Intervention of Osteoking in Rats with Myofascial Pain Syndrome / 中国实验方剂学杂志

ObjectiveTo clarify the intervention effect of Osteoking （OK） in rats with myofascial pain syndrome （MPS） and preliminarily explore the pharmacological mechanism of OK in relieving chronic pain from the perspective of anti-inflammatory disease. MethodThe 60 SD rats were divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg-1）， and positive celecoxib group （21 mg·kg-1）. The MPS rat model was established by beating combined with the centrifugal exercise method， and the OK and celecoxib were given at the same time. SMALGO paw pressure pain manometer detected the shock pain point tenderness threshold of rats， and the Von-Frey needle and acetone stimulation method detected the mechanical hyperalgesia threshold and cold hyperalgesia stimulation response respectively. Eight weeks and 10 weeks after modeling， the spontaneous discharge state and convulsion response of MPS rats were determined by electromyograph （EMG） instrument. The gait changes of MPS rats were detected using a CatWalk gait analyzer. The expression levels of interleukin-1 β （IL-1β）， tumor necrosis factor-α （TNF-α）， substance P （SP）， and bradykinin （BK） were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of nuclear transcription factor-κB （NF-κB） inhibiting protein α （IκBα）， phosphorylates （p）- IκBα， NF-κB p65， and p-NF-κB p65 were detected in MPS rats by Western blot. The positive expression of p-NF-κB p65 was detected by immunofluorescence. ResultCompared with the normal group， the model group shows 100% positive rates for EMG signal and local convulsions response at both the 8th and 10th weeks. The tenderness threshold and mechanical hyperalgesia threshold are significantly reduced. Cold hyperalgesia score is significantly increased， and gait is abnormal. The expression levels of serum and trigger points IL-1β， TNF-α， SP， BK， p-IκBα， and p-NF-κB p65， as well as the positive expression intensity of p-NF-κB p65 are significantly increased （P<0.01）. Compared with the model group， the positive rate of EMG detection and local convulsion response is significantly reduced in the medium and high dose OK groups （P<0.05）. The tenderness threshold and mechanical hyperalgesia threshold increase significantly in the medium and high dose OK groups， and the cold hyperalgesia score is significantly reduced in the high dose OK group （P<0.01）. The standing time， swing time， and walking period are significantly increased. The swing speed， maximum contact area， and maximum contact intensity are significantly decreased in the high dose OK group （P<0.05）. Moreover， the protein expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 are significantly reduced in the medium and high dose OK groups （P<0.05，P<0.01）. The positive expression intensity of p-NF-κB p65 is significantly decreased in the high dose OK group （P<0.01）. ConclusionThe mechanism of OK in relieving the pain in trigger points of MPS and improving gait abnormalities is related to the downregulation of the NF-κB p65 inflammatory signaling pathway to reduce the expression of inflammatory factors and pain mediators in blood and trigger point tissue.

Aryl hydrocarbon receptors regulate pyocyanin-induced inflammatory factor expression in macrophages via p38MAPK/p65NF-κB signaling pathway / 中国药理学通报

Aim To investigate the effect of the aryl hydrocarbon receptor (AhR) on the expression of inflammatory factors in macrophages RAW264. 7 induced by pyocyanin (PCN) and the regulatory mechanism of its signaling pathway. Methods RAW264. 7 cells were treated with different concentrations of PCN for 24 h, respectively, and the effect of PCN on cell activity was detected by CCK8 assay to determine the optimal PCN concentration for manufacturing infection models. The cells were divided into the control group (given 0. 1% dimethyl sulfoxide DMSO), PCN group, PCN + AhR inhibitor (CH223191) group, and PCN + AhR agonist (FICZ) group, and the expression of AhR was detected by immunofluorescence. The expression levels of inflammatory factors (IL-6, IL-1β, and TNF-α) were detected by ELISA. The protein expression of AhR, pp38 MAPK and p-p65NF-κB, was detected by Western blotting. Results PCN induced a significant quantitative effect on AhR expression in RAW264. 7 cells. CH223191 increased PCN-induced inflammatory factor secretion and enhanced the phosphorylation of p38MAPK and p65NF-κB compared with the control group. FICZ decreased PCN-induced inflammatory factor production and reduced the phosphorylation of p38MAPK and p65NF-κB phosphorylation capacity. Conclusions AhR can regulate PCN-induced inflammatory factor expression in RAW264. 7 cells, and the p38MAPK/p65NF-κB signaling pathway may be an essential pathway for the involvement of AhR in immune regulation.

