Browsing by Author "Swain, Mark G."
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Item Open Access Efficacy of a Peruvian Botanical Remedy (Sabell A4+) for Treating Liver Disease and Protecting Gastric Mucosal Integrity(2019-10-24) Swain, Mark G.; Wallace, John L.; Tyrrell, D. Lorne; Cabanillas, José; Aung, Steven K. H.; Liu, Hongqun; Finnie-Carvalho, Lindsay; Shrestha, Grishma; Semple, Hugh A.; Green, Francis H. Y.The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts of Curcuma longa rhizome, Cordia lutea flower, and Annona muricata leaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an “air pouch” model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.Item Open Access Epithelial dysfunction following a bout of colitis(2000) Asfaha, Samuel; Swain, Mark G.Item Open Access Hepatic cytokine profile in rats with experimental cholangitis(2004) Tjandra, Kartika; Swain, Mark G.Item Open Access Leukocyte recruitment and function in cholestasis(1996) Tjandra, Kartika; Swain, Mark G.Item Open Access Liver-brain inflammation axis: immune cell driven sickness behavior regulation(2011) D'Mello, Charlotte; Swain, Mark G.Item Open Access Natural killer t cells (nkt): regulators of the hepatic immune response(2011) Santodomingo Garzon, Tania; Swain, Mark G.Item Open Access Peripheral TregS suppress sickness behaviour development associated with inflammatory liver disease(2010) Nguyen, Kimchi; Swain, Mark G.Item Open Access Recruitment of α4β7 monocytes and neutrophils to the brain in experimental colitis is associated with elevated cytokines and anxiety-like behavior(2022-04-04) Cluny, Nina L.; Nyuyki, Kewir D.; Almishri, Wagdi; Griffin, Lateece; Lee, Benjamin H.; Hirota, Simon A.; Pittman, Quentin J.; Swain, Mark G.; Sharkey, Keith A.Abstract Background Behavioral comorbidities, such as anxiety and depression, are a prominent feature of IBD. The signals from the inflamed gut that cause changes in the brain leading to these behavioral comorbidities remain to be fully elucidated. We tested the hypothesis that enhanced leukocyte–cerebral endothelial cell interactions occur in the brain in experimental colitis, mediated by α4β7 integrin, to initiate neuroimmune activation and anxiety-like behavior. Methods Female mice treated with dextran sodium sulfate were studied at the peak of acute colitis. Circulating leukocyte populations were determined using flow cytometry. Leukocyte–cerebral endothelial cell interactions were examined using intravital microscopy in mice treated with anti-integrin antibodies. Brain cytokine and chemokines were assessed using a multiplex assay in animals treated with anti-α4β7 integrin. Anxiety-like behavior was assessed using an elevated plus maze in animals after treatment with an intracerebroventricular injection of interleukin 1 receptor antagonist. Results The proportion of classical monocytes expressing α4β7 integrin was increased in peripheral blood of mice with colitis. An increase in the number of rolling and adherent leukocytes on cerebral endothelial cells was observed, the majority of which were neutrophils. Treatment with anti-α4β7 integrin significantly reduced the number of rolling leukocytes. After anti-Ly6C treatment to deplete monocytes, the number of rolling and adhering neutrophils was significantly reduced in mice with colitis. Interleukin-1β and CCL2 levels were elevated in the brain and treatment with anti-α4β7 significantly reduced them. Enhanced anxiety-like behavior in mice with colitis was reversed by treatment with interleukin 1 receptor antagonist. Conclusions In experimental colitis, α4β7 integrin-expressing monocytes direct the recruitment of neutrophils to the cerebral vasculature, leading to elevated cytokine levels. Increased interleukin-1β mediates anxiety-like behavior.Item Open Access The role of CD154 in the pathogenesis of murine T cell mediated hepatitis(2004) Zhou, Feng; Swain, Mark G.Item Open Access The role of chemokines IP-10 and MIG in concanavalin A-induced hepatitis(2006) Carey, Jillian; Swain, Mark G.