Juglone: "A novel immunomodulatory, antifibrotic, and schistosomicidal agent to ameliorate liver damage in murine schistosomiasis mansoni".

Schistosomiasis remains one of the world's leading health concerns, affecting millions. The granulomatous reaction is the most significant immunopathological change associated with Schistosoma mansoni infection, resulting in significant mortality. Recent progress has been made in the search for new natural compounds to reduce schistosomiasis and its immunopathology. Walnuts contain the phenolic compound Juglone (5-hydroxy-1,4-naphthoquinone), which has antiparasitic, anti-inflammatory, immunoregulatory, and antioxidant properties. There were three groups of infected mice: untreated (IU), Juglone-treated (JUG T), and praziquantel-treated (PZ). In mice treated at 8 mg Juglone /kg body weight, a reduction of 63.1 % and 52.1 % were observed in the number of male and female worms, respectively. In addition, the number of eggs/g tissue was reduced by 65.7 % in the liver, 58.58 % in the intestine, and 62.31 % in the liver and intestine combined. In addition, Juglone decreased hepatic granuloma size by 55.1 % and collagen fiber deposition by 23.4 % compared to PZQ (41.18 % and 11.2 %, respectively). Interestingly, the JUG T group had significantly lower levels of IL-4, IL-13, IL-37, TNF-α, TGF-ß, and IFN-γ than PZ mice (p < 0.05). While IL-10 and IL-17 levels rose (p < 0.01), Juglone could restore hepatic ALT, AST, GGT, and LDH activities following infection. In addition, it increased catalase, SOD, GSH, and GST while decreasing NO and LPO in comparison to the infected group. Moreover, anti-SWAP, SEA, and CAP IgG levels increased significantly. IgE levels did not change significantly, however. Juglone could be used as an antifibrotic, immunomodulatory, and schistosomicidal agent; thus, it could be used in place of PZQ.

Anti-inflammatory, antioxidant, anti-fibrotic and schistosomicidal properties of plumbagin in murine schistosomiasis.

Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-ß and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.

The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) is a serious medical problem affecting millions of peoples worldwide, and has a great socio-economic impacts. Cytokines possess a pivotal role in modulation of immune reactions and disease pathogenesis. T-helper type 17 (Th17) cells, an important proinflammatory CD4+ T cell subset secreting interleukin 17 (IL-17), has been embroiled in development of DM. There are recent evidences supporting a definitive role of Th17 cells in the etiology of type 1 diabetes (T1D). In addition, IL-17 has been shown to play a crucial role in inflammation, insulin resistance, and type 2 diabetes (T2D). Recently, small molecules which have been specified to block Th17 cells differentiation are considered as potential therapeutics for the disease. Anti-IL-17 neutralizing antibodies and/or antibodies targeting Th17 cells have been investigated to protect individuals at risk from disease development. In this review we aimed to shed light on the potential role of IL-17 and Th17 cells in both T1D and T2D pathogenesis and future therapeutic strategies.