Effect of cangfudaotan decoction on TLR4/NF-κB p65 signaling pathway in obese PCOS-IR rats / 中国药理学通报

Aim To explore the regulatory effect of Cangfudaotan Decoction on the ovarian Toll receptor 4 (TLR4)/nuclear transcription factor kBp65 (NF-κB p65) signaling pathway in obese PCOS-IR rats. Methods Forty-eight female rats were randomly divided into normal group (n = 8) and model group (n = 40). The obese PCOS-IR rats were established by letrozole (1 mg · kg

Intervention effect of Tuina pressing and kneading the Huantiao (GB30) acupoint on NF-κB p65 protein at spinal cord dorsal horn in sciatica rats / 中国骨伤

OBJECTIVE@#To observe the analgesic effect of Tuina by pressing and kneading the Huantiao (GB30) acupoint on rats with chronic constriction injury (CCI) and to explore the analgesic mechanism of Tuina on sciatica rats.@*METHODS@#Thirty-two SPF male SD rats weighing 180 to 220 g were randomly divided into fore groups:blank group (without any treatment), sham group (only exposed without sciatic nerve ligating), model group (sciatic nerve ligating) and Tuina group (manual intervention after lsciatic nerve ligating). The CCI model was prepared by ligating the right sciatic nerve of the rats, on the third day of modeling, the rats in the Tuina group were given pressing and kneading the Huantiao (GB30) point for 14 days, and the changes of paw withdrawal threshold(PWT), paw withdrawal latency(PWL) were measured before and on the 1st, 3rd, 7th, 10th, 14th and 17th days after modeling. The changes of sciatic functional index(SFI) were measured before and on the 1st and 17th day after modeling. The morphological changes of the sciatic nerve were observed by hematoxylin-eosin(HE) staining;and the differences in NF-κB protein expression in the right dorsal horn of the spinal cord of rats were detected.@*RESULTS@#Following modeling, there was no significant difference in PWT, PWL and SFI between the blank group and the sham group (P>0.05), but the PWT, PWL and SFI of the model group and the Tuina group decreased significantly (P<0.01). After manual intervention, the pain threshold of rats in Tuina group increased. On the 8th day of manual intervention (the 10th day after modeling), PWT in Tuina group increased significantly compared with that in model group (P<0.01). On the 5th day of manual intervention (the 7th day after modeling), the PWL of the massage group was significantly higher than that of the model group (P<0.01). The pain threshold of rats in Tuina group continued to rise with the continuous manipulation intervention. After 14 days of manipulative intervention, the sciatic nerve function index of rats in the Tuina group increased significantly(P<0.01). Compared with the blank group and sham group, the myelinated nerve fibers of sciatic nerve in the model group were disordered and the density of axons and myelin sheath was uneven. Compared with the model group, the nerve fibers of rats in the Tuina group were gradually continuous and the axons and myelin sheath were more uniform than those in the model group. Compared with the blank group and sham group, the expression of NF-κB protein in the right spinal dorsal horn of the model group was significantly increased(P<0.01). Compared with the model group, the expression of NF-κB protein in the right spinal dorsal horn of rats in Tuina group decreased significantly(P<0.01).@*CONCLUSION@#Pressing and kneading the Huantiao (GB30) point restores nerve fiber alignment;and improves the PWT、PWL and SFI in the CCI model by decreasing NF-κB p65 protein expression in the spinal dorsal horn. There fore, Tuina demmstrates an analgesic effect and improves the gait of rats with sciatica.

