Do Herbal Supplements and Probiotics Complement Antibiotics and Diet in the Management of SIBO? A Randomized Clinical Trial.

Small intestinal bacterial overgrowth (SIBO) arises from dysbiosis in the small intestine, manifesting with abdominal symptoms. This study aims to assess the efficacy of combined antibiotic therapy, herbal supplements, probiotics, and dietary modifications in SIBO management. A total of 179 SIBO-diagnosed patients underwent clinical evaluation and breath testing. Patients were categorized into hydrogen (H2-SIBO) and methane (CH4-SIBO) groups. The control group received standard antibiotic therapy and a low-FODMAP diet, while the intervention group received additional herbal antibiotics, probiotics, and prebiotics. After treatment, both groups exhibited reduced gas levels, particularly in CH4-SIBO. Clinical remission rates were higher in the intervention group, especially in CH4-SIBO cases. Logistic regression analysis showed gas concentrations at diagnosis as significant predictors of treatment success. In conclusion, adjunctive herbal supplements and probiotics did not significantly impact gas levels, but showed potential for clinical improvement, especially in CH4-SIBO.

Flavonoid substituted polysaccharides from Tamarix chinensis Lour. alleviate H1N1-induced acute lung injury via inhibiting complement system.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is a highly pathogenic respiratory infectious disease associated with excessive activation of the complement system. Our previous studies found that the anticomplement polysaccharides from some medicinal plants could significantly alleviate H1N1-induced acute lung injury (H1N1-ALI). The leaves and twigs of Tamarix chinensis Lour. are traditionally used as a Chinese medicine Xiheliu for treating inflammatory disorders. Interestingly, its crude polysaccharides (MBAP90) showed potent anticomplement activity in vitro. AIM OF THE STUDY: To evaluate the therapeutic effects and possible mechanism of MBAP90 on viral pneumonia and further isolate and characterize the key active substance of MBAP90. MATERIALS AND METHODS: The protective effects of MBAP90 were evaluated by survival tests and pharmacodynamic experiments on H1N1-ALI mice. Histopathological changes, viral load, inflammatory markers, and complement deposition in lungs were analyzed by H&E staining, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. An anticomplement homogenous polysaccharide (MBAP-3) was obtained from MBAP90 by bio-guided separation, and its structure was further characterized by methylation analysis and NMR spectroscopy. RESULTS: Oral administration of MBAP90 at a dose of 400 mg/kg significantly increased the survival rate of mice infected with the lethal H1N1 virus. In H1N1-induced ALI, mice treated with MBAP90 (200 and 400 mg/kg) could decrease the lung index, lung pathological injury, the levels of excessive proinflammatory cytokines (IL-6, TNF-α, MCP-1, IL-18, and IL-1ß), and complement levels (C3c and C5b-9). In addition, MBAP-3 was characterized as a novel homogenous polysaccharide with potent in vitro anticomplement activity (CH50: 0.126 ± 0.002 mg/mL), containing 10.51% uronic acids and 9.67% flavonoids, which were similar to the composition of MBAP90. The backbone of MBAP-3 consisted of →4)-α-D-Glcp-(1→, →3,4,6)-α-D-Glcp-(1→, and →3,4)-α-D-Glcp-(1→, with branches comprising α-L-Araf-(1→, α-D-GlcpA-(1→, →4,6)-α-D-Manp-(1→ and →4)-ß-D-Galp-(1 â†’ . Particularly, O-6 of →4)-ß-D-Galp-(1→ was conjugated with a flavonoid, myricetin. CONCLUSIONS: MBAP90 could ameliorate H1N1-ALI by inhibiting inflammation and over-activation of the complement system. These polysaccharides (MBAP90 and MBAP-3) with relative high contents of uronic acid and flavonoid substituent might be vital components of T. chinensis for treating viral pneumonia.

TMT-Based Proteomics Reveal the Mechanism of Action of Amygdalin against Rheumatoid Arthritis in a Rat Model through Regulation of Complement and Coagulation Cascades.

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund's adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.

The Yin Yang of Complement and Cancer.

