Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Hypo-fractionation radiotherapy normalizes tumor vasculature in non-small cell lung cancer xenografts through the p-STAT3/HIF-1 alpha signaling pathway.

BACKGROUND: Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT). METHODS: The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected. RESULTS: Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT. CONCLUSION: Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway.

Retraction Note to: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

An amendment to this paper has been published and can be accessed via the original article.

18F-FDG PET/CT SUVmax and serum CEA levels as predictors for EGFR mutation state in Chinese patients with non-small cell lung cancer.

The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) contribute to an increased response rate, compared with chemotherapy, in patients with inhibitor-sensitive EGFR mutations. The present study evaluated the association between the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT), as well as serum carcinoembryonic antigen (CEA) levels and EGFR mutations prior to treatment, in patients with non-small cell lung cancer (NSCLC). Patients with histologically confirmed NSCLC (n=167), who underwent an 18F-FDG PET/CT scan, EGFR mutation analysis and a serum CEA test participated in the present study. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Receiver-operating characteristic (ROC) curve analysis was performed to determine the efficient cut-off value. Survival rate analysis was evaluated according to SUVmax and EGFR mutation status. A decreased SUVmax and an increased CEA level was observed in patients with EGFR-mutations, compared with patients with wild-type primary lesions and metastatic lymph nodes. The exon 19 EGFR mutation was associated with increased SUVmax, compared with the exon 21 L858R mutation. The ROC analysis indicated that an 18F-FDG PET/CT uptake SUVmax >11.5 may be a predictor of the wild-type EGFR genotype and increased CEA levels (CEA >9.4 ng/ml) were associated with EGFR mutations. Furthermore, patients with no smoking history, low SUVmax of the primary tumor, metastatic lymph nodes and a high CEA level were significantly associated with EGFR mutation status. The results of the present study indicated that patients with advanced NSCLC, particularly Chinese patients, with decreased SUVmax and increased CEA levels are associated with EGFR mutations, which may serve as predictors for the EGFR-TKI therapeutic response.

Correction to: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

The original article [1] contained incorrect affiliations for the authors.

MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

BACKGROUND: Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. METHODS: Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). RESULTS: miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. CONCLUSIONS: miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

Corilagin ameliorates the extreme inflammatory status in sepsis through TLR4 signaling pathways.

BACKGROUND: Sepsis is one of the serious disorders in clinical practice. Recent studies found toll-like receptors 4 (TLR4) played an important role in sepsis. In this study, we tried to find the influence of Corilagin on TLR4 signal pathways in vitro and in vivo. METHODS: The cellular and animal models of sepsis were established by LPS and then interfered with Corilagin. Real-time PCR and western blot were employed to detect the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6. ELISA was used to determine the IL-6 and IL-1ß levels in supernatant and serum. RESULTS: The survival rate was improved in the LPS + Corilagin group, and the mRNA and protein expressions of TLR4, MyD88, TRIF and TRAF6 were significantly decreased than that in the LPS group both in cellular and animal models (P < 0.01). The pro-inflammatory cytokines IL-6 and IL-1ß were greatly decreased in the LPS + Corilagin group both in supernatant and serum (P < 0.01). CONCLUSIONS: Corilagin exerts the anti-inflammatory effects by down-regulating the TLR4 signaling molecules to ameliorate the extreme inflammatory status in sepsis.

Corilagin ameliorates schistosomiasis hepatic fibrosis through regulating IL-13 associated signal pathway in vitro and in vivo.

Interleukin (IL)-13-associated signal pathway plays an important role in schistosomiasis hepatic fibrosis. In this study we tried to investigate the effects of corilagin to ameliorate schistosomiasis hepatic fibrosis through regulating IL-13-associated signal pathway in vitro and in vivo. Cellular model was set up with hepatic stellate cells-T6 cells stimulated by rIL-13 and male Balb/c mice were infected with Schistosoma japonicum cercariaeas as animal model. Liver histological changes were observed with haematoxylin and eosin staining. Masson staining was employed to observe the change of egg granulomas. Expression of Col (collagen) and Col III were examined with Immunohistochemistry. Western bolt was employed to detect the JAK-1 and IL13Rα1 proteins. The mRNA expression of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were tested by quantitative polymerase chain reaction. As a result, less inflammatory changes were found in all corilagin groups compared with model group and praziquantel group. The mRNA levels of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were significantly decreased after corilagin intervention (P < 0·01). JAK-1 and IL-13Rα1 protein levels were also greatly decreased in the corilagin groups (P < 0·01). In conclusion, corilagin could ameliorate schistosomiasis hepatic fibrosis by down-regulating the expression of IL-13 and signal molecules in IL-13 pathway.

