Protection of Taohong Siwu Decoction on PC12 cells injured by oxygen glucose deprivation/reperfusion via mitophagy-NLRP3 inflammasome pathway in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine formula used to invigorate blood circulation and resolve blood stasis. It consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H.Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. THSWD is a common prescription for the treatment of ischemic stroke. AIM OF THE STUDY: To study the protective effect and mechanism of Taohong Siwu Decoction (THSWD) on PC12 cells damaged by oxygen glucose deprivation/reperfusion (OGD/R). MATERIALS AND METHODS: OGD/R model of PC12 cells was used to simulate ischemia-reperfusion (I/R) injury of nerve cells in vitro. The experiment was grouped as follows: control, OGD/R and OGD/R + THSWD (5%, 10% and 15%) group. Oxygen and glucose was restored for 24 h after 4-6 h of deprivation. The severity of damage to PC12 cells was evaluated by CCK8, flow cytometry and lactate dehydrogenase (LDH). Mitochondrial morphology and function were examined by transmission electron microscopy (TEM), ATP and mitochondrial membrane potential (MMP) assay kits. Cellular autophagy and NLRP3 inflammasome-associated proteins were detected by Western blot and immunofluorescence staining. RESULTS: THSWD treatment improved the survival rate of PC12 cells injured by OGD/R, reduced cell damage and apoptosis. Moreover, ATP, MMP and the expression of autophagy marker proteins (LC3-II/LC3-I, Beclin1, Atg5) and mitophagy marker proteins (Parkin and PINK-1) was significantly elevated. The reactive oxygen species (ROS), NLRP3 inflammasome and pro-inflammatory cytokines induced by OGD/R were distinctly reduced. In contrast, these above beneficial effects of THSWD on mitochondrial autophagy and NLRP3 inflammasome were reversed by mitochondrial division inhibitory factor 1 (Mdivi-1). CONCLUSION: THSWD protects PC12 cells against OGD/R injury by heightening mitophagy and suppressing the activation of NLRP3 inflammasome.

Nitric-Oxide-Releasing aza-BODIPY: A New Near-Infrared J-Aggregate with Multiple Antibacterial Modalities.

The development of near-infrared (NIR) J-aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine-containing aza-BODIPY precursor (BDP-NH2 ), affording the first nitric oxide (NO)-releasing NIR J-aggregate (BDP-NO). The introduction of N-nitrosamine moieties efficiently inhibits the aromatic interactions of BDP-NH2 , which instead promotes the formation of J-aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents of BDP-NO within micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT-associated inflammation for the in vivo treatment of MRSA infection.

TMT-Based Quantitative Proteomic Analysis Identified Proteins and Signaling Pathways Involved in the Response to Xanthatin Treatment in Human HT-29 Colon Cancer Cells.

BACKGROUND: Xanthatin is a plant-derived bioactive sesquiterpene lactone from the Xanthium strumarium L., and it has been used as a traditional Chinese medicine. Recently, many studies have reported that xanthatin has anticancer activity. However, a comprehensive understanding of the mechanism underlying the antitumor effects of xanthatin is still lacking. OBJECTIVE: To systematically and comprehensively identify the underlying mechanisms of xanthatin on cancer cells, quantitative proteomic techniques were performed. METHODS: Xanthatin induced HT-29 colon cancer cells death was detected by lactate dehydrogenase (LDH) release cell death assay. Differentially abundant proteins in two groups (xanthatin treatment groups and control groups) of human HT-29 colon cancer cells were identified using tandem mass tag (TMT) quantitative proteomic techniques. All the significant differentially abundant proteins were generally characterized by performing hierarchical clustering, Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We chose Western blot analysis to validate the candidate proteins in the proteomics results. RESULTS: A total of 5637 proteins were identified, of which 397 significantly differentially abundant proteins in the groups were quantified. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we found that p53-related signaling played an important role in xanthatin-treated HT-29 colon cancer cells. p53- upregulated modulator of apoptosis (Puma), Sestrin-2 and p14ARF, which were selected from among p53-related signaling proteins, were further validated, and the results were consistent with the tandem mass tag quantitative proteomic results. CONCLUSION: We first investigated the molecular mechanism underlying the effects of xanthatin treatment on HT-29 colon cancer cells using tandem mass tag quantitative proteomic methods and provided a global comprehensive understanding of the antitumor effects of xanthatin. However, it is necessary to further confirm the function of the differentially abundant proteins and the potentially associated signaling pathways.

