Investigation of the Mechanism of Action of Periploca forrestii Schltr. Extract on Adjuvant Collagen Rats Based on UPLC-Q-Orbitrap-HRMS Non-Targeted Lipidomics.

Periploca forrestii Schltr. (P. forrestii) is a classical medicinal plant and is commonly used in traditional medicine for the treatment of rheumatoid arthritis, soft tissue injuries, and traumatic injuries. The aim of this study was to evaluate the anti-arthritic effects of three fractions of P. forrestii alcoholic extracts (PAE), P. forrestii water extracts (PWE), and total flavonoids from P. forrestii (PTF) on Freund's complete adjuvant (FCA)-induced arthritis in rats, and to use a non-targeted lipidomic method to investigate the mechanism of action of the three fractions of P. forrestii in the treatment of rheumatoid arthritis. To assess the effectiveness of anti-rheumatoid arthritis, various indicators were measured, including joint swelling, histopathological changes in the joints, serum cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6)), and the joint inflammatory substance prostaglandin E2 (PGE2). Finally, ultra-performance liquid chromatography-quadrupole-orbitrap-high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to determine the non-targeted lipid histology of the collected rat serum and urine samples to investigate the possible mechanism of action. PWE, PAE, and PTF were all effective in treating FCA-induced rheumatoid arthritis. The administered groups all reduced joint swelling and lowered serum inflammatory factor levels in rats. In the screening of lipid metabolite differences between serum and urine of the rat model group and the normal group, a total of 52 different metabolites were screened, and the levels of lipid metabolites in PWE, PAE, and PTF were significantly higher than those in the normal group after administration. In addition, PWE, PAE, and PTF may have significant therapeutic effects on FCA-induced arthritis by modulating nicotinic acid, nicotinamide, and histidine metabolic pathways.

Long Short-Term Memory-Based Multiomics Reveal Lactobacillus casei-Derived Postbiotics Inhibiting Lipids Digestion via Mediating the Upregulation of α-Helices in Lipase.

SCOPE: The antiobesity function of probiotics has been declared, while the application in high-risk patients and coding side effect has focused attention to postbiotics. This investigation profiles the mechanism of postbiotics affecting lipid digestion at molecular level, and establishes a momentous foundation for the clinical application of postbiotics in obesity suppression. METHODS AND RESULTS: An operational framework for butter digestion is constructed to collect the digests in the intestine at 0, 40, 80, and 120 min with various postbiotics supplement. A total of 227 lipids and 414 metabolites are detected by pseudo-targeted lipidomics integrated with the long short-term memory-based metabolomics, and the triacylglycerol (TG, from 134.1 to 184.7 mg kg-1 ) and diacylglycerol (DG, from 4.2 to 8.4 mg kg-1 ) are identified as significantly different lipids with or without postbiotics supplement. A total of eight substances related to the inhibition of gastric lipase and pancreatic lipase are screened through the molecular simulation computation in silicon and enzymatic reaction kinetics, and thus curtailing the bioaccessibility of lipids. CONCLUSIONS: Lactobacillus casei JCM1134-derived postbiotics propel the structure of lipase to aggregate by increasing the α-helix, and thus hampering the digestion of triglycerides through noncompetitive inhibition.

Targeted Lipidomics Reveal the Effect of Perchlorate on Lipid Profiles in Liver of High-Fat Diet Mice.

Perchlorate, commonly available in drinking water and food, acts on the iodine uptake by the thyroid affecting lipid metabolism. High-fat diets leading to various health problems continually raise public concern. In the present study, liver lipid metabolism profiles and metabolic pathways were investigated in C57BL/6J mice chronically exposed to perchlorate using targeted metabolomics. Mice were fed a high-fat diet and treated orally with perchlorate at 0.1 mg/kg bw (body weight), 1 mg/kg bw and 10 mg/kg bw daily for 12 weeks. Perchlorate induced disorders of lipid metabolism in vivo and hepatic lipid accumulation confirmed by serum biochemical parameters and histopathological examination. There were 34 kinds of lipid in liver detected by UHPLC-MS/MS and key metabolites were identified by multivariate statistical analysis evaluated with VIP > 1, p-value < 0.05, fold change > 1.2 or < 0.8. Perchlorate low, medium and high dose groups were identified with 11, 7 and 8 significantly altered lipid metabolites compared to the control group, respectively. The results of the metabolic pathway analysis revealed that the differential metabolites classified into different experimental groups contribute to the glycerophospholipid metabolic pathway. These findings provide insights into the effects of perchlorate on lipid metabolism during long-term exposure to high-fat diets and contribute to the evaluation of perchlorate liver toxic mechanisms and health effects.

Spleen Oxylipin and Polyunsaturated Fatty Acid Profiles are Altered by Dietary Source of Polyunsaturated Fatty Acid and by Sex.

As the largest secondary lymphoid organ, the spleen plays an important role in immune responses. The role of arachidonic acid (ARA) and its 20-carbon eicosanoids in modulating immune function has long been of interest. However, recent advances have enabled the identification of numerous other n-6 and n-3 polyunsaturated fatty acid (PUFA)-derived oxylipins. Here, we investigate the effects of diet and sex on the spleen nonesterified oxylipin profiles and phospholipid and neutral lipid PUFA composition in Sprague-Dawley rats supplemented with oils rich in α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or linoleic acid. Dietary ALA, EPA, and DHA resulted in lower levels of ARA and ARA oxylipins. Oxylipins derived from other n-6 PUFA were also reduced despite no or opposite effect on their PUFA levels. Each diet also resulted in higher levels of oxylipins almost exclusively derived from the supplemented PUFA, despite PUFA in the same biosynthetic pathway also often being increased. Further, while oxylipin differences often reflected changes to phospholipid PUFA, there were instances where they corresponded more closely to changes in neutral lipid PUFA. With respect to sex effects, >50% of lipoxygenase ARA-derived oxylipins were higher in males in at least one diet group, while multiple DHA oxylipins were lower in males only in rats provided the DHA diet. This fundamental description of oxylipin composition in the spleen, including the influence of diet and sex and the relationship to PUFA composition, will help inform future studies examining the functions of these oxylipins under physiological and pathological conditions.