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Background: The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. Material and methods: Pancreatitis was induced pancreatitis by cerulean (50µg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1β (IL-1β) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. Result: Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-1β and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. Conclusion: Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.

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Sepsis is the major challenge in clinical practice with high mortality. 1 Toll-like receptors (TLRs) play a fundamental role in sepsis. CD14 is a co-receptor of many Toll-like receptors. 2 In our previous study, we found integrin b3 deficiency decreased sepsis induced CD14 expression and attenuated acute lung injury. In this study we used a cecal ligation and puncture (CLP) induced sepsis model and LPS-treated macrophages to uncover the mechanism of integrin b3 modulated CD14 expression under inflammatory conditions.In vivo studies. To define the role of integrin b3 in macrophages in a septic mouse, macrophages were derived from bone marrow and retransfusion, with or without prior depletion of macrophages by clodronate-containing liposomes. To detect morphology changes, lungs were obtained at 24 h after CLP and fixed with 4% paraformaldehyde (PFA) for haematoxylineeosin (HE) stain. To detect the inflammatory response, bronchoalveolar lavage fluid (BALF) was obtained and tested for the levels of tumour necrosis factor alpha (TNFa), interleukin (IL)-6, and IL-b via enzyme-linked immunosorbent assay (ELISA). To detect CD14 expression tissue, the lung was homogenised and lysed for western blot.In vitro studies. To further investigate if integrin b3 is directly or indirectly involved in CD14 expression, we used (1) wild type macrophages pretreated with integrin b3 inhibitor P11 or antiantibody or (2) integrin b3 e/e macrophages stimulated with LPS for different times and measured the levels of TNF-a and IL-6 via ELISA and CD14 via western blot and flow cytometry. Secondly, integrin b3 e/e macrophages treated with recombinant CD14 protein and LPS for different time points were used and TNF-a and IL-6 secretion was measured by ELISA. Thirdly, macrophages were isolated from wild type mice and pretreated with polymyxin B (PMB) or TAK-242 or isolated from C3He/J mice and stimulated with LPS for 24 h to detect CD14 expression via western blot or flow cytometry. Lastly, co-transfected 293T cells with integrin b3-HA and TLR4-Flag plasmids were then stimulated with LPS for 30 or 60 min, and the interaction by coimmunoprecipitation was assessed.In wild type mice with prior depletion of macrophages followed by retransfusion of wild type macrophages, lung injury, inflammatory cytokines, and CD14 expression was significantly increased compared with retransfusion of integrin b3 deficient macrophages. In integrin b3 deficient mice with prior depletion of macrophages and retransfusion of wild type macrophages, the lung injury, inflammatory cytokines, and CD14 expression was increased compared with retransfusion of integrin b3 deficient macrophages. Blocking integrin b3 pathway by P11 or anti-antibody inhibited LPS-induced TNF-a and IL-6 release at early but not late times, but had no effect on CD14 expression in wild type macrophages. In integrin b3 deficient macrophages, LPS-induced TNF-a and IL-6 release was significantly decreased from 4 to 24 h as well as CD14 expression. Recombination mCD14 reversed integrin b3 deficiency decrea...