BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.
METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in the rats. Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats. The expression of vascular endothelial growth factor A (VEGF-A), phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), and phosphorylated Akt (p-Akt) in the small intestine was analyzed via Western blotting.
RESULTS: XBJ improved intestinal microcirculation dysfunction in septic rats, alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa, and reduced the systemic inflammatory response. Moreover, XBJ upregulated the expression of VEGF-A, p-PI3K/total PI3K, and p-Akt/total Akt in the rat small intestine.
CONCLUSIONS: XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI.
The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay.
XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis.
XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing\'s anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing\'s pharmacologically significant constituents supports the medicine\'s anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ\'s cardio-protection during sepsis and the mechanisms.
In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue.
The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1β, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining\'s results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05).
In here, we observed that XBJ\'s cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.

BACKGROUND: Xuebijing injection is a Chinese herbal-derived drug composed of radix paeoniaerubra, rhizomachuanxiong, Salvia miltiorrhiza, floscarthami, and Angelica sinensis. This study aimed to investigate the effects of Xuebijing administration on pulmonary endothelial injury and coagulation dysfunction in a cecal ligation and puncture (CLP)-induced sepsis rat model.
METHODS: A CLP-induced sepsis rat model was established. The CLP rats were treated with a vehicle or Xuebijing via intravenous infusion and sacrificed at 2, 4, 6, 8, or 12 h after CLP for lung tissue and blood sample collection. The mean arterial pressure (MAP) was monitored. Transmission microscopy examination and H&E staining were performed to observe pulmonary structural alterations. Enzyme linked immunosorbent assay (ELISA) was performed to measure the plasma levels of epithelial markers, proinflammatory cytokines, and coagulation-related proteins.
RESULTS: Compared with vehicle treatment, Xuebijing administration maintained the MAP in the normal range until 11 h after CLP. Transmission microscopy and H&E staining revealed that Xuebijing administration alleviated alveolar-capillary barrier impairments and lung inflammation in CLP rats. ELISA showed that Xuebijing administration effectively reversed CLP-induced elevations in the plasma levels of epithelial markers endothelin-1 and von Willebrand factor, starting 6 and 8 h after CLP, respectively. Xuebijing administration also significantly abolished CLP-induced rises in circulating proinflammatory cytokines interleukin 6 (IL-6) at 6 h after CLP, IL-1β at 2 and 12 h after CLP, and TNF-α at 2, 4, 6, 8, and 12 h after CLP. In addition, Xuebijing administration strongly reversed CLP-induced alterations in circulating active protein C and tissue-type plasminogen activator, starting 4 h and 2 h after CLP, respectively.
CONCLUSIONS: Xuebijing ameliorates pulmonary endothelial injury, systemic inflammation, and coagulation dysfunction in early sepsis.

In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued C. elegans lifespan to be against P. aeruginosa infection by inhibiting Pseudomonas colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by Pseudomonas infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against Pseudomonas infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the Pseudomonas biofilm formation and decrease the expression of virulence genes (lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS) and quorum sensing (QS)-related genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.

XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel. Nine marker constituents from the five herbs were selected based on XueBiJing\'s chemical composition, pharmacokinetics, and pharmacodynamics. A selectivity test (for \"similarity of response\") was developed to identify and minimize interference by non-target constituents. Then, an intercept test was developed to fulfill \"linearity through zero\" for each analyte (absolute ratio of intercept to C response, <2%). Using the newly developed assays, we analyzed samples from 33 batches of XueBiJing, manufactured over three years, and found small batch-to-batch variability in contents of the marker constituents (4.1%-14.8%), except for senkyunolide I (26.5%).