Di'ao Xinxuekang: Therapeutic Potential in Cardiovascular Diseases.

BACKGROUND: Cardiovascular disease is the leading cause of death in both developed and developing countries. Di'ao Xinxuekang (DAXXK) is a pure Chinese medicine herbal preparation refined from dioscin extracted from the roots of Dioscorea panthaica Prain et Burk and Diosorea nipponica Makino. OBJECTIVE: To evaluate the application of DAXXK in Cardiovascular disease. METHODS: We searched and summarized all the studies on DAXXK and Cardiovascular disease in Pubmed, Google, and CNKI. RESULTS: Modern pharmacological studies have shown that DAXXK has pharmacological effects such as dilating blood vessels, lowering blood pressure and cardiac load, improving hemodynamics, lowering blood lipids and anti-platelet aggregation, and is widely used for the therapy of various kinds of cardiovascular diseases, including hypertension, atherosclerosis, coronary heart disease (CHD), angina pectoris (AP) and myocardial infarction. We provide an overview of the clinical efficacy, molecular mechanisms, safety and therapeutic potential of DAXXK in the treatment of cardiovascular disease, aiming to provide clues and evidence for clinical decision-making. CONCLUSION: DAXXK exerts cardiovascular protection by regulating a variety of cardiovascular disease- related signaling pathways.

Systematic analyses on the potential immune and anti-inflammatory mechanisms of Shufeng Jiedu Capsule against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia (Coronavirus disease -19, COVID-19), has resulted in a global health emergency. However, there is no vaccine or effective antiviral treatment against the newly emerged coronavirus and identifying the available therapeutics as soon as possible is critical for the response to the spread of SARS-CoV-2. Shufeng Jiedu Capsule (SFJDC), a well-known prescription of Traditional Chinese Medicine (TCM) in China, has been widely used in treating upper respiratory tract infections and acute lung injury, owing to its immunomodulatory and anti-inflammatory effects. Despite the definite evidence of effective use of SFJDC in the diagnosis and treatment of pneumonia caused by SARS-CoV-2, the underlying action mechanism remains unknown. Currently, a systematic study integrated with absorption, distribution, metabolism and excretion (ADME) evaluation, target prediction, network construction and functional bioinformatics analyses is proposed to illustrate the potential immune and anti-inflammatory mechanisms of SFJDC against SARS-CoV-2. Additionally, to further validate the reliability of the interactions and binding affinities between drugs and targets, docking, Molecular dynamics Simulations (MD) simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area approach (MM-PBSA) calculations were carried out. The results demonstrate that SFJDC regulates the immunomodulatory and anti-inflammatory related targets on multiple pathways through its active ingredients, showing the potential anti-novel coronavirus effect. Overall, the work can provide a better understanding of the therapeutic mechanism of SFJDC for treating SARS-CoV-2 pneumonia from multi-scale perspectives, and may also offer a valuable clue for developing novel pharmaceutical strategies to control the current coronavirus.

The potential insights of Traditional Chinese Medicine on treatment of COVID-19.

Corona Virus Disease 2019 (COVID-19) broke out in 2019 and spread rapidly around the world. There is still no specific antiviral therapy to the current pandemic. In China, historical records show that Traditional Chinese Medicine (TCM) is effective in prevention and enhancing the resistance to pandemic with unique insights. To fight with COVID-19, National Health and Commission of PRC has recommended some TCM in the guideline, such as HuoxiangZhengqi, LianhuaQingwen ShufengJiedu and XueBijing, and actually displayed a remarkable effect in clinical treatment strategic for COVID-19. We review studies to provide an in-depth understanding into the effect of TCM, and also introduce the possible mechanism involved in COVID-19 treatment.

