A review of the pharmacological effects of Anacardiaceae family on controlling lipid profile (dyslipidemia)
Intan Tsamrotul Fu’adah1, Gofarana Wilar1*, Sri Adi Sumiwi1
1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Padjadjaran, West Java, Indonesia 45363.
Correspondence: Gofarana Wilar, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Padjadjaran, West Java, Indonesia 45363. [email protected]
ABSTRACT
Dyslipidemia is a chronic non-communicable disease (CNCD), induced by abnormalities in lipid metabolism resulting from excess intake of cholesterol, trans and saturated fats. Dyslipidemia is indicated by increased plasma total cholesterol, low-density lipoprotein (LDL) and triglyceride levels, and lower high-density lipoprotein (HDL) levels. Common treatments for dyslipidemia do not indicate ideal plasma cholesterol levels for every patient, which means better treatment is required. Some species of the Anacardiaceae family have pharmacological effects on controlling lipid distribution in dyslipidemia. Mango (Mangifera indica), cashew (Anacardium occidentale), and sumac (Rhus coriaria) are Anacardiaceae family species that people around the world widely consume. These species contain high fiber and saturated fat, which help improve body lipid levels. The literature used in this review was obtained from some databases, including PubMed, Google Scholar, and Science Direct. In this review, 15 species of Anacardiaceae will be reviewed for their antidyslipidemic activity in vivo and in vitro experiments for the past10 years. Some of the articles studied the mechanisms of the lowering-lipid profile, but the information remains unclear. Future trials with the study of the molecular mechanisms of those species are fascinating to understand.
Keywords: Anacardiaceae family, Pharmacological effect, Dyslipidemia, Lipid profile
Introduction
Dyslipidemia is one of the most CNCD caused by abnormalities in lipid metabolism resulting from excess intake of trans fats, saturated fats, and cholesterol [1]. This is characterized by an increase in plasma total cholesterol levels, low-density lipoprotein (LDL) and triglyceride levels, and a decrease in high-density lipoprotein (HDL) levels [2]. Abnormalities of these lipid profiles are the main risk factors in the onset of cardiovascular diseases such as atherosclerosis, hypertension, diabetes mellitus, coronary heart disease, and many others [3-5]. Although primary therapies for hyperlipidemia (such as statins) which are inhibitors of cholesterol biosynthesis have become an intervention, it has not demonstrated ideal cholesterol levels in every statin-treated patient, which requires improvement [6].
Studies on the pharmacological activities or therapeutic effects of plant extracts have been carried out [7]. One of them is the exploration of activity to improve the abnormalities of lipid levels in dyslipidemia. Anacardiaceae is a plant family, also known as a cashew family, consisting of 75 genera and over 700 species in the world. These plants are commonly found in tropical regions, consisting of fruiting plants widely consumed or as traditional medicine [8]. Some species of the Anacardiaceae family that are well known in the wider community are Anacardium occidentale (cashew), Mangifera indica (mango), and Rhus criteria (sumac). These species have been reported to have various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and even anti-diabetic [9-12]. In addition, their bioactive compounds and secondary metabolites that contribute to their pharmacological effects have been widely explored, including polyphenolic compounds, mangiferin, galoyl, ellagic acid, flavonoid, tocopherol, sterol, saponin, tannin, alkaloid, cardiac glycoside, and steroid [13-16].
Fifteen species of the Anacardiaceae family were selected to be reviewed for their pharmacological effects on controlling the lipid profile of dyslipidemia. Those species are Anacardium occidentale [17-21], Buchanania lanzan Spreng [22], Lennea edulis [23], Mangifera indica [24-28], Pistacia atlantica [29], Pistacia khinjuk [30], Pistacia lentiscus [31-33], Pleiogynium timorense [34], Protorhus longifolia [35], Rhus coriaria [36-40], Rhus mysurensis Heyne [41], Rhus verniciflua [42], Schinus terebinthifolius [43], Semecarpus anacardium [44, 45], and Spondias pinnata [46, 47]. As those species are varied, their substances are different, leading to their variety of pharmacological effects. So in this study, we will describe the differences, and maybe there will be similarities of the pharmacological effects from the species of Anacardiaceae.
In vivo evaluation
26 in vivo experiments of 15 Anacardiaceae family species selected to be reviewed in this article. This review of the in vivo evaluation of the Anacardiaceae family on controlling lipid profile is summarized in Table 1 below.
