A comprehensive investigation to the fate of phosphorus in full-scale wastewater treatment plants using aluminum salts for enhanced phosphorus removal.

This study investigated the fate of phosphorus (P) in 8 full-scale municipal wastewater treatment plants (WWTPs) in Shanghai, China, in which both biological nutrient removal and aluminum-based chemical phosphorus removal were used. The results showed that 83.8-98.9 % P was transferred to the sludge in the 8 WWTPs by both chemical and biological reactions. P speciation analysis indicated that chemical P precipitates accounted for 84.3 % in the activated sludge, of which crystalline AlPO4 and amorphous iron­phosphorus compounds (FePs) were the main components. Sludge with more water-soluble and weakly adsorbed P was generated in the anaerobic-anoxic-oxic (A/A/O) process than in other processes. Among the 8 WWTPs, the one with the largest flow rate and relatively short sludge retention time (SRT) had the best potential to release P from all types of sludge. The recovery potential of P from thickened sludge can be improved by separately thickening the sludge produced in the high-efficiency sedimentation tank or feeding it into the dewatering process directly. Different P removal chemicals and dosing points changed the amount of chemical precipitate formed but had little effect on the composition of P accumulating organisms (PAOs) at the genus level. Although aluminum-based coagulants were applied in the investigated WWTPs, Fe in wastewater had the most positive effect on the proliferation of PAOs. The synthesis of polyphosphate was also related to the metabolism of PAOs as it affected transmembrane inorganic phosphate (Pi) transport and polyhydroxybutyrate (PHB) synthesis. The in-depth understanding of the fate of P is beneficial to improve P recovery efficiency in WWTPs.

A novel approach using protein-rich biomass as co-fermentation substrates to enhance phosphorus recovery from FePs-bearing sludge.

A novel approach for the enhancement of phosphorus (P) recovery from Fe bound P compounds (FePs)-bearing sludge by co-fermentation with protein-rich biomass (PRB) is reported. Four PRBs (silkworm chrysalis meal, fish meal, corn gluten meal, and soya bean meal) were used for co-fermentation. The results revealed that PRBs with strong surface hydrophobicity and loose structure favored the hydrolysis and acidogenesis processes. Sulfide produced by PRB could react with FePs to form FeS and promote P release. Due to the neutralization of volatile fatty acids (VFAs) by a relatively high concentration of ammonia, the pH was maintained near neutral and thus prevented the dissolution of metal ions (e.g., Fe and Ca). This was beneficial to save the cost of subsequent P recovery and form high-purity struvite. Compared with the control, the soluble orthophosphate and VFAs increased by 88.3% and 531.3%, respectively, in the co-fermentation system with silkworm chrysalis meal. Cysteine was the important intermediate. The metagenomics analysis indicated that the gene abundances of phosphate acetyltransferase and acetate kinase, which were key enzymes in the acetate metabolism, increased by 117.7% and 52.2%, respectively. The gene abundances of serine O-acetyltransferase and cysteine synthase increased by 63.4% and 54.4%, respectively. Cysteine was primarily transformed to pyruvate and sulfide. This study provides an environment-friendly strategy to simultaneously recover P and VFAs resources from FePs-bearing sludge and PRB waste.

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective.

Andrographolide, a well-known natural lactone having a range of pharmacological actions in traditional Chinese medicine. It has long been used to cure a variety of ailments. In this review, we cover the pharmacokinetics and pharmacological activity of andrographolide which supports its further clinical application in cancers and inflammatory diseases. Growing evidence shows a good therapeutic effect in inflammatory diseases, including liver diseases, joint diseases, respiratory system diseases, nervous system diseases, heart diseases, inflammatory bowel diseases, and inflammatory skin diseases. As a result, the effects of andrographolide on immune cells and the processes that underpin them are discussed. The preclinical use of andrographolide to different organs in response to malignancies such as colorectal, liver, gastric, breast, prostate, lung, and oral cancers has also been reviewed. In addition, several clinical trials of andrographolide in inflammatory diseases and cancers have been summarized. This review highlights recent advances in ameliorating inflammatory diseases as well as cancers by andrographolide and its analogs, providing a new perspective for subsequent research of this traditional natural product.

