Extraction of raspberry ketone from red raspberry and its intervention in the non-alcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by diffused hepatocyte bullous fat in the liver, which is not caused by alcohol or drugs like amiodarone and tamoxifen. Presently, no drug is approved for NAFLD treatment. Therefore, it’s important to extract effective components from natural plants to alleviate NAFLD. In this study, we extracted and purified raspberry ketone, a natural phenolic compound from red raspberry (Rubus ideaus L.) by an ultrasonic-assisted ethanol extraction method. The structure of red raspberry ketone (RRK) was determined using Fourier-transform infrared spectroscopy and the purity of RRK was found as 80.06 ± 1.19%. After 28 days of intragastric administration of RRK, the bodyweight of NAFLD model rats decreased significantly (p < 0.05). Besides, the levels of low-density lipoprotein cholesterol, total cholesterol, and total triglyceride (TG) decreased and the content of high-density lipoprotein cholesterol in serum increased drastically. Moreover, the level of liver damage indicators (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and the levels of glucose, insulin, free-fatty acid, tumor necrotic factor-α in the liver decreased distinctly. The levels of TG and malondialdehyde in the liver decreased, whereas the levels of superoxide dismutase, total glutathione, and glutathione peroxidase drastically increased. We also found that RRK reduced the uneven size of liver cells and blurred boundaries of hepatic lobules, and alleviated hepatic steatosis and inflammation caused by NAFLD. We inferred that RRK could relieve NAFLD progression by regulating glucose and lipid metabolism and alleviating oxidative stress in vivo. This study sheds new light on the use of RRK as a functional food for NAFLD prevention.

Mechanistic pathway of herbs in the amelioration of NAFLD: A systematic review

“…It is noteworthy that all the studies cited in Table IV , examining the effects of herbal plant extracts on IR, found significant decreases in glucose and insulin levels, as well as IR with the oral administration of these herbal extracts, namely, Abroma augusta (28,81). Aralia elata (84)(85)(86), Crocus sativus (97)(98)(99), Cyclosorus terminans (100-102), Glossogyne tenuifolia (80,103), Morus latifolia (107,108), Panax notoginseng (109), Pluchea indica (114), and Rubus ideaus (117,118), Trigonella foenum-graecum (119)(120)(121).…”

“…Inflammation. The oral administration of extracts from various herbs, such as Antidesma bunius (83), Cassia obtusifolia (87), Crocus sativus (97), Cyclosorus terminans (101), Glossogyne tenuifolia (103), Hibiscus sabdariffa (105), Panax notoginseng (109) and Rubus ideaus (117), were found to lead to an improvement in the levels of inflammatory markers linked to liver damage. These herbal extracts have been found to reduce the levels of pro-inflammatory cytokines and inflammation.…”

“…This is achieved by the suppression of inflammatory signaling pathways, controlling dyslipidemia, and enhancing liver function in patients with NAFLD (127). Herbal remedies, such as Antidesma bunius (83), Cassia obtusifolia (87), Crocus sativus (97), Cyclosorus terminans (101), Glossogyne tenuifolia (103), Hibiscus sabdariffa (105), Panax notoginseng (109) and Rubus ideaus L. (117), and (Table IV) have been shown to reduce the expression levels of hepatic inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-1β) and to further ameliorate liver fibrosis. Hou et al (109) demonstrated that 30 mg/kg Panax notoginseng ethanol extract reduced the levels of inflammatory markers, namely TNF-α, IL-6, IL-8, IL-1 and IL-1β, and no signs of toxicity were observed at the highest chronic dose evaluated at 1,200 mg/kg for 28 days.…”

“…Abroma augusta (28,81), Antidesma bunius (82,83), Cassia obtusifolia (87-89), Curuma longa (94-96), Crocus sativus (97)(98)(99), Hibiscus sabdariffa (104,105), Rubus ideaus (117,118), and Trigonella foenum-graecum (119-121)_ were found to be safe at the highest toxicity dose evaluated and significantly reduce the levels of pro-oxidants, namely, malondialdehyde, ER stress, ROS and oxidative end products, such as 4-hydroxynonenal (Table IV).…”

Physiological and transcriptomic analysis reveal the crucial factors in heat stress response of red raspberry ‘Polka’ seedlings

“…Additionally, recent studies have revealed that raspberry ketones in cranberries can reduce non-alcoholic fatty liver disease by regulating glycolipid metabolism and reducing oxidative stress. Furthermore, raspberry leaf extract showed antioxidant, antibacterial, and anti-inflammatory activities ( Ma et al., 2022 ; Maslov et al., 2022 ). The high nutritional and medicinal value of raspberries opens possibilities for further development of therapeutics against lifestyle diseases gaining popularity worldwide, giving it the reputation of being the “fruit of life”.…”