Dendritic cells treated with a prostaglandin I2 analog,iloprost, promote antigen-specific regulatory T cell differentiation in mice

Iloprost, a stable prostaglandin I₂ (PGI₂) analog, can inhibit allergic inflammation in an ovalbumin (OVA)-induced asthma model via inhibition of airway dendritic cell (DC) function. However, the underlying mechanism of PGI₂ signaling-mediated immunosuppression remains unclear. This study explored whether iloprost-treated DCs can suppress inflammation by promoting antigen-specific regulatory T cell (Treg) differentiation through PGI₂-G-protein-coupled receptor (IP). We established an allergic lung inflammation model using a hydrogel biomaterial delivery system and observed that iloprost significantly suppressed OVA-induced Th2 lung inflammation and increased the frequency of OVA-specific Tregs in vivo. We further observed that iloprost-treated DCs displayed tolerogenic characteristics, including low inflammatory cytokine (IL-12, TNF-α, IL-6, IL-23) expression levels, high anti-inflammatory cytokine (IL-10) production, and a semimature phenotype. In addition, iloprost-treated DCs increased OVA-specific CD4⁺Foxp3⁺ T cell differentiation from naïve T cells in an IP-dependent pathway in vitro and in vivo. Blocking experiments showed that iloprost-treated DCs promoted Treg differentiation, at least in part, through programmed death ligand 1 (PD-L1), whereas iloprost-induced PD-L1 expression in DCs was through the IP receptor. Furthermore, iloprost treatment suppressed DC-mediated airway inflammation and increased the frequency of OVA-specific Tregs through PD-L1 in vivo. Taken together, these results show that PGI₂-IP signaling mediated by iloprost in DCs may lead to immune tolerance, suggesting that the PGI₂ analog has the potential to be applied therapeutically for tolerogenic DC immunotherapy in autoimmune diseases or allergic asthma.     

Green synthesis and characterization of gold nanoparticles from Pholiota adiposa and their anticancer effects on hepatic carcinoma

Gold nanoparticles (AuNPs) were successfully fabricated by Pholiota adiposa polysaccharide (PAP-1a) without employing any other chemicals. The physical and chemical properties of PAP-AuNPs were determined using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDXR), Fourier-transform infrared spectroscopy (FT-IR), and atomic force microscopy (AFM). In an attempt to analyze the immune regulation, antitumor effect, and biological safety, the production of NO and TNF-α, IL-12p70, and IL-1β from RAW264.7 as well as the proliferation of RAW264.7 were detected in vitro. Flow cytometry was conducted to determine the ratio of the CD4⁺/CD8⁺ cell in peripheral blood and immunohistochemical analysis involving hematoxylin and eosin (H&E) and proliferating cell nuclear antigen (PCNA) staining were conducted in vivo. The results of this study showed that PAP-AuNPs had a significantly improved immune regulation and anti-tumor effect in comparison to PAP-1a alone. PAP-AuNPs showed no toxicity both in vivo and in vitro. This study demonstrates a useful application of PAP-AuNPs as a novel nanomedicine for hepatic carcinoma.     

BAFF and its receptors involved in the inflammation progress in adjuvant induced arthritis rats

This study is in order to clear the roles of BAFF and its receptors in the inflammation course of autoimmune arthritis. We used a T cell-mediated experimental autoimmune model adjuvant-induced arthritis (AA) rat to study the profiles of BAFF and its receptors in spleen during the inflammation arthritis induction and the effects of BAFF on DCs functions. In vivo, the levels of BAFF and the expression of BAFF-R, TACI were increased in spleen from very early stage of AA. The lesions of spleen were definite correlated with increased levels of BAFF in homogenization. The mature of DCs and increased number in spleen were mainly at early stage of arthritis. In addition, the levels of Interleukin (IL)-12 were found highest and IL-10 were found lowest at this time too. In vitro recombinant BAFF promoted maturation of DCs and inhibited the phagocytosis of DCs. Under stimulation of BAFF on DCs, the levels of tumor necrosis factor (TNF)-α, IL-6, IL-12 were increased, IL-10 and transforming growth factor (TGF)-β1 were decreased. Moreover, BAFF-treated DCs induced proliferation of CD4⁺ T cell. These findings support the crucial pathogenic role of DCs, BAFF, and its receptors in the development of experimental arthritis.     

