Smilax glabra Roxb. flavonoids protect against pathological cardiac hypertrophy by inhibiting the Raf/MEK/ERK pathway: In vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb., the dry rhizome of Sarsaparilla, which is also known as Tu fuling (TFL) in China, is a well-known traditional CHINESE medicine that is widely used for detoxication, relieving dampness and as a diuretic. We have previously shown that the extracted TFL flavonoids (designated TFLF) possess anti-cardiac hypertrophy effects in vitro. However, the anti-cardiac hypertrophy effects of TFLF in vivo and the underlying mechanisms remain to be elucidated. AIM OF THE STUDY: To reveal the underlying therapeutic mechanism of TFLF on cardiac hypertrophy by using transverse aortic constriction (TAC) model and cellular assays in vitro. MATERIAL & METHODS: Cardiac hypertrophy was replicated by TAC surgery in rats or by isoprenaline treatment of rat H9C2 myocardial cells in vitro. Cardiac structure and function were evaluated by echocardiographic and hemodynamic examinations in vivo and histological analysis of tissues ex vivo. Biochemical kits and quantitative PCR were used to analyze markers of cardiac hypertrophy. Expression and phosphorylation of key proteins in the Raf/MEK/ERK pathway were quantified by Western blotting. We further confirmed our findings in H9C2 rat cardiomyocytes treated with isoprenaline and the ERK inhibitor in vitro. RESULTS: TFLF attenuated cardiac hypertrophy and fibrosis and improved cardiac dysfunction in TAC rats. TFLF treatment induced a strong reduction in serum NT-proBNP levels. Cardiac hypertrophy marker gene (ANP, BNP and ß-MHC) expression and the phosphorylation levels of c-Raf and ERK1/2 were decreased by TFLF treatment. TFLF also protected H9C2 cells from isoprenaline-induced hypertrophy in vitro via a similar molecular mechanism as that observed in the rat heart. Moreover, pretreatment with TRLF and the ERK inhibitor further inhibited the mRNA overexpression of hypertrophic genes in vitro. CONCLUSIONS: TFLFs may protect against pathological cardiac hypertrophy via negative regulation of the Raf/MEK/ERK pathway. Thus, TFLFs are implicated as a potential pharmacological agent for treating cardiac hypertrophy in clinical practice.

Mirabilite with Ice Pack after Total Knee Arthroplasty: A Randomized Controlled Trial Study.

BACKGROUND: Total knee arthroplasty (TKA) is a well-established procedure for end-stage arthritis of the knee with complications such as swelling and pain. The aim of this study is to estimate the effect of mirabilite with ice pack versus ice pack in relieving pain, swelling, range of motion (ROM), and serum CRP level on patients after TKA. METHODS: Eighty patients undergoing primary unilateral TKA were randomly assigned to two groups (MIP group and WIP group). We used VAS to measure knee pain at 24 h, 48 h, and 72 h after the surgery, respectively. Knee swelling degree was evaluated by measuring the girth of the leg at the center of the patella and 10 cm above and below it at the same frequency. The active ROM of the knee was measured by using a universal goniometer of plastic material at 72 h postoperatively. The serum CRP level was also measured at 72 h postoperatively. RESULTS: The MIP group showed statistically significant lower knee girth at 48 h (p < 0.05) and 72 h (p < 0.05) postoperatively and VAS score at 72 h (p=0.018) postoperatively after TKA than the WIP group. The ROM of the MIP group was significantly wider than the WIP group (p=0.024). The CRP level (p=0.036) and length of stay (LOS) (p=0.037) of the MIP group were significantly lower than the WIP group. CONCLUSION: Mirabilite with ice pack after TKA showed superiority in relieving pain, reducing swelling, and improving ROM than ice pack only.