Identification of Hub Genes and Pathways of Middle Cerebral Artery Occlusion in Aged Rats Using the Gene Expression Omnibus Database.

Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signaling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signaling pathway, the IL-17 and other signaling pathways were significantly correlated with the aged MCAO rats. Our study indicates that multiple genes and pathological processes involved in the aged people of stroke. The immune response might be the key pathway in the intervention of cerebral infarction in aged people.

Circ_0027470 promotes cadmium exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and stimulating SHH signaling pathway.

Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.

The exosome-circ_0001359 derived from cigarette smoke exposed-prostate stromal cells promotes epithelial cells collagen deposition and primary ciliogenesis.

Cigarettes consumption is continued to be popular. We found that cigarette smoke (CS) exposure promoted prostatic fibrosis. In this study, human prostate epithelial RWPE-1 cells were co-cultured with exosomes derived from CS exposed-WPMY-1 cells (CS-WPMY-1-exo). The collagen deposition, primary ciliogenesis, epithelial-mesenchymal transition (EMT) and transforming growth factor (TGF)-ß1 level of RWPE-1 were evaluated. The circRNAs profiles of WPMY-1-exo were explored by high-throughput RNA sequencing. It was found that CS-WPMY-1-exo significantly promoted RWPE-1 collagen deposition, EMT and primary ciliogenesis. There were 17 differentially expressed (DE) circRNAs (including circ_0001359) between CS-WPMY-1-exo and the negative control. Functional enrichment analyses showed that the DE circRNAs played important roles in ciliary basal body, spindle microtubule and TGF-ß signaling pathway. Circ_0001359 siRNA attenuated CS-WPMY-1 induced RWPE-1 cells collagen deposition, EMT and primary ciliogenesis, as well as inhibited the level of TGF-ß1. The whole results showed that circ_0001359 derived from CS-WPMY-1-exo contributed to prostatic fibrosis via stimulating epithelial cells phenotypes changes and collagen deposition.

The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition.

Benign prostatic hyperplasia (BPH) is an age-related disease in men. Mesenchymal /stromal and epithelial cells interactions are essential to prostate functions. In this study, human nonmalignant prostate epithelial RWPE-1 cells were cocultured with testosterone (TE) -exposed prostate stromal fibroblasts WPMY-1 cells (TE-WPMY-1). The survival rate, epithelial-mesenchymal transition (EMT) and collagen deposition of RWPE-1 were observed. The expression profiles of circRNAs, lncRNAs and mRNAs in WPMY-1-derived exosome-like vesicles (WPMY-1-exo) were explored by high-throughput RNA sequencing. Firstly, both TE-WPMY-1 and TE-WPMY-1-exo significantly promoted RWPE-1 cells proliferation. Secondly, 41 circRNAs, 132 lncRNAs and 1057 mRNAs were differentially expressed (DE) between TE-WPMY-1-exo and the control. Functional enrichment analyses, co-expression analyses and quantitative real-time PCR verification showed that the DE RNAs played important roles in cell proliferation, structure, phenotype and fibrosis. Lastly, blocking WPMY-1-exo biogenesis/release by GW4869 can attenuate TE-WPMY-1-stimulated RWPE-1 cells EMT and collagen deposition. Taken together, our results indicated that WPMY-1-exo modulated the phenotypes changes and collagen deposition of prostate epithelial cells. It provided a novel basis for understanding the underlying mechanisms of RWPE-1 cells EMT and fibrosis induced by WPMY-1 in BPH.

Potential ameliorative effects of epigallocatechin-3-gallate against cigarette smoke exposure induced renal and hepatic deficits.

The environmental pollution caused by cigarette smoke (CS) seriously endangers people's health. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea. In this study, rats were exposed to CS for 90 days. Kidney function was evaluated by detecting the levels of serum creatinine and blood urea nitrogen. Liver function was evaluated by detecting the activities of alanine aminotransferase and aspartate transaminase. The renal and hepatic oxidative stress and inflammation were assessed by detecting the levels of malondialdehyde, reduced glutathione, antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and proinflammatory cytokines. Organ fibrosis was evaluated by observing collagen deposition via masson staining, by examining the hydroxyproline level, by measuring the mRNA levels of fibrosis-associated genes collagen (Col)-1A1 and Col-3A1, as well as by assessing the activity of profibrotic TGF-ß1 pathway. Additionally, renal and hepatic epithelial-mesenchymal transition (EMT) were evaluated. It was observed that EGCG ameliorated the renal and hepatic oxidative stress, inflammation, EMT, as well as inhibited the activation of TGF-ß1 signaling pathway induced by CS. These results showed that EGCG could attenuate CS-induced renal and hepatic fibrosis.

