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In this experiment, we investigated the effects of adding chlorogenic acid (CGA) to the diet on growth performance, immune function, inflammation response, antioxidant capacity and its related mechanisms of common carp (Cyprinus carpio). A total of 600 fish were selected and randomly divided into five treatment groups and fed with CGA containing 0 mg/kg (CK), 100 mg/kg (L100), 200 mg/kg (L200), 400 mg/kg (L400) and 800 mg/kg (L800) for 56 days. The results of the experiment were as follows: addition of CGA significantly increased the WGR, SGR, FER, and PER of common carp (P < 0.05). The addition of 400–800 mg/kg of CGA significantly increased the serum levels of LZM, AKP activity, C3 and C4 concentration, and increased immune function of common carp (P < 0.05). Regarding antioxidant enzyme activities, adding CGA significantly increased SOD, CAT, and GsH-Px activities, while decreasing MDA content (P < 0.05). Compared with the CK group, the mRNA expression levels of NF-κB , TNF-α , and IL-1β were decreased. The IL-10 and TGF-β were increased in the liver and intestines of the CGA supplemented group. Meanwhile, the addition of CGA also significantly up-regulated the mRNA expression levels of Nrf2 , HO-1 , SOD , CAT , and GPX (P < 0.05). CGA also positively contributed to the development of the carp intestinal tract, as demonstrated by decreased serum levels of DAO, D-LA, and ET-1. And the mucosal fold height was increased significantly with increasing levels of CGA. In conclusion, the addition of CGA in the feed can enhance the growth performance, immune function and antioxidant capacity of common carp, and improve the health of the intestine and liver. According to the results of this experiment, the optimal addition amount in common carp diets was 400 mg/kg. • Addition of 400 mg/kg chlorogenic acid can improve the growth performance of common carp. • Chlorogenic acid could improve the health of the liver and intestines of common carp. • Chlorogenic acid could enhance antioxidant capacity and immunity by modulating Nrf2 / NFκB signalling pathways. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer. Methods: The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes. Results: There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, p < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, p < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, p53 signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients (p < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer. Conclusion: The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and p53 signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Corydalis saxicola Bunting, affiliated with the Papaveraceae Juss., has been proven to work well in anti-inflammation, hemostasis, and analgesia. This study was designed to observe the effect and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Rats were injected 2 mg/kg paclitaxel 4 times and administrated with 30 or 120 mg/kg CSBTA. Mechanical and thermal allodynia and hyperalgesia were tested. After 40 days, serum was collected to detect PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and Western-blot or RT-qPCR analyzed protein and gene levels of pro-inflammatory cytokines, p38 MAPK, PKCε, and TRPV1. The PIPN cell model was established with paclitaxel (300 nM, 5 d) in primary DRG neurons. We examined the effect of CSBTA (25 μg/ml or 50 μg/ml) by measuring the mRNA levels in PGE2, TNF-α and CGRP, and the protein expression on the PKCε/p38 MAPK/TRPV1 signaling pathway in the PIPN cell model. Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia, and regulated cytokines' contents (PGE2, TNF-α, and IL-1β) and neuropeptides (CGRP and SP) in different tissues in vivo. In addition, CSBTA significantly decreased cytokine gene levels of DRG neurons (PGE2, TNF-α, and CGRP) and the protein expressions of PKCε/p38 MAPK/TRPV1 signaling pathway in vivo and in vitro. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Summary Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue damage. Hence, it is critical to program activated T cells to achieve ROS equilibrium. Here, we determined that miR-23a is indispensable for effector CD4 + T cell expansion, particularly by providing early protection from excessive necrosis. Mechanistically, miR-23a targeted PPIF, gatekeeper of the mitochondria permeability transition pore, thereby restricting ROS flux and maintaining mitochondrial integrity. Upon acute Listeria monocytogenes infection, deleting miR-23a in T cells resulted in excessive inflammation, massive liver damage, and a marked mortality increase, which highlights the essential role of miR-23a in maintaining immune homeostasis. [ABSTRACT FROM AUTHOR]

