This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(P<0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(P<0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(P<0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(P<0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.
Animals ; Female ; Rats ; Anti-Inflammatory Agents/therapeutic use* ; Cytokines ; Dinoprostone ; Drugs, Chinese Herbal/therapeutic use* ; Dual-Specificity Phosphatases ; Dysmenorrhea/genetics* ; Endometriosis/genetics* ; Gestrinone/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Mitogens/therapeutic use* ; RNA, Messenger ; Tumor Necrosis Factor-alpha/metabolism*

The present study investigated the pharmacodynamic material basis of Laportea bulbifera in the treatment of rheumatoid arthritis. Firstly, human rheumatoid arthritis fibroblast-like synoviocyte line MH7A was cultured in vitro and treated with tumor necrosis factor alpha(TNF-α, 50 ng·mL~(-1)). The proliferation and the levels of inflammatory cytokines such as prostaglandin E2(PGE2), interleukin-1β(IL-1β), and interleukin-6(IL-6) of the MH7A cells exposed to the serum containing L. bulbifera were determined to evaluate the anti-rheumatoid arthritis effects of the serum. Furthermore, the ultra-performance liquid chromatography tandem mass spectrometry fingerprints of the L. bulbifera crude extract, the drug-containing serum, and the drug-free serum were compared to identify the compounds newly generated in the serum after oral administration of the extract. According to the peak areas of common peaks and the results of anti-rheumatoid arthritis effect test, the active components were identified. The serum containing L. bulbifera significantly inhibited the proliferation of the MH7A cells activated by TNF-α and the expression of PGE2, IL-6, and IL-1β. Thirty newly generated compounds were detected in the drug-containing serum. Among them, neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, rutin, isoquercitrin, luteoloside, kaempferol-3-O-rutinoside, and quercitrin were also present in the crude extract. Twelve characteristic peaks(3, 7, 8, 14, 18, 19, 21, 23, 24, m6, m7, and m15) were significantly correlated with the pharmaceutical effect. According to the correlations, neochlorogenic acid, cryptochlorogenic acid, and chlorogenic acid had great contributions to the anti-rheumatoid arthritis activity. This study preliminarily clarified the potential pharmacodynamic substances of L. bulbifera in the treatment of rheumatoid arthritis, which laid a theoretical and experimental foundation for further development and application of the medicinal plant.
Animals ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Chlorogenic Acid/analogs & derivatives* ; Cytokines/metabolism* ; Dinoprostone ; Humans ; Interleukin-1beta/genetics* ; Interleukin-6 ; Plant Extracts/therapeutic use* ; Quinic Acid/analogs & derivatives* ; Rutin ; Tumor Necrosis Factor-alpha/metabolism* ; Urticaceae/chemistry*

BACKGROUNDS: At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios. METHODS: We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups. RESULTS: The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8%, [11/141] P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50). CONCLUSIONS Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.
Administration, Intravaginal ; Catheters ; Dinoprostone/therapeutic use* ; Female ; Fetal Weight ; Humans ; Infant, Newborn ; Labor, Induced/methods* ; Nuchal Cord ; Oligohydramnios ; Oxytocics ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies

AIM: To investigate the cytotoxicity, anti-inflammatory activity, and action mechanism of root bark extracts of Acanthopanax henryi. METHOD: The hot methanol extract of the root bark of A. henryi was subjected to XAD-4 column chromatography eluting with a gradient of methanol in water. The cytotoxicity and anti-inflammatory effects of the MeOH fractions were evaluated on the inhibition on lipopolysaccharide (LPS)-induced nitric oxide, prostaglandin E2, interleukin-1β, and interleukin-6 production in RAW 264.7 macrophages. RESULTS: The 80% MeOH fraction was a better inhibitor of LPS-induced NO, PGE2, IL-1β, and IL-6 production, and expression of inducible nitric oxide synthase (iNOS) at the protein levels in a concentration-dependent manner. CONCLUSION The 80% MeOH fraction of A. henryi root bark has significant anti-inflammatory activity. This provides a pharmacological basis for clinical application for the treatment of inflammation.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Dinoprostone ; metabolism ; Dose-Response Relationship, Drug ; Eleutherococcus ; Inflammation ; chemically induced ; drug therapy ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; Macrophages ; drug effects ; metabolism ; Mice ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phytotherapy ; Plant Bark ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots

OBJECTIVETo study the efficacy and mechanism of Weiyangning pills against experimental gastric ulcer.

METHODThe gastric ulcer model were established by acetic acid, water-immersion stress, aspirin induction, pyloric ligation in rats, in order to observe the effect of Weiyangning pills against experimental gastric ulcer and study its effect on the content of nitric oxide (NO) and epidermal growth factor (EGF), gastric mucosal blood flow, the content of PGE2, gastric secretion, gastric acid content and the activity of pepsin.

RESULTWeiyangning pills markedly reduced index of gastric ulcers of various types, increased the content of NO, EGF, PGE2 and gastric mucosal blood flow, inhibited gastric secretion and gastric acid content, and decreased the activity of pepsin.