Tongxie Yaofang Regulates T Lymphocyte Subsets to Improve Immune Microenvironment of Colorectal Cancer Under Chronic Stress / 中国实验方剂学杂志

ObjectiveTo explore the effect of Tongxie Yaofang on the immune microenvironment of colorectal cancer in mice under chronic stress and the underlying mechanism. MethodA total of 40 male SPF BABL/C mice were randomized into normal group， stress group， Tongxie Yaofang group （13.65 g·kg-1）， and Tongxie Yaofang-stress group （13.65 g·kg-1）， with 10 in each group. Chronic restraint stress was induced in mice and administration （ig） of Tongxie Yaofang began after 7 days of stress. On the 14th day， forced swim and tail suspension tests were used to examine the behavioral changes of mice after stress and the subcutaneous colorectal tumor was implanted in each group of mice. The effect of this prescription on the body mass and tumor volume of mice was observed. After the last administration， mouse serum and tumor samples were collected. The content of T lymphocytes （CD3+， CD4+， CD8+， and CD4+/CD8+） in tumor was detected by immunohistochemistry and flow cytometry and levels of corticosterone （CORT） in peripheral blood， and interleukin （IL）-2， interferon-γ （IFN-γ）， IL-6， and IL-10 in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of inhibitor of nuclear factor-κB（IκB） kinase α/β （IKKα/β）， nuclear factor-κB （NF-κB）α （IκBα）， NF-κB p65， and phosphorylated （p）-NF-κB p65 was measured by Western blot. ResultCompared with the normal group， the stress group had large tumor volume （P<0.05）， low content of CD3+， CD4+， and CD4+/CD8+ （P<0.05， P<0.01）， high content of CD8+， low content of T helper 1 （Th1）-secreted IFN-γ （P<0.05）， high content of T helper 2 （Th2）-secreted IL-10 （P<0.05） and CORT （P<0.05）， high protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and low protein expression of IκBα （P<0.05）. Compared with the normal group， the Tongxie Yaofang group showed slow tumor growth， high content of CD3+， CD4+， and CD4+/CD8+ （P<0.01）， low content of CD8+ （P<0.05）， high content of Th1-secreted IL-2 and IFN-γ （P<0.05）， low content of Th2-secreted IL-6 and IL-10 （P<0.05）， low content of CORT， low protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and high protein expression of IκBα （P<0.01）. Tongxie Yaofang-stress group demonstrated slower tumor growth， higher content of CD3+， CD4+， and CD4+/CD8+ （P<0.01）， smaller content of CD8+ （P<0.05）， higher content of IL-2 and IFN-γ （P<0.05）， lower content of IL-6， IL-10 （P<0.05）， and CORT （P<0.05）， lower protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05，P<0.01）， and higher protein expression of IκBα （P<0.01） than the stress group. ConclusionTongxie Yaofang can delay the growth of colorectal cancer under chronic stress and alleviate the deterioration of the immune microenvironment， possibly by inhibiting NF-κB signaling pathway， regulating the function of T lymphocyte subsets， and thus suppressing the secretion of pro-inflammatory factors.

Changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 and interleukin-6 levels in patients with acute ischemic cerebrovascular diseases / 中国基层医药

