Effect of hirudin on pulmonary fibrosis by regulating p38MAPK/NF-kB signaling pathway and its mechanism / 中国药理学通报

Aim To observe the effect of hirudin on pulmonary inflammation and fibrosis in rats with bleo-myc in-induced pulmonary fibrosis and the underlying mechanism.Methods Sixty male SD rats were ran¬domly divided into control group, model group, hirudin treatment group ( low,medium and high concentration) and prednisone group.The control group received en-dotracheal injection of saline, while the remaining five groups carried out endotracheal one-time injection of blemycin to establish rat pulmonary fibrosis model.From the second day after modeling, hirudin treatment groups were respectively administered different concen¬trations of hirudin subcutaneous injection, while control group was given saline, and prednisone was gavaged with 5 mg • kg~1 prednisone acetate, then all rats were sacrificed on day 28.Lung lesions were observed by HE and Masson staining.The relative expression levels of COL 1 and ot-SMA mRNA were detected by real¬time fluorescence quantitative PCR.The content of hydroxy proline ( HYP) in lung tissues was determined by kit.The expression levels of p38MAPK/NF-KB sig¬naling pathway related proteins in lung tissues were de¬tected by Western blot, and IL-6 and TNF-cx levels were detected by ELISA.Results Compared with model group, the inflammatory response and interstitial fibrosis of lung tissues were improved, the content of hvdroxvproline decreased, the expression of p-p38 MAPK,NF-kB p-p65and p~IkB protein decreased, and the concentration of TNF-cx and IL-6 decreased after hirudin intervention.Conclusions Hirudin can effec¬tively inhibit alveolar inflammation and reduce the de¬velopment of pulmonary fibrosis, which may be related to regulating p38 MAPK/NF-kB signaling pathway,re¬ducing the inflammatory response of lung tissues and reducing the deposition of extracellular matrix.

Virtual screening of anti-inflammatory components in Blumea balsamifera(L.)DC.And effect of ergosterol peroxide on NF-kB Signaling pathways / 中国药理学通报

Aim To target the key proteins of TLR4 signaling pathway to sereen the compounds of Blumea baisamifera ( L.) DC.in order to explore the anti-in- flammatorv active components and the mechanism of action of key proteins targeting TLR4 signaling pathway in Blumea balsamifera( L.) DC.Methods The effects of ergosterol peroxide ( EP) on cell activity, LPS in¬duced inflammatory factor secretion and NF-kB related protein expression were detected by MTT, EL1SA, Western blot and Subcellular Structural Localization.Results The results showed EP, (3-sitosterol, 16- kaurene, carosterol, luteolin, ergosterol, hyperin and genkwa had more optimal interconnection score.EP (2.3 x 10"5 ~ 9.3 x 10 5 mol • L"1) inhibited the degradation and phosphorylation of inflammatory pro¬tein IkB and phosphorylation of NF-kB p65 down¬stream of TLR4 signaling pathway induced by LPS in BAW264.7 cells,and further inhibit the entrv of NF-kB p65 into the nucleus, thus inhibiting the secretion of cytokines IL-lp and 1L-6.Conclusions The antiin¬flammatory components of Blumea balsamifera ( L.) DC are identified by molecular docking technology and ac-tivity detection technique, and the anti-inflammatory action anrl mechanism of EP as active substances are e- luci dated.

Soy isoflavones inhibit inflammation and apoptosis of hippocampal neurons induced by Ap, -42 through NF-kB p65 signaling pathway / 中国药理学通报