Shenqi fuzheng injection attenuates irradiation-induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation.

AIM: Radiation-induced brain injury (RIBI) is the most common and severe adverse effect induced by cranial radiation therapy (CRT). In the present study, we examined the effects of the traditional Chinese medicine Shenqi Fuzheng Injection (SFI) on RIBI in mice, and explored the underlying mechanisms. METHODS: C57BL/6J mice were subjected to a single dose of 20-Gy CRT. The mice were treated with SFI (20 mL·kg(-1)·d(-1), ip) for 4 weeks. Morris water maze test was used to assess the cognitive changes. Evans blue leakage and a horseradish peroxidase (HRP) assay were used to evaluate the integrity of the blood-brain barrier (BBB). The expression of inflammatory factors and microglial activation in brain tissues were detected using RT-PCR, Western blotting and immunofluorescence staining. RESULTS: CRT caused marked reductions in the body weight and life span of the mice, and significantly impaired their spatial learning. Furthermore, CRT significantly increased the BBB permeability, number of activated microglia, expression levels of TNF-α and IL-1ß, and the levels of phosphorylated p65 and PIDD-CC (the twice-cleaved fragment of p53-induced protein with a death domain) in the brain tissues. Four-week SFI treatment (administered for 2 weeks before and 2 weeks after CRT) not only significantly improved the physical status, survival, and spatial learning in CRT-treated mice, but also attenuated all the CRT-induced changes in the brain tissues. Four-week SFI pretreatment (administered for 4 weeks before CRT) was less effective. CONCLUSION: Administration of SFI effectively attenuates irradiation-induced brain injury via inhibition of the NF-κB signaling pathway and microglial activation.

Corrigendum to "Ethanol Extract from Ampelopsis sinica Root Exerts Anti-Hepatitis B Virus Activity via Inhibition of p53 Pathway In Vitro".

[This corrects the article DOI: 10.1093/ecam/neq011.].

Involvement of TLR2 and TLR9 in the anti-inflammatory effects of chlorogenic acid in HSV-1-infected microglia.

AIMS: There is no effective medication to date for herpes simplex virus encephalitis (HSE). In this study, we investigated the anti-inflammatory effect of chlorogenic acid (CGA) on herpes simplex virus (HSV)-1-induced responses in BV2 microglia. MAIN METHODS: The cellular model was established with BV2 cells stimulated by HSV-1 and then treated with CGA at different concentrations. Cell viability was assayed by the MTT assay. The mRNA expression of Toll-like receptor (TLR)-2, TLR9 and myeloid differentiation factor88 (Myd88) was assayed by real-time quantitative PCR, and the protein expression was assayed by flow cytometry or Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured by ELISA as well as real-time quantitative PCR. Nuclear NF-κB p65 protein was assayed by Western blotting. KEY FINDINGS: The cell survival rate was significantly improved after CGA treatment, and CGA prevented increases in TLR2, TLR9 and Myd88 following HSV-1 challenge in BV2 cells both at the mRNA and protein levels. Moreover, CGA could attenuate HSV-induced TNF-α and IL-6 release into the supernatant. The mRNA levels of TNF-α and IL-6 were also significantly inhibited by CGA. The expression of NF-κB p65 increased significantly in the nucleus in HSV-1-stimulated microglia but could be reduced by CGA. SIGNIFICANCE: CGA inhibits the inflammatory reaction in HSE via the suppression of TLR2/TLR9-Myd88 signaling pathways. CGA may serve as an anti-inflammatory agent and provide a new strategy for treating HSE.

Corilagin Protects Against HSV1 Encephalitis Through Inhibiting the TLR2 Signaling Pathways In Vivo and In Vitro.