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-ß1/Smad Pathways.

BACKGROUND/AIMS: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. METHOD: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. RESULTS: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-ß1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. CONCLUSION: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-ß1/Smad pathways.

Bisphenol A exposure stimulates prostatic fibrosis via exosome-triggered epithelium changes.

Fibrosis is the pathological basis for the clinical progression of benign prostatic hyperplasia (BPH). Prostatic fibrosis is an important risk factor in patients with BPH who experience lower urinary tract symptoms. Bisphenol A (BPA) is an environmental endocrine disruptor (EED) that causes prostate defects. The effects of BPA on the prostate were investigated in this study using mouse and human prostate cell models. BPA-induced mouse prostatic fibrosis is characterized by collagen deposition and an increase in hydroxyproline concentration. Furthermore, BPA-exposed prostatic stromal fibroblasts exosomes promote the epithelial-mesenchymal transition of epithelial cells. High-throughput RNA sequencing and functional enrichment analyses show that substantially altered mRNAs, lncRNAs and circRNAs play roles in cellular interactions and the hypoxia-inducible factor-1 signaling pathway. The results showed that exosomes participated in the pro-fibrogenic effects of BPA on the prostate by mediating communication between stromal and epithelial cells and triggering epithelial changes.

(2S)-5, 2', 5'-trihydroxy-7-methoxyflavanone, a natural product from Abacopteris penangiana, presents neuroprotective effects in vitro and in vivo.

The aim of this study was to investigate the neuroprotective effects of (2S)-5, 2', 5'-trihydroxy-7-methoxyflavanone (TMF), a natural product from Abacopteris penangiana (Hook.) Ching, in oxidative stress-induced neurodegeneration models in vitro and in vivo. In PC12 cells, preincubation of TMF (3-20 µM) for 24 h decreased the dopamine-induced toxicity and attenuated the redox imbalance in PC12 cells through regulating the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG), which is a sensitive marker of oxidative stress. Additionally, long-term intraperitoneal (i.p.) injection of TMF (4 or 8 mg/kg/day) for 2 weeks significantly improved the behavioral performance of D-galactose (D-gal) treated mice in a Morris water maze test. Biochemical analysis revealed that TMF inhibited the activation of AP-1 (activator protein-1) and upregulated the level of BDNF (brain derived neurophic factor) as well as the ratio of GSH/GSSG in the hippocampus of D-gal treated mice. Furthermore, western blotting analysis indicated that TMF increased phosphorylation of cAMP-response element-binding protein (CREB). Therefore, the natural product TMF possessed a potential for the treatment of neurodegenerative diseases.

Prostatic protective nature of the flavonoid-rich fraction from Cyclosorus acuminatus on carrageenan-induced non-bacterial prostatitis in rat.

Abstract Context: Cyclosorus acuminatus (Houtt.) Nakai (Thelypteridaceae) is used in Chinese traditional medicine for inflammation and pyretic stranguria. Objective: This study investigates the prostatic protective potential of the flavonoid-rich [(2S)-5,7,5'-trihydroxyflavanone glycosides] fraction from C. acuminatus (FCA). Materials and methods: Chronic non-bacterial prostatitis (CNBP) was induced by injecting 20 µl of 1% carrageenan into the rat prostate. Subsequently, FCA (150 or 300 mg/kg/d) was orally given once a day for 4 weeks. Finally, the levels of proinflammatory cytokines and the prostatic expression of peroxisome proliferator activated receptor-γ (PPAR-γ) were evaluated. Results: Treatment with 300 mg/kg/d FCA ameliorated the carrageenan-induced higher prostatic index (PI) state and proinflammatory cytokines levels (NFκB from 2602 ± 588 to 1348 ± 300 pg/ml, TNF-α from 151.6 ± 10.4 to 126.0 ± 3.52 pg/ml, IL-1ß from 153.7 ± 14.8 to 63.9 ± 6.7 pg/ml, COX-2 from 313.3 ± 16.5 to 263.1 ± 15.1 pg/ml, PGE from 1532 ± 130 to 864 ± 126 pg/ml, NOS from 33.7 ± 3.0 to 23.6 ± 1.6 U/mg protein, and NO from 40.3 ± 2.9 to 27.1 ± 2.9 µmol/g protein) as well as regulated the prostatic expression of PPAR-γ (increased about 3.50-fold) when compared to the rat model of prostatitis. Discussion and conclusion: FCA could exert a prostatic protective response via modulating the prostatic expression of PPAR-γ and eventually alleviating the NFκB dependent inflammatory response.