Cancer-related inflammation is a crucial component of the tumor microenvironment (TME). Complement activation occurs in cancer and supports the development of an inflammatory microenvironment. Complement has traditionally been considered a mechanism of immune resistance against cancer, and its activation is known to contribute to the cytolytic effects of antibody-based immunotherapeutic treatments. However, several studies have recently revealed that complement activation may exert protumoral functions by sustaining cancer-related inflammation and immunosuppression through different molecular mechanisms, targeting both the TME and cancer cells. These new discoveries have revealed that complement manipulation can be considered a new strategy for cancer therapies. Here we summarize our current understanding of the mechanisms by which the different elements of the complement system exert antitumor or protumor functions, both in preclinical studies and in human tumorigenesis. Complement components can serve as disease biomarkers for cancer stratification and prognosis and be exploited for tumor treatment.

Extracellular vesicles: A new communication paradigm of complement in neurological diseases.

The complement system is crucial to the innate immune system. It has the function of destroying pathogens by activating the classical, alternative, and lectin pathways. The complement system is important in nervous system diseases such as cerebrovascular and neurodegenerative diseases. Activation of the complement system involves a series of intercellular signaling and cascade reactions. However, research on the source and transport mechanisms of the complement system in neurological diseases is still in its infancy. Studies have increasingly found that extracellular vesicles (EVs), a classic intercellular communication paradigm, may play a role in complement signaling disorders. Here, we systematically review the EV-mediated activation of complement pathways in different neurological diseases. We also discuss the prospect of EVs as future immunotherapy targets.

The yin and the yang of early classical pathway complement disorders.

The classical pathway of the complement cascade has been recognized as a key activation arm, partnering with the lectin activation arm and the alternative pathway to cleave C3 and initiate the assembly of the terminal components. While deficiencies of classical pathway components have been recognized since 1966, only recently have gain-of-function variants been described for some of these proteins. Loss-of-function variants in C1, C4, and C2 are most often associated with lupus and systemic infections with encapsulated bacteria. C3 deficiency varies slightly from this phenotypic class with membranoproliferative glomerulonephritis and infection as the dominant phenotypes. The gain-of-function variants recently described for C1r and C1s lead to periodontal Ehlers Danlos syndrome, a surprisingly structural phenotype. Gain-of-function in C3 and C2 are associated with endothelial manifestations including hemolytic uremic syndrome and vasculitis with C2 gain-of-function variants thus far having been reported in patients with a C3 glomerulopathy. This review will discuss the loss-of-function and gain-of-function phenotypes and place them within the larger context of complement deficiencies.

Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research - 20 years of experience and future perspectives.

The complex molecular and cellular biological systems that maintain host homeostasis undergo continuous crosstalk. Complement, a component of innate immunity, is one such system. Initially regarded as a system to protect the host from infection, complement has more recently been shown to have numerous other functions, including involvement in embryonic development, tissue modeling, and repair. Furthermore, the complement system plays a major role in the pathophysiology of many diseases. Through interactions with other plasma cascades, including hemostasis, complement activation leads to the broad host-protective response known as thromboinflammation. Most complement research has been limited to reductionistic models of purified components and cells and their interactions in vitro. However, to study the pathophysiology of complement-driven diseases, including the interaction between the complement system and other inflammatory systems, holistic models demonstrating only minimal interference with complement activity are needed. Here we describe two such models; whole blood anticoagulated with either the thrombin inhibitor lepirudin or the fibrin polymerization peptide blocker GPRP, both of which retain complement activity and preserve the ability of complement to be mutually reactive with other inflammatory systems. For instance, to examine the relative roles of C3 and C5 in complement activation, it is possible to compare the effects of the C3 inhibitor compstatin effects to those of inhibitors of C5 and C5aR1. We also discuss how complement is activated by both pathogen-associated molecular patterns, inducing infectious inflammation caused by organisms such as Gram-negative and Gram-positive bacteria, and by sterile damage-associated molecular patterns, including cholesterol crystals and artificial materials used in clinical medicine. When C3 is inhibited, it is important to determine the mechanism by which inflammation is attenuated, i.e., whether the attenuation derives directly from C3 activation products or via downstream activation of C5, since the mechanism involved may determine the appropriate choice of inhibitor under various conditions. With some exceptions, most inflammatory responses are dependent on C5 and C5aR1; one exception is venous air embolism, in which air bubbles enter the blood circulation and trigger a mainly C3-dependent thromboembolism, with the formation of an active C3 convertase, without a corresponding C5 activation. Under such conditions, an inhibitor of C3 is needed to attenuate the inflammation. Our holistic blood models will be useful for further studies of the inhibition of any complement target, not just C3 or C5. The focus here will be on targeting the critical complement component, activation product, or receptor that is important for the pathophysiology in a variety of disease conditions.