Potential therapeutic targets and promising drugs for combating SARS-CoV-2.

As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.

Xanthatin mediates G2/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells.

Xanthatin is a natural plant bicyclic sesquiterpene lactone extracted from Xanthium plants (Asteraceae). In the present study, we demonstrated for the first time that Xanthatin inhibited cell proliferation and mediated G2/M phase arrest in human colon cancer cells. Xanthatin also activated caspase and mediated apoptosis in these cells. Concomitantly, Xanthatin triggered cell autophagic response. We found down-regulation of X-linked inhibitor of apoptosis protein (XIAP) contribute to the induction of apoptosis and autophagy. Moreover, reactive oxygen species (ROS) production was triggered upon exposure to Xanthatin in colon cancer cells. ROS inhibitor N-acetylcysteine (NAC) significantly reversed Xanthatin-mediated XIAP down-regulation, G2/M phase arrest, apoptosis and autophagosome accumulation. In summary, our findings demonstrated that Xanthatin caused G2/M phase arrest and mediated apoptosis and autophagy through ROS/XIAP in human colon cancer cells. We provided molecular bases for developing Xanthatin as a promising antitumor candidate for colon cancer therapy. AbbreviationsROSreactive oxygen speciesDMSOdimethyl sulfoxide5-FU5-Fluorouracil3-MA3-MethyladenineDCFH-DA2'7'-dichlorfluorescein-diacetateNACN-acetylcysteineXIAPX-linked inhibitor of apoptosis protein.

Xin-Ji-Er-Kang Alleviates Myocardial Infarction-Induced Cardiovascular Remodeling in Rats by Inhibiting Endothelial Dysfunction.

The present study was designed to elucidate the beneficial effects of XJEK on myocardial infarction (MI) in rats, especially through the amelioration of endothelial dysfunction (ED). 136 Sprague-Dawley rats were randomized into 13 groups: control group for 0wk (n = 8); sham groups for 2, 4, and 6 weeks (wk); MI groups for 2, 4, and 6 wk; MI+XJEK groups for 2, 4, and 6w k; MI+Fosinopril groups for 2, 4, and 6 wk (n = 8~10). In addition, 8 rats were treated for Evans blue staining and Tetrazolium chloride (TTC) staining to determine the infarct size. Cardiac function, ECG, and cardiac morphological changes were examined. Colorimetric analysis was employed to detect nitric oxide (NO), and enzyme-linked immunosorbent assay (ELISA) was applied to determine N-terminal probrain natriuretic peptide (NT-ProBNP), endothelin-1 (ET-1), angiotensin II (Ang II), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4), and endothelial NO synthase (eNOS) content. The total eNOS and eNOS dimer/(dimer+monomer) ratios in cardiac tissues were detected by Western blot. We found that administration of XJEK markedly ameliorated cardiovascular remodeling (CR), which was manifested by decreased HW/BW ratio, CSA, and less collagen deposition after MI. XJEK administration also improved cardiac function by significant inhibition of the increased hemodynamic parameters in the early stage and by suppression of the decreased hemodynamic parameters later on. XJEK also continuously suppressed the increased NT-ProBNP content in the serum of MI rats. XJEK improved ED with stimulated eNOS activities, as well as upregulated NO levels, BH4 content, and eNOS dimer/(dimer+monomer) ratio in the cardiac tissues. XJEK downregulated ET-1, Ang II, and ADMA content obviously compared to sham group. In conclusion, XJEK may exert the protective effects on MI rats and could continuously ameliorate ED and reverse CR with the progression of MI over time.

Xin-Ji-Er-Kang ameliorates kidney injury following myocardial infarction by inhibiting oxidative stress via Nrf2/HO-1 pathway in rats.

