A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action
Abstract
:1. Introduction
2. Rhubarbs as Ethnomedicinal Plants
3. Rhubarb-Based Preparations in a Contemporary Pharmaceutical and Food Market
4. Hypolipidemic Effects of Rhubarb: Not Only the Fibre
5. Molecular Targets for Rhubarb-Derived Substances
5.1. Inhibitory Effects on Key Enzymes Related to Lipid Absorption and Metabolism
5.2. Modulation of the Adipose Tissue Physiology
5.3. Metabolism and Glucose Level Regulation
5.4. Anti-Obesity Action of Rhubarb Extracts in Animal Studies
5.5. Anti-Obesity Action of Rhubarb Extracts in Clinical Trials
5.6. Laxative Effects of Rhubarb-Based Extracts and Preparations
6. Concluding Remarks
Funding
Conflicts of Interest
References
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The Examined Substances | Type of Study | Experimental Model, Doses and Concentrations | Main Effects of the Rhubarb Fibre and Stilbenes Administration | References |
---|---|---|---|---|
ANIMAL STUDIES | ||||
R. rhaponticum stalk-derived preparation containing 74% of dietary fibre/dry mass (incl. 66% insoluble and 8% soluble) | animal | mice fed with cholesterol-enriched diet with 5% of rhubarb stalk fibre, for 4 weeks | ↓ the acyl CoA: cholesterol acyltransferase (ACAT) activity; no effects on the cholesterol-rich diet enhancement of the β-hydroxyβ-methyl coenzyme A reductase (HMGR) activity | [22] |
R. rhaponticum stalk fibre | animal | cholesterol-fed C57BL/6J mice receiving the fibre-rich diet (50 g/kg b.w.) for 4 weeks | ↓ plasma cholesterol (−13%); ↓ the hepatic concentrations of total cholesterol (by 34%) and cholesteryl esters (by 34%); ↓ acyl CoA: cholesterol acyltransferase activity; ↓ the faecal bile acid loss; ↓the gallbladder bile acid pool | [19] |
R. rhaponticum stalk fibre | animal | the diabetes-prone and the streptozotocin-induced diabetic rats receiving the fibre-rich diet (50 g/kg b.w.) for 2 weeks | No effect on the plasma cholesterol and triacylglycerol levels in diabetic rats | [26] |
HUMAN STUDIES | ||||
the rhubarb-stalk-derived preparation containing 74% dietary fibre/dry mass (incl. 66% insoluble and 8% soluble) | human | Ten hypercholesterolemic men (BMI of 27.9 ± 3.8 kg/m2); 27 g of rhubarb fibre/day, for 4 weeks | ↓ serum total cholesterol (−8%) and LDL cholesterol (−9%); no changes in HDL cholesterol level; a return of the cholesterol-lowering effect to baseline after the fibre supplementation withdrawal for one month | [23] |
The Examined Substances | Experimental Model, Doses and Concentrations | Main Effects of the Stilbene Administration | References |
---|---|---|---|
Rhaponticin and rhapontigenin isolated from R. rhabarbarum roots | rats fed a high-cholesterol diet, followed by oral rhapontin or rhapontigenin treatment (1, 2.5 and 5 mg/kg b.w. (body weight)/day) | ↓ the serum lipid level; ↑ HDL cholesterol; improvement in the degenerating fatty liver structure; the aspartate aminotransferase (AST) and the alanine aminotransferase (ALT) levels comparable to the control group | [33] |
Rhaponticin from R. rhabarbarum roots | KK/Ay type 2 diabetic mice treated with rhaponticin (125 mg/kg b.w., 4 weeks) | ↓ the plasma triglyceride, LDL, cholesterol, non-esterified free fatty acids; ↓ lactate dehydrogenase, creatine kinase, AST and ALT activities | [34] |
Resveratrol | high-fat diet (HFD)-fed C57BL/6 J mice, a daily dose of 200 mg/kg b.w. of resveratrol, for 8 weeks | anti-hypercholesterolemic effects: improvement in serum lipid parameters, ↓ hepatic cholesterol, ↓ body weight, ↑ bile acid pool size, ↑ liver CYP7A1 mRNA expression and CYP7A1 enzyme activity | [30] |