Inhibition of NLRP3 inflammasome activation in myeloid-derived suppressor cells by andrographolide sulfonate contributes to 5-FU sensitization in mice.

5-Fluorouracil (5-FU)-based chemotherapy is the first-line recommended regimen in colorectal cancer (CRC), but resistance limits its clinical application. Andrographolide sulfonate, a traditional Chinese medicine, is mainly used to treat infectious diseases. In the present study, we reported that andrographolide sulfonate could significantly inhibit the growth of transplanted CT26 colon cancer in mice and improve survival when combined with 5-FU. Furthermore, TUNEL assay and immunohistochemistry analysis of proliferating cell nuclear antigen, Ki-67 and p-STAT3 confirmed that co-treatment could inhibit tumor proliferation and promote apoptosis. In tumor tissues of groups that received 5-FU and andrographolide sulfonate, CD4+ and CD8+ T cell infiltration was increased, and the expression of IFN-γ and Granzyme B detected by immunohistochemistry and qPCR was upregulated, reflecting improved antitumor immunity. Finally, we verified that 5-FU significantly activated the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in myeloid-derived suppressor cells (MDSCs) and that andrographolide sulfonate reversed this process to sensitize cells to 5-FU. In summary, andrographolide sulfonate synergistically enhanced antitumor effects and improved antitumor immunity by inhibiting 5-FU-induced NLRP3 activation in MDSCs. These findings provide a novel strategy to address 5-FU resistance in the treatment of CRC.

Andrographolide sulfate inhibited NF-κB activation and alleviated pneumonia induced by poly I:C in mice.

Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.

Pidotimod enhanced the anti-growth effect of cisplatin on lung cancer in mice via promoting anti-tumor immune response.

Cisplatin-based chemotherapeutics represent a mainstay of lung cancer therapy, but resistance limits their curative potential. In the current study, we reported that Pidotimod, which is an immunostimulant and used for the prevention of acute respiratory infections, elevated cisplatin sensitivity, leading to the synergistic attenuation of tumor growth in mouse lewis lung cancer (LLC) model. With further exploration, we found that Pidotimod enhanced the anti-growth effect of cisplatin on LLC via promoting anti-tumor response, such as increased infiltration of dendrite cells (DCs) and CD8+ T cells as well as enhancement of IFN-γ and Granzyme B expression. In summary, Pidotimod affects the anti-tumor function of cisplatin via promoting anti-tumor immune response and these findings provide a novel approach for the development of therapeutic strategies for lung cancer.

Andrographolide potentiates PD-1 blockade immunotherapy by inhibiting COX2-mediated PGE2 release.

Cancer immunotherapy has now become a first line therapy for several kinds of tumors. However, the clinical performance of immnuocheckpoint blockade therapy is usually limited by low response rate or side effects including cytokine storm. Andrographolide, a natural diterpenoid from Andrographis paniculata, has been used in Asia for treatment of bronchitis, paristhmitis and bacillary dysentery for its unique anti-inflammatory effect. However, its effect on anti-tumor immunity remains elusive. In this study, we found that andrographolide in combination with anti-PD-1 antibody showed a higher therapeutic benefit than individual therapy in murine xenograft model of CT26 colon cancer. Consequently, andrographolide and anti-PD-1 antibody co-treatment boosted the function of CD4+ and CD8+ T cells evidenced by considerable tissue infiltration, elevated IFN-γ secretion and enhanced expression of cytotoxic T-cell related molecules including FasL, perforin and Granzyme B, which significantly decreases the tumor load. Mechanistically, andrographolide treatment inhibited COX2 activity and PGE2 release both in vivo and in vitro, which augments anti-tumor efficiency of anti-PD-1 therapy. Finally, we confirmed that COX2 level in human colon cancer sample positively correlated with tumor-promoting factors. Our study here provides a potential combination strategy for immunotherapy against colorectal cancer.

