Triterpenoids with diverse skeletons from the roots of Rhus chinensis and their protective effects on isoproterenol-induced heart failure in zebrafish.

In the ongoing quest to discover previously unreported lead compounds that provide protection against heart failure (HF), ten formerly undescribed (1-10) and nine known (11-19) triterpenoids were obtained from the roots of Rhus chinensis Mill. The isolated triterpenoids exhibited distinct skeletal types, including rare 17-epi-dammarane (1, 6, 7, 11, and 12), conventional dammarane (2-5, 8, and 9), oleanane (10 and 13-17) and lupane (18 and 19). Their structures were elucidated via a comprehensive analysis of the HRESIMS, NMR, and ECD data, as well as quantum chemical calculations of NMR parameters. Notably, compounds 1-5, 10-15, and 19 possessed an unusual 3,19 (or 25)-hemiketal structure bridging over ring A, while the remaining compounds were classified as 3-oxotriterpenoids. The skeletal diversity observed in these compounds was further elaborated from a biosynthetic perspective. Subsequently, the protective effects of fourteen compounds (1, 3, 4, 6-9, 11-14, and 16-18) against HF were evaluated using zebrafish models of isoproterenol-induced HF at a concentration of 1 µg/mL. Remarkably, all fourteen compounds significantly ameliorated pericardial edema, with five compounds (3, 6, 11, 14, and 16) also attenuating impaired cardiac output (CO), and eight compounds (1, 3, 4, 7-9, 14, and 16) inhibiting cardiomyocyte apoptosis. Notably, certain compounds even restored the impaired pericardium and CO to near-normal levels. These findings highlight the therapeutic potential of triterpenoids derived from R. chinensis as promising agents for the treatment of HF.

Corydalis decumbens Alleviates the Migration, Phagocytosis, and Inflammatory Response of Macrophages.

Background: The role of Corydalis decumbens (CD) in macrophage activation remains unclear, particularly in the Ras homolog family member A (RhoA) signaling pathway. Therefore, the present study aimed to investigate the effect of CD on the viability, proliferation, morphological changes, migration, phagocytosis, differentiation, and release of inflammatory factors and signaling pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Methods: Cell counting kit-8 and water-soluble tetrazolium salt assays were used to evaluate the viability and proliferation of RAW264.7 macrophages. A transwell assay was examined to assess cell migration. The ingestion of lumisphere assay was employed to detect the phagocytic capacity of macrophages. Phalloidin staining was performed to observe morphological changes in the macrophages. An enzyme-linked immunosorbent assay was performed to quantify inflammation-related cytokines in cell culture supernatants. Cellular immunofluorescence and western blotting were adopted to show the expression of inflammation-related factors, biomarkers of M1/M2 subset macrophages, and factors of the RhoA signaling pathway. Results: We found that CD increased the viability and proliferation of RAW264.7 macrophages. CD also impaired the migration and phagocytic capacity of macrophages, induced anti-inflammatory M2 macrophage polarization, such as M2-like morphological changes, and upregulated M2 macrophage biomarkers and anti-inflammatory factors. We also observed that CD inactivated the RhoA signaling pathway. Conclusions: CD mediates the activation of LPS-stimulated macrophages, alleviates the inflammatory responses of macrophages, and activates related signaling pathways induced by LPS.

Pien-Tze-Huang alleviates CCl4-induced liver fibrosis through the inhibition of HSC autophagy and the TGF-ß1/Smad2 pathway.