AIM: Cardiovascular diseases, such as coronary heart disease and myocardial infarction (MI) are currently considered as the leading causes of death and disability. The aim of the present study is to investigate the effects of Xin-Ji-Er-Kang (XJEK) on kidney injury and renal oxidative stress. In addition, the associated mechanism involved in these processes was examined in an MI model, and particularly focused on the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase-1 (HO-1) pathway. MATERIALS AND METHODS: A total of 138 Sprague-Dawley rats were used in the present study. The control group was designated as 0 wk (n = 8). A total of 3 phases (2, 4, 6 wk) of administration were used in the sham-operated groups (sham, n = 10), MI groups (MI, n = 10), MI + XJEK groups (XJEK, n = 10) and MI + fosinopril groups (fosinopril, n = 10). Additional 10 rats were used to evaluate the infarct area. At 2, 4 or 6 wk post-MI, the hemodynamic parameters were monitored, the rats were sacrificed, then blood, heart and renal tissues were collected for furtherly analysis. RESULTS: The results indicated that XJEK administration continuously ameliorated renal hypertrophy index, blood urea nitrogen and cystatin C concentrations. XJEK further improved post-MI cardiac function by limiting scar formation and caused a downregulation in the hemodynamic parameters at the end of 2 and 4 wk. The hemodynamic parameters were upregulated after 6 wk treatment with XJEKcompared with those noted in the MI groups. Similarly, XJEK treatment for 2 wk potentiated Nrf2 nuclear translocation and HO-1 expression and inhibited the deficiency of nuclear Nrf2 and HO-1 at 6 wk post-MI compared with that of the MI groups, indicating the attenuation of the renal oxidative stress condition. The levels of malondialdehyde and angiotensin II (Ang II) in plasma and renal tissues, as well as the levels of aldosterone, 8-hydroxydeoxyguanosine, angiotensin II type 1 receptor and NADPH Oxidase-4 in the kidney tissue significantly decreased following XJEK treatment for 6 wk. In addition, the XJEK treatment groups revealed a significant upregulation in the activity of superoxide dismutase and in the total antioxidant capacity activity compared with those noted in the corresponding MI groups. CONCLUSION: These results demonstrated that progressive nephropathy in MI rats was associated with intrarenal activation of the renin-angiotensin-aldosterone system. Concomitantly, this process was associated with oxidative stress and impaired Nrf2 activation. The improvement in the severity of nephropathy by XJEK in this model may be associated with the reversal of these abnormalities.

Protective effect of Xin-Ji-Er-Kang on cardiovascular remodeling in high-salt induced hypertensive mice: Role ofoxidative stress and endothelial dysfunction.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. OBJECTIVE: The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. METHODS: The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n=10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4) concentration and l-arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ETA) expression (determined by western blotting). RESULTS: Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH4 and decreasing ETA content. In addition, treatment with XJEK decreased ADMA content in the myocardium. CONCLUSION: In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP.

Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics.

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

Trends analysis for drug utilization in county public hospitals: a sample study of the pilot area of health care reform in China.

BACKGROUND: Changes in the national drug policy always have impact on the drug utilization. In the context of China health care reform, what changes had happened in the trend of drug utilization in public hospitals? Has this change met the expectations of policy design? This study was conducted to explore the trend of medicine consumption in county public hospitals before and after health care reform, and to provide real-world evidence to help assess the effectiveness of national drug policy. METHODS: A cross-sectional study was performed to investigate the drug utilization trends of 6 county public hospitals in Anhui Province, which is the first pilot area of China health care reform. Data were collected before and after the implementation of the China National Essential Medicine Policy (NEMP) to analyse the drug utilization indicators, such as the drug utilization constituent ratio, the rate of essential medicine usage and the rate of antibiotic consumption. RESULTS: Chemicals are used most frequently and account for 60%~ 70%, followed by oral agents of proprietary Chinese medicine. The results also show increased consumption of Chinese medicine injections (χ2 = 28.428, P < 0.01). The top 3 chemical medicines consumed were anti-infective drugs (12.92%), cardiovascular system drugs (11.61%), and digestive system drugs (8.42%). For Chinese traditional medicine, the top 3 drugs consumed were internal medicine drugs (66.03%), surgical drugs (8.45%), and gynaecological drugs (7.70%). The total sales amounts of drugs covered by medical insurance are at a high level (all above 80%), whereas essential medicines are less than 50% at almost all county-level medical institutions. CONCLUSIONS: This study uncovered the changing tendency of medicine usage under the implementation of the reform. Chinese medicine injections and anti-infective drugs have always been a sustained concern of pharmacovigilance. It is noteworthy that although essential medicines are advocated for as a priority for use in the government-run hospital, the consumption proportion of these medicines is lower than expected.

