3-4-dihydroxyphenyllactic-acid and Edema

In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study.. Eighty Wistar rats were randomly divided into four groups (n = 20).. SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively.. 48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring.. Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury.. EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.

Topics: Aldehydes; Animals; Ascitic Fluid; Drug Synergism; Drugs, Chinese Herbal; Edema; Emodin; Enzyme Inhibitors; Interleukin-1beta; Lactates; Male; NF-kappa B; Pancreas; Pancreatitis, Acute Necrotizing; Peroxidase; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. The methanolic extract from Cordia verbenacea (Cv) significantly inhibited paw edema induced by Bothrops jararacussu snake venom and by its main basic phospholipase A2 homologs, namely bothropstoxins I and II (BthTXs). The active component was isolated by chromatography on Sephadex LH-20 and by RP-HPLC on a C18 column and identified as rosmarinic acid (Cv-RA). Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid [2-O-cafeoil-3-(3,4-di-hydroxy-phenyl)-R-lactic acid]. This is the first report of RA in the species C. verbenacea ('baleeira', 'whaler') and of its anti-inflammatory and antimyotoxic properties against snake venoms and isolated toxins. RA inhibited the edema and myotoxic activity induced by the basic PLA2s BthTX-I and BthTX-II. It was, however, less efficient to inhibit the PLA2 activity of BthTX-II and, still less, the PLA2 and edema-inducing activities of the acidic isoform BthA-I-PLA2 from the same venom, showing therefore a higher inhibitory activity upon basic PLA2s. RA also inhibited most of the myotoxic and partially the edema-inducing effects of both basic PLA2s, thus reinforcing the idea of dissociation between the catalytic and pharmacological domains. The pure compound potentiated the ability of the commercial equine polyvalent antivenom in neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA2s in experimental models. CD data presented here suggest that, after binding, no significant conformation changes occur either in the Cv-RA or in the target PLA2. A possible model for the interaction of rosmarinic acid with Lys49-PLA2 BthTX-I is proposed.

Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Caffeic Acids; Cinnamates; Cordia; Depsides; Edema; Enzyme Inhibitors; Lactates; Neurotoxins; Phospholipases A; Phospholipases A2; Rosmarinic Acid; Snake Venoms; Time Factors