CONCLUSIONWeiyangning pills has a significant effect against experimental gastric ulcer, which is related to the reduction of gastric mucosa damage factors (gastric acid and pepsin) and the increase in gastric mucosa's function as a barrier and its recovery effects, such as NO, EGF, PGE2 and gastric mucosal blood flow.

Acetic Acid ; adverse effects ; Animals ; Aspirin ; adverse effects ; Dinoprostone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epidermal Growth Factor ; metabolism ; Female ; Gastric Acid ; metabolism ; secretion ; Ligation ; adverse effects ; Male ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow ; drug effects ; Stomach Ulcer ; drug therapy ; etiology ; metabolism ; physiopathology

OBJECTIVETo compare the effects of sanjie zhentong capsule (SZC) and danazol on rats with endometriosis (EMT).

METHODSTotally 48 adult female Lewis rats were selected, 12 as the blank control group, and the rest 36 rats in the estrus cycle were used to establish the EMT model. After modeling they were randomly divided into 3 groups, i.e., the model control group, the SZC treatment group, and the danazol treatment group, 12 in each group. Four weeks later the focus was measured by a second laparotomy. The normal saline at 1 mL/day was administered to rats in the model control group, SZC at 86.4 mg/day to those in the SZC treatment group, and danazol at 7.2 mg/day to those in the danazol treatment group. All the treatment lasted for 4 weeks. At the end of the treatment, a third laparotomy was performed to measure the size of focus. The expression of proliferating cell nuclear antigen (PCNA) was detected using immunohistochemical assay. The cell apoptosis rate was detected using terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling (TUNEL). The concentration of prostaglandin E2 (PGE2) in the peritoneal fluid and the serum were detected using ELISA.

RESULTSThere was statistical difference in the change of the focus volume between the SZC treatment group (-23.27 +/- 18.18) and the danazol treatment group (-12.28 +/- 10.04) and the model control group (13.97 +/- 7.54, P < 0.01). The expression of ectopic PCNA significantly decreased and the positive expression rate of TUNEL obviously increased in the two treatment groups when compared with the model control group (P < 0.05, P < 0.01). The expression of ectopic PCNA decreased and the positive expression rate of TUNEL increased more obviously in the SZC treatment group than in the danazol treatment group (P < 0.01). The concentration of PGE2 in the peritoneal fluid and the serum was significantly lower in the two treatment group when compared with the model control group (P < 0.01). The concentration of PGE2 in the peritoneal fluid and the serum was significantly lower in the SZC treatment group than in the danazol treatment group (P < 0.01).

CONCLUSIONSSZC and danazol both could inhibit the focus growth in EMT rats. SZC showed better effects. It was an effective drug for treating EMT.

Animals ; Capsules ; Danazol ; therapeutic use ; Dinoprostone ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Endometriosis ; drug therapy ; Female ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Inbred Lew ; Treatment Outcome

OBJECTIVETo observe the effects of three different doses of polydatin (PD) on pulmonary interstitial fibrosis in rats induced by bleomycin.

METHODOne hundred and twenty-nine healthy Sprague-Dawley rats three months old, were randomly divided into six groups. Group A: normal control group; group B: model group treated with bleomycin (pretreatment with saline 1 mL x kg(-1) intraperitoneally before bleomycin); group C: PD 10 mg x kg(-1) (pretreatment with PD 10 mg x kg(-1) intraperitoneally before bleomycin); group D: PD 20 mg x kg(-1) (pretreatment with PD 20 mg x kg(-1) intraperitoneally before bleomycin); group E: PD 40 mg x kg(-1) (pretreatment with PD 40 mg x kg(-1) intraperitoneally before bleomycin), group F: dexamethason (DXM) treated group (pretreatment with saline 1 mL x kg(-1) intraperitoneally before bleomycin and then with DXM 1 mg x kg(-1) x d(-1)). At day 3, 7, 14, 28 after injection of bleomycin, eight rats in each group were randomly chosen to be killed. The right lungs of dead rats were removed and appropriately processed for hematoxylin and eosin (H&E) stain, histologically observed under light microscope. The hydroxyproline content and the PLA2 activity in pulmonary homogenate were measured with alkaline hydrolysis assay and acid modified microtitrimetic method. The levels of leukotriene C4 (LTC4), prostaglandin E2 (PGE2), transforming growth factor-beta1 (TGF-beta1) in bronchoalveolar lavage fluid (BALF) were measured with enzyme-linked immunosorbent assay (ELISA).