Anticolitis activity of chinese herbal formula Yupingfeng powder via regulating colonic enterochromaffin cells and serotonin

Objective:

To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved.

Materials and Methods:

YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability.

Results:

The results showed that the body weight of colitis mice was markedly decreased by 10, 12, 14, and 17% at 1, 3, 5, and 7 days (P < 0.05), whereas stool consistency score (3.6 vs. 0.4, P < 0.05), histopathological score (3.6 vs. 0.3, P < 0.05), and MPO activity (2.7 vs. 0.1, P < 0.05) in colitis mice were significantly increased compared to that of the normal mice; YPF powder treatment dose-dependently increased the body weight (7–13% increase) and decreased the stool consistency score (0.4–1.4 decrease), histopathological score (0.2–0.7 decrease), and MPO activity (0.1–0.9 decrease) in colitis mice. Colonic EC cell density (70% increase) and 5-HT content (40% increase) were markedly increased in colitis mice (P < 0.05), YPF powder treatment dose-dependently reduced EC cell density (20–50% decrease), and 5-HT content (5–27% decrease) in colitis mice.

Conclusion:

The findings demonstrate that the anti-inflammatory effect of YPF powder on TNBS - induced colitis may be mediated via reducing EC cell hyperplasia and 5-HT content. The important role of YPF powder in regulating colonic EC cell number and 5-HT content may provide an alternative therapy for colonic inflammation.KEY WORDS: Colonic inflammation, enterochromaffin cell, serotonin, ulcerative colitis     

Paeoniflorin inhibits the maturation and immunostimulatory function of allergen-induced murine dendritic cells

Dendritic cells (DCs) as the front lines of defense play a crucial role in allergic contact dermatitis (ACD). Paeoniflorin (PF) has been clinically proven to be effective in the treatment of inflammatory skin diseases such as ACD. However, the mechanisms underlying the anti-inflammatory effect of PF remain unclear. The aim of this study was to explore the effect of PF on the maturation and immunostimulatory function of DCs in the murine model of ACD in vitro. Murine bone marrow-derived DCs were stimulated with the contact sensitizer 1-chloro-2, 4-dinitrobenze (DNCB) in vitro. Surface antigen expression of DCs (MHC II, CD40, CD80, and CD86), as an indicator of maturation DCs and cytokines (IL-12, IFN-γ, IL-10, and TGF-β) after DNCB stimulation in the absence or presence of PF at different doses, was detected. Then, we detected that PF-treated DCs stimulated T cells in response to DNCB. PF inhibited the up-regulation of MHC II, CD80, CD86, and CD40, decreased IL-12p70 secretion, while increased the production of IL-10 and TGF-β, and had no effect on IFN-γ cytokine production by murine bone marrow-derived DCs in response to DNCB. DCs exposed to PF had diminished capacity to stimulate allogeneic T cell proliferation and to activate IFN-γ-producing CD4⁺ T cells and induced CD4⁺CD25⁺Foxp3⁺ T cells and IL-10-producing T cell expansion from naïve CD4⁺ T cells. These results indicate that PF may be effective in preventing and treating ACD in vitro and other inflammatory responses possibly through inhibiting maturation of DCs and limiting their capacity to stimulate T cell responses.     