apoE-deficient mice fed an atherogenic diet containing 0.02% resveratrol (w/w), for 12 weeks | ↓ the plasma total cholesterol, LDL cholesterol, non-high-density-lipoprotein cholesterol, apoB/apoA1 ratio, hepatic cholesterol and triglyceride; ↑ the plasma HDL cholesterol | [31] | |
mice fed standard diet plus resveratrol (4 g/kg of food to provide a 400-mpk dose), for 8 weeks | ↑ brown adipose tissue thermogenesis; ↑ mRNA of thermogenesis-related genes, incl. uncoupling protein 1 (UCP1), sirtuin 1 (SIRT1), phosphatase and tensin homolog (PTEN) and bone morphogenetic protein 7 (BMP-7) expression; ↓ fat accumulation in adipose tissue; ↓ total cholesterol and glucose levels in plasma | [35] | |
C57BL/6 mice fed a high-fat diet with a low dose of resveratrol, i.e., 200 mg/kg b.w./day (HFD-RES/L) or with a high dose of resveratrol, i.e., 400 mg/kg b.w./day (HFD-RES/H) | ↓ insulin resistance; ↑ expressions of pAkt, glucose transporter type 4 (GLUT4) and insulin receptor substrate 1 (IRS-1) in white adipose tissue (WAT); ↓ proinflammatory cytokine levels in serum; ↓ macrophage infiltration and C-C chemokine receptor type 2 (CCR2) chemokine expression in white adipose tissue (WAT) | [36] | |
rats with hyperlipidemia; a daily dose of 20 mg/kg b.w., of resveratrol, for 30 days | ↓ LDL and triglyceride levels; ↑ HDL levels in animals; | [32] |
Number of Participants (n), Resveratrol Doses and Study Duration | Participant Diagnosis | Main Effects of Resveratrol Supplementation in the Context of an Anti-Obesity Action | References |
---|---|---|---|
n = 11; 150 mg/day, for 30 days; a randomized, placebo-controlled, double-blind and cross-over study | obesity | Calorie-restriction-like effects; reduction in the sleeping and resting metabolic rate; ↓ intrahepatic lipid content, circulating glucose and triglycerides; ↓ inflammation markers; ↓ the systolic blood pressure; improvement in the HOMA index | [37] |
n = 24; 500 mg, 3 times/day, for 4 weeks; a randomized, placebo-controlled study | obesity (BMI > 30 kg/m2) | No effect on the total cholesterol, HDL, LDL, plasma triglyceride and blood pressure; no changes in the resting metabolic rate and lipid oxidation | [38] |
n = 28; 75 mg/day, for 6 weeks; a randomized, placebo-controlled, double-blind, cross-over study | obesity (BMI of 33.3 ± 0.6 kg/m2) | No effects on blood pressure; the flow-mediated dilatation (FMD) increased by 23% | [39] |
n = 45; 150 mg/day, for 4 weeks; a randomized, placebo-controlled, cross-over study | overweight or obesity (BMI of 25–35 kg/m2) | No effects on metabolic risk markers related to cardiovascular health | [40] |
n = 50; 500 mg/day, for 12 weeks; a randomized, placebo-controlled, double-blind study | overweight (BMI of 28.35 ± 3.49 and 28.75 ± 3.50 kg/m2, for the intervention and placebo group, respectively); non-alcoholic fatty liver disease | Reduction in BMI, waist circumference, HDL cholesterol and apo A1 both in intervention and placebo group; no differences in the above parameters between these groups; ↓ alanine transferase (ALT) and hepatic steatosis, compared to placebo | [41] |
n = 8; 1000 mg once a day for a week, then 2000 mg/day for the next week; a randomized, placebo-controlled study | overweight or obesity (BMI of 27.0–40.0 kg/m2), mild hypertriglyceridemia | No effects on insulin sensitivity and blood plasma triglyceride level; ↓ apoB-48 and apoB-100 production rate | [42] |
