Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) often leads to sudden cardiac death. Persistent myocardial ischemia increases oxidative stress and impairs mitochondrial function, contributing significantly to postinfarction cardiac dysfunction and remodeling, and the subsequent progression to heart failure (HF). Tetrahydrocurcumin (THC), isolated from the rhizome of turmeric, has antioxidant properties and has been shown to protect against cardiovascular diseases. However, its effects on HF after MI are poorly understood. PURPOSE: The objective was the investigation of the pharmacological effects of THC and its associated mechanisms in the pathogenesis of HF after MI. METHODS: A total of 120 mice (C57BL/6, male) were used for the in vivo experiments. An MI mouse model was created by permanent ligation of the left anterior descending coronary artery. The mice received oral dose of THC at 120 mg/kg/d and the effects on MI-induced myocardial injury were evaluated by assessment of cardiac function, histopathology, myocardial oxidative levels, and mitochondrial function. Molecular mechanisms were investigated by intraperitoneal injection of 50 mg/kg of the SIRT3 selective inhibitor 3-TYP. Meanwhile, mouse neonatal cardiomyocytes were isolated and cultured in a hypoxic incubator to verify the effects of THC in vitro. Lastly, SIRT3 and Nrf2 were silenced using siRNAs to further explore the regulatory mechanism of key molecules in this process. RESULTS: The mouse hearts showed significant impairment in systolic function after MI, together with enlarged infarct size, increased myocardial fibrosis, cardiac hypertrophy, and apoptosis of cardiomyocytes. A significant reversal of these changes was seen after treatment with THC. Moreover, THC markedly reduced reactive oxygen species generation and protected mitochondrial function, thus mitigating oxidative stress in the post-MI myocardium. Mechanistically, THC counteracted reduced Nrf2 nuclear accumulation and SIRT3 signaling in the MI mice while inhibition of Nrf2 or SIRT3 reversed the effects of THC. Cell experiments showed that Nrf2 silencing markedly reduced SIRT3 levels and deacetylation activity while inhibition of SIRT3 signaling had little impact on Nrf2 expression. CONCLUSION: This is the first demonstration that THC protects against the effects of MI. THC reduced both oxidative stress and mitochondrial damage by regulating Nrf2-SIRT3 signaling. The results suggest the potential of THC in treating myocardial ischemic diseases.

[Qilin pills combined with bromocriptine for idiopathic hyperprolactinemic oligoasthenozoospermia].

OBJECTIVE: To observe the therapeutic effect of Qilin Pills combined with bromocriptine on idiopathic hyperprolactinemic (HPRL) oligoasthenospermia. METHODS: We conducted a randomized controlled study on 40 cases of idiopathic HPRL oligoasthenospermia, who were equally assigned to a trial group and a control group to be treated with Qilin Pills (6 g tid) combined with bromocriptine and bromocriptine alone, respectively, both for a course of 12 weeks. Then we observed the changes in the semen volume, sperm concentration, sperm motility and the levels of serum prolactin and testosterone, and compared the therapeutic results between the two groups before and after medication. RESULTS: Compared with the parameters before medication, both the trial and the control group showed significant improvement after treatment in sperm concentration ([11.60 +/- 3.90] x 10(6)/ml vs [28.10 +/- 13.50] x 10(6)/ml and [12.03 +/- 4.10] x 10(6)/ml vs [18.85 +/- 8.50] x 10(6)/ml), the percentage of grade a sperm ([8.75 +/- 6.65]% vs [24.35 +/- 13.25 ]% and [8.70 +/- 6.70] % vs [19.65 +/- 10.05]%), the percentage of grade a + b sperm ( [28.45 +/- 11.35]% vs [45.80 +/- 16.55]% and [27.65 +/- 10.65]% vs [35.66 +/-13.25]%), and sperm motility ([38.22 +/- 16.35]% vs [60.05 +/- 20.65]% and [37.25 +/- 15.75 ]% vs [52.65 +/- 18.25 ]%) (all P<0.01). No significant differences were found in semen volume (P>0.05). The serum prolactin levels were significantly decreased in the trial and control groups ([152.00 +/- 22.32] and [160.45 +/- 26.65] mIU/L), as compared with premedication ([482.25 +/- 65.32] and [477.32 +/- 60.25] mIU/L) (P<0.01), while the serum testosterone levels were remarkably higher ([16.35 +/- 5.52] and [11.15 +/- 4.65] nmol/L) than before treatment ([3.75 +/- 1.10] and [4.05 +/- 1.30] nmol/L) (P<0.01). There were no statistically significant differences in the serum prolactin and testosterone levels between the two groups after treatment (P>0.05). CONCLUSION: Qilin Pills combined with bromocriptine have a significantly better efficacy than bromocriptine alone in the treatment of idiopathic HPRL oligoasthenospermia.