top 3 drugs in terms of the probability of reducing the incidence of cognitive impairment in patients with AF with different oral anticoagulants were VKAs (87%), rivaroxaban (62.2%), and dabigatran (60.8%). CONCLUSION: Based on the results of this study, VKAs may be the best intervention measure for reducing the risk of cognitive decline in patients with AF. Owing to the limitations of this study, more high-quality randomized controlled trials with large sample sizes and multiple centers are required to provide more evidence.

Buyang Huanwu decoction promotes angiogenesis after cerebral ischemia through modulating caveolin-1-mediated exosome MALAT1/YAP1/HIF-1α axis.

BACKGROUND: Angiogenesis is an effective method for promoting neurological function recovery after cerebral ischemia (CI). Buyang Huanwu decoction (BHD) is a traditional Chinese medicinal recipe that is frequently employed for CI treatment. Previous investigations have validated that it promotes angiogenesis following CI. Nevertheless, the precise mechanism by which it does this has yet to be completely understood. OBJECTIVE: This study aims to examine the underlying mechanism through which BHD facilitates angiogenesis following CI by regulating the exosomal MALAT1/YAP1/HIF-1α signaling axis, specifically via the involvement of caveolin-1 (Cav1), an endocytosis-associated protein. METHODS: A CI model was created using middle cerebral artery occlusion (MCAO). Following the administration of multiple doses of BHD, various parameters, including the neurobehavioral score, pathological damage, and angiogenesis, were assessed in each group of mice to identify the optimal dosage of BHD for treating CI. The molecular processes underlying the angiogenic implications of BHD following CI were investigated exhaustively by employing single-cell sequencing. Finally, the involvement of Cav1 was confirmed in Cav1 knockout mice and Cav1-silenced stably transfected strains to validate the mechanism by which BHD increases angiogenesis following CI. RESULTS: BHD could promote angiogenesis after CI. Single-cell sequencing results suggested that its potential mechanism of action might be connected with Cav1 and the exosomal MALAT1/YAP1/HIF-1α signaling axis. BHD could promote angiogenesis after CI by regulating the exosomal MALAT1/YAP1/HIF-1α axis through Cav1, as validated in vivo and in vitro experiments. Accordingly, Cav1 may be a key target of BHD in promoting angiogenesis after CI. CONCLUSION: This investigation represents the initial attempt to comprehensively ascertain the underlying mechanism of action of BHD in treating CI using single-cell sequencing, gene-knockout mice, and stable transfected cell lines, potentially associated with the modulation of the exosomal MALAT1/YAP1/HIF-1α axis by Cav1. Our findings offer novel empirical evidence for unraveling the regulatory pathways through which Cav1 participates in angiogenesis following CI and shed light on the potential mechanisms of BHD.

Interaction of microplastics with heavy metals in soil: Mechanisms, influencing factors and biological effects.

Microplastics (MPs) and heavy metals (HMs) in soil contamination are considered an emerging global problem that poses environmental and health risks. However, their interaction and potential biological effects remain unclear. Here, we reviewed the interaction of MPs with HMs in soil, including its mechanisms, influencing factors and biological effects. Specifically, the interactions between HMs and MPs mainly involve sorption and desorption. The type, aging, concentration, size of MPs, and the physicochemical properties of HMs and soil have significant impacts on the interaction. In particular, MP aging affects specific surface areas and functional groups. Due to the small size and resistance to decomposition characteristics of MPs, they are easily transported through the food chain and exhibit combined biological effects with HMs on soil organisms, thus accumulating in the human body. To comprehensively understand the effect of MPs and HMs in soil, we propose combining traditional experiments with emerging technologies and encouraging more coordinated efforts.

Integrating network pharmacology and bioinformatics to explore and experimentally verify the regulatory effect of Buyang Huanwu decoction on glycolysis and angiogenesis after cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation. AIM OF THE STUDY: This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI. MATERIALS AND METHODS: According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA-mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA-mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways. RESULTS: PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis. CONCLUSION: BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important.

Buyang Huanwu Decoction alleviates cerebral ischemic injury through modulating caveolin-1-mediated mitochondrial quality control.