n = 10; 150 mg/a day, for 30 days; a randomized, placebo-controlled, double-blind, cross-over study | obesity (BMI of 32 ± 1 kg/m2) | Suppression of postprandial glucagon responses; no changes in fasting glucagon levels | [43] |
n = 32; 300 mg/day or 1000 mg/day for 90 days; a randomized, placebo controlled, double-blind study | overweight or obesity (BMI of 25.0–34.9 kg/m2) | ↓ glucose levels compared to placebo; no changes in blood pressure, body weight and waist circumference | [47] |
n = 11; 150 mg/day for 30 days; a randomized, placebo-controlled, double-blind, cross-over study | obesity (BMI of 28–36 kg/m2) | ↓ adipocyte size; changes in the adipose tissue morphology: reduction in the proportion of large and very large adipocytes; increase in small adipocytes; enhanced adipogenesis | [44] |
n = 23; 200 mg/day for 26 weeks, a placebo-controlled study | overweight (BMI of 25–30 kg/m2), healthy older adults (50–80 years) | ↓ body fat and leptin increase compared to placebo; no significant changes in body weight, BMI or blood pressure compared to placebo | [45] |
n = 161; 100 mg of resveratrol or 120 mg orlistat + 100 mg resveratrol (O-R group), 3 times a day, for 6 months; the participants consumed 500 k calories fewer than the usual diet; a randomized, placebo-controlled study | obesity (BMI of 30.0–39.9 kg/m2) | No significant changes in the group treated with resveratrol solely; ↓ BMI, waist circumference and fat mass in the orlistat-treated and O-R groups; the most effective one was the O-R combination | [55] |
n = 74; 150 mg or 1000 mg/day, for 16 weeks; a randomized, placebo-controlled study | obesity (BMI of 33.8 ± 0.44 kg/m2) | No effect on blood pressure, body composition, lipid deposition in the liver or striated muscle; no beneficial effect on glucose and lipid metabolism; 1000 mg dose increased the total cholesterol and LDL compared to placebo group | [46] |
n = 45; 75 mg twice a day, for 4 weeks; a randomized, placebo-controlled study | overweight or slight obesity (BMI of 28.3 ± 3.2 kg/m2) | No changes in plasma biomarkers of endothelial function or inflammation (both in the fasting state and postprandial phase); no changes in serum triglyceride and insulin level | [49] |
n = 38; a combination of 282 or 80 mg/day of the epigallocatechin-3-gallate and resveratrol (EGCG + RES), for 12 weeks; a randomized, placebo-controlled study | overweight or obesity (BMI of 29.7 ± 0.5 kg/m2) | ↓ visceral adipose tissue mass; no effect on insulin-stimulated glucose disposal, endogenous glucose production or lipolysis; | [53] |
n = 25; 282 or 80 mg/day of the EGCG + RES, for 12 weeks; a randomized, placebo-controlled study | overweight or obesity (BMI of 29.7 ± 1.1 kg/m2) | No changes in adipocyte size or surface area in abdominal subcutaneous adipose tissue; EGCG + RES downregulated pathways contributing to adipogenesis, cell cycle and apoptosis in the abdominal subcutaneous adipose tissue | [54] |
n = 112; 75 mg, twice a day, for 12 weeks; a randomized, placebo-controlled study | overweight or obesity (BMI ≥ 27 kg/m2), insulin resistance | No effects on cardiometabolic risk parameters and liver fat content | [48] |
n = 28; 1000 mg, twice a day, for 30 days; a randomized, placebo-controlled study | obesity (BMI of 30–40 kg/m2), metabolic syndrome | No changes in insulin resistance; no changes in adipose tissue metabolism | [50] |
n = 41; 150 mg/day, for 6 months; a randomized, placebo-controlled study | overweight or obesity (BMI of 27–35 kg/m2) | No effects on intrahepatic lipid level, energy metabolism, blood pressure, physical performance, quality of life and sleep | [51] |