Effective Virtual Screening Strategy toward heme-containing proteins: Identification of novel IDO1 inhibitors.

Developing small molecules occupying the heme-binding site using computational approaches remains a challenging task because it is difficult to characterize heme-ligand interaction in heme-containing protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular heme-containing dioxygenase which is associated with the immunosuppressive effects in cancer. With IDO1 as an example, herein we report a combined virtual screening (VS) strategy including high-specificity heme-binding group (HmBG)-based pharmacophore screening and cascade molecular docking to identify novel IDO1 inhibitors. A total of four hit compounds were obtained and showed proper binding with the heme iron coordinating site. Further structural optimization led to a promising compound S18-3, which exerted potent anti-tumor efficacy in BALB/c mice bearing established CT26 tumors by activating the host's immune system. These results suggest that S18-3 merits further study to assess its potential for the intervention of cancer. Furthermore, our study also unveils a novel in silico-based strategy for identifying potential regulators for hemeproteins within short timeframe.

Targeting Peroxiredoxin 1 by a Curcumin Analogue, AI-44, Inhibits NLRP3 Inflammasome Activation and Attenuates Lipopolysaccharide-Induced Sepsis in Mice.

Aberrant activation of the NLRP3 inflammasome contributes to the onset and progression of various inflammatory diseases, making it a highly desirable drug target. In this study, we screened a series of small compounds with anti-inflammatory activities and identified a novel NLRP3 inflammasome inhibitor, AI-44, a curcumin analogue that selectively inhibited signal 2 but not signal 1 of NLRP3 inflammasome activation. We demonstrated that AI-44 bound to peroxiredoxin 1 (PRDX1) and promoted the interaction of PRDX1 with pro-Caspase-1 (CASP1), which led to the suppression of association of pro-CASP1 and ASC. Consequently, the assembly of the NLRP3 inflammasome was interrupted, and the activation of CASP1 was inhibited. Knockdown of PRDX1 significantly abrogated the inhibitory effect of AI-44 on the NLRP3 inflammasome. Importantly, AI-44 alleviated LPS-induced endotoxemia in mice via suppressing NLRP3 inflammasome activation. Taken together, our work highlighted PRDX1 as a negative regulator of NLRP3 inflammasome activation and suggested AI-44 as a promising candidate compound for the treatment of sepsis or other NLRP3 inflammasome-driven diseases.

Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells.

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8+ T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8+ T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.

Small-molecule RL71-triggered excessive autophagic cell death as a potential therapeutic strategy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca2+ from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity. The disruption of calcium homeostasis induced ER stress, leading to apoptosis. More importantly, the elevated intracellular calcium signals induced autophagy through the activation of the CaMKK-AMPK-mTOR pathway and mitochondrial damage. In two TNBC xenograft mouse models, RL71 also displayed strong efficacy including the inhibition of tumor growth, the reduction of metastasis, as well as the prolongation of survival time. These findings suggest SERCA2 as a previous unknown target candidate for TNBC treatment and support the idea that autophagy inducers could be useful as new therapeutics in TNBC treatment.

Antibacterial and antioxidant properties of various solvents extracts of Abutilon theophrasti Medic. leaves.