Objective:To investigate the changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 (NF-κB p65) and interleukin-6 (IL-6) levels in patients with acute ischemic cerebrovascular diseases.Methods:A total of 141 patients with acute ischemic cerebral infarction (AICI; AICI group) and 20 patients with transient ischemic attack (TIA; TIA group) who received treatment in Northern Jiangsu People's Hospital from April to November 2020 were included in this study. According to the volume of cerebral infarct, the AICI group was subdivided into small-volume cerebral infarct (SCI group, n = 78), moderate-volume cerebral infarct (MCI group, n = 32) and large-volume cerebral infract (LCI group, n = 31) groups. An additional 31 healthy controls who concurrently received physical examination were included as controls (HC group). S100A1, NF-κB p65, and IL-6 levels were compared between AICI, TIA and HC groups and between SCI, MCI and LCI groups. S100A1, NF-κB p65, and IL-6 levels were correlated with the National Institutes of Health Stroke Scale score and the volume of cerebral infarct. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of S100A1, NF-κB p65, and IL-6 levels for AICI. Results:S100A1, NF-κB p65, and IL-6 levels in the AICI group were (230.96 ± 39.37) ng/L, (3.99 ± 0.65) mg/L, (13.32 ± 1.57) ng/L, respectively, which were significantly higher than (185.85 ± 43.24) ng/L, (3.58 ± 0.74) mg/L, (11.61 ± 1.67) ng/L in the TIA group ( t = 4.95, 2.39, 4.14, all P < 0.05) and (181.47 ± 27.39) ng/L, (3.51 ± 0.99) mg/L, (11.42 ± 2.34) ng/L in the HC group ( t = 6.54, 3.32, 5.55, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between TIA and HC groups (all P > 0.05). S100A1, NF-κB p65, and IL-6 levels in the LCI group were (254.25 ± 37.07) ng/L, (4.41 ± 0.45) mg/L, and (14.00 ± 1.40) ng/L, respectively, which were significantly higher than (225.42 ± 30.92) ng/L, (3.85 ± 0.64) mg/L, (12.77 ± 1.31) ng/L in the MCI group ( t = 3.04, 3.60, 3.20, all P < 0.05) and (223.98 ± 40.21) ng/L, (3.88 ± 0.66) mg/L, (13.27 ± 1.65) ng/L in the SCI group ( t = 3.79, 4.01, 2.25, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between MCI and SCI groups (all P > 0.05). S100A1 and NF-κB p65 levels in patients with AICI were positively correlated with the volume of cerebral infarct ( r = 0.24, 0.27, both P < 0.05). S100A1 and IL-6 levels in patients with AICI were positively correlated with the National Institutes of Health Stroke Scale score ( r = 0.24, 0.28, both P < 0.05). The areas under the curves plotting S100A1, NF-κB p65, and IL-6 levels against AICI diagnosis were 0.818, 0.667 and 0.754, respectively. The optimal cutoff values were 181.03, 3.50 and 10.79, respectively. The corresponding sensitivities were 95.0%, 76.6% and 97.2%, respectively, and the specificities were 37.3%, 45.1% and 49.0%, respectively. Conclusion:Increased S100A1, NF-κB p65, and IL-6 levels in patients with AICI are closely related to the severity of AICI.

Dioscin attenuates inflammatory injury in uric acid-induced renal tubular epithelial cells by suppression of NF-κB signaling pathway / 中国临床药理学与治疗学

AIM: To observe the effect of Dioscin treatment on NF-κB signaling pathway and cellular inflammatory injury and explore its potential mechanism in uric acid-induced mouse tubular epithelial cells (mTECs). METHODS: After 1.2 mol/L uric acid induced mTECs, Dioscin and NF-κB P65 inhibitor BAY11-7082 were given to intervene respectively. IκB-α, NF-κB P65, PP65, NLRP3, IL-1β and β-actin were detected by Western Blot, immunofluorescence staining and real-time PCR. RESULTS: Western Blot, immunofluorescence staining and real-time PCR analysis showed that expression levels of PP65, NLRP3 and IL-1β were significantly downregulated in the uric acid-induced mTECs with Dioscin and BAY11-7082 treatment. CONCLUSION: Dioscin attenuates uric acid-induced cellular inflammatory damage by suppression NF-κB signaling pathway.