UNASSIGNED: To investigate the efficacy of xuebijing combined with ulinastatin in the treatment of traumatic sepsis and analyze the effects on inflammatory factors and immune function of patients.
UNASSIGNED: 182 patients with traumatic sepsis were selected from June 2017 to September 2021 in our hospital. The patients were divided into the control group and the observation group. Patients in both groups were given routine treatments such as initial resuscitation, blood transfusion, monitoring of lactic acid to guide fluid replacement, early control of infection source, selection of appropriate antibiotics, correction of acidosis, treatment of primary disease, prevention of hypothermia and stress ulcer, application of vasoactive drugs, application of glucocorticoid and nutritional support. The control group was treated with Xuebijing injection on the basis of routine treatment, and the observation group was given Xuebijing injection combined with ulinastatin treatment on the basis of routine treatment. The APACHE II score was applied to evaluate the patients before and after treatment, and the routine blood indicators, inflammatory factor indicators, immune function indicators and liver function indicators were tested.
UNASSIGNED: After the treatment, the APACHE II score of the observation group was (10.35 ± 3.04) lower than that of the control group (15.93 ± 4.52) (P < 0.05). After treatment, the WBC and neutrophils in the observation group (15.19 ± 2.91) and (0.65 ± 0.04) were lower than those in the control group (16.42 ± 3.44) and (0.79 ± 0.05), and the PLT(162.85 ± 43.92) was higher than that in the control group (122.68 ± 36.89) (P < 0.05). After treatment, the levels of serum PCT, IL-6, TNF-α in the observation group were (11.38 ± 3.05), (10.74 ± 3.82) and (9.82 ± 2.35) lower than those in the control groups (17.34 ± 3.29), (15.28 ± 4.05) and (13.24 ± 3.06) (P < 0.05). After treatment, the levels of CD3+, CD4+, CD8+, CD4+/CD8+ in the observation group were (50.64 ± 4.98), (40.56 ± 4.82), (27.22 ± 3.29), (1.49 ± 0.24) higher than those in the control groups (46.08 ± 4.75), (34.69 ± 4.08), (25.14 ± 3.18), (1.38 ± 0.19) (P < 0.05). After treatment, the levels of TBIL and AST in the observation group were (12.35 ± 3.82), (25.66 ± 4.49) lower than those in the control group (18.43 ± 4.06), (34.58 ± 5.06) (P < 0.05).
UNASSIGNED: Xubijing combined with ulinastatin has a good effect in the treatment of patients with traumatic sepsis, which can effectively improve the condition, reduce the body\'s inflammatory response, and promote the recovery of patients\' immune function and liver function.

OBJECTIVE: To explore the protective effect of ulinastatin combined with Xuebijing on myocardial injuries in patients with severe pneumonia.
METHODS: The clinical data of 86 patients with severe pneumonia treated in our hospital were analyzed retrospectively. According to the treatment method each patient was administered, they were divided into a control group (43 cases, routine treatment + Xuebijing) and an observation group (43 cases, routine treatment + Xuebijing + ulinastatin). All the patients were treated for 2 weeks. The clinical efficacy, the inflammatory factor levels (TNF-α, C-reactive protein (CRP), and procalcitonin (PCT)), the myocardial index levels (creatine kinase-myocardial band (CK-MB), lactic dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac troponin I (cTn I)), the blood gas index levels (arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and oxygenation index (OI)), the coagulation functions (prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB)) and the acute physiology and chronic health evaluation (APACHE-II) scores were compared between the two groups.
RESULTS: After the treatment, the total effective rate in the observation group was higher than it was in the control group (P<0.05). After the treatment, the serum TNF-α, CRP, PCT, CK-MB, LDH, α-HBDE, NT-proBNP, and cTnI levels and the APACHE-II scores were decreased in the two groups, and they were even lower in the observation group (all P<0.05). The PaO2, SaO2, and OI levels were increased in the two groups, and they were higher in the observation group (all P<0.05). Compared with before the treatment, the patients\' PT and APTT levels in both groups were prolonged after the treatment, and the observation group was longer than the control group. The plasma FIB levels were decreased in both groups, and they were lower in the observation group than in the control group (P<0.05).
CONCLUSIONS: Ulinastatin combined with Xuebijing can significantly alleviate pulmonary inflammation, improve the blood gas, and protect the damaged myocardia in patients with severe pneumonia.