Hepcidin and Erythroferrone Complement the Athlete Biological Passport in the Detection of Autologous Blood Transfusion.

PURPOSE: We investigated whether hepcidin and erythroferrone (ERFE) could complement the athlete biological passport (ABP) in indirectly detecting a 130-mL packed red blood cells (RBC) autologous blood transfusion. Endurance performance was evaluated. METHODS: Forty-eight healthy men ( n = 24) and women ( n = 24) participated. Baseline samples were collected weekly followed by randomization to a blood transfusion (BT, n = 24) or control group (CON, n = 24). Only the BT group donated 450 mL whole blood from which 130 mL red blood cell was reinfused 4 wk later. Blood samples were collected 3, 7, 14, 21, and 28 d after donation, and 3, 6, and 24 h and 2, 3, and 6 d after reinfusion. In the CON group samples were collected with the same frequency. Endurance performance was evaluated by a 650-kCal time trial ( n = 13) before and 1 and 6 d after reinfusion. RESULTS: A time-treatment effect existed ( P < 0.05) for hepcidin and ERFE. Hepcidin was increased ( P < 0.01) ~110 and 89% 6 and 24 h after reinfusion. Using an individual approach (99% specificity, e.g., allowing 1:100 false-positive), sensitivities, i.e., true positives, of 30% and 61% was found for hepcidin and ERFE, respectively. For the ABP, the most sensitive marker was Off-hr score ([Hb] (g·L -1 ) - 60 × âˆšRET%) ( P < 0.05) with a maximal sensitivity of ~58% and ~9% after donation and reinfusion, respectively. Combining the findings for hepcidin, ERFE, and the ABP yielded a sensitivity across all time-points of 83% after reinfusion in BT. Endurance performance increased 24 h (+6.4%, P < 0.01) and 6 d after reinfusion (+5.8%, P < 0.01). CONCLUSIONS: Hepcidin and ERFE may serve as biomarkers in an antidoping context after an ergogenic, small-volume blood transfusion.

Serum levels of immunoglobulin and complement in UTI of patients caused by Proteus mirabilis and using AgNPs as antiswarming.

The use of plant extracts represents a promising approach for the synthesis of silver nanoparticles (AgNPs). This study reports the low-cost, green synthesis of AgNPs using the extract of clove and black seeds. The biosynthesized AgNPs were confirmed and characterized by analysis of the spectroscopy profile of the UV-visible spectrophotometer. The purpose of the present study is to evaluate the inhibitory effect concentration (MIC) of AgNPs, clove, and black cumin seed extracts on the growth and swarming of P. mirabilis. Clinical isolates of P. mirabilis were isolated from patients suffering from urinary tract infections. Thirteen types of antibiotics were used in the present study to detect their ability to inhibit P. mirabilis's resistance. Immunological findings included the determination of serum levels of IgG, IgM, IgA and complement protein C3 and C4. Results showed that IgG and IgA concentrations significantly increased (1311.13 ± 72.54 and 279 ± 21.31) respectively in UTI patients in comparison to the healthy control group which was 1089.88 ± 37.33 and 117.611 ± 4.19 respectively, While IgM concentrations were increased non significantly in UTI patients (153.331 ± 6.45) in comparison to healthy control (145.2 ± 13.49). Complement components C3 showed a significant increase in UTI patients with mean values of 125.95 ± 6.22 compared to the control group with mean values of 55.191 ± 9.64, while C4 showed statically non-significant among UTI patients in comparison with the control group (35.195 ± 2.34 and 34.371 ± 1.22) respectively.

Horticultural therapy, nutrition and post-traumatic stress disorder in post-military veterans: developing non-pharmaceutical interventions to complement existing therapeutic approaches.

Non-pharmaceutical interventions for veterans living with post-traumatic stress disorder are becoming a more popular way to address some of the social and personal needs identified by this group. Horticultural therapy or growing and eating food together provides several ways to increase mood, improve nutritional status, reduce loneliness and reduce the physical health impacts of mental illnesses such as post-traumatic stress disorder. In this paper we will discuss some of the issues people living with post-traumatic stress disorder might face. We will also provide an overview of the therapeutic effects of these approaches and how they will be applied in a locally identified group.

Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella.

The engineered "obligate" anaerobic Salmonella typhimurium strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS+ and CD68+ cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.