Research of proliferation inhibition and apoptosis promotion mechanism of brusatol on H1299 cells / 中国药理学通报

Aim To preliminarily investigate the effect of brusatol(BRU), the monomer components fromChinese medicines on H1299 cells and its mechanisms.Methods CCK-8 and EdU staining experiment were used to detect the effect of BRU on cell prolifera-tion.Clone formation experiment was performed to measure the effect of drugs on cell clone formation.Hoechst33258 staining experiment and flow cytometry were employed to observe the cell apoptosis.Western blot assay was used to detect the protein expression levels of Bcl-xL, Bax, Bcl-2, cleaved-caspase-3, caspase-3, Gadd45α, PI3K, p-PI3K, Akt, p-Akt and NF-κB-p65.Results CCK-8 assay revealed that the inhibitory effect of H1299 cells gradually increased with the rising of BRU concentration and action time.Compared with control group, the EdU incorporation rate of the BRU treatment group decreased significantly.Treated with different concentrations of BRU for 24 h, the clone formation rate was significantly reduced in a concentration-dependent manner.Hoechst33258 experiment and flow cytometry showed that BRU could induce apoptosis in H1299 cell nucleus and increase its apoptotic rate.Western blot results revealed that BRU could significantly up-regulate the protein levels of Bax, cleaved-caspase-3, Gadd45α, and significantly down-regulate the expression of Bcl-xL, Bcl-2, caspase-3.In addition, BRU could significantly decrease the expression level of p-PI3K, p-Akt, NF-κB-p65 in cell nucleus.Conclusions BRU can inhibit the proliferation and induce apoptosis of H1299 cells in a concentration and time-dependent manner.The mechanism may be related to the inhibition of PI3K/Akt signaling pathway and the nuclear shuttle of NF-κB-p65.

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.

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.

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.

Mechanism of Tibetan medicine Ershiwuwei Songshi Pills against liver injury induced by acetaminophen in mice based on Keap1/Nrf2 and TLR4/NF-κB p65 signaling pathways / 中国中药杂志

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.

Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia / 中国中药杂志

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

Dihydromyricetin improves cardiac insufficiency by inhibiting HMGB1 in diabetic rats / 南方医科大学学报

OBJECTIVE@#To investigate the effect of dihydromyricetin (DHM) on cardiac insufficiency in diabetic rats and explore the underlying mechanism.@*METHOD@#Twenty-four male SD rats were randomized equally into normal control group, type 2 diabetes (T2DM) group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin (STZ) injection, metformin (MET) group with daily intragastric administration of MET (150 mg/kg) for 8 weeks after T2DM modeling, and dihydromyricetin (DHM) group with daily intragastric administration of DHM (250 mg/kg) for 8 weeks after modeling. The levels of fasting blood glucose, low density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C) and glycosylated hemoglobin (HbA1c) of the rats were measured, and plasma levels of insulin and high mobility group protein-1 (HMGB1) were detected with ELISA. The cardiac function of the rats was assessed using color echocardiography, ECG was measured using a biological signal acquisition system, and myocardial pathology was observed with HE staining. The protein expressions of HMGB1, nuclear factor-κB (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in the myocardial tissue were detected using Western blotting.@*RESULTS@#Compared with the control group, the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1, NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue (P < 0.05 or 0.01). Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats (P < 0.05 or 0.01), decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue (P < 0.05 or 0.01).@*CONCLUSION@#DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.

Efficacy of Fufang Huangbaiye Tuji on Inflammation on Skin with Deep Ⅱ Degree Burn and Its Dose-effect Relationship / 中国实验方剂学杂志