n = 25; 250 mg/day, with physical training and diet, for 3 months; a randomized, placebo controlled, double-blind study | obesity (BMI ≥ 30 kg/m2), metabolic syndrome | Resveratrol potentiated beneficial effects of diet and physical training; ↓ VLDL and the total cholesterol in blood plasma | [52] |
Compound | Phytochemical Classification | Pancreatic Lipase Inhibitory Effects | References | |
---|---|---|---|---|
IC50 for the Examined Compound | IC50 for Orlistat | |||
Caffeic acid | Phenolic acids | 401.5 μM | 4.0 μM | [64] |
Chlorogenic acid | 110.0 μM 114.0 μM | 0.23 μM ND | [65] | |
p-Coumaric acid | 170.2 μM | 4.0 μM | [64] | |
Ellagic acid | 44.78 μM | 0.23 μM | [65] | |
Ferulic acid | 2.49 μM | 4.0 μM | [65] | |
Cyanidin-3-rutinoside | Anthocyanidins and their derivatives | 188.28 μM | ND | [67] |
59.4 μM | 31.7 μM | [68] | ||
Delphinidin-3-glucoside | 223.26 μM | ND | [68] | |
Procyanidin B2 | Proanthocyanidins | 7.96 μM | ND | [69] |
cis-Piceid | Stilbene derivatives | 76.1 μM | 0.7 μM | [70] |
trans-Piceid | 121.5 μM | 0.7 μM | [70] | |
trans-Resveratrol | >200 μM | 0.7 μM | [70] | |
Kaempferol-3-O-rutinoside | Flavonoids and their glycosides | 2.9 μM | 1.45 μM | [71] |
Quercetin | 421.1 μM | ND | [72] | |
146 μM | 1.45 μM | [71] | ||
Quercetin-3-O-β-D-glucuronide | 94 μM | ND | [73] | |
Rutin | 149 μM | 1.45 μM | [71] |
The Examined Rhubarb Compounds or Extracts | Experimental Model/Doses | Main Findings | References |
---|---|---|---|
desoxyrhapontigenin, emodin and chrysophanol, from roots of R. rhabarbarum | mice | ↓ postprandial hyperglycaemia by 35.8, 29.5, 42.3%, respectively | [109] |
70% ethanol Rhei Rhizoma extract | streptozotocin-induced diabetes in mice/5 mg/kg b.w. (body weight), 8 weeks | ↑ insulin-stimulated glucose uptake, ↓ carbohydrate digestion via inhibiting alpha-glucoamylase | [109] |
decoction from R. turkestanicum rhizome | diabetic rats/200–600 mg/kg b.w, 3 weeks | no effects on serum glucose, ↓ serum triglyceride level | [113] |
standardized extract from R. turkestanicum roots | streptozotocin-induced diabetes in rats/100, 200 and 300 mg/kg b.w., 4 weeks | ↓ blood glucose, ↓ diabetic changes in kidneys, liver and heart | [110] |
R. emodi extract | rats treated with glucocorticoids/10, 20 and 30 g of rhubarb powder/kg of diet, 8 weeks | ↓ blood glucose and immunity markers | [111] |
anthraquinone-glycoside preparation from R. palmatum | high-fat diet-induced type 2 diabetes mellitus in rats/100, 200, and 400 mg/kg b.w., 6 weeks | ↓ fasting blood glucose, ↓ total cholesterol and triglyceride levels, improvement in pathological changes in the liver, kidney and pancreatic tissues | [112] |
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Liudvytska, O.; Kolodziejczyk-Czepas, J. A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action. Nutrients 2022, 14, 2053. https://doi.org/10.3390/nu14102053
Liudvytska O, Kolodziejczyk-Czepas J. A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action. Nutrients. 2022; 14(10):2053. https://doi.org/10.3390/nu14102053
Chicago/Turabian StyleLiudvytska, Oleksandra, and Joanna Kolodziejczyk-Czepas. 2022. "A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action" Nutrients 14, no. 10: 2053. https://doi.org/10.3390/nu14102053
APA StyleLiudvytska, O., & Kolodziejczyk-Czepas, J. (2022). A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action. Nutrients, 14(10), 2053. https://doi.org/10.3390/nu14102053