Aim To explore the effeet of soy isofla- vones (SI) on p-amyloid 1 -42 ( Ap, _42 ) -induced hippocampal neuroinflammation and neuronal apoptosis and the underlying mechanism.Methods The prima¬ry hippocampal neurons cultured in vitro were divided into control group (control), Ap,_42 treatment group f model) , SI low-dose group ( Sl-L, 10 mg • L 1 ) , and SI medium-dose group (SI-M, 20 mg • L_l ) and SI high-dose group (SI-H, 40 mg • L 1 ).The model group was treated with 30 (xmol • L"1 Ap, _42 for 48 h; the SI-L, SI-M and SI-H groups were treated with SI for 2 hours, and Ap,_42 was treated for 48 h; the con¬trol group was routinely cultured for 48 h.MTT method was used to detect the survival rate of hippocampal neurons; TUNEL staining was used to detect the apop¬tosis rate of hippocampal neurons; Western blot was used to detect COX-2, TNF-a, NF-kB p65 , P-NF-kB p65, Bcl-2 and caspase-3 protein expression levels.Results Compared with the control group, the surviv¬ al rate of hippocampal neurons was significantly re- duced (P <0.01) , and the apoptotie rate significantly increased (P<0.01).COX-2, TNF-a, p-NF-KB p65 , caspase-3 protein expressions markedly increased (P <0.05 or P <0.01 ) , and the expression of Bcl-2 protein significantly decreased in the model group ( P <0.01 ).Compared with the model group, the surviv¬al rate of hippocampal neurons, Bcl-2 protein in-creased, and the apoptotic rate, the expression of COX-2, TNF-a, p-NF-KB p65 , caspase-3 protein de¬creased (P < 0.05 or P < 0.01 ) in SI each dose group.Conclusion SI can reduce the hippocampal neuroinflammation and neuronal apoptosis induced by APi _42 by inhibiting the activation of NF-kB p65 signa¬ling pathway.

Inhibition of salidroside on airway remodeling in asthmatic mice by modulating NF-κB/TGF-β1 signaling pathway / 中草药

Objective: To investigate the effects of salidroside on airway remodeling and NF-κB and TGF-β1 signal transduction pathway in asthmatic mice. Methods: Forty female BALB/c mice of clean grade were randomly divided into four groups (n = 10), such as control, egg protein (OVA) asthma, low-, and high-dose salidroside groups. OVA was used to establish the asthmatic mice model, and the left lung tissues of all mice were treated by HE, PAS, and Masson trichrome staining after the last excitation in 24 h. The right lung tissues were detected by enzyme linked immunosorbent assay (ELISA) to observe the expression levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), by RT-PCR to investigate the expression level of TGF-β1 mRNA, and by Western blotting to detect the expression levels of TGF-β1 and NF-κB p65 proteins. Results: Compared with the control group, the inflammatory cell counts and the expression levels of IL-4, IL-5, and IL-13 in asthmatic model group were increased. The expression levels of TGF-β1 mRNA and NF-κB protein from lung tissues were significantly higher than those in the control group (P 0.05). Conclusion: Salidroside might inhibit the development of airway remodeling in asthmatic mice, and the mechanism might be partly achieved through the inhibition of NF-κB/TGF-β1 signal transduction pathway.

Effect of chinese traditional herb Epimedium grandiflorum C.Morren and its extract Icariin on osteoarthritis via suppressing NF-kB pathway.

Osteoarthritis (OA), which is also called degenerative arthritis, is the leading cause of disabilities in the old people. The Chinese traditional herb Epimedium grandiflorum had long been found to attenuate osteoarthritis process, but the detailed mechanism was not clear. To study the mechanisms of E. grandiflorum in the treatment of osteoarthritis, rabbit osteoarthritis model combined with D-galactose was used. After different treatments for 10 weeks, cartilage sections were analyzed by immunohistochemistry for uPA, uPAR and PAI expression level. E. grandiflorum could significantly attenuate OA condition and decrease uPA, uPAR and PAI expression. The extract of E. grandiflorum, icariin also had a similar effect when compared with E. grandiflorum treatment alone. Rabbit chondrocytes were further isolated to be stimulated by TNFα combined with different reagents treatment. Here, icariin treatment significantly reduced nuclear factor kappa B NF-B (P65) activity, decreased uPA expression level and increased IBα protein level. The results indicated that E. grandiflorum and its extract icariin could attenuate OA condition, reduce the expression of uPA and uPAR and increase PAI in experimental rabbit model and this effect may be conducted by suppressing NF-kB activity by increasing IkBα level.