13 research outputs found
The Protective Effect of Magnesium Lithospermate B on Hepatic Ischemia/Reperfusion via Inhibiting the Jak2/Stat3 Signaling Pathway
Acute inflammation is an important component of the pathogenesis of hepatic ischemia/reperfusion injury (HIRI). Magnesium lithospermate B (MLB) has strong neuroprotective and cardioprotective effects. The purpose of this study was to determine whether MLB had underlying protective effects against hepatic I/R injury and to reveal the potential mechanisms related to the hepatoprotective effects. In this study, we first examined the protective effect of MLB on HIRI in mice that underwent 1 h ischemia followed by 6 h reperfusion. MLB pretreatment alleviated the abnormal liver function and hepatocyte damage induced by I/R injury. We found that serum inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were significantly decreased by MLB during hepatic ischemia/reperfusion (I/R) injury, suggesting that MLB may alleviate hepatic I/R injury via inhibiting inflammatory signaling pathways. Second, we investigated the protein level of p-Jak2/Jak2 and p-Stat3/Stat3 using Western blotting and found that MLB could significantly inhibit the activation of the Jak2/Stat3 signaling pathway, which was further verified by AG490 in a mouse model. Finally, the effect of MLB on the Jak2/Stat3 pathway was further assessed in an in vitro model of RAW 264.7 cells; 1 µg/ml LPS induced the secretion of inflammatory mediators, including IL-6, TNF-α, and activation of the Jak2/Stat3 signaling pathway. MLB significantly inhibited the abnormal secretion of inflammatory factors and the activation of the Jak2/Stat3 signaling pathway in RAW264.7 cells. In conclusion, MLB was found for the first time to reduce inflammation induced by hepatic I/R via suppressing the Jak2/Stat3 pathway
Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling
Pulmonary fibrosis is a severe and irreversible interstitial pulmonary disease with high mortality and few treatments. Magnesium lithospermate B (MLB) is a hydrosoluble component of Salvia miltiorrhiza and has been reported to have antifibrotic effects in other forms of tissue fibrosis. In this research, we studied the effects of MLB on pulmonary fibrosis and the underlying mechanisms. Our results indicated that MLB treatment (50 mg/kg) for seven days could attenuate bleomycin (BLM)-induced pulmonary fibrosis by reducing the alveolar structure disruption and collagen deposition in the C57 mouse model. MLB was also found to inhibit transforming growth factor-beta (TGF-β)-stimulated myofibroblastic transdifferentiation of human lung fibroblast cell line (MRC-5) cells and collagen production by human type II alveolar epithelial cell line (A549) cells, mainly by decreasing the expression of TGF-β receptor I (TGF-βRI) and regulating the TGF-β/Smad pathway. Further studies confirmed that the molecular mechanisms of MLB in BLM-induced pulmonary fibrosis mice were similar to those observed in vitro. In summary, our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment
Pd-Catalyzed Acetoxylation of γ‑C(sp<sup>3</sup>)–H Bonds of Amines Directed by a Removable Bts-Protecting Group
Pd-catalyzed
acetoxylation of γ-CÂ(sp<sup>3</sup>)–H
bonds directed by Bts-protected amines using inexpensive PhIÂ(OAc)<sub>2</sub> as oxidant is reported. The Bts-protecting group is easily
introduced and removed under mild conditions. This protocol provides
an important strategy for the construction of γ-hydroxyl amine
derivatives
Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Depside Salts from Salvia miltiorrhiza
Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from <i>Hapsidospora irregularis</i>
Seven cyclic depsipeptides were isolated
from <i>Hapsidospora
irregularis</i> and structurally characterized as the calcium channel blocker leualacin
and six new analogues based on the NMR and HRESIMS data. These new
compounds were named leualacins B–G. The absolute configurations
of the amino acids and 2-hydroxyisocaproic acids were determined by
recording the optical rotation values. Biological studies showed that
calcium influx elicited by leualacin F in primary human lobar bronchial
epithelial cells involves the TRPA1 channel. Through genome sequencing
and targeted gene disruption, a noniterative nonribosomal peptide
synthetase was found to be involved in the biosynthesis of leualacin.
A comparison of the structures of leualacin and its analogues indicated
that the A<sub>2</sub> and A<sub>4</sub> domains of the leualacin
synthetase are substrate specific, while A<sub>1</sub>, A<sub>3</sub>, and A<sub>5</sub> can accept alternative precursors to yield new
molecules