Importance of antibody isotypes in antitumor immunity by monocytes and complement using human-immune tumor models.

Monoclonal antibodies (mAbs) have revolutionized clinical medicine, especially in the field of cancer immunotherapy. The challenge now is to improve the response rates, as immunotherapy still fails for many patients. Strategies to enhance tumor cell death is a fundamental aim, but relevant model systems for human tumor immunology are lacking. Herein, we have developed a preclinical human immune - three-dimensional (3D) tumor model (spheroids) to map the efficiency of tumor-specific isotypes for improved tumor cell killing. Different anti-CD20 Rituximab (RTX) isotypes alone or in combination, were evaluated for mediating complement-dependent cytotoxicity and antibody-dependent phagocytosis by human monocytic cells in 3D spheroids, in parallel with monolayer cultures, of human CD20+ B-cell lymphomas. We demonstrate that the IgG3 variant of RTX has the greatest tumoricidal effect over other isotypes, and when combined with apoptosis-inducing RTX-IgG2 isotype the therapeutic effect can be substantially enhanced. The results show further that the treatment outcome by RTX isotypes is influenced by tumor morphology and expression of the complement inhibitor CD59. Hence, the human immune-3D tumor model is a clinical relevant and attractive ex vivo system to predict mAbs for best efficacy in cancer immunotherapy.

Quantitative proteomics reveal the protective effects of EDS against osteoarthritis via attenuating inflammation and modulating immune response.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim, Dioscorea nipponica Makino, and Salvia miltiorrhiza Bunge formula (EDS) are three traditional Chinese medicines commonly combined and used to treat osteoarthritis (OA). However, the mechanism of its therapeutic effect on OA is still unclear. AIM OF THE STUDY: The aim of this study was to investigate the potential anti osteoarthritis mechanism of EDS in the treatment of OA rats' model by quantitative proteomics. MATERIALS AND METHODS: A papain-induced rat OA model was established, and then EDS was intragastrically administered for 28 days. A label-free quantification proteomics was performed to evaluate the holistic efficacy of EDS against OA and identify the possible protein profiles mechanisms. The expression levels of critical changed proteins were validated by RT-qPCR and Western blotting. The effects of EDS were then assessed by evaluating pathologic changes in the affected knee joint and measuring pressure pain threshold, acoustic reflex threshold, angle of joint curvature. RESULTS: Proteomics analysis showed that 62 proteins were significantly upregulated and 208 proteins were downregulated in OA group compared to control group. The changed proteins were involved in activation of humoral immunity response, complement cascade activation, leukocyte mediated immunity, acute inflammatory response, endocytosis regulation, and proteolysis regulation. The EDS treatment partially restored the protein profile changes. The protective effects of EDS on pathologic changes in OA rats' knee joint and pain threshold assessment were consisted with the proteomics results. CONCLUSIONS: The results suggest that EDS exerted synergistic therapeutic efficacies to against OA through suppressing inflammation, modulating the immune system, relieving joint pain, and attenuating cartilage degradation.

The effect of Pediococcus acidilactici on mucosal immune responses, growth, and reproductive performance in zebrafish (Danio rerio).

A completely randomized experimental design carried out to investigate the effects of different levels of Pediococcus acidilactici (PA) including 0 (basal diet as a control diet), 1 × 106, 2 × 106, 4 × 106, and 8 × 106 colony-forming unit (CFU) per gram of the diet for 60 days on the mucosal immunity responses, growth, and reproductive performance, in zebrafish, Danio rerio (with mean weigh ± SE: 120 ± 10 mg). The obtained results revealed that the best growth and reproduction indices were related to the concentration of 4 × 106 CFU PA g-1 diet (P < 0.05). The maximum activities of mucosal immune responses including total protein, alternative complement system, IgM, and lysozyme were observed in the fish fed with 4 × 106 CFU PA g-1 diet (P < 0.05). Furthermore, the maximum alkaline phosphatase activity of skin mucus was recorded in the fish fed with 8 × 106 CFU PA g-1 diet (P < 0.05). Fish fed with 4 × 106 CFU PA g-1 diet had the highest villus length and width of the intestine (P < 0.05). Supplementing the diet with 4 × 106 CFU PA g-1 diet more significantly enhanced Cyp19a gene expression in comparison with this in other groups. Hence, PA with a concentration of 4 × 106 CFU g-1 diet can be considered as a proper level of probiotic for improving the health, growth, and reproductive performance of the D. rerio.

