Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

Modulating the tumor microenvironment improves antitumor effect of anti-PD-L1 mAb in breast cancer.

Introduction: Immune checkpoint inhibitors (ICIs) have provided noteworthy benefits in multiple cancer patients. However, the efficacy of monotherapy of ICIs was very limited. In this study, we endeavored to explore whether losartan can modulate the solid tumor microenvironment (TME) and improve the therapeutic efficacy of anti-PD-L1 mAb in 4T1 mouse breast tumor model and the underlying mechanism. Methods: The tumor-bearing mice were treated with control agents, losartan, anti-PD-L1 mAb or the dual agents. The blood and tumor tissues were respectively used for ELISA and immunohistochemical analysis. CD8-depletion and lung metastatic experiments were performed. Results: Compared to control group, losartan inhibited the expression of alpha-smooth muscle actin (α-SMA), deposition of collagen I in the tumor tissues. The concentration of transforming growth factor-ß1 (TGF-ß1) in the serum was low in the losartan treated group. Although losartan alone was ineffective, the combination of losartan and anti-PD-L1 mAb elicited dramatic antitumor effect. Immunohistochemical analysis revealed that there were more intra-tumoral infiltration of CD8+ T cells and increased granzyme B production in the combination therapy group. In addition, the size of spleen was smaller in the combination therapy group, compared to monotherapy. The CD8-depleting Abs abrogated the antitumor efficacy of losartan and anti-PD-L1 mAb in vivo. The combination of losartan and anti-PD-L1 mAb significantly inhibited 4T1 tumor cells lung metastatic in vivo. Conclusion: Our results indicated that losartan can modulate the tumor microenvironment, and improve the efficacy of anti-PD-L1 mAb.

Oleanolic Acid Inhibits SCD1 Gene Expression to Ameliorate Fructose-Induced Hepatosteatosis through SREBP1c-Dependent and -Independent Mechanisms.

SCOPE: The mechanisms of oleanolic acid (OA) regulating hepatic sterol regulatory element-binding protein (SREBP) 1c/stearoyl-CoA desaturase (SCD) 1 pathway to ameliorate fructose-induced hepatosteatosis are investigated. METHODS AND RESULTS: Rats treated with 10% w/v fructose solution are co-administered by OA for 5 weeks, and then sacrifice after fasting for 14 h. OA reverses the fructose-induced increase in hepatic triglyceride (TG) content and downregulates Scd1 mRNA expression. However, two upstream transcription factors, ChREBP and SREBP1c, remain at normal levels with or without fructose and/or OA. In vivo and in vitro studies using SREBP1c-/- mice and HepG2 cell models show that OA also inhibits SCD1 gene overexpression and high hepatic TG levels induced by fructose. On the other hand, in SCD1-/- mice, when the fructose diet is supplemented with high levels of oleic acid (OLA) to compensate for the deficiency of SCD1, OA inhibits hepatic SREBP1c and lipogenic gene expression and reduces hepatic OLA (C18:1) production to improve fructose and/or OLA induced liver lipid deposition. Furthermore, OA promotes PPARα and AMPK to enhance fatty acid oxidation in fructose + OLA-fed SCD1-/- mice. CONCLUSION: OA may inhibit SCD1 gene expression to ameliorate fructose-induced hepatosteatosis through SREBP1c-dependent and -independent mechanisms.

Baicalin ameliorates alcohol-induced hepatic steatosis by suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL.

Baicalin is a flavonoid compound abundant in multiple edible and medicinal plants such as Scutellaria baicalensis Georgi. In this study, we provide evidence to support the fact that baicalin ameliorates alcohol-induced hepatic steatosis via regulating SREBP1c elicited PNPLA3 competitive binding to ATGL. Results showed that baicalin significantly attenuated the development of metabolic disorders and hepatic steatosis in alcohol-induced rats after four weeks of treatment. It was evident that baicalin treatment significantly normalized the serous contents of hepatic triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and attenuated the increase of hepatic vacuolization and Oil Red O staining area caused by alcohol. Meanwhile, baicalin relieves alcohol-induced hepatic fibrosis by masson staining and RT-qPCR analysis. Mechanistically, alcohol aggravated the nuclear expression of SREBP1c, which contributed to the high expression of PNPLA3 and FASN, thereby enhancing the binding of PNPLA3 to ABHD5, and indirectly impairing the binding ability between ATGL and ABHD5, ultimately causing a decline in the hydrolysis capacity in liver lipid droplets. As expected, these alcohol-induced pathobolism were reversed by baicalin treatment both in vivo and in vitro. In conclusion, this study has demonstrated that baicalin can protect against alcohol-induced hepatic lipid accumulation by activating hepatic lipolysis via suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL. Baicalin is a promising natural product for preventing alcohol-induced hepatic steatosis.

[Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats].

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1ß and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

A mycophenolic acid derivative from the fungus Penicillium sp. SCSIO sof101.

Mycophenolic acid (MPA) is a group of metabolite derived from several species of Penicillium, which shows potent bioactivity. In this study, a new derivative of MPA compound named penicacid D (1), was isolated from the marine derived fungus Penicillium sp. SCSIO sof101, along with seven known compounds (2-8). Their structures were elucidated based on the HR-ESI-MS and NMR data. Moreover, the 1H and 13C NMR data of compound 2 and the 13C NMR data of compound 3 are reported. Compounds 1, 4 and 6 exhibited weak activities against Escherichia coli (clinical isolation number 100385570) and Acinetobacter baumannii (clinical isolation number 100069).

Paeoniflorin exerts neuroprotective effects by modulating the M1/M2 subset polarization of microglia/macrophages in the hippocampal CA1 region of vascular dementia rats via cannabinoid receptor 2.

BACKGROUND: Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model. METHODS: One week after surgery, PF was intraperitoneally administered at a dose of 40 mg/kg once a day for 28 successive days. The effects of PF on memory deficit were investigated by a Morris water maze test, and the effects of PF on hippocampal neuronal damage were evaluated by light microscope and electron microscope. The mRNA and protein expression levels of key molecules related to the M1/M2 polarization of microglia/macrophages were assessed by RT-qPCR and Western blotting, respectively. RESULTS: Administration of PF could significantly attenuate cerebral hypoperfusion-induced impairment of learning and memory and reduce the morphological and ultrastructural changes in the hippocampal CA1 region of rats. Moreover, PF promoted an M1 to M2 phenotype transition in microglia/macrophages in the hippocampus of rats. In addition to its inhibitory property against proinflammatory M1 mediator expression, such as IL-1ß, IL-6, TNF-α and NO, PF dramatically up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-ß1. Importantly, CB2R antagonist AM630 abolished these beneficial effects produced by PF on learning, memory and hippocampus structure in rats, as well as the polarization of microglia/macrophages to the M2 phenotype. Additionally, PF treatment significantly inhibited cerebral hypoperfusion-induced mTOR/NF-κB proinflammatory pathway and enhanced PI3K/Akt anti-inflammatory pathway. Effects of PF on these signaling pathways were effectively attenuated when rats were co-treated with PF and AM630, indicating that the mTOR/NF-κB and PI3K/Akt signaling pathways were involved in the PF effects through CB2R activation. CONCLUSION: These findings demonstrated PF exerts its neuroprotective effect and shifts the inflammatory milieu toward resolution by modulation of microglia/macrophage polarization via CB2R activation.

[Effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs].

OBJECTIVE: To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs. METHOD: Beagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration. RESULT: Compared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine. CONCLUSION: Methyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

The effects of Polygonum cuspidatum extract on wound healing in rats.

AIM OF THE STUDY: Polygonum cuspidatum has long been used as a traditional medicine inducing wound healing. In this study, the extract from the Chinese medicinal herb Polygonum cuspidatum was investigated on its wound healing activity, in order to obtain an accurate elucidation of its traditional use value. MATERIALS AND METHODS: After creating wound healing model on the back of rats, the extract from the Chinese medicinal herb Polygonum cuspidatum was applied. Wound healing rates were calculated at 3, 7, 14, and 21 days after the wounding, and tissues were harvested at 1, 3, 7, 14 and 21 days for histological and immunohistochemistry analysis. The stages of wound granulation tissues were evaluated histopathologically. The expression of TGF-ß1 was determined by immunohistochemically. RESULTS: Wound healing rates were significantly higher at 3, 7, 14 and 21 days in the extract group than in the control (p<0.05). Histological results showed more well-organized bands of collagen, more fibroblasts and hair follicle and less inflammatory cells in the extract group. The immunohistochemical results revealed that TGF-ß1 increased in the extract group on day 1, 3 and 7 post-wounding (p<0.05). CONCLUSION: The present study has shown that the extract from the Chinese medicinal herb Polygonum cuspidatum possesses wound healing activity, and thus provided the evidence for its traditional use value.