This paper described the extraction procedure of six extracts from Abutilon theophrasti Medic. leaves and evaluated antioxidant and antibacterial activity of different extracts by hydroxyl radical, DPPH radical scavenging, broth micro-dilution and agar-well diffusion methods. The six extracts were prepared by the two extraction procedures: (I) water was the extraction solvent; (II) 90% alcohol extract was extracted by petroleum ether, chloroform, ethyl acetate and n-butanol in turn. Extract yields were 7.34%, 7.31%, 0.45%, 0.12%, 2.70% and 5.68% for extract I to VI. It was revealed that the various extracts had effective antibacterial activity against four test strains from Staphylococcus aureus (ATCC 25923), Streptococcus (ATCC 49619), Escherichia coli (ATCC 25922) and Salmonella (ATCC 01303); meanwhile, the six extracts demonstrated potent antioxidant activity, achieved by hydroxyl radical and DPPH radical scavenging assay. Minimum inhibitory concentrations (MICs) for the bacterial species ranged from 2.21 to 539.46 mg/ml, diameter of inhibition zone ranged from 2.08 to 15.05mm. The scavenging •OH and DPPH• rates were 62.37% to 81.86% with the concentration 0.06 to 1.89mg/ml and 37.80% to 81.23% with the concentration 1.07 to 35.52mg/ml. According to the results, these extracts have antioxidant and antibacterial activity. In view of all the facts collectively, the six extracts will become natural and nontoxic antioxidant and antibacterial agent, and be applied in food and pharmaceutical industries for the prevention or treatment caused by microorganisms and free radicals.

Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells.

In this study, we investigated the antitumor activity of Silymarin in a mouse model of colon cancer xenograft of Lewis lung cancer (LLC) cells. Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50mg/kg. Silymarin treatment enhanced the infiltration and function of CD8(+) T cells. In the meantime, Silymarin decreased the level of IL-10 while elevated the level of IL-2 and IFN-γ in the serum of tumor-bearing mice. Finally, Silymarin reduced the proportion of myeloid-derived suppressor cells (MDSC) in the tumor tissue and also the mRNA expressions of inducible nitric oxide synthases-2 (iNOS2), arginase-1 (Arg-1) and MMP9, which indicated that the function of MDSC in tumor tissues were suppressed. Altogether, our data here showed that Silymarin inhibited the MDSC and promoted the infiltration and function of CD8(+) T cells thus suppressed the growth of LLC xenografts, which provides evidence for the possible use of Silymarin against lung cancer.

Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis.

BACKGROUND: In March 2009, the first reported case infected with influenza A (H1N1) virus was identified in Mexico. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The objective of this study was to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of influenza A (H1N1) infection. METHODS: We electronically and manually searched electronic databases, reference lists, and conference compilations to identify randomized clinical trials that compared the treatment of influenza A (H1N1) using TCM with a control group receiving oseltamivir or antivirus therapy. The Jadad score was used to assess trial quality. Duration of viral shedding, time to defervescence, and effective rate were taken as outcome measurements; additionally, heterogeneity analysis and meta-analysis were performed. RESULTS: A total of 30 studies were included in our investigation, and these studies together included 3444 cases. Based on the Jadad score, each of these studies were divided as follows: high-quality studies (n = 3), medium-quality studies (n = 2), and low quality studies (n = 25). A meta analysis was performed, which indicated that the time to defervescence between the TCM treatment group and the control group was statistically significant, the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was statistically significant, but it was not statistically significant between the two groups, the effective rate between the two groups was not statistically significant. A total of 18 studies described adverse drug reactions. CONCLUSION: The results of our study indicated that the mean time to defervescence in the TCM treatment group was less than noted in the control group, and that the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was less than that noted in the control group. However, the available evidence does not consider the fact that the difference in duration of viral shedding and effective rate between the two groups was statistically similar. No obvious adverse events were reported in the included studies.

Clinacanthus nutans (Burm. f.) Lindau Ethanol Extract Inhibits Hepatoma in Mice through Upregulation of the Immune Response.

Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⁺ T cells and decreased the number of IL-4⁺ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.

Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation.

In the present study, the effect of asiatic acid, a natural triterpenoid compound, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of asiatic acid dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco and myeloperoxidase activity were also significantly reduced by asiatic acid treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1ß, IL-6 and IFN-γ, were markedly suppressed by asiatic acid. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in asiatic acid-treated mice, which suggested that the NLRP3 inflammasome activation was suppressed. In addition, we also found that asiatic acid dose-dependently inhibited IL-1ß secretion, caspase-1 activation as well as inflammasome assembling in vitro. Furthermore, the mechanism of asiatic acid was related to the inhibition of mitochondrial reactive oxygen species generation and prevention of mitochondrial membrane potential collapse. Taken together, our results demonstrate the ability of asiatic acid to inhibit NLRP3 inflammasome activation and its potential usage in the treatment of inflammatory bowel diseases.