High efficacy and economical procedure of oral vaccination against Lactococcus garvieae/Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

The present study was aimed to examine the efficacy of chitosan-alginate coated vaccines against pathogenicity of Lactococcus garvieae and Streptococcus iniae in rainbow trout. Fish were divided into four groups including: Group A: fish immunized by chitosan-alginate coated vaccine, Group B: fish immunized by non-coated vaccine, Group C: fish feed by chitosan-alginate coated pellets without vaccine and Group D: fish feed by basic diet (non-coated and without vaccine). In groups A and B, the vaccination was carried out for 14 days and after that supplemented with fundamental diet (control diet). Comparable to groups A and B, fish of group C were also fed 14 days with test diets and after that fed control food. On day 0, 20, 40 and 60 of the experiment, serum samples were given. Fish have been challenged with live L. garvieae and S. iniae after 60 days. The levels of bactericidal activity and complement activity among innate immunity components extended on day 20 of the research and after that decreased in group A and B (P < 0.05) all through the examination. The relative expression of IL-6 and IgM in groups A and B extended on examination day 20. The expression of these genes illustrated no advancements in different groups in during the examination (P > 0.05). In group A, the serum antibody titer against L. garvieae and S. iniae broadly raised on day 40 and 60 of examination, whereas in group B, the immune response titer against S. iniae and L. garvieae illustrated a significant elevation on day 60 of the trial (P < 0.05). After challenge with live bacteria, survival rate of 83 ± 9.1%(challenged with S. iniae) and 72.18 ± 9.8% (challenged with L. garvieae) were gotten independently in group A, which were higher than survival of other exploratory groups (P < 0.05). In conclusion, the results of the present examination appear that the orally vaccination of rainbow trout with chitosan-alginate covered vaccine stimulates immunity system and also efficiently protects rainbow trout against Lactococcus garvieae and Streptococcus iniae.

Structural characterization and anticomplement activities of three acidic homogeneous polysaccharides from Artemisia annua.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. is a heat-clearing Chinese medicine and well-known for its antimalarial constituent, artemisinin. It has gained increasing attention for its anti-inflammatory and immunoregulatory activities. Interestingly, the crude polysaccahrides of A. annua exhibited potent anticomplement activity. This study was to isolate and characterize its anticomplement homogeneous polysaccharides from A. annua, and reveal the relationship between structures and anticomplement activities of the isolated polysaccharides. MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of A. annua were extracted and fractionated by DEAE-cellulose and Sephacryl S-300 gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, methylation and NMR analysis were performed to characterize the structures of homogeneous polysaccharides. Their anticomplement activities and targeting components in the complement activation cascade were evaluated by hemolytic assays. RESULTS: Three homogeneous polysaccharides (AAP01-1, AAP01-2 and AAP01-3) were obtained from A. annua. AAP01-1 was composed of seven monosaccharides, including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose. AAP01-2 and AAP01-3 had similar monosaccharides with AAP01-1, except the absence of glucuronic acid. They were all branched acidic heteropolysaccharides with different contents of galacturonic acid (8%, 28% and 15% for AAP01-1, AAP01-2 and AAP01-3, respectively). AAP01-2 showed potent anticomplement activity with CH50 value of 0.360 ±â€¯0.020 mg/mL through the classical pathway and AP50 value of 0.547 ±â€¯0.033 mg/mL through the alternative pathway. AAP01-3 exhibited slightly weaker activity (CH50: 1.120 ±â€¯0.052 mg/mL, AP50: 1.283 ±â€¯0.061 mg/mL), while AAP01-1 was inactive. Moreover, AAP01-2 acted on C1q, C3, C4, C5 and C9 components and AAP01-3 interacted with C3, C4 and C5 components in the activation cascade of complement system. CONCLUSION: These results indicated that the relatively high contents of galacturonic acid were important for anticomplement activities of the polysaccharides from A. annua. The anticomplement polysaccharides are another kind of bioactive constituents conferring heat-clearing effects of A. annua.

Inhibitory Effect of Supercritical Extracts from Arctium lappa L. on the Lectin Pathway of the Complement System.

