Hanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, Korea.
College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 54538, Korea.
Nutrients. 2021 Sep 30;13(10):3484. doi: 10.3390/nu13103484.
Cardiac hypertrophy can lead to congestive heart failure and is a leading cause of morbidity and mortality worldwide. In recent years, it has been essential to find the treatment and prevention of cardiac hypertrophy. Betulinic acid (BA), the main active ingredient in many natural products, is known to have various physiological effects. However, as the potential effect of BA on cardiac hypertrophy and consequent renal dysfunction is unknown, we investigated the effect of BA on isoprenaline (ISO)-induced cardiac hypertrophy and related signaling. ISO was known to induce left ventricular hypertrophy by stimulating the β2-adrenergic receptor (βAR). ISO was injected into Sprague Dawley rats (SD rats) by intraperitoneal injection once a day for 28 days to induce cardiac hypertrophy. From the 14th day onwards, the BA (10 or 30 mg/kg/day) and propranolol (10 mg/kg/day) were administered orally. The study was conducted in a total of 5 groups, as follows: C, control; Is, ISO (10 mg/kg/day); Pr, positive-control, ISO + propranolol (10 mg/kg/day); Bl, ISO + BA (10 mg/kg/day); Bh, ISO + BA (30 mg/kg/day). As a result, the total cardiac tissue and left ventricular tissue weights of the ISO group increased compared to the control group and were significantly reduced by BA treatment. In addition, as a result of echocardiography, the effect of BA on improving cardiac function, deteriorated by ISO, was confirmed. Cardiac hypertrophy biomarkers such as β-MHC, ANP, BNP, LDH, and CK-MB, which were increased by ISO, were significantly decreased by BA treatment. Also, the cardiac function improvement effect of BA was confirmed to improve cardiac function by inhibiting calcineurin/NFATc3 signaling. Renal dysfunction is a typical complication caused by cardiac hypertrophy. Therefore, the study of renal function indicators, creatinine clearance (Ccr) and osmolality (BUN) was aggravated by ISO treatment but was significantly restored by BA treatment. Therefore, it is thought that BA in cardiac hypertrophy can be used as valuable data to develop as a functional material effective in improving cardiac-renal dysfunction.
心肌肥厚可导致充血性心力衰竭，是全世界发病率和死亡率的主要原因。近年来，寻找心肌肥厚的治疗和预防方法至关重要。白桦脂酸（BA）是许多天然产物中的主要活性成分，已知具有多种生理作用。然而，由于 BA 对心肌肥厚和随之而来的肾功能障碍的潜在影响尚不清楚，我们研究了 BA 对异丙肾上腺素（ISO）诱导的心肌肥厚和相关信号的影响。ISO 通过刺激β2-肾上腺素能受体（βAR）诱导左心室肥厚。ISO 通过腹腔注射每天一次注射到 Sprague Dawley 大鼠（SD 大鼠）中，共 28 天以诱导心肌肥厚。从第 14 天开始，BA（10 或 30mg/kg/天）和普萘洛尔（10mg/kg/天）口服给药。该研究共分为 5 组，如下所示：C，对照组；Is，ISO（10mg/kg/天）；Pr，阳性对照，ISO+普萘洛尔（10mg/kg/天）；Bl，ISO+BA（10mg/kg/天）；Bh，ISO+BA（30mg/kg/天）。结果，与对照组相比，ISO 组的总心脏组织和左心室组织重量增加，BA 处理后明显减少。此外，通过超声心动图证实了 BA 改善 ISO 导致的心脏功能恶化的作用。ISO 增加的心肌肥厚生物标志物如β-MHC、ANP、BNP、LDH 和 CK-MB 经 BA 处理后显著降低。此外，BA 通过抑制钙调神经磷酸酶/NFATc3 信号改善心脏功能的作用也得到了证实。肾功能障碍是由心肌肥厚引起的典型并发症。因此，研究了 ISO 处理加重的肾功能指标肌酐清除率（Ccr）和渗透压（BUN），但 BA 处理显著恢复了这些指标。因此，BA 在心肌肥厚中可作为有价值的数据，用于开发有效改善心肾功能障碍的功能性材料。