Enzyme mediated phosphoinositide signaling plays important regulatory roles in diverse cellular processes and has close implication in human diseases. However, detection of phosphoinositide enzymes remains a challenge because of the difficulty in discriminating the phosphorylation patterns of phosphoinositide. Here we develop a novel enzyme-activated gold nanoparticles (AuNPs) assembly strategy as a homogeneous colorimetric biosensor for activity detection of phosphoinositide kinases and phosphatases. This strategy utilizes a biomimetic mechanism of phosphoinositide signaling, in which AuNP supported phospholipid membranes are constructed to mimic the cellular membrane substrate, and AuNPs modified with the pleckstrin homology (PH) domain of cytosolic proteins are designed for specific, multivalent recognition of phosphorylated phosphoinositides. This biomimetic strategy enables efficient enzymatic reactions of the substrate and highly selective detection of target enzyme. The biosensor is demonstrated for the detection of phosphoinositide 3-kinase (PI3K) and phosphatase with tensin homology (PTEN). The results revealed that it allows sensitive, rapid visual detection of the enzymes with pM detection limits and four-decade wide dynamic ranges, and is capable of detecting enzyme activities in complex cell lysate samples. This biosensor might provide a general biosensor platform for high-throughput detection of phosphoinositide enzymes with high sensitivity and selectivity in biomedical research and clinical diagnostics. [ABSTRACT FROM AUTHOR]

Changes in gut motility and visceral hypersensitivity are two major features of irritable bowel syndrome (IBS). Current drug treatments are often poorly efficacious, with many side effects for patients with IBS. Complementary therapies, such as acupuncture or abdominal massage, have received more attention in recent years. In this study, a rat model of IBS with diarrhea (IBS-D) was established by instillation of acetic acid from the colon. The effects of abdominal massage on changes in gut motility, visceral hypersensitivity, and the possible mechanism were investigated. Continuous abdominal massage could decrease the stool consistency score and increase the efflux time of glass beads compared with model groups, while also decreasing mast cell counts in IBS-D rats. The mRNA and protein expressions of neuronal nitric oxide synthase (nNOS), choline acetyl transferase (CHAT), and protein gene product 9.5 (PGP9.5) were significantly upregulated by continuous abdominal massage compared with model groups. Continuous abdominal massage also improved the ultrastructure of enteric glial cells (EGCs) by decreasing the number of mitochondria and increasing the level of the heterochromatin. Meanwhile, continuous abdominal massage could upregulate the expression of glial cell line-derived neurotrophic factor (GDNF) and P-Akt/Akt. Furthermore, it could reduce visceral hypersensitivity and improve the IBS-D symptoms by regulating the phosphoinositide 3-kinase (PI3K)-Akt pathway, which would provide a novel method for the treatment of IBS-D in the clinical setting. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R–Ankrd1–P53 signaling pathway. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chemical investigation of Fritillaria verticillata Willd. led to the isolation of eight novel isosteroidal alkaloids (1—4, 6, 9—11) and four known alkaloids (5, 7—8, 12), including three unprecedented cis‐fused D/E (13α, 17α) cevanine alkaloids (1—3), one rarely cis‐fused E/F (22α) cevanine alkaloid (6), and one uncommon 5β‐jervine‐type isosteroidal alkaloid featuring a cis‐fused A/B ring moiety (11). In order to establish the structures of 1, the calculated NMR with DP4+ evaluation was applied from the plausible structure candidates. The characteristic proton signals for distinguishing D/E conjunction of cevanine alkaloids were summarized. In addition, some proton and carbon signals α to nitrogen in 6 and 7 are unobservable due to the 14N nuclear quadrupolar relaxation, based on the NMR experiments in different solvents, calculated NMR method and X‐ray technology, their structures were determined. The NMR characteristics of cevanine alkaloids to distinguish orientation of long‐pair on nitrogen atom with β‐hydroxyl at C‐20 were also concluded. The anti‐inflammatory effects of compounds 1 and 4 were evaluated in LPS‐activated RAW 264.7 macrophages. Compound 4 decreased LPS‐induced releases of IL‐1β and IL‐17α in RAW264.7 cells in a dose‐dependent manner. Further mechanistic study revealed that 4 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases. [Display omitted] • The potential of Chuanminshen violaceum stems and leaves to be used as agricultural by-products is exploited. • Ultrasound-assisted extraction was efficient to extract polysaccharide from the stems and leaves of Chuanminshen violaceum. • A polysaccharide (CVP-AP-Ⅰ) was obtained and characterized as a typical pectic polysaccharide. • CVP-AP-Ⅰ exhibited potent anti-inflammatory and antioxidant effects in vitro. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0–6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0–6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals. [Display omitted] • N-acetylcysteine (NAC) could improve the morphology and health of hepatopancreas in common carp. • The anti-inflammatory and antioxidant effects of NAC via the MAPK/NF-κB/Nrf2 signalling pathway. • We recommend adding 3.0 g/kg NAC to the diets of juvenile common carp. [ABSTRACT FROM AUTHOR]

