UNASSIGNED: Infection is a major problem in advanced liver disease secondary to monocyte dysfunction. Elevated prostaglandin (PG)E2 is a mediator of monocyte dysfunction in cirrhosis; thus, we examined PGE2 signalling in outpatients with ascites and in patients hospitalised with acute decompensation to identify potential therapeutic targets aimed at improving monocyte dysfunction.
UNASSIGNED: Using samples from 11 outpatients with ascites and 28 patients hospitalised with decompensated cirrhosis, we assayed plasma levels of PGE2 and lipopolysaccharide (LPS); performed quantitative real-time PCR on monocytes; and examined peripheral blood monocyte function. We performed western blotting and immunohistochemistry for PG biosynthetic machinery expression in liver tissue. Finally, we investigated the effect of PGE2 antagonists in whole blood using polychromatic flow cytometry and cytokine production.
UNASSIGNED: We show that hepatic production of PGE2 via the cyclo-oxygenase 1-microsomal PGE synthase 1 pathway, and circulating monocytes contributes to increased plasma PGE2 in decompensated cirrhosis. Transjugular intrahepatic sampling did not reveal whether hepatic or monocytic production was larger. Blood monocyte numbers increased, whereas individual monocyte function decreased as patients progressed from outpatients with ascites to patients hospitalised with acute decompensation, as assessed by Human Leukocyte Antigen (HLA)-DR isotype expression and tumour necrosis factor alpha and IL6 production. PGE2 mediated this dysfunction via its EP4 receptor.
UNASSIGNED: PGE2 mediates monocyte dysfunction in decompensated cirrhosis via its EP4 receptor and dysfunction was worse in hospitalised patients compared with outpatients with ascites. Our study identifies a potential drug target and therapeutic opportunity in these outpatients with ascites to reverse this process to prevent infection and hospital admission.
UNASSIGNED: Patients with decompensated cirrhosis (jaundice, fluid build-up, confusion, and vomiting blood) have high infection rates that lead to high mortality rates. A white blood cell subset, monocytes, function poorly in these patients, which is a key factor underlying their sensitivity to infection. We show that monocyte dysfunction in decompensated cirrhosis is mediated by a lipid hormone in the blood, prostaglandin E2, which is present at elevated levels, via its EP4 pathway. This dysfunction worsens when patients are hospitalised with complications of cirrhosis compared with those in the outpatients setting, which supports the EP4 pathway as a potential therapeutic target for patients to prevent infection and hospitalisation.

BACKGROUND: Rutin is a common dietary flavonoid that is widely consumed from plant-derived beverages and foods as traditional and folkloric medicine worldwide. Rutin is believed to exhibit significant pharmacological activities, including anti-oxidation, anti-inflammation, anti-diabetic, anti-adipogenic, neuroprotective and hormone therapy. Till date, over 130 registered therapeutic medicinal preparations are containing rutin in their formulations. This article aims to critically review the extraction methods for plant-based rutin and its pharmacological activities. This review provides comprehensive data on the performance of rutin extraction methods and the extent of its pharmacological activities using various in vitro and in vivo experimental models.
METHODS: Literatures including journals, patents, books and leaflets reporting on rutin from natural resources are systematically reviewed, particularly in the aspect of its extraction methods and biological activities. Factors affecting the efficiency of rutin extraction such as extraction temperature, duration and solvent to sample ratio are presented based on the findings of previous studies. The observed biological activities followed by clear explanation are also provided accordingly.
RESULTS: The biological activities of rutin varied largely dependent on the geographical and plant origins. The complexity of natural rutin has impeded the development of rutin derived drugs. The detail mechanism of rutin in human body after consumption is still unclear. Therefore, studies are intensively carried out both in vitro and in vivo for the better understanding of the underlying mechanism. The studies are not limited to the pharmacological properties, but also on the extraction methods of rutin. Many studies have focused on the optimization of extraction method to increase the extraction yield of rutin. Currently, the performances of modern extraction approaches have also been compared to the conventional heat reflux method as a benchmark.
CONCLUSIONS: There are various extraction methods for plant-based rutin ranging from conventional method up to the use of modern techniques such as ultrasound, mechanochemical, microwave, infrared and pressurized assisted methods. However, proper comparison between the methods is very difficult because of the variance in plant origin and extraction conditions. It is important to optimize the extraction method in order to produce high yield and acceptable purity of rutin with a reasonable cost. Even though rutin has been proven to be effective in numerous pharmacological activities, the dosage and toxicity of rutin for such activities are still unknown. Future research should relate the dosage and toxicity of rutin for the ethnobotanical claims based on the underlying mechanisms.