In this study, we tried to explore the molecular mechanism that Corilagin protected against herpes simplex virus-1 encephalitis through inhibiting the TLR2 signaling pathways in vivo and in vitro. As a result, Corilagin significantly prevented increase in the levels of TLR2 and its downstream mediators following Malp2 or HSV-1 challenge. On the other hand, in spite of TLR2 knockdown, Corilagin could still significantly suppress the expression of P38 and NEMO, phosphor-P38, and nuclear factor kappa B. The mRNA and protein expression of TLR2 and its downstream mediators in the brain tissue were also significantly lowered in mice treated with Corilagin. In addition, Corilagin inhibited expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 protein. In conclusion, Corilagin shows the potential to protect against HSV-1-induced encephalitis, and the beneficial effects may be mediated by inhibiting TLR2 signaling pathways.

NF-κB signaling modulates radiation­induced microglial activation.

Microglial activation has been suggested to be associated with the incidence of radiation-induced brain injury. The present study investigated the molecular mechanism(s) involved in radiation-induced activation of the microglia. Mouse microglial BV-2 cells were exposed to different doses of radiation. The release of inflammatory factors was evaluated by enzyme-linked immunosorbent assay and real-time reverse transcriptase polymerase chain reaction. Protein expression was determined by immunocytochemistry and immunoblotting. Microglial activation was induced by radiation [>16 Gray (Gy)]. Activated cells exhibited a stouter spherical morphology and the levels of ionized calcium-binding adapter molecule-1 and CD68 were considerably upregulated. The generation of inflammatory factors, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6, toll­like receptor 8 (TLR-8) and cyclooxygenase 2 (COX-2), was increased and peaked at either 3 or 6 h after radiation treatment. Phosphorylated γ-histone 2A, member X (γ-H2AX), which facilitates DNA double-strand breaks (DSBs), was upregulated at 3 h post-radiation treatment. This was accompanied by the nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit. Moreover, 3 h following radiation treatment, the NF-κB essential modulator (NEMO) was markedly elevated, whereas the NF-κB regulatory inhibitor-α (IκB-α) was considerably decreased. Our results demonstrate that the NF-κB signaling pathway may trigger microglial activation and release of inflammatory factors following irradiation. These findings may provide valuable insight into understanding the molecular mechanism(s) involved in brain injury induced by radiation therapy.

Anti-inflammatory and anti-oxidative effects of corilagin in a rat model of acute cholestasis.

BACKGROUND: Nowadays, treatments for cholestasis remain largely nonspecific and often ineffective. Recent studies showed that inflammatory injuries and oxidative stress occur in the liver with cholestasis. In this study, we would use corilagin to treat the animal model of acute cholestasis in order to define the activity to interfere with inflammation-related and oxidative stress pathway in cholestatic pathogenesis. METHODS: Rats were administrated with alpha-naphthylisothiocyanate to establish model of cholestasis and divided into corilagin, ursodeoxycholic acid, dexamethasone, model and normal groups with treatment of related agent. At 24h, 48h and 72h time points after administration, living condition, serum markers of liver damage, pathological changes of hepatic tissue, nuclear factor (NF)-kappaB, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were examined and observed. RESULTS: Compared to model group, corilagin had remarkable effect on living condition, pathological manifestation of liver tissue, total bilirubin, direct bilirubin, (P<0.01), but no effect on alanine aminotransferase (ALT) and aspartate aminotransferase (AST). With corilagin intervention, levels of MPO, MDA and translocation of NF-κB were notably decreased, and levels of SOD and NO were markedly increased (P<0.05 or P<0.01). CONCLUSIONS: It is shown that corilagin is a potential component to relieve cholestasis through inflammation-related and oxidation-related pathway.

S-methylisothiourea induces apoptosis of herpes simplex virus-1-infected microglial cells.

