[What the surgeon needs to know about basic new concepts of inflammation and their therapeutic consequences: sanitation of inflammation is not a passive but rather an active process regulated by lipid mediators]. / Was der Chirurg über grundlegend neue Konzepte zur Entzündung und deren therapeutische Konsequenzen wissen sollte: Die Ausheilung der Entzündung ist kein passiver, sondern ein durch Lipidmediatoren regulierter aktiver Prozess.

The acute inflammatory response as a physiological programme that protects the organism against injurious pathogens is characterised by highly regulated actions of pro- and anti-inflammatory mediators. Intensive investigations during the last decades have led to the identification of these mediators and their complex interplay as well as the design and development of anti-inflammatory therapies. However, the resolution of acute inflammation has long been considered to be a passive process. In consequence, little was known about the mechanisms which guide acute inflammation either to complete resolution, repair of inflamed tissue and restoration of normal function or to a chronic inflammatory process characterised by persistent signs of inflammation, tissue damage and impaired function. Predominantly during the last decade the so-called specialised proresolving mediators (SPM) have been identified. These essential fatty acid-derived mediators - lipoxins, resolvins, protectins, and maresins - terminate the acute inflammatory responses and stimulate their complete resolution. SPM possess both anti-inflammatory and proresolving activities in that they inhibit pro-inflammatory cytokines, limit infiltration of neutrophils, enhance macrophage uptake, and finally stimulate their non-phlogistic activation and clearance of apoptotic neutrophils and microbial particles. It has been demonstrated in multiple animal models of human inflammatory diseases that, e.g., atherosclerosis, diabetes, and inflammatory bowel diseases are caused by a decreased synthesis and/or an impaired signal transduction of the proresolving mediators. Future studies are warranted to clarify whether these proresolving lipid mediators will participate in healing human inflammatory diseases and their complications.

Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract.

Hepatocytes of a primary cell culture that are exposed to high glucose, insulin, and linoleic (LA) acid concentration respond with lipid accumulation, oxidative stress up to cell death. Such alterations are typically found in patients with non-alcoholic fatty liver disease (NAFLD). We used this cellular model to study the effect of an ethanolic Gynostemma pentaphyllum (GP) extract in NAFLD. When hepatocytes were cultured in the presence of high insulin, glucose, and LA concentration the extract completely protected the cells from cell death. In parallel, the extract prevented accumulation of triglycerides (TGs) and cholesterol as well as oxidative stress. Our data further demonstrate that GP stimulates the production of nitric oxide (NO) in hepatocytes and affects the molecular composition of the mitochondrial phospholipid cardiolipin (CL). We conclude that GP is able to protect hepatocytes from cell death, lipid accumulation, and oxidative stress caused by diabetic-like metabolism and lipotoxicity. Therefore, GP could be beneficial for patients with diabetes mellitus and NAFLD.

Protection of hippocampal slices against hypoxia/hypoglycemia injury by a Gynostemma pentaphyllum extract.

In transverse hippcampus slices a short period of hypoxia/hypoglycemia induced by perfusion with O(2)/glucose-free medium caused early loss and incomplete restoration of evoked field potentials to only 50% in the CA(1) region. We report about a study investigating the effect of an ethanolic Gynostemma pentaphyllum extract in this system. When given with reperfusion the extract completely protected the cells of the slices from functional injury. The extract also protected at the subcellular level isolated mitochondria which had been subjected to hypoxia/reoxygenation in combination with elevated extramitochondrial Ca(2+) concentration from functional injury. In isolated mitochondria the extract protected from Ca(2+)-induced opening of the mitochondrial permeability transition pore and reduced lipid peroxidation. Our data demonstrate that the ethanolic extract of Gynostemma pentaphyllum has a high potential to protect from ischemia/reperfusion injury. It should be beneficial as prophylactic nutrition supplement and during revascularization of arterial blood vessels from stroke and other ischemic events such as coronary occlusion.