Comprehensive evaluation of caloric restriction-induced changes in the metabolome profile of mice.

OBJECTS: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice. METHODS: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography-mass spectrometry approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. RESULTS: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 6 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, L-isoleucine, L-proline, L-aspartic acid, L-serine, L-hydroxyproline, L-alanine, L-valine, L-threonine, L-glutamic acid, and L-phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 7 different functional pathways related to the metabolism of AAs, lipids, and energy. CONCLUSION: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.

Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway.

CONTEXT: Osteoarthritis (OA) is a degenerative disease. Senkyunolide A (SenA) is an important phthalide from Ligusticum chuanxiong Hort (Umbelliferae) with anti-spasmodic and neuroprotective effects. OBJECTIVE: We explored the effect of SenA on IL-1ß-stimulated chondrocytes and OA mice. MATERIALS AND METHODS: Chondrocytes were stimulated by IL-1ß (10 ng/mL) to establish an OA model in vitro. Cells were treated with SenA (20, 40, 80 and 160 µg/mL) for 48 h. The in vivo OA model was established by cutting off the medial meniscus tibial ligament (MMTL) at right knee incision of male C57BL/6 mice. One week after surgery, mice were injected with SenA (intraperitoneally one week) and divided into four groups (n = 6 per group): Sham, OA, OA + SenA 20 mg/kg and OA + SenA 40 mg/kg. The OA progression was examined by haematoxylin and eosin (H&E) staining. RESULTS: SenA treatment increased cell viability (33%), proliferation (71%), inhibited apoptosis (21%), decreased levels of catabolic marker proteins (MMP13, 23%; ADAMTS4, 31%; ADAMTS5, 19%), increased levels of anabolic marker proteins (IGF-1, 57%; aggrecan, 75%; Col2a1, 48%), reduced levels of inflammation cytokines (TNF-α, 31%; IL-6, 19%; IL-18, 20%) and decreased levels of NLRP3 (21%), ASC (20%) and caspase-1 (29%) of chondrocytes. However, NLRP3 agonist nigericin increased levels of MMP13 (55%), ADAMTS4 (70%), ADAMTS5 (53%), decreased levels of IGF-1 (36%), aggrecan (26%), Col2a1 (25%), inhibited proliferation (61%) and promoted apoptosis (76%). DISCUSSION AND CONCLUSIONS: SenA alleviates OA progression by inhibiting NLRP3 signalling pathways. These findings provide an experimental basis for the clinical application of drugs in the treatment of OA.