Parathelypteriside attenuates cognition deficits in d-galactose treated mice by increasing antioxidant capacity and improving long-term potentiation.

Parathelypteriside (PG), a stilbenoid compound, was extracted from Parathelypteris glanduligera (kze.) ching that exhibits antioxidative and anti-inflammatory effects. The aim of this study was to investigate the protective effect of PG against the d-galactose (d-gal)-induced neurotoxicity in mice. It was found that long-term intraperitoneal (i.p.) injection of PG (5 or 10 mg/(kg day)) for two weeks significantly improved the behavioral performance of d-gal-treated mice in both Morris water maze test and step-down avoidance test. Biochemical examination revealed that PG reduced the increased levels of malondialdehyde (MDA), and attenuated the decreased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the hippocampus of d-gal-treated mice. Furthermore, the electrophysiological assay showed that PG significantly rescued the long-term potentiation (LTP) impairment in mice hippocampus, and western blotting analysis indicated that the effects of PG on LTP might be attributed to the activation of cAMP-response element-binding protein (CREB). Together, these results suggested that the natural product PG represented a potential source of medicine for the treatment of the neurodegenerative diseases.

The anti-inflammation, anti-oxidative and anti-fibrosis properties of swertiamarin in cigarette smoke exposure-induced prostate dysfunction in rats.

Chronic cigarette smoke (CS) exposure induces prostate deficits. We previously found that swertiamarin had prostatic protective potential. This study was to investigate the possible protective effect of swertiamarin against CS-induced prostate dysfunction on human prostate epithelial cells, stromal cells and rats. Rat prostate collagen deposition and fibrosis were assessed by sirius red staining and measuring hydroxyproline content, as well as by qPCR and western blot analysis for fibrotic extracellular matrix components. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. In order to explore its underling mechanisms, the activities of Hedgehog signaling pathway and epithelial-mesenchymal transition of human prostate cells and rat prostate tissue were estimated. It was found that swertiamarin ameliorated CS-induced prostatic collagen deposition, relieved oxidative stress and local inflammation, inhibited the activation of Hedgehog signaling pathway and attenuated epithelial-mesenchymal transition. It indicated that swertiamarin could ameliorate CS-induced prostatic fibrosis by inhibiting epithelial-mesenchymal transition and Hedgehog pathway.

Potential ameliorative effects of epigallocatechin­3­gallate against testosterone-induced benign prostatic hyperplasia and fibrosis in rats.

Green tea is among the most popular beverages in the world and is an important source of phytoestrogens. Epigallocatechin­3­gallate (EGCG) is the major polyphenol in green tea. The aim of this study was to investigate the anti-benign prostatic hyperplasia (BPH) activity and underling mechanisms of EGCG in testosterone-induced BPH rats and in BPH-1 cells. Prostatic levels of oxidative stress and inflammation makers, as well as angiogenesis related growth factors were measured. Additionally, the prostatic levels of sex hormonal mediators (androgen receptor (AR), estrogen receptor (ER)-α and ER-ß), hypoxia-inducible factor (HIF)-1α, transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad3, phosphorylation-Smad3 (p-Smad3), epithelial-mesenchymal transition (EMT) markers (E-cadherin, collagen-I, fibronectin and α-SMA) and microRNA (miR)-133a/b were analyzed by immunohistochemistry assay, western blot and/or quantitative RT-PCR. It was observed that EGCG attenuated the prostatic oxidative stress and inflammatory microenvironment, ameliorated prostatic hyperplasia and collagen deposition, reduced the levels of angiogenesis related growth factors, inhibited the over-expression of AR, ER-α, HIF-1α, TGF-ß1, TGF-ßRI and p-Smad3, enhanced the expression of ER-ß, increased the levels of miR-133a/b, as well as relieved prostatic EMT in rats. Both HIF-1α inhibitor and EGCG decreased the expression of HIF-1α and TGF-ß1, as well as attenuated EMT in BPH-1 cells. It indicated that EGCG could attenuate testosterone-induced BPH and fibrosis.

