ATP Citrate Lyase Inhibitor(University of Chinese Academy of Sciences)

The aim of this study is to develop roselle ( Hibiscus sabdariffa L.) extracts with high amounts of phytochemicals and in vitro antioxidant and antibacterial effects using green extraction technique. Roselle extract prepared by ultrasonic extraction with 80% ethanol and 1% hydrochloric acid (RSUEH) promoted the highest yield and high total phenolic (5.21 ± 0.05 g% gallic acid equivalent of dried extract), total flavonoid (1.29 ± 0.06 g% quercetin equivalent of dried extract), and total anthocyanin contents (0.21 ± 0.00 and 0.44 ± 0.00 g% cyanidin 3‐glucoside equivalent of dried extract determined by pH‐differential method with standard calculation and pH‐differential method with standard curve of cyanidin 3‐glucoside, respectively). From the validated high‐performance liquid chromatography analysis, delphinidin‐3‐sambubioside, delphinidin‐3‐glucoside, and cyanidin‐3‐glucoside were found to be the major anthocyanins in roselle extract. This extract exhibited moderate 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) scavenging effect (EC 50 289.61 ± 0.16 µg/mL) and strong inhibitory effects against Escherichia coli , Staphylococcus aureus , Staphylococcus intermedius , Proteus mirabilis , and Pseudomonas aeruginosa with the inhibitory concentration (IC 50 ) values in the range of 0.15 ± 0.05 to 4.64 ± 0.07 mg/mL and the minimum inhibitory concentration (MIC) values ranged from 1.66 ± 0.06 to 7.11 ± 1.05 mg/mL. From partial purification, fraction 28 (F28) contained higher amounts of all analyzed phytochemicals than roselle extracts and promoted stronger DPPH scavenging effects (EC 50 54.88 ± 2.23 µg/mL). F28 showed antibacterial activity with IC 50 values against all tested bacteria in the range of 0.19 ± 0.07 to 4.69 ± 0.09 mg/mL, and the MIC values ranged from 2.46 ± 0.08 to 6.24 ± 0.09 mg/mL.

Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17-28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.