Objective:To observe the effect of different doses of Fufang Huangbaiye Tuji asin the treatment onof the inflammatory response in healing process for of skin with deep Ⅱ degree burn. Methods in healing process. Methods:The 120 cses patients with deep Ⅱ degree burn of fire-toxin injuring fluid syndrome diagnosed in the affiliated hospital of Chengde Medical University between June 2019 and March 2020 were randomly divided into control group，low -dose treatment group and high -dose treatment group，with 40 cases in each group and once. They got a dressing change perevery day. Control group was locally administered with lodophor solution 35 mL per 1% on the body surface area. Low-dose treatment group was locally administered with compound cortex phellodendri fluid 17.5 mL per 1% on the body surface area，while high-dose treatment group was locally administered with compound cortex phellodendri fluid 35 mL per 1% on the body surface area. Observe theThe inflammatory reaction of wound surface in each group onwas observed at admission and after treatment. The pathological changes of each groupsgroup were observed， and determination of nuclear factor kappa-B（NF-<italic>κ</italic>B） p65 expression inon the wound surface was determined by immunohistochemistry on the 4th day after the treatment. The levels of interleukin（IL）-2，IL-8 and tumor necrosis factor（TNF）-α in wound tissue were measured with ELISA and Bacterial culture and count were performed in each group on the 4^th，10^th and 21^st daydays after treatment. The levels of IL-2，IL-8 and TNF-α in wound tissue were measured with ELISA. Results:There was no significant difference in the degree of wound inflammation in each group at admission，and the degree of relief after treatment was positively correlated with the treatment time. At the simultaneous phase point，the inflammatory reaction was severest in control group，which was followed by low-dose treatment group and high-dose treatment group. Bacterial growth were observed on the 4^th day in control group，which was found in low-dose and high-dose treatment groups on the 10^th day，the detection rates of Staphylococcus aureus and Pseudomonas aeruginosa were the highest. Compared with control group，the mean integrated optical density of NF-<italic>κ</italic>B p65 in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4th day after treatment（<italic>P</italic><0.05），the bacterial count decreased significantly in low-dose and high-dose treatment groups on the 10^th and 21^st days after treatment（<italic>P</italic><0.05），and the levels of IL-2，IL-8 and TNF-<italic>α</italic> in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4^th，10^th and 21^st days after treatment（<italic>P</italic><0.05），with statistically significant differences between low-dose and high-dose treatment groups（<italic>P</italic><0.05）. Histopathological examination showed that inflammatory granulocytes and edema were improved in low-dose and high-dose treatment groups compared with control group，with a more significant performance in high-dose treatment group. Conclusion:The external application of compound cortex phellodendri fluid can reduce thebacterial growth of bacteria in on the wound surface，which may reduce the inflammatory reaction by inhibiting the production and release of inflammatory mediators，with a certain dose-effcteffect relationship，and is worth clinical promotion.

CircHMGCS1 Activates the NF-κB Signaling Pathway and Promotes Proliferation and Invasion in Cervical Cancer Cells / 中国生物化学与分子生物学报

Circular RNAs play an important role in tumorigenesis. In this study, we explored the role of aberrant expression of circHMGCS1 in cervical cancer cells with TNF-α treatment. RT-qPCR assays showed that circHMGCS1 was highly expressed after TNF-α treatment. And then we investigated the cyclization and stabilization of circHMGCS1 by RNase R and half-life analysis. We further revealed that overexpression of circHMGCS1 promoted the malignancy of cervical cancer cells and the expression of the epithelial-mesenchymal transition (EMT) markers by Transwell analysis, MTT, clone formation and Western blotting. Furthermore, we found that circHMGCS1 activated the NF-κB signaling pathway. Altogether, this study provides an experimental basis for elucidating the role of circHMGCS1 in cervical cancer cells, and provides a potential biomarker for the diagnosis and treatment of cervical cancer.

Paeonol suppresses fibroblast synovitis by increasing MANF expression / 中国药理学通报

Aim To investigate the possible mechanism of paeonol inhibiting the inflammatory response of fibroblast synovial cells (RA-FLSS) in rheumatoid arthritis. Methods CCK-8 assay was used to detect Paeonol's inhibitory level on the abnormal proliferation of arthritis human fibroblast synovial cells (RA-FLSs). The levels of endoplasmic reticulum stress-related proteins MANF and ATF6 were detected by Western blot. Cell localization of transcription factor p65 and Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF) was detected by immunofluorescence. RT-qPCR detected the changes of p65 target genes. Results Paeonol could significantly inhibit the abnormal proliferation of RA-FLSS cells. Paeonol activates ATF6 and increases the expression of MANF. Paeonol promoted the nuclear transfer of MANF protein and inhibited the transcriptional activity of p65. Conclusion Paeonol promotes the expression of MANF and nuclear transfer through the endoplasmic reticulum stress pathway and affects the progression of RA by inhibiting the transcriptional activity of p65.