Introduction: Mitochondrial quality control (MQC) is an important mechanism of neural repair after cerebral ischemia (CI). Recent studies have shown that caveolin-1 (Cav-1) is an important signaling molecule in the process of CI injury, but its mechanism of regulating MQC after CI is still unclear. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine formula that is often used to treat CI. Unfortunately, its mechanism of action is still obscure. Methods: In this study, we tested the hypothesis that BHD can regulate MQC through Cav-1 and exert an anti-cerebral ischemia injury effect. We used Cav-1 knockout mice and their homologous wild-type mice, replicated middle cerebral artery occlusion (MCAO) model and BHD intervention. Neurobehavioral scores and pathological detection were used to evaluate neurological function and neuron damage, transmission electron microscopy and enzymology detection of mitochondrial damage. Finally, western blot and RT-qPCR expression of MQC-related molecules were tested. Results: After CI, mice showed neurologic impairment, neuronal damage, and significant destruction of mitochondrial morphology and function, and MQC was imbalanced. Cav-1 deletion aggravated the damage to neurological function, neurons, mitochondrial morphology and mitochondrial function after CI, aggravated the imbalance of mitochondrial dynamics, and inhibited mitophagy and biosynthesis. BHD can maintain MQC homeostasis after CI through Cav-1 and improve CI injury. Discussion: Cav-1 can affect CI injury by regulating MQC, and this mechanism may be another target of BHD for anti-cerebral ischemia injury.

Meta-analysis of the relations between gut microbiota and pathogens and Parkinson's disease.

BACKGROUND: The motor symptoms in patients with Parkinson's disease (PD) are commonly preceded by gastrointestinal (GI) symptoms. The enteric nervous system (ENS) has also been reported to exhibit neuropathological characteristics of PD. OBJECTIVES: To evaluate the relationship between the incidence of parkinsonism and alteration in gut microbiota and pathogens. MATERIAL AND METHODS: Studies in different languages that evaluate the relationship between gut microorganisms and PD were included into this meta-analysis. The outcomes of these studies were analyzed using a random effects model; it was also used to calculate the mean difference (MD) with 95% confidence interval (95% CI) in order to quantify the impact of different rehabilitation techniques on clinical parameters. Dichotomous and continuous models were used for the analysis of extracted data. RESULTS: A total of 28 studies were included in our analysis. The analysis of small intestinal bacterial overgrowth showed a significant correlation with Parkinson's subjects compared with controls (p < 0.001). In addition, the presence of Helicobacter pylori (HP) infection was significantly related to the Parkinson's group (p < 0.001). On the other hand, there was a significantly higher abundance level of Bifidobacteriaceae (p = 0.008), Verrucomicrobiaceae (p < 0.001) and Christensenellaceae (p = 0.003) in Parkinson's subjects. In contrast, a significantly lower abundance levels in Parkinson's subjects were found in Faecalibacterium (p = 0.03), Lachnospiraceae (p = 0.005) and Prevotellaceae (p = 0.005). No significant difference was related to Ruminococcaceae. CONCLUSION: Parkinson's subjects showed a higher degree of alteration of gut microbiota and pathogens compared with normal human subjects. Future multicenter randomized trials are needed.

A UPLC-Q-TOF/MS and network pharmacology method to explore the mechanism of Anhua fuzhuan tea intervention in nonalcoholic fatty liver disease.

The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.

Study of crosslinker size on the rheological properties of borate crosslinked guar gum.

Borate crosslinked guar gum gels have played a vital role in stimulating oil and gas wells for many years; however, the high dosage of guar gum in the existing fracturing fluid will increase the cost and cause more damage to the reservoir and ultimately affect the effect of stimulation. In this study, borate esters are modified onto polyethyleneimine (PEI) of different molecular weights, affording organic borate crosslinkers of different sizes. By analyzing the effect of crosslinker size on gel rheology, sand-carrying properties, and microstructure, it is observed that the crosslinking efficiency is most significantly enhanced when the crosslinker size is similar to the diameter of the guar gum molecules. This makes it possible for the gel to maintain good performance at low polymer concentrations and meet the performance requirements of fracturing, which provides new ideas for developing the next generation of economical, clean, and green fracturing fluids.

Evidence-based evaluation of adjuvant therapy with Chinese medicine for cerebral small vessel disease: A systematic review and meta-analysis.