Tupistra chinensis extract attenuates murine fulminant hepatitis with multiple targets against activated T lymphocytes.

OBJECTIVES: The extract of Tupistra chinensis (TCE) is traditionally used for the treatment of inflammatory diseases in southwestern China for hundreds of years. The present study was designed to investigate the effects of the TCE against experimental hepatitis and to illustrate its potential mechanisms. METHODS: Effects of TCE were investigated on Con A-induced hepatitis. Profiles of multiple cytokines were measured with biometric immuno-sandwich ELISA. Proliferation, activation and apoptosis of T lymphocytes were evaluated using Western blot, MTT analysis and flow cytometry. KEY FINDINGS: TCE significantly inhibited levels of serum transaminases and lactic dehydrogenase in mice with Con A-induced hepatitis, accompanied with marked alleviation of the liver microscopic appearances. Moreover, it decreased levels of inflammatory cytokines in a concentration-dependent manner both in vivo and in vitro. It also suppressed mitogen-activated protein kinases and NF-κB-signalling in liver. These effects of TCE are attributed to its inhibition on activated T cells but not to hepatocytes protection. Flow cytometry and immunoblot assay data showed its effects on STAT1/NF-κB-signalling blockage and apoptosis induction in activated T cells. CONCLUSION: Our findings illustrate the significant potential of TCE as a novel approach for treatment of T cell-mediated inflammatory diseases.

Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine which involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies or drug candidates for the treatment of IBD are desperately needed. In the present study we found that icariin, a major bioactive compound from plants in Epimedium family, exerted protective effect on intestinal inflammation in mice induced by dextran sulfate sodium. Oral administration of icariin significantly attenuated the disease progression and alleviated the pathological changes of colitis. It also inhibited the production of pro-inflammatory cytokines and expression of p-p65, p-STAT1 and p-STAT3 in colon tissues. Further study showed that icariin dose-dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro-inflammatory cytokine levels of activated T cells. Moreover, icariin treatment inhibited the phosphorylations of STAT1 and STAT3 in CD4(+) T cells, which were the crucial transcription factors for Th1 and Th17 respectively. Taken together, these results indicate that icariin is a potential therapeutic agent for IBD.

Water-soluble andrographolide sulfonate exerts anti-sepsis action in mice through down-regulating p38 MAPK, STAT3 and NF-κB pathways.

Andrographolide is a prescribed drug used for preventing and treating the common cold, influenza, viral infections or allergies. However, its poor water solubility enormously limits its bioavailability. In the present study, we aimed at examining and comparing the effect of andrographolide sulfonate (trade name: Xi-Yan-Ping Injection), a water-soluble form made from andrographolide through sulfonating reaction, on the treatment of murine sepsis model induced by lipopolysaccharide (LPS). Pretreatment with andrographolide sulfonate significantly decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and transaminase activities in serum, attenuated liver and lung damage, and improved the survival of mice with experimental sepsis. Andrographolide sulfonate also remarkably reduced the expression levels of TNF-α, IL-1ß, IL-6 and inducible nitric oxide synthase in the injured liver from septic mice. Moreover, andrographolide sulfonate time-dependently suppressed the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK1/2) or c-Jun NH(2)-terminal kinase (JNK). Furthermore, pretreatment with andrographolide sulfonate markedly inhibited the activation of p65 subunit of nuclear factor-κB (NF-κB) as well as signal transducers and activators of transcription 3 (STAT3) in the injured liver from mice with endotoxic shock. Notably, andrographolide sulfonate showed a much stronger alleviation of LPS-induced sepsis in mice compared with andrographolide. Taken together, these results reveal that andrographolide sulfonate ameliorates sepsis in mice through suppressing p38 MAPK, STAT3 and NF-κB pathways and suggest that andrographolide sulfonate has an advantage of andrographolide for the treatment of endotoxin shock.