Effect of CysLT / 中国药理学通报

Aim To investigate the effect of CysLT

Therapeutic effect and mechanism of sodium formononetin-3′-sulphonate on collagen-induced rheumatoid arthritis / 中国药科大学学报

@#To investigate the therapeutic effect and mechanism of sodium formononetin-3′-sulphonate (SFS) on collagen-induced rheumatoid arthritis in mice, C57 mice were induced with chicken type II collagen to establish a model of rheumatoid arthritis (collagen-induced arthritis, CIA), and were injected intraperitoneally with different doses of SFS (50,100,200 mg/kg). Body weight, food intake and foot swelling of all groups were observed during the experiment.After the treatment, TNF-α, IL-6, and IL-10 in the serum were detected with the CBA kit; NF-κB p65, p-NF-κB p65 (p-p65), TIPE2, PCNP and IκB-α in spleen tissue were determined by Western blot; the organ index, pathological changes of ankle joint cartilage tissue and the positive expression of NF-κB p65 in ankle joint tissue were also observed.The results showed that, compared with the model group, the body weight and food intake of mice in the treatment group increased, while the degree of foot swelling decreased; the expression levels of inflammatory factors TNF-α and IL-6 in serum decreased, while the expression of anti-inflammatory factor IL-10 increased; the expression levels of NF-κB p65, p-p65 and PCNP in spleen tissue decreased, while the expression of TIPE2 and IκB-α protein increased; the index of spleen and thymus of the CIA mice in the treatment group, the infiltration of inflammatory cells in the ankle joint, the destruction of synovial tissue and cartilage, and the positive expression of NF-κB p65 decreased.Among them, the high-dose group of SFS showed a better therapeutic effect.It is suggested that SFS has a therapeutic effect on CIA mice, and the mechanism may be achieved by regulating the NF-κB p65 signaling pathway and inhibiting the expression of inflammatory factors.

Piperine treating sciatica through regulating inflammation and MiR-520a/P65 pathway / 中国天然药物

Although the etiology of sciatica remains uncertain, there is increasing evidence that the disease process of sciatica is associated with the levels of inflammatory factors. Piperine, an alkaloid isolated from Piper nigrum, has previously been demonstrated to inhibit inflammation and analgesic effects. The purpose of this study is to verify the regulatory relationship between miR-520a and p65 and to explore how miR-520a/P65 affects the level of cytokines under the action of piperine, so as to play a therapeutic role in sciatica. Through ELISA experiment, we confirmed that four inflammatory factors (IL-1β, TNF-α, IL-10, TGF-β1) can be used as evaluation indexes of sciatica. The differentially expressed miRNA was screened as miR-520a, by microarray technology, and the downstream target of miR-520a was P65 by bioinformatics. Real-time fluorescence quantitative PCR confirmed that the expression of miR-520a was negatively correlated with pro-inflammatory cytokines, positively correlated with anti-inflammatory cytokines and negatively correlated with p65 expression at mRNA level. The expression of p65 was positively correlated with pro-inflammatory cytokines and negatively correlated with anti-inflammatory cytokines at the protein level verified by ELISA and Western blot. HE staining analysis showed that the nerve fibers were repaired by piprine, the vacuoles were significantly reduced, and the degree of nerve fiber damage was also improved. Immunohistochemical analysis showed that the expression of p65 decreased after administration of piperine. Dual-luciferase reporter gene assay confirmed that the luciferase signal decreased significantly after cotransfection of miR-520a mimics and p65 3'UTR recombinant plasmid. To sum up, in the rat model of non-compressed lumbar disc herniation, piperine plays a significant role in analgesia. MiR-520a can specifically and directly target P65, and piperine can promote the expression of miR-520a, then inhibit the expression of p65, down-regulate the pro-inflammatory factors IL-1β and TNF-α, and up-regulate the effects of anti-inflammatory factors IL-10 and TGF-β1, so as to treat sciatica.