Ethnopharmacological relevance: Pien-Tze-Huang (PZH)-a traditional Chinese medicine (TCM) compound-has been employed to treat various liver inflammation and tumors for over 10 decades. Interestingly, most of the pharmacological effects had been validated and explored toward liver ailment along with pro-inflammatory conditions and cancer at the cellular and molecular level to date. Aim of the study: The present study aimed to investigate the therapeutic effect of PZH on autophagy and TGF-ß1 signaling pathways in rats with liver fibrosis and hepatic stellate cell line (HSC). Materials and methods: Male SD rats with carbon tetrachloride (CCl4)-induced liver fibrosis were used as the animal model. Next, PZH treatment was given for 8 weeks. Afterward, the therapeutic effects of PZH were analyzed through a hepatic tissue structure by hematoxylin-eosin (H&E), Van Gieson (VG) staining, and transmission electron microscopy (TEM), activity of ALT and AST by enzyme-associated immunosorbent assay as well. Subsequently, mRNA and protein expression were examined by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC). Then, the cell vitality of PZH-treated HSC and the expression of key molecules prevailing to autophagy were studied in vitro. Meanwhile, SM16 (a novel small molecular inhibitor which inhibits TGFß-induced Smad2 phosphorylation) was employed to confirm PZH's effects on the proliferation and autophagy of HSC. Results: PZH pharmacologically exerted anti-hepatic fibrosis effects as demonstrated by protecting hepatocytes and improving hepatic function. The results revealed the reduced production of extracellular collagen by adjusting the balance of matrix metalloproteinase (MMP) 2, MMP9, and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) in PZH-treated CCl4-induced liver fibrosis. Interestingly, PZH inhibited the activation of HSC by down-regulating TGF-ß1 and phosphorylating Smad2. Furthermore, PZH down-regulated yeast Atg6 (Beclin-1) and microtubule-associated protein light chain 3 (LC3) toward suppressing HSC autophagy, and PZH exhibited similar effects to that of SM16. Conclusion: To conclude, PZH alleviated CCl4-induced liver fibrosis to reduce the production of extracellular collagen and inhibiting the activation of HSC. In addition, their pharmacological mechanisms related to autophagy and TGF-ß1/Smad2 signaling pathways were revealed for the first time.

Overexpression of Long Noncoding RNA HOTAIR Is a Unique Epigenetic Characteristic of Myxopapillary Ependymoma.

Ependymomas are a heterogeneous group of central nervous system tumors. Despite the recent advances, there are no specific biomarkers for ependymomas. In this study, we explored the role of homeobox (HOX) genes and long noncoding RNA (LncRNA) HOTAIR in ependymomas along the neural axis. Bioinformatics analysis was performed on publicly available gene expression data. Quantitative RT-PCR was used to determine the mRNA expression level among different groups of ependymomas. RNA in situ hybridization (ISH) with probes specific to HOTAIR was performed on tumor tissue microarray (TMA) constructed with 19 ependymomas formalin-fixed paraffin-embedded tissue. Gene expression analysis revealed higher expression of posterior HOX genes and HOTAIR in myxopapillary ependymoma (MPE), in comparison to other spinal and intracranial ependymoma. qRT-PCR confirmed the high HOXD10 expression in spinal MPEs. There was a significant upregulation of HOTAIR expression in spinal MPE and elevated HOTAIR expressions were further confirmed by RNA ISH on the TMA. Intriguingly, HOXD10 and HOTAIR expressions were not elevated in nonependymoma spinal tumors. Our collective results suggest an important role for the lncRNA HOTAIR and posterior HOX genes in the tumorigenesis of spinal MPE. HOTAIR may also serve as a potential diagnostic marker for spinal MPE.

[Intestinal absorption of phenolic acids in Rhus chinensis extracts by in situ single-pass perfusion model in rats].

The intestinal absorption properties of four main effective components(gallic acid, ocinolglucoside, ethyl gallate and penta-O-galloyl-ß-D-glucose) in Rhus chinensis extracts were investigated by in situ single-pass intestinal perfusion model in rats. The liquid accumulation of perfusion was corrected by gravimetry. The HPLC method was established to determine the concentration of the four effective components in the intestinal perfusion. It showed significant differences(P<0.05) in absorption rate constant(K_a) and effective permeability(P_(eff)) among the three concentrations of components, and the absorption of the four effective components in different intestinal segments was saturated at high concentrations. At the same concentration, there were significant differences in K_a and P_(eff) of the four components in each intestinal segment(P<0.05). The order of K_a and P_(eff) of the four components in the intestine was penta-O-galloyl-ß-D-glucose>ethyl gallate>gallic acid>ocinolglucoside, with significant differences between them(P<0.05). In conclusion, gallic acid, orpheolglucoside, ethyl gallate and pentacyl-glucose could be absorbed in the whole intestine. Their absorption rate and permeation ability were related to the intestinal section and the perfusate concentration. These results indicated potential active transport or facilitated diffusion in the intestinal transport process of the four effective components.

[Preparation of Rhus chinensis total phenolic acid pellets by extrusion-spheronisation method].