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Oral route colon-targeted drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC). However, CDDSs are challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT). In this study, we developed an effective enzyme-triggered controlled release system using curcumin–cyclodextrin (CD–Cur) inclusion complex as core and low molecular weight chitosan and unsaturated alginate resulting nanoparticles (CANPs) as shell. The formed CD–Cur–CANPs showed a narrow particle-size distribution and a compact structure. In vitro drug release determination indicated that CD–Cur–CANPs showed pH-sensitive and α-amylase-responsive release characteristics. Furthermore, in vivo experiments demonstrated that oral administration of CD–Cur–CANPs had an efficient therapeutic efficacy, strong colonic biodistribution and accumulation, rapid macrophage uptake, promoted colonic epithelial barrier integrity and modulated production of inflammatory cytokines, reshaped the gut microbiota in mice with dextran sodium sulfate (DSS)-induced colitis. Taken together, our synthetic CD–Cur–CANPs are a promising synergistic colon-targeted approach for UC treatment.     

Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer

Aim:

IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects.

Methods:

IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected.

Results:

IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02±0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4⁺ T cell proliferation without affecting CD8⁺ T cell proliferation.

Conclusion:

IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.     

Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.KEY WORDS: Hepatocellular carcinoma, Synergetic delivery, Triptolide, Ce6, Photo-activatable liposomes, Photosensitizer, Process of photodynamic therapy, PDX model     

Mechanochemical preparation of triptolide-loaded self-micelle solid dispersion with enhanced oral bioavailability and improved anti-tumor activity

Triptolide (TP), a compound isolated from a Chinese medicinal herb, possesses potent anti-tumor, immunosuppressive, and anti-inflammatory properties, but was clinically limited due to its poor solubility, bioavailability, and toxicity. Considering the environment-friendly, low-cost mechanochemical techniques and potential dissolution enhancement ability of Na₂GA, an amorphous solid dispersion (Na₂GA&TP-BM) consisting of TP and Na₂GA were well-prepared to address these issues. The performance of Na₂GA&TP-BM was improved through ball milling, such as from crystalline state to an amorphous solid dispersion, suitable nano micelle size and surface potential, and increased solubility. This change had a significant improvement of pharmacokinetic behavior in mice and could be able to extend the blood circulation time of the antitumor drug. Moreover, in vitro and in vivo anti-tumor study showed that Na₂GA&TP-BM displayed more potent cytotoxicity to tumor cells. The work illustrated an environment-friendly and safe preparation of the TP formulation, which was promising to enhance the oral bioavailability and antitumor ability of TP, might be considered for efficient anticancer therapy.     

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.     

Effects of NO‐Hybridization on the Immunomodulatory Properties of the HIV Protease Inhibitors Lopinavir and Ritonavir

HIV protease inhibitors (PIs) are antiretroviral agents, which have been found to also affect several cellular processes, such as inflammation and cell progression. In studies on non‐steroidal, anti‐inflammatory drugs, the addition of a nitric oxide (NO) moiety has been shown to both reduce their toxicity and enhance their pharmacological efficacy. Along this line of research, several derivatives of PIs have been synthesized by covalent attachment of NO moiety to the parental molecules. Previous work has indicated that NO‐hybridization of the prototypical PI, Saquinavir leads to a derivative named Saquinavir‐NO that while retaining the antiretroviral effect, acquires antitumoural and immunomodulatory properties along with reduced toxicity in vitro and in vivo. These data prompted us to evaluate the effects of NO‐hybridization on two other PIs, Lopinavir and Ritonavir. The two NO‐derivatives were compared head to head with their parental compounds on human primary peripheral blood mononuclear cells as well as on human primary macrophages. Lopinavir‐NO and Lopinavir were also screened in an in vivo model of autoimmune hepatitis. Our results prove that Lopinavir‐NO exerts markedly superior effects as compared to the parental compound both in vitro and in vivo. On the contrary, Ritonavir‐NO effects overlapped those of Ritonavir. These data demonstrate that NO‐hybridization of Lopinavir generates a derivative with significantly stronger immunomodulatory effects that are apparently related to an action of the compound on T‐cell secretory capacity. Lopinavir‐NO deserves additional studies for its possible use in T‐cell‐mediated autoimmune diseases including, but not limited to autoimmune hepatitis.     