BACKGROUND: As the population ages, the prevalence of cerebral small vessel disease (CSVD) steadily increases, resulting in a significant economic burden on society. In East Asian nations, Chinese medicine has been used extensively to teat CSVD and has been reported to improve the cognitive function of patients. The present study aimed to comprehensively assess the efficacy and safety of Chinese medicine as adjuvant therapy for CSVD. METHODS: A literature search of the CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library, and ChiCTR databases were searched for RCTs investigating the use of TCM as an adjuvant in the treatment of CSVD, published up to July 27, 2023, was performed. Based on the Cochrane Collaboration Network bias risk assessment criteria, Review Manager version 5.3 was used to perform a meta-analysis. RESULTS: Meta-analysis of 27 RCTs, including 2554 subjects, revealed that the majority of the RCTs exhibited risk for ambiguous bias. The findings demonstrated that the use of Chinese medicine as an adjuvant treatment for CSVD effectively enhanced the cognitive function, as evidenced by improvements in the MMSE score (mean difference (MD) = 2.42, 95% confidence interval (CI) [1.79,3.17], P < .00001), MoCA score (MD = 2.39, 95% CI [1.78,2.99], P < .00001) and ADL score (MD = 4.13, 95% CI [1.74,6.51], P = .0007). Furthermore, the study also demonstrated the advantages of Chinese medicine adjuvant therapy in enhancing the Chinese medicine syndrome score (MD = -2.57, 95% CI [-3.31, -1.83], P < .00001), CRP (MD = -1.35, 95% CI [-2.27, -0.43], P = .004), Hcy (MD = -3.44,95% CI [-4.05, -2.83], P < .00001), and blood flow velocity (CBV) (MD = 1.37,95% CI [0.24,2.50], P = .02). Moreover, there was no statistical difference in the incidence of adverse reactions between the 2 groups. CONCLUSION: Findings of the present study indicate that the Chinese medicine, as an adjuvant to conventional treatment, appeared to be efficacious in enhancing cognitive function, reducing Chinese medicine syndrome score, improving blood biochemical markers, and improving cerebral blood flow perfusion in patients with CSVD, without any notable adverse reactions. However, it is imperative to validate these conclusions in future high-quality investigations.

Moxibustion for uterine contraction pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Uterine contraction pain is a common postpartum condition that often plagues mothers and can interfere with feeding and normal life for young children. Many investigations have demonstrated that moxibustion has certain advantages in the treatment of uterine contraction pain, but the effectiveness, safety, and advantages of various methods have not been confirmed by high-quality meta-analyses. This study will conduct a systematic review and meta-analysis to evaluate the safety and effectiveness in moxibustion, in order to provide a reference for further clinical treatment for uterine contraction pain. METHODS: Nine electronic databases, including PubMed, Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Wan-Fang Database and 1 clinical trial register platforms: ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched using English and Chinese search strategies. All eligible studies are randomized controlled trials of moxibustion treatment for uterine contraction pain, published on or before December 31, 2021. The screening process will be developed by 2 independent authors, and network meta-analysis will be performed with RevMan (V5.3) software. RESULTS: This study will provide a high-quality review that will be used to evaluate the safety and effectiveness of moxibustion for the treatment of uterine contraction pain. CONCLUSION: The results of this study will provide evidence to support whether moxibustion can effectively intervene in uterine contraction pain.

N6-methyladenosine-modified lncRNA and mRNA modification profiles in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is common in ischemic stroke and seriously affects the prognosis of patients. At present, N6-methyladenosine (m6A) modification of lncRNAs and mRNAs has been reported in other diseases, such as cancer, but its role in CIRI has not been clarified. In this study, we aimed to investigate the m6A lncRNA and m6A mRNA modification profiles in CIRI. First, we detected the total level of m6A and the changes in related m6A methyltransferases and demethylases in the brain tissue of rats with CIRI and then identified differentially modified lncRNAs and mRNAs in CIRI by lncRNA and mRNA epigenetic transcriptomic microarray. In addition, bioinformatics analysis was used to predict the underlying functions and related pathways of related lncRNAs and mRNAs. We found that the total m6A methylation level was significantly increased, and the expression of fat mass and obesity-associated protein (FTO) was downregulated after CIRI. In addition, a large number of m6A-modified lncRNAs and mRNAs appeared after CIRI, and these genes were mainly enriched for the Toll-like receptor signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Our findings provide the basis and insights for further studies on m6A modification in CIRI.

Apolipoprotein E knockout may affect cognitive function in D-galactose-induced aging mice through the gut microbiota-brain axis.