Cordyceps is a parasitic edible fungus, which is a unique Chinese medicinal material. It has been reported to have immunomodulatory effects and use in kidney disease. Especially, Cordyceps has been used in the treatment of lupus nephritis (LN). Cordyceps proteins (CP) have a favorable bidirectional immunomodulatory functions and may have therapeutic potential for LN. However, the underlying molecular mechanism remains unknown. So this study aimed to examine the activities of CP in LN and possible mechanism. So proteomics was performed to detect proteins components of Cordyceps, and analysis it. In addition, MRL/lpr mice were used to study the progression of LN. The MRL/lpr mice were fed either CP (i.g, 0.5, 1.0, 1.5 g/kg/d), prednisolone acetate (PA, i.g, 6 mg/kg/d), or Bailing capsule (BC, i.g, 0.75 g/kg/d) for 8 weeks. Hematoxylin-eosin (H&E), Periodic Acid Schif (PAS) and Masson's stainings, Immunofluorescence, and Immunohistochemistry were performed to verify the therapeutic effect of CP on MRL/lpr mice. The mechanism by CP alimerated LN was uncovered by Western blotting (WB) and Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. Our results revealed that CP blocked proteinuria production and renal inflammatory infiltratation in MRL/lpr mice to reduce the renal fibrosis. In addition, CP worked better than BC which is artificial Cordyceps fungus powder in regulating proteinuria to urine creatinine ratio and interleukin-4(IL-4) protein amount. Especially, CP modulated the STAT3/mTOR/NF-кB signaling pathway in LN mice and brought a more pronounced lowering effect on the contents of IL-6 and IL-1β than the PA. CP could be a potential anti-inflammatory immune product with strong regulatory effects and potency than BC and PA in nephritis therapeutics. [Display omitted] • For the first time, Cordyceps protein has been shown to improve proteinuria in lupus nephritis. • The inhibitor prednisolone acetate improved renal inflammatory infiltration in lupus nephritis. • Trichospora chinensis powder is involved in the regulation of renal fibrosis in lupus nephritis. • Cordyceps protein has a negative regulatory effect on STAT3/mTOR/NF-кB signaling pathway. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-β/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro . NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-β1-induced CTGF expression and ROS generation. In addition, small-interfering RNA (siRNA) silencing of Smad3 or Nox4 significantly suppressed TGF-β1-mediated CTGF expression in VSMC. Furthermore, Nox4 silencing or inhibition eliminated TGF-β1-induced Smad3 activation and interaction between Nox4 and Smad3. In vivo studies further identified a positive correlation of Nox4 levels with Smad3 activation and CTGF expression in atherosclerotic arteries of patients and animal models. These data established that a novel mechanistic link of Nox4-dependent activation of Smad3 to increased TGF-β1-induced CTGF in the process of vascular remodeling, which suggested a new potential pathway for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Lanthanum (La) can damage the blood brain barrier when it enters the brain tissue, causing learning and memory dysfunction. Currently, few studies have focused on La-induced oxidative stress in choroid plexus epithelial cells, which can severely impair the normal function of the blood-cerebrospinal fluid barrier (BCSFB) and ultimately cause central nervous system dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element(ARE) signaling pathway is one of the major antioxidant systems and is vital in protecting cells against oxidative injury in rodents. In this study, Z310 cells were employed to construct BCSFB in vitro and treated with lanthanum chloride (LaCl 3); meanwhile, 40 μmol/L tert-butylhydroquinone and the corresponding concentration of LaCl 3 was used as the intervention groups. The results showed that LaCl 3 treatment markedly decreased Z310 cell viability, increased the necrosis rate, and then reduced the transepithelial electrical resistance value of BCSFB in vitro ; reactive oxygen species levels gradually increased, catalase and glutathione peroxidase activities decreased; furthermore, Nrf2 was significantly downregulated, and the expression of Nrf2 downstream genes such as heme oxygenase1, NADP(H): dehydrogenase quinone1, glutathione thiotransferase etc. noticeably decreased; in addition, interleukin-1β and tumour necrosis factor-α associated with Nrf2 activation noticeably increased. However, tert-butylhydroquinone could activate the Nrf2/AER signaling pathway and attenuate the Z310 cell oxidative damage induced by LaCl 3. Thus, the Nrf2/ARE signaling pathway is probably involved in weakening the BCSFB in vitro that is created by La-induced oxidative stress. Tert-butylhydroquinone can activate this pathway to reverse severe oxidative damage, which significantly strengthen the function of BCSFB. The nuclear factor erythroid 2-related factor/antioxidant response element pathway is probably involved in weakening the blood-cerebrospinal fluid barrier underlying resistance oxidative stress created by lanthanum. Tert-butylhydroquinone can reverse the oxidative damage in choroid plexus epithelial cells though activation of this pathway, which significantly strengthen the function of blood-cerebrospinal fluid. [Display omitted] • Lanthanum (La) can increase the permeability of the blood-cerebral spinal fluid barrier. • La led to oxidative stress resulting in the weaker antioxidant capacity of Z310 cell. • Tert-butylhydroquinone reduced the injured blood-cerebral spinal fluid barrier led by La. [ABSTRACT FROM AUTHOR]

