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Lactate can serve as both an energy substrate and a signaling molecule, exerting diverse effects on skeletal muscle physiology. Due to the apparently positive effects, it would be interesting to consider it as a sports supplement. However, the mechanism behind these effects are yet to be comprehensively understood. In this study, we observed that lactate administration could improve the ability of antifatigue, and we further found that lactate upregulated the expression of myosin heavy chain (MYHC I) and MYHC IIa, while downregulating the expression of MYHC IIb. Besides, transcriptomics and metabolomics revealed significant changes in the metabolic profile of gastrocnemius muscle following lactate administration. Furthermore, lactate enhanced the activities of metabolic enzymes, including HK, LDHB, IDH, SDM, and MDH, and promoted the expression of lactate transport‐related proteins MCT1 and CD147, thereby improving the transport and utilization of lactate in both vivo and vitro. More importantly, lactate administration increased cellular Ca2+ concentration and facilitated nuclear translocation of nuclear factor of activated T cells (NFATC1) in myotubes, whereas inhibition of NFATC1 significantly attenuated the effects of lactate treatment on NFATC1 nuclear translocation and MyHC expression. Our results elucidate the ability of lactate to induce metabolic remodeling in skeletal muscle and promote myofiber‐type transitions by activating the Ca2+‐NFATC1 signaling pathway. This study is useful in exploring the potential of lactate as a nutritional supplement for skeletal muscle adaptation and contributing to a mechanistic understanding of the central role of lactate in exercise physiology. [ABSTRACT FROM AUTHOR]

• Twenty seven sesquiterpenoids, including 17 undescribed compounds were isolated from deep sea sediment-derived fungus Aspergillus sydowii MCCC 3A00324. • Compounds 1 and 2 are the first examples of bisabolane sesquiterpenoids featuring a 6/6/6 tricyclic nucleus. • Compound 3 possessed a novel seco -bisabolane skeleton featuring a rare dioxolane ring moiety. • Compound 11 represents the first case of bisabolanes bearing a rare methylsulfonyl group. • Compound 12 exerted the anti-inflammatory activity by inhibiting the NF-κB-activated pathway in dose-dependent manner. Seventeen undescribed sesquiterpenoids including 14 phenolic bisabolanes, namely asperbisabolanes A-N (1 – 14), and 3 cuparenes (aspercuparenes A-C, 15 – 17), together with 10 known bisabolane analogues (18 – 27) were isolated from the EtOAc extract of fermented cultures of the deep sea sediment-derived fungus Aspergillus sydowii MCCC 3A00324. The new structures were established on the basis of extensive NMR and HRESIMS spectroscopic data analyses, while their absolute configurations were assigned by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra or reported data in literature. Asperbisabolanes A (1) and B (2) are the first examples of bisabolane sesquiterpenoids featuring a 6/6/6 tricyclic nucleus. Compound 3 possessed a novel seco -bisabolane skeleton with a rare dioxolane ring moiety, while asperbisabolane K (11) represents the first case of bisabolanes bearing a rare methylsulfonyl group. All the isolated compounds (1 – 27) were evaluated their activities against NO secretion in LPS-activated BV-2 microglia cells. As a result, 6 , 12 , 16 , and 25 – 27 exhibited the inhibition rate over 45% at a concentration of 10 µM. Moreover, 12 exerted the anti-inflammatory activity by inhibiting the NF-κB-activated pathway in dose-dependent manner. [ABSTRACT FROM AUTHOR]

Lactate can serve as both an energy substrate and a signaling molecule, exerting diverse effects on skeletal muscle physiology. Due to the apparently positive effects, it would be interesting to consider it as a sports supplement. However, the mechanism behind these effects are yet to be comprehensively understood. In this study, we observed that lactate administration could improve the ability of antifatigue, and we further found that lactate upregulated the expression of myosin heavy chain (MYHC I) and MYHC IIa, while downregulating the expression of MYHC IIb. Besides, transcriptomics and metabolomics revealed significant changes in the metabolic profile of gastrocnemius muscle following lactate administration. Furthermore, lactate enhanced the activities of metabolic enzymes, including HK, LDHB, IDH, SDM, and MDH, and promoted the expression of lactate transport-related proteins MCT1 and CD147, thereby improving the transport and utilization of lactate in both vivo and vitro. More importantly, lactate administration increased cellular Ca 2+ concentration and facilitated nuclear translocation of nuclear factor of activated T cells (NFATC1) in myotubes, whereas inhibition of NFATC1 significantly attenuated the effects of lactate treatment on NFATC1 nuclear translocation and MyHC expression. Our results elucidate the ability of lactate to induce metabolic remodeling in skeletal muscle and promote myofiber-type transitions by activating the Ca 2+ -NFATC1 signaling pathway. This study is useful in exploring the potential of lactate as a nutritional supplement for skeletal muscle adaptation and contributing to a mechanistic understanding of the central role of lactate in exercise physiology., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the effect of Angelicae Pubescentis Radix (APR) on the activity of endocannabinoid hydrolase and N-acylethanolamine-hydrolyzing acid amidase (NAAA), and to demonstrate the mechanism of anti-inflammatory effect of APR by in vitro lipopolysaccharide (LPS)-induced inflammation model., Method: APR essential oil was extracted by steam distillation, and the chemical components were identified by GC-MS. Enzymatic activity was performed by using recombinant NAAA-overexpressing protein and detected by LC-MS. Lipids were extracted by methonal/chloroform mixure and analyzed by LC-MS. mRNA and protein expression levels of proinflammatory genes were examined by Real time-PCR and ELISA assay kit, respectively. The content of nitro oxide (NO) was detected by Griess reaction., Result: Twenty active components were identified from APR essential oil which inhibited NAAA activity in a dose-dependent manner. On the LPS-induced RAW264.7 cells, APR essential oil reversed LPS-suppressed N-palmitoylethanolamide (PEA) contents in a dose-dependent manner and reduced LPS-induced proinflammatory genes, TNF-alpha and IL-6. Moreover, APR essential oil reduced the mRNA expression of iNOS, subsequently reduced the release of NO, a classic inflammatory marker., Conclusion: The research demonstrated that the effect of APR on inflammation is mediated by the inhibition of NAAA activity, which increase the cellular endobioactor PEA levels and decrease proinflammatory factor. The results suggest that APR can serve as a nature NAAA inhibitor.