Potential ameliorative effects of grape seed-derived polyphenols against cadmium induced prostatic deficits.

Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl2. GSP also inhibited the over-generation of TGF-ß1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits.

Antiplatelet drug ticagrelor delays gastric ulcer healing in rats.

Adenosine diphosphate P2Y12 receptor antagonist clopidogrel is not sufficiently safe for the gastric mucosa in patients with high risk of peptic ulcer, since it may impair healing of gastric erosions. However, the safety of the novel P2Y12 receptor antagonist ticagrelor in the gastric mucosa has not been elucidated to date. The present study aimed to examine whether ticagrelor delays gastric ulcer healing and to elucidate the involved mechanisms. Gastric kissing ulcers were produced in rats by luminal application of acetic acid solution, and ticagrelor was administered at dose of 10 or 20 mg/kg/day orally for 7 days. On day 8 after ulcer induction, the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and signal transduction pathways for cell proliferation and angiogenesis were measured and compared between the ticagrelor-treated and untreated model groups. The results revealed that the ulcer size was significantly greater in the ticagrelor-treated group compared with the model group, while the mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the ticagrelor-treated group. In addition, ticagrelor significantly decreased the ulcer-stimulated expression levels of EGF, VEGF, phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated P38 mitogen-activated protein kinase and nuclear factor-κB P65 at the ulcer margin (P<0.05). These findings suggested that ticagrelor delayed gastric ulcer healing. Furthermore, the possible mechanisms underlying the effect of ticagrelor were associated with its functions of attenuating the expression levels of VEGF and EGF, as well as suppressing the phosphorylation activation of ERK1/2, P38 and nuclear factor-κB P65. Finally, the gastric epithelial cell proliferation and angiogenesis were also inhibited.

Protective potential of epigallocatechin-3-gallate against benign prostatic hyperplasia in metabolic syndrome rats.

Epigallocatechin-3-gallate (EGCG) is a major catechin in green tea with functions of antioxidant, anti-proliferative, anti-inflammatory and attenuating metabolic syndrome. In this study, rat model of benign prostatic hyperplasia (BPH) accompanied with metabolic syndrome was induced by fed on high-fat diet for 12 weeks combined with testosterone injection (10mg/kg/d) from 9th to 12th weeks. EGCG was orally given from 9th to 12th weeks. Finally, the levels of glucose, total cholesterol, triglyceride, prostate weight, insulin-like growth factors (IGFs), inflammatory cytokines, antioxidant enzymes, and prostatic expression of IGF binding protein-3 (IGFBP-3) and peroxisome proliferator activated receptors (PPARs) were evaluated. It was found that EGCG significantly decreased the levels of glucose, total cholesterol, triglyceride, IGFs, and inflammatory cytokines, normalized the activities of antioxidant enzymes, as well as increased the prostatic expression of IGFBP-3 and PPARs. These results indicated that EGCG was able to exert anti-BPH activities in metabolic syndrome rats.

Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis.

Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-ß1 (TGF-ß1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-ß1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury.

Anti-hyperplasia effects of Rosa rugosa polyphenols in rats with hyperplasia of mammary gland.

Rosa rugosa (Thunb.) is used in Chinese traditional medicine with the functions of promoting blood circulation, relieving the depressed liver and attenuating breast disorders. This study was to investigate the anti-hyperplasia effects of the polyphenols-rich fraction from R. rugosa (FRR) in rat. Rat model of hyperplasia of mammary gland (HMG) was induced by intramuscularly injected with estrogen (0.5mg/kg/d) for 25 days, and followed with progestogen (5mg/kg/d) for another 5 days. Meanwhile, FRR was orally given for 30 days. Then, the levels of estradiol and oxidative stress were assessed. The mammary expressions of AKT and JNK were evaluated by Western blot analysis. The expressions of NFκB-p65, COX-2 and VEGF were measured by immunohistochemical analysis. The whole results indicated that FRR could exert anti-hyperplasia effects in rat via modulating the mammary expression of JNK and AKT, as well as alleviating the NFκB related oxidative stress and inflammatory responses.

Epigallocatechin-3-gallate attenuates lipopolysaccharide-induced mastitis in rats via suppressing MAPK mediated inflammatory responses and oxidative stress.

