Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/13/10/3484 |
| _version_ | 1797513554727796736 |
|---|---|
| author | Mi-Hyeon Hong Se-Won Na Youn-Jae Jang Jung-Joo Yoon Yun-Jung Lee Ho-Sub Lee Hye-Yoom Kim Dae-Gill Kang |
| author_facet | Mi-Hyeon Hong Se-Won Na Youn-Jae Jang Jung-Joo Yoon Yun-Jung Lee Ho-Sub Lee Hye-Yoom Kim Dae-Gill Kang |
| author_sort | Mi-Hyeon Hong |
| collection | DOAJ |
| description | 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 (β<sub>2</sub>AR). 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. |
| first_indexed | 2024-03-10T06:18:13Z |
| format | Article |
| id | doaj.art-6b846a540ae34852bfc7a02f142817f2 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T06:18:13Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-6b846a540ae34852bfc7a02f142817f22023-11-22T19:29:16ZengMDPI AGNutrients2072-66432021-09-011310348410.3390/nu13103484Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 SignalingMi-Hyeon Hong0Se-Won Na1Youn-Jae Jang2Jung-Joo Yoon3Yun-Jung Lee4Ho-Sub Lee5Hye-Yoom Kim6Dae-Gill Kang7Hanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaHanbang Cardio-Renal Research Center, Wonkwang University, Iksan 54538, KoreaCardiac 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 (β<sub>2</sub>AR). 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.https://www.mdpi.com/2072-6643/13/10/3484betulinic acidcardiac hypertrophyisoprenalinecalcineurin-NFATc3 signaling |
| spellingShingle | Mi-Hyeon Hong Se-Won Na Youn-Jae Jang Jung-Joo Yoon Yun-Jung Lee Ho-Sub Lee Hye-Yoom Kim Dae-Gill Kang Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling Nutrients betulinic acid cardiac hypertrophy isoprenaline calcineurin-NFATc3 signaling |
| title | Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling |
| title_full | Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling |
| title_fullStr | Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling |
| title_full_unstemmed | Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling |
| title_short | Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling |
| title_sort | betulinic acid improves cardiac renal dysfunction caused by hypertrophy through calcineurin nfatc3 signaling |
| topic | betulinic acid cardiac hypertrophy isoprenaline calcineurin-NFATc3 signaling |
| url | https://www.mdpi.com/2072-6643/13/10/3484 |
| work_keys_str_mv | AT mihyeonhong betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT sewonna betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT younjaejang betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT jungjooyoon betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT yunjunglee betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT hosublee betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT hyeyoomkim betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling AT daegillkang betulinicacidimprovescardiacrenaldysfunctioncausedbyhypertrophythroughcalcineurinnfatc3signaling |