(+)-Turicine

Stachydrine ameliorates pressure overload-induced diastolic heart failure by suppressing myocardial fibrosis.[Pubmed:28979698]

Am J Transl Res. 2017 Sep 15;9(9):4250-4260. eCollection 2017.

Stachydrine (Sta), a major constituent of Leonurus japonicus Houtt, has been reported to possess numerous cardioprotective effects. In this study, we evaluated the effect of Sta on pressure overload-induced diastolic heart failure in rats and investigated the mechanisms underlying the effect. Wistar rats were randomized to transverse aortic constriction (TAC) or sham operation. After 3 days, the rats that underwent TAC were randomized to treatment for a total of four experimental groups (n=10 each group): sham operation, TAC only, TAC + telmisartan (Tel), and TAC + stachydrine (Sta). After 12 weeks, we evaluated left ventricular hypertrophy, function, and fibrosis by echocardiography, pressure-volume loop analysis, and histology. In addition, levels of fibrosis-related proteins in the heart were determined by Western blot analysis. Our results showed that Sta significantly suppressed TAC-induced cardiac hypertrophy, and TAC-induced increases in heart weight/body weight and heart weight/tibial length. In addition, Sta attenuated TAC-induced decreases in left ventricular ejection fraction and improved other hemodynamic parameters. Compared with the TAC only group, rats treated with Sta exhibited significant decreases in interstitial and perivascular fibrosis, TGF-betaR1 protein levels, and phosphorylation of Smad2/3; however, protein levels of TGF-beta1, TGF-betaR2, and Smad4 did not differ significantly between the two groups. Taken together, our results demonstrate that Sta protects against diastolic heart failure by attenuating myocardial hypertrophy and fibrosis via the TGF-beta/Smad pathway.

Stachydrine ameliorates carbon tetrachloride-induced hepatic fibrosis by inhibiting inflammation, oxidative stress and regulating MMPs/TIMPs system in rats.[Pubmed:29378386]

Biomed Pharmacother. 2018 Jan;97:1586-1594.

Inflammation and oxidative stress are two crucial factors mediating liver fibrosis. Stachydrine (STA) is a naturally occurring compound extracted from a medicinal plant Leonuru heterophyllus, which can inhibit the proliferation and induce the apoptosis of breast cancer cells, relieve high glucose-induced endothelial cell senescence and isoproterenol-induced cardiac hypertrophy, and exert antitumor effects. However, its roles in hepatic fibrosis remain largely unknown. We aimed to evaluate the effect of STA on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and to elucidate the possible mechanisms. STA alleviated the pathological changes caused by CCl4 injection in livers compared to the normal liver. Hematoxylin-eosin staining further showed that STA treatment remarkably improved the liver histology, as evidenced by mitigated hepatic steatosis, necrosis, and fibrotic septa. STA reduced the liver/body weight ratio and the serum levels of aminotransferase, aspartate aminotransferase and alkaline phosphatase. It also significantly decreased collagen deposition and hydroxyproline level. Both mRNA and protein levels of alpha-SMA, alpha1(I)-procollagen and fibronectin were decreased by STA compared to those of the model group. STA significantly inhibited the expressions of inflammatory factors interleukin-6 (IL-6), IL-8, IL-1beta, tumor necrosis factor-alpha, inducible nitric oxide synthase and cyclooxygenase-2. It suppressed oxidative stress by decreasing malondialdehyde level as well as increasing glutathione level and enzymatic activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. STA also significantly increased the protein expressions of tissue inhibitor of metallopeptidase-1 (TIMP-1) and TIMP-2 but decreased those of matrix metalloproteinase-2 (MMP-2) and MMP-9, indicating excessive basement membrane in the fibrotic liver. Collectively, STA has potent protective effects on the liver, with therapeutic implication for liver fibrosis.

Stachydrine suppresses viability & migration of astrocytoma cells via CXCR4/ERK & CXCR4/Akt pathway activity.[Pubmed:29873242]

Future Oncol. 2018 Jun;14(15):1443-1459.

AIM: Pilocytic astrocytomas (PAs) are a common adolescent malignancy. We evaluated the effects of the betaine stachydrine on human PA cells as well as its associated molecular mechanism(s). MATERIALS & METHODS: Various experiments assessing stachydrine's effects on the human PA cell line Res186 were performed. RESULTS & CONCLUSION: Stachydrine dose-dependently suppressed proliferation and colony formation in Res186 cells with no such effect on normal astrocytes. Stachydrine downregulated CXCR4 transcription through enhancing IkappaBalpha-based NF-kappaB inhibition. Stachydrine promoted apoptosis and cyclin D1/p27(Kip1)-associated G0/G1 phase arrest in a CXCR4/ERK- and CXCR4/Akt-dependent manner. Stachydrine suppressed MMP-associated migration and invasiveness via inhibiting CXCR4/Akt/MMP-9/2 and CXCR4/ERK/MMP-9/2 pathway activity. Stachydrine inhibits the viability, migration and invasiveness of human PA cells via inhibiting CXCR4/ERK and CXCR4/Akt signaling.