High mobility group-box 3 overexpression is associated with poor prognosis of resected gastric adenocarcinoma.

AIM: To elucidate high mobility group-box 3 (HMGB3) protein expression in gastric adenocarcinoma, its potential prognostic relevance, and possible mechanism of action. METHODS: Ninety-two patients with gastric adenocarcinomas surgically removed entered the study. HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded, and regular follow-up was made for all patients. The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests. Survival analysis was carried out by Kaplan-Meier (log-rank) and multivariate Cox (Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 expression to determine the prognosis value of HMGB3 expression on overall survival. Further, HMGB3 expression was knocked down by small hairpin RNAs (shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics. The MTT method was utilized to detect gastric cancer cell proliferation changes, and cell cycle distribution was analyzed by flow cytometry. RESULTS: Among 92 patients with gastric adenocarcinomas surgically removed in this study, high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues (P < 0.001). Further correlation analysis with patients' clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration (P = 0.005), a positive nodal status (P = 0.004), and advanced tumor-node-metastasis (TNM) stage (P = 0.001). But there was no correlation between HMGB3 overexpression and the age and gender of the patient, tumor localization or histologic grade. Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group (P = 0.006). The expected overall survival time was 31.00 ± 3.773 mo (95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo (95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression. Additionally, older age (P = 0.040), extensive wall penetration (P = 0.008), positive lymph node metastasis (P = 0.005), and advanced TNM tumor stage (P = 0.007) showed negative correlation with overall survival. Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age, gender, histologic grade, extent of wall penetration, lymph nodal metastasis, and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis (hazard ratio = 2.791, 95%CI = 1.233-6.319, P = 0.019). In the gene function study, after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA, the cell proliferation rate was reduced at 24 h, 48 h and 72 h. Compared to BGC823 shRNA-negative control (NC) cells, the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased (P < 0.01). Finally, cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase. The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%, and 73.03% ± 3.51% respectively (P = 0.001), whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%. CONCLUSION: HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.

[Experiment study of total anthraquinone in cassiae semen on lipid peroxidation and PPAR-gamma expression in liver tissues of rats with alcoholic fatty liver].

OBJECTIVE: To investigate the effect of total anthraquinone in Cassiae Semen on lipid peroxidation and peroxisome proliferator activated receptors gamma (PPAR-gamma) expression in liver tissues of rats with alcoholic fatty liver. METHOD: Referring to literature, it was established animal models of fatty liver feeding with alcohol. Rats were randomized into 6 groups, except the normal group, the other 5 groups of rats had been administered alcohol two times a day for 3 months. Rats were killed at the end of this experiment. It were respectively measured that the contents of ALT, AST, AKP, TG, TC, HDL-C, LDL-C, MDA, SOD, FFA in the serum and TG, TC, MDA, SOD, HL, LPL, FFA in the liver. The left leaf of liver was observed by histopathological staining, the immunohistochemical staining and RT-PCR were used to observe the effects on the expressions of PPAR-gamma mRNA. RESULT: Compared with the model group, total anthraquinone in Cassiae Semen could remarkably decrease the content of ALT, AST, TC, TG, MDA and increase the content of SOD in the serum of the experimental fatty liver induced by alcohol; remarkably decrease the content of TC, TG, FFA and increase the content of HL, LPL, SOD in the liver of the experimental fatty liver with induced by alcohol. Total anthraquinone in Cassiae Semen group was the similar the model group, but remarkably lighten inflammatory cell intiltration and fibrosis increasing. The RT-PCR and immunohistochemical staining results showed that: compared with the normal group,the model group could remarkably decrease the expression of PPAR-gamma mRNA in the liver (P < 0.01). Compared with the model group, total anthraquinone in Cassiae Semen could remarkably increase the expression of PPAR-gamma mRNA in the liver of the experimental fatty liver (P < 0.01). CONCLUSION: The results showed that total anthraquinone in Cassiae Semen has good effects on the treatment of hepatic fat induced by alcohol diet in rats. the possible action mechanism of total anthraquinone in Cassiae Semen possess obvious effect of regulating the disorder of lipid metabolism, ameliorating hepatic function, as well as anti-lipidperoxidation, increasing the expression of PPAR-gamma in hepatic cells of rats.