Extrusion-spheronisation method was used to prepare Rhus chinensis total phenolic acid pellets. The formula and preparation of R. chinensis total phenolic acid pellets were optimized. The formulas( drug loading capacity,diluent,wetting agent and anti-sticking agent) were determined by the single factor test with yield,appearance and performance as the indexes. The preparation was optimized by Box-Behnken design and response surface method,with the rate of extrusion,rate of spheronization and time of spheronization as the independent variables and the overall desirability value of yield,friability and roundness as the dependent variables. The optimal formula of pellets was as follows: drug loading capacity 28. 7%,MCC-lactose 9 ∶1,silicon dioxide as anti-sticking agent,and 60% ethanol as wetting agent. The optimal preparation was determined as follows: the rate of extrusion was 43 r·min-1,the rate of spheronization was 1 800 r·min-1,and the time of spheronization was 4 min. The absolute deviation between predicted value and estimated value under the conditions was less than 5. 0%,with a high degree of model fit. The preparation parameters obtained were accurate,reliable and reproducible. Under scanning electron microscopy( SEM),R. chinensis total phenolic acid pellets were uniform in diameter,round and smooth. The optimal formulation and process are stable and feasible for preparing R. chinensis total phenolic acid pellets.

Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pien Tze Huang (PZH), a Chinese herbal formula, has various forms of pharmacological activity including anti-inflammation, liver protection and anti-tumor. AIM OF THE STUDY: To investigate the anti-hepatic fibrosis effect of PZH and its potential mechanisms on experimental animal model of hepatic fibrosis and hepatic stellate cell (HSC). MATERIAL AND METHODS: Rats were intraperitoneally administered with CCl4 to induce hepatic fibrosis and were simultaneously treated with PZH. Liver pathology were observed by hematoxylin and eosin (H&E) staining and Masson staining. Serum pro-inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the effects of PZH on HSC proliferation and apoptosis were assessed via MTT, flow cytometry and immunofluorescence analysis. Nuclear factor-κB (NF-κB) pathway activation and Bcl-2 family members were evaluated by reverse transcription quantitative polymerase chain reaction (real-time PCR) and western blotting. RESULT: PZH significantly alleviated CCl4-induced liver injury, inflammation and fibrogenesis in rats. PZH also markedly decreased the production of hepatic-fibrosis biomarker, including ALT, AST, IV collagen and PCIII (Procollagen III), as well as inflammatory cytokines such as IL-1ß, IL-6 and TNF-α. Importantly, PZH strongly inhibited HSC proliferation correlated with cell apoptosis induction as evidenced by modulating Bcl-2 family members and caspase activity. Moreover, PZH administration significantly increased the expression IκB-α, an inhibitor of NF-κB and suppressed expression of anti-apoptotic genes (Bcl-2, etc.). Collectively, these results suggested that PZH could promote HSC apoptosis through inhibiting NF-κB signaling pathway. CONCLUSION: Our study demonstrates that PZH ameliorates hepatic fibrosis and inflammation, chiefly through suppressing the NF-κB pathway and promoting HSC apoptosis. PZH is more likely to be a promising antifibrotic agent in chronic disease.

Huaier Augmented the Chemotherapeutic Sensitivity of Oxaliplatin via Downregulation of YAP in Hepatocellular Carcinoma.

For unresectable Hepatocellular carcinoma (HCC), chemotherapy is still an important treatment strategy. Oxaliplatin (Oxa) is an effective treatment of HCC after sorafenib treatment failure. However, the intrinsic or acquired resistance of Oxa affected the chemotherapeutic sensitivity. By analyzing the data of GEO Database, we found that Oxa aberrantly increased the expression of Cysteine-rich61 (Cyr61) in HCC cell lines. Subsequently, in Bel-7404 and SMMC-7721 cells after treated with Oxa, it was verified that the expression of Cyr61 and Yes-associated protein (YAP) was increased. Moreover, we found that blockade of YAP promoted Oxa-induced cell apoptosis for the first time. Meanwhile, our previous study demonstrated that Huaier (HE) inhibited the expression of YAP. Further study found that combination treatment of Oxa and HE had a significantly synergistic anti-cancer effect and significantly inhibited the expression of YAP and apoptosis related proteins. Taken together, we have observed that overexpression of YAP significantly reduced the chemotherapeutic sensitivity of Oxa in HCC for the first time. Combination treatment of Oxa and HE solved this problem.

