Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach

Abstract

Hookworm is one type of soil-transmitted helminth, which could exert an anti-inflammatory effect in human or animal host, which provides a beneficial possibility for the discovery of inflammatory-related disease interventions. The identification of hookworm-derived anti-inflammatory molecules is urgently needed for future translational research. The emergence of metabolomics has become a powerful approach to comprehensively characterize metabolic alterations in recent times. Herein, excretory and secretory products (ESPs) were collected from cultured adult worm, while small intestinal contents were obtained from Nippostrongylus brasiliensis (N. brasiliensis, Nb)-infected mice. Through ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) platform, metabolomics analysis was used to explore the identification of anti-inflammatory molecules. Out of 45 differential metabolites that were discovered from ESPs, 10 of them showed potential anti-inflammatory properties, which could be subclassed into amino acids, furanocoumarins, linear diarylheptanoids, gamma butyrolactones, and alpha-keto acids. In terms of intestinal contents that were derived from N. brasiliensis-infected mice, 14 out of 301 differential metabolites were discovered to demonstrate anti-inflammatory effects, with possible subclassification into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. Furthermore, nine of the differential metabolites appeared both in ESPs and infected intestinal contents, wherein four were proven to show anti-inflammation properties, namely, L-glutamine, glutamine (Gln), pyruvate, and alanine-Gln (Ala-Gln). In summary, we have provided a method for the identification and analysis of parasite-derived molecules with potential anti-inflammatory properties in the present study. This array of anti-inflammatory metabolites could provide clues for future evaluation and translational study of these anti-inflammatory molecules.

Anti-Inflammatory Responses Produced with Nippostrongylus brasiliensis-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model

“…A previous study reported the metabolomics profiling of the excretory–secretory (ES) products of helminths ( Nippostrongylus brasiliensis and Trichuris muris ) and up to 17 metabolites known to have various pharmacological activities, including wound-healing, anti-inflammatory, and cardioprotective activities [ 22 ]. Our results also revealed partially overlapping metabolites with different activities from ES products reported in previous studies including uridine [ 22 , 24 ], which further indicates the important key position of ES products for helminth-derived active molecules or the mining of pharmaceutical molecules. In addition to the metabolic analysis for N. brasiliensis ES products, to further investigate the N. brasiliensis -derived metabolites with activities, another metabolic analysis was performed for the intestinal contents of N. brasiliensis -infected mice, and the overlapping metabolites were selected for follow-up.…”

“…The parasite was introduced into Sprague–Dawley rats (male, 300 g) provided by the Animal Center of the Jiangsu Institute of Parasitic Diseases (JIPD, Wuxi, China) according to the previously published protocol [ 15 ]. N. brasiliensis adult worms (L5 stage) were collected from infected rats on day 7 post-infection and used to prepare ES products according to our previous report [ 24 ]. Briefly, adult worms were collected from the small intestine of infected rats using serial methods, including washing with Dulbecco’s phosphate-buffered saline (DPBS) (Gibco-Thermo Fisher, Waltham, MA, USA), incubated for 2 h at 37 °C, and separated with debris of the host.…”

Inhibition Effects of Nippostrongylus brasiliensis and Its Derivatives against Atherosclerosis in ApoE-/- Mice through Anti-Inflammatory Response

“…However, translation from rodent hookworm to human hookworm is another key consideration in subsequent research. Furthermore, N. brasiliensis -derived excretory-secretory products could be another important source for active molecule screening; these contain various anti-inflammatory metabolites, as demonstrated previously; these could be investigated for AS intervention in the near future [ 26 , 37 ].…”

“…L3-stage larvae were collected from the Petri dishes of cultured and infected rat fecal samples, as described previously [ 23 ]. L5 stage larvae (pre-adult worms) of N. brasiliensis were collected from the small intestine of infected rats as described previously [ 26 ]. Proteins derived from L3 and L5 larvae were extracted by grinding under cold conditions in parallel with repeated freezing and thawing.…”