[Effect of traditional Chinese medicine injections on type I allergy].

OBJECTIVE: To investigate allergic reactions of traditional Chinese medicine (TCM) injections, and to determine the contents of serum IgE and histamine in sensitized animal. The correlation between the preceding contents in serum and allergic reactions may be found, thus offering experimental evidences for advancing the accuracy of anticipation by type I allergy. METHOD: We carried out passive cutaneous anaphylaxis (PCA) tests,active systemic anaphylaxis (ASA) tests and anaphylactoid reactions using three TCM injections, and determined the contents of serum OVA-sIgE, total serum IgE and histamine in sensitized animals by ELISA method. RESULT: The results of PCA test were negative, and there was no significant difference for total serum IgE level between experimental group and normal saline group. In the study of adjuvant effect in TCM injections + OVA (at the dose level that doesn't cause allergic reactions), the PCA results of SHL and YXC were positive and there was a increase in content of serum OVA-sIgE, while the PCA result of QKL was negative with a unobvious increase in the content of serum OVA-sIgE. The content of total serum IgE wasn't remarkably increased in each group and the results of ASA test were all positive. Three injections all caused anaphylactoid symptoms in guinea pigs in different doses or injection speed and the response intensity was found to be dosage and injection speed dependant. Furthermore, there was no significant difference for the content of total serum IgE in each group, whereas serum histamine concentration in every experimental group was markedly higher than normal saline group. CONCLUSION: SHL and YXC increase the sensitivity of guinea pigs on OVA, and three TCM injections can cause allergic reactions in guinea pig. Allergic reactions of three TCM injections are correlated with specific IgE antibodies and histamine contents.

[Determination of plasma concentration of N-methylcantharidimide by HPLC and its pharmacokinetics after intravenous administration in dogs].

OBJECTIVES: To establish a HPLC method for determination of N-methylcantharidimide in dogs' plasma and to study the pharmacokinetics of N-methylcantharidimide in dogs'. METHOD: The plasma samples were extracted by methanol. The acetonitrile and the purified water composed mobile phase. The flow rate was 0. 7 mL x min(-1), ultraviolet detection wavelength was at 212 nm. RESULT: The calibration curve was linear over the range from 0.01-10.0 mg x L(-1) with a correlation coefficiency of 0.996 3. The lower limit of quantitation was 0.01 mg x L(-1). The mean recovery was 92.3%. the relative standard deviation (RSD) of intra-day and inter-day were all less than 10%. After intravenous administration of N-methylcantharidimide with 3 dosages of 10, 15, 20 mg x kg(-1) to dogs, the corresponding distribution half-livers (t1/2alpha) were 1.8, 2.1, 1.7 min, and the elimination half-lives (t1/2beta) were 144,139, 146 min, respectively. CONCLUSION: This method is convenient, accurate and reliable. It can be used for determination of N-methylcantharidimide in dogs' plasma and pharmacokinetic studies.

[Effects of Tripterygium hypoglaucum on serum IL-1, IL-6, and TNF-alpha in chronic nephritis rats].

OBJECTIVE: To investigate the effects and mechanism of Tripterygium hypoglaucum (THH) on serum IL-1, IL-6, and TNF-alpha in chronic, nephritis rats. METHOD: The rabbit serum of anti-rat kidney was initially prepared, and then injected into normal rats to induce the formation of chronic glomerulonephritis. In this model, THH was administrated for 4 weeks, while saline and prednisone were respectively used as negative and positive controls. Some of laboratory parameters were observed from the rats above. RESULT: THH not only significantly decreased urine protein, reduced serum urea nitrogen, but also decreased the releases of inflammatory mediators (such as IL-1, IL-6 and TNF-alpha). CONCLUSION: THH is effective in treating rat nephrotoxic serum glormerulonephritis, its mechanism probably related to decreasing inflammatory mediator levels.