The gut microbiota plays an important role in central nervous system (CNS) disorders. Apolipoprotein E (ApoE) can affect the composition of the gut microbiota and is closely related to the CNS. However, the mechanism by which ApoE affects cognitive dysfunction through the gut microbiota-brain axis has thus far not been investigated. In this study, we used wild-type mice and ApoE knockout (ApoE-/-) mice to replicate the aging model and examined the effects of ApoE deletion on cognitive function, hippocampal ultrastructure, synaptophysin (SYP) and postsynaptic density 95 (PSD-95) in aging mice. We also explored whether ApoE deletion affects the gut microbiota and the metabolite profile of the hippocampus in aging mice and finally examined the effect of ApoE deletion on lipids and oxidative stress in aging mice. The results showed that the deletion of ApoE aggravated cognitive dysfunction, hippocampal synaptic ultrastructural damage and dysregulation of SYP and PSD-95 expression in aging mice. Furthermore, ApoE deletion reduced gut microbial makeup in aging mice. Further studies showed that ApoE deletion altered the hippocampal metabolic profile and aggravated dyslipidemia and oxidative stress in aging mice. In brief, our findings suggest that loss of ApoE alters the composition of the gut microbiota, which in turn may affect cognitive function in aging mice through the gut microbiota-brain axis.

Therapeutic Effect of Buyang Huanwu Decoction on the Gut Microbiota and Hippocampal Metabolism in a Rat Model of Cerebral Ischemia.

Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus, Faecalibacterium, Ruminococcaceae_UCG-002, etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2, Enterococcus, etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI.

Liuwei Dihuang Decoction Alleviates Cognitive Dysfunction in Mice With D-Galactose-Induced Aging by Regulating Lipid Metabolism and Oxidative Stress via the Microbiota-Gut-Brain Axis.

Background: Aging is an important cause of cognitive dysfunction. Liuwei Dihuang decoction (LW), a commonly applied Chinese medicine formula, is widely used for the treatment of aging-related diseases in China. Previously, LW was confirmed to be effective in prolonging life span and reducing oxidative stress in aged mice. Unfortunately, the underlying mechanism of LW remains unclear. The aim of this study was to interpret the mechanism by which LW alleviates cognitive dysfunction related to aging from the perspective of the microbiota-gut-brain axis. Method: All C57BL/6 mice (n = 60) were randomly divided into five groups: the control, model, vitamin E (positive control group), low-dose LW and high-dose LW groups (n = 12 in each group). Except for those in the control group, D-galactose was subcutaneously injected into mice in the other groups to induce the aging model. The antiaging effect of LW was evaluated by the water maze test, electron microscopy, 16S rRNA sequencing, combined LC-MS and GC-MS metabolomics, and ELISA. Results: Liuwei Dihuang decoction ameliorated cognitive dysfunction and hippocampal synaptic ultrastructure damage in aging mice. Moreover, LW decreased Proteobacteria abundance and increased gut microbiota diversity in aging mice. Metabolomic analysis showed that LW treatment was associated with the significantly differential abundance of 14 metabolites, which were mainly enriched in apelin signaling, sphingolipid metabolism, glycerophospholipid and other metabolic pathways. Additionally, LW affected lipid metabolism and oxidative stress in aging mice. Finally, we also found that LW-regulated microbial species such as Proteobacteria and Fibrobacterota had potential relationships with lipid metabolism, oxidative stress and hippocampal metabolites. Conclusion: In brief, LW improved cognitive function in aging mice by regulating lipid metabolism and oxidative stress through restoration of the homeostasis of the microbiota-gut-brain axis.

Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia.

BACKGROUND AND AIM: Buyang Huanwu Decoction (BHD) is a traditional Chinese herbal medicine that is effective for treating cerebral ischemia (CI). However, the molecular mechanisms of BHD in CI have not been fully elucidated. In this study, we integrated the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) network of middle cerebral artery occlusion (MACO) rats treated with BHD. METHODS: SD rats were randomly divided into a control group, model group, model+BHD group (2.5, 5, 10 g/kg) and model+butylphthalide (NBP) group (54 mg/kg). The neurological functions of the rats were evaluated by a modified neurological severity scoring (mNSS) system. Pathological lesions were assessed by Nissl staining, and the effects of BHD on neurovascular unit (NVU) associated protein microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP) and von Willebrand factor (VWF) were assessed by immunohistochemistry. CeRNA and miRNA microarrays were used to establish the circRNA, miRNA, and mRNA profiles. Finally, a circRNA-miRNA-mRNA ternary transcription network was constructed. RESULTS: BHD improved the neurobehavioral test scores (P < 0.01) and the histopathological changes in ischemic brain tissue in MCAO rats. The expression of MAP2 and VWF decreased and the expression of GFAP increased in the ischemic side brain tissue of MCAO rats (P < 0.01), and treatment with BHD reversed the above changes (P < 0.01 or 0.05). We identified seven, three, and 86 significantly dysregulated circRNAs, miRNAs, and mRNAs, respectively, that were associated with the neuroprotective effects of BHD. Furthermore, bioinformatics analysis showed that these targets may exert therapeutic effects through multiple pathways, such as the VEGF and Hippo signaling pathways. Finally, we constructed a circRNA-miRNA-mRNA network. CONCLUSIONS: In brief, our study provides novel insights into ceRNA-mediated gene regulation in the progression of NVU after CI and the mechanism of action for BHD.