[Discussion on Supervision of 3D Printing Medical Device Related Software].

This article describes softwares and their functions in each phase of 3D printing process in medical device production, and gives the advices on supervision. For software with specific medical purposes, the registration of the software should be carried out. The softwares used in the printing process need to be verified according to the corresponding risk.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis.

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)­6, IL­8, tumor necrosis factor­α and nuclear factor­κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription­polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE­treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.

Lumican as a novel potential clinical indicator for acute aortic dissection: A comparative study, based on multi-slice computed tomography angiography.

The aim of the present study was to investigate the association between serum lumican levels and acute aortic dissection (AAD) severity. A total of 82 patients with chest or back pain and 30 healthy volunteers were recruited. Among the patients, there were 70 cases of AAD and 12 cases of intramural hematoma (IMH). AAD severity was determined using multi-slice computed tomography angiography (MSCTA). Serum was collected from the patients upon admission, and lumican levels were detected using an enzyme-linked immunosorbent assay. In addition, correlation analyses were conducted between lumican levels and AAD severity by designing a 'SCORE X, RANGE Y' system to measure the number of affected vital arteries and vertical range of false lumen, based on the MSCTA. Lumican levels differed significantly among the AAD patients (2.32±4.29 ng/ml), IMH patients (0.72±0.32 ng/ml) and healthy volunteers (0.85±0.53 ng/ml; P=0.003). In the AAD patients presenting within 12-72 h of symptom onset, the Spearman's rho correlation coefficient between lumican and SCORE or RANGE was 0.373 (P=0.046) and 0.468 (P=0.010), respectively. The present results suggest that lumican may be a potential marker for aiding the diagnosis and screening for AAD, and may be used to predict the severity of AAD.

Extracts of Bauhinia championii (Benth.) Benth. inhibit NF-B-signaling in a rat model of collagen-induced arthritis and primary synovial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia championii (Benth.) Benth. is used in Chinese traditional medicine to treat arthritis, especially has been used a long time ago on rheumatoid arthritis (RA) in She ethnic minority group. AIM OF THE RESEARCH: To investigate the anti-RA effect of Bauhinia championii (Benth.) Benth ethyl acetate extract (BCBEE) and the molecular bases of it. MATERIALS AND METHODS: BCBEE was studied on a rat model of RA induced by Ⅱcollagen in vivo, as well as on primary synovial cells in vitro. RESULTS: After BCBEE treatment, in vivo, it was showed that paw and joint edema was inhibited, pathological joint changes was ameliorated and the levels of interleukin (IL)-1ß and tumor necrosis factor-(TNF-α) was decreased significantly. The protein and mRNA expressions of nuclear factor-B (NF-κB)(p65), IκB, p-IκB and IκB kinase beta (IκKß) were also down-regulated. Moreover, the in vitro study revealed that BCBEE treatment inhibited primary synovial cells proliferation, and promoted down-regulation of NF-κB(p65), IκB, p-IκB and IκKß. CONCLUSIONS: Taken together, the present study demonstrates that BCBEE produces a protection in a rat model of RA induced by Ⅱcollagen via inhibiting paw and joint edema, ameliorating pathological joint changes and regulating the levels of cytokines and its action mechanism maybe is via down-regulating NF-κB(p65), IκB, p-IκB and IκKß expression.

Methanolic Extract of Pien Tze Huang Induces Apoptosis Signaling in Human Osteosarcoma MG63 Cells via Multiple Pathways.

Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and the possible action mechanism on osteosarcoma remains unclear. After treatment with PZH, cell viability of MG-63 cells was dose-dependently inhibited compared to control cells. Moreover, a DNA ladder characteristic of apoptosis was observed in the cells treated with PZH, especially 500 µg/mL, 750 µg/mL. Further investigation showed that PZH treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and Bcl-xL expression. In addition, our results suggested that PZH activated PI3K/Akt signal pathway, and the phosphorylation of Akt and ERK1/2 were associated with the induction of apoptotic signaling. These results revealed that PZH possesses antitumoral activity on human osteosarcoma MG63 cells by manipulating apoptotic signaling and multiple pathways. It is suggested that PZH alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments.

MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of ß-catenin signaling.

Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through ß-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and ß-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC.

Treatment of Nonalcoholic Fatty Liver Disease with Total Alkaloids in Rubus aleaefolius Poir through Regulation of Fat Metabolism.

Total alkaloids in Rubus aleaefolius Poir (TARAP) is a folk medicinal herb that has been used clinically in China to treat nonalcoholic fatty liver disease (NAFLD) for many years. However, the mechanism of its anti-NAFLD effect is largely unknown. In this study, we developed a NAFLD rat model by supplying a modified high-fat diet (mHFD) ad libitum for 8 weeks and evaluated the therapeutic effect of TARAP in NAFLD rats as well as the underlying molecular mechanism. We found that TARAP could reduce the serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels and increase the serum high-density lipoprotein (HDL-C) level in NAFLD rats. In addition, TARAP treatment reduced expression of fatty acid synthetase (FAS), and acetyl-CoA carboxylase (ACC) and upregulated the expression of carnitine palmitoyltransferase (CPT). Our results suggest that regulation of lipid metabolism may be a mechanism by which TARAP treats NAFLD.

Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non­alcoholic fatty liver disease in rats.

The plant Rubus alceaefolius Poir is used as a hepatic protectant in Traditional Chinese Medicine. The aim of the present study was to confirm the protective effect of the total alkaloids of Rubus alceaefolius Poir (TARAP) on the liver and to evaluate the potential molecular mechanisms associated with adipocytokines underlying non-alcoholic fatty liver disease (NAFLD) in rats. To generate the NAFLD model, Sprague-Dawley rats were administered a high­fat diet and following 12 weeks of model construction, rats were orally treated with a positive control drug and different doses of TARAP daily for 28 days. The rats were then sacrificed and the livers were collected to evaluate the liver index (LI) and observe histological changes by hematoxylin and eosin (H&E) staining. The secretion levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined by ELISA. Finally, the expression levels of leptin (LEP), resistin and adiponectin (APN) in liver tissues were determined by immunohistochemistry (IHC). The results demonstrated that, in the group treated with methionine and choline bitartrate tablets and in the groups treated with different doses of TARAP, there was a significant reduction in the LI (P<0.05 or P<0.01), a downregulation of the secretion levels of ALT and AST, reduced levels of LEP and resistin and an increased expression of APN in the liver of NAFLD rats compared with the model group. Furthermore, the effect of TARAP treatment of NAFLD rats was dose dependent. In conclusion, TARAP is a potential agent for downregulating LEP and resistin and upregulating APN expression in rats with NAFLD. Furthermore, TARAP may be a potential candidate for improving treatment responses in patients with NAFLD.

Effects of shuangtengbitong tincture on collagen­induced arthritis in rats.

Shuangtengbitong tincture (STBT), a clinical prescription from the Fujian University of Traditional Chinese Medicine (TCM) Affiliated People's Hospital (Fuzhou, China), has been used in the treatment of rheumatoid arthritis (RA) for ~10 years. The aim of the current study was to confirm the anti-RA effect of STBT and to evaluate the potential mechanisms underlying collagen-induced arthritis (CIA) in rats. CIA model Wistar rats were induced with bovine type II collagen. The rats were immunized with CIA and were treated with STBT (0.5 and 2 ml/injection) and votalin (~1 cm/injection) continuously for ~1 month. Following treatment, the pathological sections of CIA rat joints were observed by hematoxylin and eosin staining, expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) were investigated by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Following treatment, STBT significantly suppressed paw swelling (P<0.05) compared with the model group and increased body weight. STBT also reversed pathological changes, STBT­treated rats showed a significant improvement of synovial hyperplasia, inflammatory infiltration, and cartilage and bone destruction. The levels of protein and mRNA expression of TLR4, MyD88 and NF-κB were markedly suppressed in the synovial tissue of STBT­ and votalin-treated rats. In addition, STBT showed marked inhibition of the levels of protein and mRNA expression of TLR4, MyD88 and NF-κB at an STBT volume ranging between 1 and 4 ml/day, indicating that the inhibition was volume dependent. These results show that STBT inhibits CIA and may be correlated with TLR4, MyD88 and NF-κB expression.