Green tea (Camellia sinensis) is an extremely popular beverage worldwide. Epigallocatechin-3-gallate (EGCG) is one of the major catechins isolated from green tea and contributes to its beneficial therapeutic functions including antioxidant, anti-inflammatory and anti-cancer effects. However, the effect of EGCG on mastitis is not yet known. This study was to investigate the protective potential of EGCG against mastitis in rats. The rat mastitis model was induced by injecting lipopolysaccharide (LPS) into the duct of mammary gland. The mammary gland was collected after the experimental period. The levels of mammary oxidative stress and inflammatory responses were assessed by measuring the local activities of antioxidant enzymes and the levels of inflammatory cytokines. The mammary expressions of mitogen-activated protein kinases (MAPKs), nuclear factor κB-p65 (NFκB-p65) and hypoxia-inducible factor-1α (HIF-1α) were evaluated by western blot analysis. It was found that EGCG obviously normalized LPS-induced low activities of antioxidant enzymes as well as decreased the high levels of inflammatory cytokines. Additionally, EGCG inhibited the mammary over-expression of MAPKs, NFκB-p65 and HIF-1α. These results indicated that EGCG was able to attenuate LPS-induced mastitis in rats by suppressing MAPK related oxidative stress and inflammatory responses.

Multitargeted protective effect of Abacopteris penangiana against carrageenan-induced chronic prostatitis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Abacopteris penangiana (Hook.) Ching (AP) is traditionally used in Chinese medicine to promote blood circulation, remove blood stasis and dampness and for the treatment of edema and inflammation. In order to further support and develop the traditional use of Abacopteris penangiana as Chinese folk medicine, the aim of this study is to investigate the protective effect of the total flavanol glycosides (TFA) from AP and its acid hydrolysate (AHT) on chronic non-bacterial prostatitis (CNP) by measuring the levels of oxidative stress and inflammatory responses in rats. MATERIALS AND METHODS: First, the antioxidant and anti-inflammatory activities of AHT and TFA were investigated. Then the experimental chronic non-bacterial prostatitis was induced by carrageenan. The prostate index (PI) and prostate specific antigen (PSA) were determined. The activities of AHT and TFA on inhibiting free radicals and oxidative stress were investigated. Subsequently, the degree of chronic inflammatory cell infiltrates, acinar changes and interstitial fibrosis were evaluated by histopathological examination. In addition, the relative inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), cyclooxygenase-2 (COX-2), prostaglandin E2 (PEG2), transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) were measured. Finally, the prostatic expression of nuclear transcription factor-κB (NF-κB) was determined by immunohistochemistry and western blot analysis. RESULTS: The whole results showed that AHT and TFA had strong antioxidant and anti-inflammatory activities. In CNP model, AHT and TFA successfully decreased PI and PSA. The activities of antioxidant enzymes in AHT or TFA group were enhanced. Additionally, a morphometric analysis of the prostate gland of AHT or TFA treated rats demonstrated a significant reduction in chronic inflammatory cell infiltrates and interstitial fibrosis compared to model group. The reduced values of TNF-α, IL-1ß, COX-2, PEG2, inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were observed both in AHT and TFA treated groups. Moreover, the levels of TGF-ß1 and CTGF in AHT and TFA treated groups were significantly decreased along with the alleviation of the inflammatory state of the prostate gland. Besides, the prostatic expression of NF-κB was inhibited. CONCLUSIONS: These results suggest that AHT and TFA have anti-prostatitis properties via inhibiting oxidative stress, NF-κB dependent pro-inflammatory cytokines, fibrosis-related factors and antinociceptive activity. Hence, AP represents a potential herb for the treatment of prostatitis.

Renoprotective potential of Macrothelypteris torresiana via ameliorating oxidative stress and proinflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Macrothelypteris torresiana is traditionally used in Chinese folk medicine for the treatment of edema for patients suffering from kidney/bladder problems due to its satisfactory therapeutic effectiveness. AIM OF THE STUDY: The aim of this study was to investigate the renoprotective nature of the total polyphenols fraction from Macrothelypteris torresiana (PMT). MATERIALS AND METHODS: The biochemical criterions of plasma and kidney tissues were evaluated to study the effects of PMT on puromycin aminonucleoside-induced chronic nephrotic syndrome (NS) in hyperlipidemic mice. RESULTS: In this study, the NS and hyperlipidemia were ameliorated after 9 weeks administration of PMT. Besides, PMT was able to modulate the level of renal oxidative stress and vascular endothelial growth factor-nitric oxide (VEGF-NO) pathway. CONCLUSIONS: It represented a potential resource of PMT for the treatment of NS involved in metabolic syndrome.