Fu brick tea alleviates high fat induced non-alcoholic fatty liver disease by remodeling the gut microbiota and liver metabolism.

Fu brick tea (FBT) and its extracts have good lipid-lowering effects and have been used in the treatment of obesity in previous studies. Unfortunately, the therapeutic effect of FBT on non-alcoholic fatty liver disease (NAFLD) has not been thoroughly studied. In this study, we explored the mechanism by which FBT alleviates NAFLD from the perspective of the gut microbiota and liver metabolites. The results showed that FBT could reduce the body weight, liver weight and abdominal fat of NAFLD mice, and improve liver pathological morphology, liver lipid deposition, blood lipids and liver function. Moreover, FBT improved the diversity of the gut microbiota and changed the profile of liver metabolism in NAFLD mice. Further studies showed that FBT could ameliorate the cecum barrier, and regulate the effects of factors related to lipid synthesis in the cecum and liver of NAFLD mice. In conclusion, the present study confirmed that FBT can alleviate high fat induced NAFLD by regulating the homeostasis of the gut microbiota and liver metabolites.

The effectiveness of herbal acupoint application for functional diarrhea: Protocol for a meta-analysis and data mining.

BACKGROUND: Functional diarrhea (FDr), one of the most common functional gastrointestinal diseases, is a kind of functional bowel disease characterized by repeated paste feces or watery feces. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of herbal acupoint application (HAA) on FDr. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: We will search the following 8 databases from their inception to October 15, 2021, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure. The primaryoutcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software (Available at: https://community.cochrane.org/help/tools-and-software/revman-5). Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the overall quality of evidence supporting the primary outcomes. We will also use SPASS software (Version 19.0 (Available at: https://www.ibm.com/analytics/spss-statistics-software)) for complex network analysis to explore the potential core prescription of acupoint herbal patching for FDr. RESULTS: This study will analyze the clinical effective rate, bristol stool scale, number of daily bowel movements, clinical symptom scale of diarrhea, and effective prescriptions of HAA for patients with FDr. CONCLUSION: The conclusion of our findings will provide evidence for the effectiveness and potential treatment prescriptions of HAA for patients with FDr.

Efficacy and safety of Zaoren Anshen capsules in the treatment of insomnia: A meta-analysis of randomized controlled trials.

BACKGROUND: Zaoren Anshen capsules (ZRAS) have been widely used to treat patients with insomnia. However, the efficacy and safety of ZRAS for insomnia treatment is not entirely clear. Therefore, it is necessary to clarify the effect of ZRAS for the treatment of insomnia by a systematic meta-analysis. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases and performed a manual search to retrieve relevant articles (available through January 2019) describing randomized controlled trials (RCTs) of ZRAS for the treatment of insomnia. The quality of the selected articles was assessed with the Cochrane risk-of-bias tool. A meta-analysis of the selected articles was performed with RevMan 5.3 software. RESULTS: A total of 13 articles including 1175 patients were included in the study. Overall, our results showed that ZRAS was slightly higher than that of the conventional Western medicine for insomnia in terms of clinical efficacy rate; but there was no statistical difference between the 2 groups (relative risk [RR] = 1.03, 95% confidence interval [CI] = [0.97, 1.09], P = .34). However, it should be noted that ZRAS treatment causes far fewer adverse reaction than treatment with conventional Western medicine (RR = 0.20, 95% CI = [0.14, 0.28], P < .00001). CONCLUSION: Our results suggested that ZRAS is an effective and safe treatment for insomnia, especially in adverse reaction. However, multi-regional and well-designed RCTs studies are needed in the future to validate the results.