• AMSP-30 m as a HIF-1α inhibitor relieved the development and severity of rat AIA. • AMSP-30 m showed anti-proliferative and pro-apoptotic effects on AIA synovial cells. • AMSP-30 m exhibited an effective anti-angiogenic effect within AIA rat synovium. • AMSP-30 m inhibited the activation of Shh signaling pathway in AIA rat synovium. Growing evidence indicates that synovial hypoxia-inducible factor 1α (HIF-1α) can be as a promising target for RA therapy. We previously reported that AMSP-30 m as a novel HIF-1α inhibitor had potent activities of anticancer metastasis. This study clarified the therapeutic effects of HIF-1α inhibitor AMSP-30 m on adjuvant-induced arthritis (AIA) in rats and explored the possible mechanisms. AMSP-30 m was given intraperitoneally to AIA rats, and its therapeutic effects and anti-inflammatory activity were evaluated. The influences of AMSP-30 m on synovial apoptosis, angiogenesis and sonic hedgehog (Shh) pathway were examined. We found that, accompanied with the inhibition of synovial HIF-1α expression, AMSP-30 m had potent anti-arthritic and anti-inflammatory effects on AIA rats, evidenced by the reduction in paw swelling, arthritis index, histopathological scores, and the production of IL-1β, IL-6, TNF-α in serum and synovial tissues. AMSP-30 m reduced synovial Ki67 expression and increased TUNEL-positive index, indicating its anti-proliferative and pro-apoptotic effects on AIA synovial cells, which was related to reducing Bcl-2 protein level and increasing Bax, cleaved caspase 3 protein levels. Additionally, AMSP-30 m showed anti-angiogenic effects within AIA synovium, indicated by the reduction of synovial VEGF expression and blood vessels number (especially CD31+/αSMA- immature vessels, but not CD31+/αSMA+ mature vessels). Moreover, AMSP-30 m inhibited the activation of synovial Shh pathway, suggested by the reduction of pathway-related proteins, like Shh, Smo, Gli-1, cyclin D1 and c-Myc. Collectively, HIF-1α inhibitor AMSP-30 m exerted potent anti-arthritic effects on AIA rats possibly by promoting synovial apoptosis, reducing synovial angiogenesis and inhibiting Shh pathway. [ABSTRACT FROM AUTHOR]

Xuebijing (XBJ) injection is a Chinese medicine containing extracts from Carthamus tinctorius L. (Carthami Flos, hong hua, Asteraceae), Paeonia lactiflora Pall. (Paeoniae radix rubra, chi shao, Ranunculaceae), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong, Umbelliferae), Salvia miltiorrhiza Bge. (S alviae miltiorrhizae Radix Et Rhizoma, dan shen, Labiatae) and Angelica sinensis (Oliv.) Diels (Angelicae sinensis Radix, dang gui, Umbelliferae). It has been approved for the treatment of sepsis in China since 2004 and has been widely used as an add-on treatment for sepsis or septic shock with few side effects. The aim of the present review was to analyse up-to-date information related to the treatment of sepsis with XBJ, including the bioactive constituents, clinical studies and potential mechanisms, and to discuss possible scientific gaps, to provide a reliable reference for future studies. Scientific resources concentrating on treating sepsis with XBJ were searched through PubMed, the Chinese National Knowledge Infrastructure (CNKI) and WanFang databases from inception to November 2018. Dissertations were also searched, and eligible dissertations were selected. Studies related to the identification of constituents, bioactive components and their targets of action or pathways, clinical trials, and animal or cellular experiments that explored pharmacological mechanisms were manually selected. The quality of reporting and methodology of the included pharmacological experiments were assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool. A total of 108 relative studies were eventually included, containing 12 bioactivity research studies, 10 systematic reviews on clinical trials and 86 animal or cellular experiments. We noted that as identification methods progressed, further constituents could be detected in XBJ. XBJ was also found to have "multi-ingredient, multi-target and multi-pathway" effects. The systematic review revealed that XBJ could improve the 28-day mortality and other indexes, such as the APACHE II score, body temperature, and white blood cell (WBC) count, to some extent. A major organ protection effect was demonstrated in septic rats. Pharmacological investigations suggested that XBJ acts in both the early and late stages of sepsis by anti-inflammatory, anti-coagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms. However, most of the included studies were poorly reported, and the risk of bias was unclear. With respect to the multiple therapeutic mechanisms contributing to both the early and late stages of sepsis, the multiple effective constituents detected and randomized controlled trials (RCTs) performed to prove its efficacy, XBJ is a promising therapy for the treatment of sepsis. However, although XBJ has shown some efficacy for the treatment of sepsis, there are currently some scientific gaps. More studies concerning the pharmacokinetics, interactions with antibiotics, real-world efficacy and safety, pharmacological mechanisms of the bioactive components and large-scale clinical trials should be conducted in the future. Image 1 [ABSTRACT FROM AUTHOR]