Traditional Chinese medication for oral submucous fibrosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of various drug therapy methods for treating oral submucous fibrosis (OSF) in terms of increasing mouth opening, reducing VAS score, decreasing lesion area, minimizing side effects, and determining effective proportion. METHOD: A database search was conducted. Only randomized clinical trials were included, and Cochrane checklist was used for assessing the risk of bias. Stata.17 software was employed and effective treatment ranking was used. RESULTS: Thirty-one RCT studies, with a total of 2986 patients, were included in the period of 2010-2022. The combination of oral Chinese herbal medicine formulas (OC) and intralesional Salvia miltiorrhiza (ISM) was found to be the most effective treatment in improving mouth opening. For reducing the burning pain, the combination of intralesional steroids (IS) and oral Salvia miltiorrhiza (OSM) was found to be more effective than the others. In terms of lesion area, IS combined with OC was more effective than the others. IS combined with ISM had the highest effective proportion while having the lowest incidence of side effects which mentioned the incidence of side effects. CONCLUSION: This study indicates that OC and SM can be employed by clinicians for treating OSF effectively.

Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating Nrf2.

Sleep deprivation (SD) can induce cognitive and memory impairments. This impairment is in part due to oxidative stress damage in the hippocampus region of the brain. Corilagin (CL), a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica, shows strong antioxidant and neuroprotective effects. NF-E2-related factor (Nrf2)/heme oxygenase-1 (HO-1) and NADPH oxidase (NOX) are critical targets involved in cellular defense mechanisms against oxidative injury. Thus, we hypothesized that CL could be a preventive treatment for SD-induced memory impairments by inhibiting NOX2 and activating Nrf2. The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice. CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD (P <0.05, p<0.01) caused by SD. In hippocampal tissues, CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD (P <0.05, P <0.01). Meanwhile, in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL versus Glu-induced toxicity, while the effect of CL was enhanced in NOX2 siRNA-transfected neurons. Overall, these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2.

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2.

Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.

Study on the multi-targets mechanism of triphala on cardio-cerebral vascular diseases based on network pharmacology.

BACKGROUND & AIMS: Numerous references made clear that Triphala is revered as a multiuse therapeutic and perhaps even panacea historically. Nevertheless, the protective mechanism of Triphala on cardio-cerebral vascular diseases (CCVDs) remains not comprehensive understanding. Hence, a network pharmacology-based method was suggested in this study to address this problem. METHODS: This study was based on network pharmacology and bioinformatics analysis. Information on compounds in herbal medicines of Triphala formula was acquired from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of Triphala, candidate targets of each component and known therapeutic targets of CCVDs were collected. Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources. In addition, key targets and pathway enrichment were analyzed by STRING database and DAVID database. Moreover, we verified three of the key targets (PTGS2, MMP9 and IL6) predicted by using western blot analysis. RESULTS: Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening, and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs. And 10 compounds, which actually linked to more than three genes, are determined as crucial chemicals. Core genes in this network were IL6, TNF, VEGFA, PTGS2, CXCL8, TP53, CCL2, IL10, MMP9 and SERPINE1. And pathways in cancer, TNF signaling pathway, neuroactive ligand-receptor interaction, etc. related to CCVDs were identified. In vitro experiments, the results indicated that compared with the control group (no treatment), PTGS2, MMP9 and IL6 were up-regulated by treatment of 10 ng/mL TNF-α, while pretreatment with 20-80 µg/mL Triphala could significantly inhibit the expression of PTGS2, MMP9 and IL6. With increasing Triphala concentration, the expression of PTGS2, MMP9 and IL6 decreased. CONCLUSIONS: This study revealed the complex components and pharmacological mechanism of Triphala, and obtained some potential therapeutic targets of CCVDs, which could provide theoretical basis for the research and development of new drugs for treating CCVDs.

Proteomic Analysis of Hydroxysafflor Yellow A Against Cerebral Ischemia/Reperfusion Injury in Rats.

Hydroxysafflor yellow A (HSYA), an active component from Chinese medicinal herb, has been applied to the prevention and treatment of cerebral ischemia/reperfusion injury (CIRI). To clarify the comprehensive mechanisms HSYA for stroke, we used label-free quantitative proteomic analysis to investigate the modulated proteins of rats subjected to CIRI and their alteration by HSYA. Neurological examination, infarct assessment, and biochemical assay were performed to validate the effects of HSYA, and the results indicated that HSYA played a significant role in brain protection. A total of 13 proteins were identified as overlapped proteins by label-free quantitative proteomic analysis. Gene Ontology and pathway analysis showed that these differentially expressed proteins were mainly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Furthermore, networks were constructed with respect to protein function interactions. The results suggested that seven proteins were identified as hub proteins between model and sham groups, while 25 proteins were identified as hub proteins between HSYA and model groups. In addition, the expressions of three overlapping proteins were validated by Western blot, and their levels were consistent with the results of label-free analysis. In conclusion, Eftud2, mTOR, Rab11, Ppp2r5e, and HIF-1 signaling pathways have been detected as key hub proteins and pathways in HSYA against CIRI through proteomic analysis. Our research has provided convincing explanations for the mechanism of HSYA against CIRI and the identified key proteins and pathways might provide novel therapeutics for CIRI.