Our study showed that S-methylisothiourea (SMT) had anti-inflammatory effects in treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of herpes simplex virus (HSV-1)-infected microglial cells. Both animal and cell models were employed in this study. Both models included the following five groups: a normal control group, a virus group (HSV-1 infected), an SMT group (HSV-1-infected + SMT (0.1 mg/10 g)), a dexamethasone group (HSV-1 infected + dexamethasone (2 µg/10 g)), and an APS group (HSV-1-infected + APS (0.8 mg/10 g)). ELISA was used to measure tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-10, and Greiss method was used for measuring nitric oxide (NO) secretion. HE staining was performed for detecting changes in mice brain. Flow cytometry assay for caspase-3, caspase-8, caspase-9, and caspase-12 expressions was also carried out to assess apoptosis. Expressions of TNF-α, IL-1ß, and NO were significantly elevated after stimulation of microglial cells with HSV-1. Following SMT intervention, TNF-α, IL-1ß, and NO levels were significantly decreased. The inflammatory changes in HSV-1-infected murine brain tissues were also reduced. SMT induction of apoptosis of HSV-stimulated microglia seemed to be through three pathways: the death receptor, mitochondrially gated, and endoplasmic reticulum. SMT can reduce HSV-induced inflammatory insult to the brain. Its mechanism of action is most probably due to the induction of microglial cell apoptosis.

In vitro antiviral activity of lutein against hepatitis B virus.

Despite the availability of an effective vaccine, the hepatitis B virus (HBV) infection and its treatment remains one of the foremost public health problems in the world. The present study was performed in order to investigate the anti-HBV activity of lutein in vitro. The antiviral activity of lutein was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNA in stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells. It was found that lutein effectively suppressed the secretion of HBsAg from HepG2 2.2.15 cells in a dose-dependent manner, and it also suppressed the amount of extracellular HBV DNA. A luciferase reporter gene assay was used to determine the effects of lutein on the activities of HBV promoters. The results showed that lutein inhibited the activity of HBV full-length promoter (Fp). These data indicate that lutein possesses an anti-HBV activity and exerts its antivirus effects via inhibition of HBV transcription.

Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis.

Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8(+) T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8(+) T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1ß. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.

Corilagin inhibits the double strand break-triggered NF-kappaB pathway in irradiated microglial cells.

Microglia, the resident immune cells of the central nervous system (CNS), are activated by various stimuli. Resting microglia are the basis of normal neurogenesis, while activated microglia may inhibit neurogenesis through the production of pro-inflammatory mediators and cytokines. Recent research suggests that microglia are activated by irradiation. This may play a role in radiation-induced brain injury (RIBI). DNA double-strand breaks (DSBs), the most deleterious form of DNA damage after ionizing radiation, may rapidly trigger the activation of the NF-kappaB pathway via p53-induced protein leading to the release of pro-inflammatory mediators and cytokines. Thus, a negative regulator of the NF-kappaB pathway that inhibits radiation-induced microglia activation could be used to treat RIBI. Corilagin, a member of the tannin family, inhibits NF-kappaB pathway activation. In the present study, we examined the inhibitory effects of corilagin on radiation-induced microglia activation using a variety of techniques. Our data suggest that corilagin inhibits radiation-induced microglia activation via suppression of the NF-kappaB pathway and the compound is a potential treatment for RIBI.

Effect of Corilagin on anti-inflammation in HSV-1 encephalitis and HSV-1 infected microglias.

The aim of this explore is to study the anti-inflammatory effect of Corilagin in herpes simplex virus (HSV)-1 infected microglial cells and HSV-1 infected mouse brain. The cellular model was set with microglial cells stimulated by HSV-1 and divided respectively, into virus, astragalus polysaccharides (APS), Dexamethasone and Corilagin group. A normal control group consisting of uninfected microglial cells was also included. ELISA for measuring TNF-alpha, IL-1beta and IL-10 and Greiss method for detecting NO secretion in supernatant, flow cytometry assay for examining apoptosis rate, expression of caspase-3, caspase-8, caspase-9 and caspase-12, and western-blot for measuring protein expression of cytochrome c were performed. The animal model was set up using Balb/c male mice that were intracranially inoculated with HSV-1. Animals were then divided in groups as described for the cellular model. Here, too a normal control group was included. HE staining was used to assay pathological changes in brain. As results, after Corilagin intervention, the release of TNF-alpha, IL-1beta and NO from HSV-stimulated migroglia cells was significantly inhibited. Furthermore, Corilagin induced apoptosis of HSV-stimulated microglia through all the 3 known apoptotic pathways. The animal model treated with Corilagin also displayed significant decrease of herpes simplex encephalitis induced brain pathological changes. In conclusion, Corilagin has the potential to reduce HSV-1-induced inflammatory insult to the brain, and its mode of action is through the induction of apoptosis of microglias and reduction of cytokines production.