RESULTAt day 3, 7, 14, 28 after intratracheal instillation of bleomycin in rats of group B, the PLA2 activity in lung homogenate and the levels of its metabolic products PGE2, LTC4 as well as TGF-beta1 in BALF increased significantly compared with those in group A (P < 0.01). And lung hydroxyproline concentration began to grow up markedly at day 7 compared with those in group A (P < 0.05), reaching its maximum at day 28. Compared with group B, three different doses of PD and DXM significantly reduced the activity of the PLA2 and hydroxyproline concentration in lung homogenate as well as the levels of PGE2, LTC4, TGF-beta1 in BALF at various periods (P < 0.05). There was statistically significant difference between three different doses of PD groups (P < 0.05). And the group E (PD 40 mg x kg(-1)) was lower than group D (PD 20 mg x kg(-1)), group D was lower than group C (PD 10 mg x kg(-1)) (respectively, P < 0.01). Group E and DXM group were no significant difference. However, all these observation parameters were higher than the normal level (compared with group A, P < 0.01). Histological studies revealed that it was showed less inflammation and a lower degree of fibrosis in the lungs treated with PD than bleomycin model group.

CONCLUSIONPD has the protective effect on pulmonary interstitial fibrosis. However, it can't completely block the process of pulmonary fibrosis.

Animals ; Bleomycin ; toxicity ; Dinoprostone ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glucosides ; therapeutic use ; Leukotriene C4 ; analysis ; Male ; Phospholipases A2 ; analysis ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; therapeutic use

A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-alpha , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.
Animals ; Atherosclerosis/*drug therapy ; Cell Adhesion/drug effects ; Cell Line ; Cell Movement/drug effects ; Chemokine CCL2/metabolism ; Dinoprostone/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukotriene B4/metabolism ; Macrophages/cytology/drug effects ; Male ; Mice ; Monocytes/cytology/*drug effects ; Random Allocation ; Receptors, LDL/deficiency/genetics ; Thiazolidinediones/*therapeutic use ; Tumor Necrosis Factor-alpha/pharmacology

OBJECTIVETo compare the effects of Atractylodes lancea from different producing area on collagen-induced arthritis (CIA) in rats.

METHODWistar rats were induced by type II bovine collagen. CIA rats were treated daily with oral administration of A. lancea from the geo-authentic and non-authentic producing area of Maoshan, Jiangsu province, and non-geo-authentic and non-authentic producing areas of Yingshan, Hubei province and Huayin, Shanxi province from day 7 after the day of the first immunization to day 35. Clinical symptoms as well as clinical scores and incidence were observed. All rats were sacrificed on day 35 after immunization to observe histopathologic and radiologic changes. Antibody to type II collagen in sera was measured by enzyme-linked immunosorbent assay (ELISA), the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in sera and article-homogenated supernants by radiommunoassay, and inflammatory mediator of PGE2 in sera using ELISA.

RESULTA. lancea from Jiangsu province can ameliorate clinical symptom, reduce arthritis index and arthropathy of inflammatory joints, inhibit the production of IgG and IgM in sera, directly suppress the production of exogenous and endogenous cytokines of IL-1beta, TNFalpha and IL-6 and PGE2. A. lances from Hubei and Shanxi provinces can inhibit the production of IgM in sera, and A. lanceas from Hubei province also depress the production of IL-1beta in sera and IL-6 in supernants.

CONCLUSIONA. lancea from Jiangsu province is effective in CIA rats through inhibiting the production of pro-inflammatory cytokines and the inflammatory mediators.

Animals ; Arthritis, Experimental ; drug therapy ; immunology ; Atractylodes ; Cytokines ; blood ; Dinoprostone ; blood ; Male ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo observe the effect of Cuichan Zhunsheng Decoction (CZD) on the cervical ripening factors in late pregnancy.

METHODSNinety women with full-term pregnant ready for labor inducing were equally assigned to 3 groups. The treated group was orally treated with CZD, the control group was with pitocin by adding 1 U into 500 mL of 5% glucose for intravenous dripping in 6 h, and the placebo group was orally treated with simulator of CZD as placebo, with the medication lasted for 3 days. Changes of cervical length and width, and neck tube diameter were measured by vaginal B-ultrasonography to estimate the degree of cervical maturation referring to the clinical Bishop scale; meanwhile, changes in blood levels of prostaglandin E2alpha(PGE2alpha), interleukin-8 (IL-8) and endothelin-1 (ET-1) were measured.

RESULTSThe total effective rate on cervical ripening was 96.7% in the treated group, which was significantly superior to those in the control group (83.3%) and the placebo group (26.7%, P < 0.05). The blood levels of PGE2alpha, IL-8, and ET-1 after treatment in the treated group were significantly higher than those in the placebo group (P < 0.05), and levels of PGE2alpha and IL-8 were higher in the control group than in the placebo group (P < 0.05).

CONCLUSIONCZD can promote the cervical ripening through raising blood levels of PGE2alpha, IL-8 and ET-1, altering the structure of cervical tissue to reduce the cervical tension, which could increase the maturation of cervix, induce delivery sign, so as to elevate the vaginal delivery rate and reduce the percentage of caesarean birth.

Adult ; Cervical Ripening ; drug effects ; Dinoprostone ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelin-1 ; blood ; Female ; Humans ; Interleukin-8 ; blood ; Phytotherapy ; Pregnancy ; Pregnancy Trimester, Third ; drug effects