The complement system participates in host defense by eliminating microorganisms and triggering inflammation. However, insufficient control or exacerbated complement activation contributes to inflammatory diseases. Since promising antioxidant and anti-inflammatory activities have been identified in Arctium lappa L. extracts, this study aims to explore the effect of A. lappa extracts on the lectin pathway (LP) of complement activation. Four extracts were obtained by supercritical extraction using scCO2 with or without ethanol as co-solvent, at different temperatures and pressures (E1: 2.2 mg/mL, E2: 2.6 mg/mL and E3: 2.0 mg/mL, E4: 1.5 mg/mL). To evaluate the effect of A. lappa extracts on the LP activation, an ELISA assay using mannose binding lectin pathway of complement was carried out with C4 detection. All extracts showed a concentration-dependent inhibitory effect on the activation of complement by the LP. The following IC50 were observed for E1, E2, E3 and E4: 179.4 µg/mL, 74.69 µg/mL, 119.1 µg/mL and 72.19 µg/mL, respectively. Our results suggest that A. lappa extracts are potential candidates for the treatment of inflammatory disorders that are complement-related.

Sheep and goats raised in mixed flocks have diverse immune status around parturition.

Several physiological and metabolic changes take place in dairy ruminants around parturition (late pregnancy, parturition, and early lactation). Dairy species are genetically selected for their higher milk production compared with non-dairy species. This fact causes a constant stress that impairs the immune status of the animal, with consequences for its welfare and performance. In the present study, we assessed the immune status of high-yield dairy sheep and goats by quantifying IgG and IgM concentrations, as well as chitotriosidase (ChT) and complement system [total complement system (TC) and alternative complement pathway (AC)] activity in blood plasma around parturition. We also measured IgG and IgM concentrations and ChT activity in colostrum and milk during the first 40 d postpartum. The lowest blood IgG concentration was at parturition in both species. We detected no differences in blood IgG concentrations between species. Blood IgM concentrations were constant in both species throughout the study period. However, blood IgM concentrations were greater in sheep than in goats. Blood ChT activity was greater in goats than in sheep, and both species showed constant activity of this enzyme throughout the study period. We observed no differences in complement system (TC and AC) activity between sheep and goats. In addition, both TC and AC activity were constant in both species throughout the experiment. In general, IgG and IgM concentrations were greater in sheep colostrum than in goat colostrum, but these differences disappeared after d 4 (IgG) and d 3 (IgM) postpartum. In both species, the highest IgG and IgM concentrations were measured in colostrum, gradually decreasing during the first days postpartum. Chitotriosidase activity decreased in both species from colostrum to milk, although goats always showed greater ChT activity than sheep. Both sheep and goats seemed to be more susceptible to infectious diseases around parturition. As well, goats showed greater ChT activity in blood, colostrum, and milk than sheep. This fact may give these animals additional protection against parasite and fungal infections.

Screening of anti-complement active ingredients from Eucommia ulmoides Oliv. branches and their metabolism in vivo based on UHPLC-Q-TOF/MS/MS.

Eucommia ulmoides Oliv. (E. ulmoides) is a kind of plant with high medicinal value, there are known as the "gold plants". Some components and contents of barks and branches from E. ulmoides are similar, the barks are mainly used as medicine, but the branches have not been systematically studied and were discarded. In this paper, five fractions extracted from E. ulmoides branches were detected by the classical anti-complement activity assay in vitro. The n-butanol fraction of E. ulmoides branches showed excellent anti-complement activities with a CH50 value of 0.016 ±â€¯0.0014 mg·mL-1. A total of 76 compounds were identified from the n-butanol fraction, including 9 alkaloids, 18 organic acids, 22 lignans, 15 phenylethanoid glycosides and 12 other compounds. To further prove the anti-complement activity of potential active compounds, those compounds detectable in rat plasma after oral administration were tested by classical anti-complement activity assays. Genipin and pinoresinol 4-O-glucopyranoside had a certain complement inhibitory activity in the 17 potential anti-complements, their CH50 values were 0.050 ±â€¯0.0038 and 0.022 ±â€¯0.0018 mg·mL-1. UHPLC-Q-TOF/MS/MS was developed to profile and characterize the metabolites of genipin and pinoresinol 4-O-glucopyranoside in rat plasma. Twenty-one and seventeen metabolites were found, respectively. In summary, this study reported important clues for the further pharmacological and clinical studies of E. ulmoides branches. Meanwhile, it provided a practical strategy for rapid screening and identifying of in vivo anti-complement in traditional Chinese medicine.