Reversal effect of quercetin on multidrug resistance via FZD7/ß-catenin pathway in hepatocellular carcinoma cells.

BACKGROUND: Chemotherapy has been widely used to treat cancer, but the appearance of multidrug resistance (MDR) is the biggest obstacle to successful chemotherapy. One of the conventional mechanisms of MDR is overexpression of ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated proteins (MRPs/ABCCs) that limits the prolonged and efficient use of chemotherapeutic drugs. To enhance the chemosensitivity of tumor cells, attentions have been focused on effective MDR modulators. PURPOSE: This study aimed to investigate the reversal effect of quercetin on MDR, and explored its mechanism of action in vitro. STUDY DESIGN/METHODS: The effect and mechanism of quercetin on MDR was examined by using MTT assay, flow cytometry, real-time PCR and western blot analysis in human hepatocellular carcinoma cells. RESULTS: Our data found that the intracellular accumulation of rhodamine-123 (Rh123) and doxorubicin (ADR) were increased, the sensitivity of BEL/5-FU cells to chemotherapeutic drugs were increased, and the expressions of ABCB1, ABCC1 and ABCC2 were all down-regulated, which indicated that the functions and expressions of ABCB1, ABCC1 and ABCC2 efflux pump were inhibited by quercetin treatment. Moreover, the suppression of ABCB1, ABCC1 and ABCC2 by quercetin was dependent on the FZD7 through the Wnt/ß-catenin pathway. Further research revealed that reduction of FZD7 by RNA interference (siFZD7) enhanced the sensitivity to chemotherapeutic drugs, increased the cellular accumulation of Rh123 and ADR, and induced inhibitory effects on the expression of FZD7, ABCB1, ABCC1, ABCC2 and ß-catenin, similar to quercetin. In the meanwhile, overexpression of FZD7 showed the inversely effect on the expressions. Interesting, it was confirmed that quercetin could inhibit the expression levels of FZD7, ABCB1, ABCC1, ABCC2 and ß-catenin in BEL-7402 cells; furthermore, treatment by quercetin combined with siFZD7 in BEL/5-FU cells, the expressions of these genes were effectively decreased in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Overall, these data suggested the effectiveness of using quercetin, at least in part, via inhibiting FZD7 to combat chemoresistance and showed that quercetin could be developed into an efficient natural sensitizer for resistant human hepatocellular carcinoma.

Total flavonoids of Bidens bipinnata L. ameliorate experimental adjuvant-induced arthritis through induction of synovial apoptosis.

BACKGROUND: Bidens bipinnata are widely distributed in China, which have been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of total flavonoids of Bidens pilosa L. (TFB) on adjuvant arthritis (AA) and its possible mechanisms. METHODS: The macroscopic scoring of paw edema, secondary paw swelling, and polyarthritis index were measured. Histological examination of the joints and the serum concentrations of IL-6, IL-1beta, and TNF-alpha were examined. Apoptosis in synovial tissue was detected. The expression of Caspase 3 cleavage, serves as a marker undergoing apoptosis, was confirmed by Western blot. RESULTS: TFB attenuated the severity of arthritis on paw edema, hind paw volume, and polyarthritis index of AA rats, improved the histological status in AA rats as well. TFB can inhibit the production of IL-6, IL-1beta, and TNF-alpha from serum. Clear DNA ladder formation was observed in DNA extraction of synovium from TFB treated AA rats. The number of apoptosis was increased with TFB treatment in TUNEL assay. TFB treatment on AA rats significantly increased the expression of Caspase 3 in synovium. CONCLUSIONS: Our data suggest that TFB has a significant anti-arthritic effect in AA through the induction of apoptosis in synovial.