Bauhinia championii extraction treatment of collagen-induced arthritis via downregulation of the expression of TLR4, MyD88 and NF-κB.

Rheumatoid arthritis (RA) has emerged as an important worldwide public health problem. Due to the lack of efficacy and major side effects related to many Western medical treatments, traditional Chinese medicine or herbal medicine is very often used to treat this disease. In the present study, we evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model of RA induced by type-II collagen. Wistar rats with type-II collagen-induced arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling and weight were measured, and pathological joint sections of CIA rats were observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor κB (NF-κB) were determined by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis in synovial tissue. During therapeutic treatment, BCBE significantly suppressed paw swelling, increased weight loss and ameliorated pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and NF-κB were downregulated in the CIA model when treated with BCBE. In conclusion, these results suggest that the treatment of RA with BCBE confers anti-RA activity and has therapeutic potential in this CIA model.

Shuangtengbitong tincture treatment of collagen-induced arthritis via downregulation of the expression of IL-6, IL-8, TNF-α and NF-κB.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease and may lead to joint damage, synovial membrane destruction and cartilage and bone damage. RA is closely associated with increased expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) and nuclear transcription factor-κB (NF-κB). Therefore, inhibition of the expression of IL-6, IL-8, TNF-α and NF-κB is a promising strategy for the development of novel anti-RA therapies. The aim of this study was to investigate the effect of shuangtengbitong tincture (STBT) on the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of rats with collagen-induced arthritis (CIA). STBT as a clinical prescription created at Fujian University of Traditional Chinese Medicines (TCM) Affiliated People's Hospital has been shown to be clinically effective in the treatment of RA. The model of Wistar rats with CIA was created using bovine type II collagen. The two treatment groups with CIA were administered STBT (1 ml per time) or Votalin (∼1 cm per time) for ∼1 month continuously. Following treatment, STBT suppressed paw swelling significantly (P<0.05) compared with the model group. STBT also improved pathological changes, STBT-treated rats showed a significant improvement in synovial hyperplasia, inflammatory infiltration, cartilage and bone destruction and other symptoms. The protein expression levels of IL-6, IL-8, TNF-α and NF-κB were markedly suppressed in synovial tissues of STBT-treated and Votalin-treated rats. Our findings demonstrate for the first time that STBT markedly reduces paw swelling, improves pathological changes and increases the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of CIA rats, which may partially explain the anti-RA activity of STBT.

Anti-inflammatory effects of total alkaloids from Rubus alceifolius Poir [corrected]. on non-alcoholic fatty liver disease through regulation of the NF-κB pathway.

We aimed to explore the anti-inflammatory effects of total alkaloids inRubus alceifolius Poir [corrected]. (TARAP) on non-alcoholic fatty liver disease, and to investigate the possible molecular mechanisms. A rodent non-alcoholic fatty liver disease (NAFLD) model was established by administration of a modified high-fat diet ad libitum for 8 weeks. Rats were treated with polyene phosphatidylcholine (PP), TARAP low­dose (0.72 g/kg body weight/day) and TARAP high-dose (1.44 g/kg body weight/day). The model group and the control group received distilled water. After treatment for 4 weeks, the blood samples were obtained from the abdominal aorta, and the levels of serum ALT, AST, GGT, ALP, TG, TC, HDL-C and LDL-C were measured. Changes in liver tissue morphology were evaluated by H&E staining. The expression levels of nuclear factor (NF)-κB, cyclooxygenase-2 (COX­2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in rat livers were assayed by reverse transcription­polymerase chain reaction (RT-PCR) and immunohistochemistry. Both TARAP and PP attenuated hepatic steatosis induced by the high-fat diet. The modified high-fat diet caused a significant increase in ALT, AST, GGT, ALP, TG, TC, LDL-C levels and a decrease in HDL-C levels. TARAP and PP treatment abrogated the increase in the levels of liver enzymes and the levels of TG, TC, LDL-C, as well as suppressed the increase in HDL-C levels. The results of RT-PCR and immunohistochemical assay showed that PP and TARAP treatment decreased the expression of NF-κB, COX-2, IL-6 and TNF-α. In conclusion, these results suggest that TARAP may protect against NAFLD through regulation of the NF-κB pathway.