A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide

Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In the presence of LPS, RGMa siRNA transfection markedly reduced levels of CD80, CD86, CD40, and MHC II expression, as well as the secretion of IL-12p70 and TNF-α. With LPS treatment, RGMa siRNA-transfected DCs also showed increased levels of IL-10 and endocytosis. Moreover, in the presence of LPS, RGMa siRNA-transfected DCs displayed a low ability to induce T cell proliferation and differentiation, compared with negative control (NTi)-transfected or control DCs (p < 0.05 for both). We conclude that after LPS stimulation, RGMa siRNA-transfected DCs show immunoregulatory and tolerogenic characteristics, which provides new insights into the immune system.     

Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and fibrosis

Inflammatory bowel disease could result in diarrhea and abdominal pain, as well as potential complications such as tissue fibrosis. The therapeutic effect of andrographolide sulfonate on acute murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) has been confirmed. In the study here, chronic colitis triggered by repeated intrarectal administration of TNBS was established and the effect of andrographolide sulfonate was examined. Repeated TNBS administration induced substantial mice death, which was significantly decreased by andrographolide sulfonate treatment. The elevation of inflammatory cytokines including IL-6, IL-17A, TNF-α as well as IFN-γ in colonic tissues levels were decreased after administration of andrographolide sulfonate. Next, CD4⁺ T cell and macrophage infiltration was found to descend. The subset of pathogenic CD4⁺ T cell subset including CD4⁺IFN-γ⁺ (Th1) and CD4⁺IL-17A⁺ (Th17) were also suppressed by andrographolide sulfonate. Further, the restrain of p38 and p65 activation were also observed after andrographolide sulfonate administration. Finally, TNBS-induced colonic epithelial damage as well as fibrosis were significantly mitigated by andrographolide sulfonate. Based on the results got here, we can make a conclusion that andrographolide sulfonate could decrease inflammation and epithelial damage as well as fibrosis thus ameliorating chronic colitis in mice. Our study suggest the possible use of andrographolide sulfonate for chronic colitis treatment in clinical.     

Curcumin attenuates prostatic hyperplasia caused by inflammation via up-regulation of bone morphogenetic protein and activin membrane-bound inhibitor

ContextInflammation and epithelial-mesenchymal transition (EMT) play important roles in the occurrence and development of benign prostatic hyperplasia (BPH); curcumin exerts anti-proliferative, anti-inflammatory, and anti-EMT effects.ObjectiveTo explore the anti-inflammatory and anti-EMT mechanisms of curcumin in BPH.Materials and methodsTen-week-old male C57BL/6 mice were administered lipopolysaccharide (LPS, 100 µg/kg) in the prostate lobules to establish an inflammatory BPH model (LPS group), and curcumin (120 mg/kg) was administered into the abdominal cavity for 2 weeks (three times a week, curcumin-treated group). A group of healthy mice served as the control group. The expression of Toll-like receptor 4 (TLR4), bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), EMT markers, inflammatory cytokines, and transforming growth factor β1 (TGF-β1) was detected by PCR and western blotting. TGF-β1 (0.1 ng/mL) and LPS (100 ng/mL) were used to induce EMT in benign prostatic hyperplasia epithelial cells (BPH-1).ResultsIn vivo, curcumin reduced the size of the prostate, suppressed the expression of vimentin and TLR4, and increased the expression of E-cadherin and BAMBI in the LPS-induced BPH mouse model. Moreover, curcumin decreased the levels of IL-6 and TNF-α by 44.52 and 46.17%, respectively. In vitro, curcumin attenuated cell proliferation, suppressed the expression of vimentin and TLR4, and increased the expression of E-cadherin and BAMBI in BPH-1 cells. Furthermore, BAMBI knockdown reversed the expression of vimentin and E-cadherin induced by curcumin.Discussion and conclusionThis study demonstrated that curcumin alleviated hyperplasia, EMT, and inflammation in vivo. Furthermore, curcumin suppressed EMT by targeting BAMBI via the TLR4/BAMBI/TGF-β1 signalling pathway in vitro, demonstrating its potential utility in BPH treatment.     

Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases

IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4⁺ regulatory cells able to prevent in vitro bystander T-cell proliferation and to cure ongoing chronic colitis in mice. In order to assess the efficacy and tolerance of Tr1 cell therapy in a Phase I/IIa clinical trial in patients displaying severe Crohn's disease, we set up a reproducible manufacturing process for the GMP production of human ovalbumin specific Tr1 cells. Procedures used for Tr1-cell production include the use of Drosophila derived artificial Antigen Presenting Cells transfected with specific stimulatory molecules. Characterization of the human cell therapy product shows an in vitro suppressive activity on T-cell proliferation dependent on the production of both IL-10 and TGF-beta. Manufactured Tr1 cells display a regulatory phenotype including Foxp3, GITR and CTLA-4 surface expression. In vitro toxicity studies of human Tr1 cell product show a safety profile compatible with the use of these regulatory Tr1 lymphocytes for cell therapy.     

Dendritic cell activation by polysaccharide isolated from Angelica dahurica

Angelica dahurica is used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. In the present study, we examined the effect of A. dahurica polysaccharide (ADP) on dendritic cell (DC) maturation. ADP increased the expressions of CD86 and MHC-II molecules, the production of IL-12, IL-1β, and TNF-α, and allogeneic T cell activation ability of DCs, and reduced DC endocytosis. As a mechanism of action, the knockdown of TLR4 with small interfering RNA decreased the ADP-induced production of nitric oxide and IL-12 by DCs, suggesting the membrane receptor candidate of ADP. After binding to TLR4, ADP increased the phosphorylation of ERK, JNK, and p38 MAPKs, and the nuclear translocation of NF-κB p50/p65. These results indicate that ADP activates DCs through TLR4 and downstream signalings.     

Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation

Context Tanshinone IIA is a natural extract derived from a Chinese medicinal herb with multiple bioactivities; however, whether and how tanshinone IIA protects against colorectal cancer (CRC) are uncertain.Objective We investigated the potential beneficial effects of tanshinone IIA in a colitis-associated colorectal tumorigenesis mouse model and its underlying mechanisms.Materials and methods Male C57BL/6 mice were treated with azoxymethane (AOM) 10 mg/kg body weight and dextran sulphate sodium (2.5% DSS) to induce a colitis-associated cancer model. Tanshinone IIA (200 mg/kg body weight) was given to the mice intraperitoneally. After 12 weeks, all mice were sacrificed to measure tumour formation, intestinal permeability, neutrophil infiltration, and colonic inflammation. In addition, whether tanshinone IIA has inhibitory effects on neutrophil activation was determined through in vitro investigations.Results We observed that tanshinone IIA significantly decreased tumour formation in AOM/DSS-treated mice compared to AOM/DSS-treated alone mice (0.266 ± 0.057 vs. 0.78 ± 0.153, p = 0.013). Tanshinone IIA also decreased intestinal permeability compared to that in AOM/DSS-treated alone mice (3.12 ± 0.369 vs. 5.06 ± 0.597, p = 0.034) and consequently reduced neutrophil infiltration of the colonic mucosa (53.25 ± 8.85 vs. 107.6 ± 13.09, p = 0.014) as well as intestinal inflammation in mice. Mechanistically, tanshinone IIA downregulated the NF-κB signalling pathway in the colonic tumours of AOM/DSS-treated mice. In vitro assays further validated that tanshinone IIA suppressed LPS-induced neutrophil activation.Conclusion These data suggest that tanshinone IIA alleviates colorectal tumorigenesis through inhibition of intestinal inflammation. Tanshinone IIA may have a therapeutic potential for CRC in clinical practice.