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Table 1. In Vivo Experiments of Anacardiaceae Family On Lipid Profile |
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Species |
Methods |
Plant part |
Parameter |
Doses |
Result |
Reference |
|
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Anacardium occidentale L. |
Cerebral Ischemic Rats Induced by the Occlusion of Right Middle Cerebral Artery |
Nuts |
TC, TG, LDL, HDL |
50 mg/kg BW |
↓TC 15,65 mg/dL (16,94%) ↓TG 25,96 mg/dL (36%) ↓LDL 8,73 mg/dL (40%) ↑HDL 11,92 mg/dL (27,5%) |
(Wattanathorn et al., 2017) [19] |
|
|
Dyslipidemic Female Wistar Rats |
Nuts |
TC, TG, LDL, HDL, VLDL |
400 mg/kg BW |
↓TC 32,43 mg/dL (34%) ↓TG 3,6 mg/dL (30,77%) ↓LDL 27 mg/dL (37,50%) ↓VLDL 0,9 mg/dL (20%) ↑HDL 2,34 mg/dL (35%) |
(Batista et al., 2018) [17] |
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|
Atherogenic Diet-Induced Obese Rats |
Fruits |
TC, TG, LDL, HDL, VLDL |
400 mg/kg BW |
↓TC 231,44 mg/dL (75,6%) ↓TG 120,35 mg/dL (63,1%) ↓LDL 57,72 mg/dL (75,3%) ↓VLDL 58,65 mg/dL (74%) ↑HDL 7,74 mg/dL (83,59%) |
(Jhansyrani et al., 2019) [20] |
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Dyslipidemic Rats |
Nuts |
TC, TG, HDL |
4000 mg/kg BW |
↓TG 40 mg/dL (28,57%) ↑HDL 20 mg/dL (66,67%) |
(Dias et al., 2019) [18] |
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Buchanania lanzan Spreng |
Streptozotocin-Induced Types I and II Diabetic Rats |
Leaves |
TC, TG, LDL, HDL |
100 mg/kg BW |
↓TC 51,34 mg/dL (37%) ↓TG 119,33 mg/dL (56%) ↓LDL 43,14 mg/dL (51%) ↑HDL 15,67 mg/dL (152%) |
(Sushma et al., 2013) [22] |
|
|
Lennea edulis |
Alloxan-Induced Diabetic Rats |
Leaves |
TC, TG, LDL, HDL, VLDL |
500 mg/kg BW |
↓TC 201,5 mg/dL (65%) ↓TG 223 mg/dL (65,7%) ↓LDL 179,23 mg/dL (80%) ↓VLDL 44,6 mg/dL (65,7%) ↑HDL 22,33 mg/dL (126%) |
(Banda et al., 2018) [23] |
|
|
Mangifera indica L. |
High Cholesterol Diet-Induced Hypercholesterolemic Rats |
Leaves |
TC and TG |
90 mg/kg BW |
↓TC 103,5 mg/dL (67%) ↓TG 133,6 mg/dL (63%) |
(Gururaj et al., 2017) [25] |
|
|
Hypercholesterolemic Diet-Induced Dyslipidemic Wistar Rats |
Leaves |
TC, TG, HDL |
400 mg/kg BW |
↓TC 100 mg/dL (50%) ↓TG 90 mg/dL (47%) |
(Sandoval-Gallegos, 2017) [24] |
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Pistacia atlantica |
Streptozocin-Induced Diabetic Mice |
Hulls |
TC, TG, LDL, HDL, VLDL |
200 mg/kg BW |
↓TC 48,2 mg/dL (36%) ↓TG 48,4 mg/dL (39%) ↓LDL 18,9 mg/dL (32%) ↓VLDL 9,7 mg/dL (39%) ↑HDL 3 mg/dL (12%) |
(Hosseini et al., 2020) [29] |
|
|
Pistacia khinjuk |
High Fat Diet-Induced Hyperlipidemic Rats |
Leaves |
TC, TG, HDL, LDL |
300 mg/kg BW |
↓TC 78,6 mg/dL (40,5%) ↓TG 183,4 mg/dL (42,3%) ↓LDL 91,8 mg/dL (57,5%) ↑HDL 38,8 mg/dL (100,9%) |
(Kamal et al., 2017) [30] |
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Pistacia lentiscus |
Streptozocin-Indiced Diabetic Mice |
Mastic gum (resin) |
TC, TG, LDL, HDL |
20 mg/kg BW |
↓TC 18,7 mg/dL (19%) ↓TG 75,4 mg/dL (63%) ↓LDL 15,7 mg/dL (44%) ↑HDL 12,11 mg/dL (32%) |
(Georgiadis et al., 2013) [31] |
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Egg Yolk Diet-Induced Hyperlipidemic Rabbits |
Fatty oil |
TC, TG, LDL, HDL |
2 mL/kg BW |
↓TC 2,37 g/L (34,9%) ↓TG 1,69 mg/L (50,75%) ↓LDL 2,20 mg/L (38,06%) |
(Djerrou, 2014) [32] |
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Alloxan-Induced Diabetic rats |
Leaves |
TC, TG, LDL, HDL |
300 mg/kg BW |
↓TC 40 mg/dL (40%) ↓TG 80 mg/dL (66%) ↓LDL 20 mg/dL (60%) |
(Cherbal et al., 2017) [33] |
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Pleiogynium timorense |
Hyperlipidemic Diet-Induced Hyperlipidemic Rats |
Seeds |
TC, TG, LDL, HDL, TL |
300 mg/kg BW |
↓TC 26,01 mg/dL (24%) ↓TG 31,93 mg/dL (34%) ↓LDL 27,1 mg/dL (48%) ↓TL 103,1 mg/dL (30%) ↑HDL 8,9 mg/dL (45%) |
(Said et al., 2018) [34] |
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Rhus coriaria L. |
High Cholesterol Diet-Induced Hypercholesterolemic Rats |
Fruits |
TC and TG |
200 mg/kg BW |
↓TC 52,62 mg/dL (34.17%) ↓TG 78,64 mg/dL (55.92%) |
(Shafiei et al., 2011) [36] |
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Dietary Rhus coriaria L. Powder Fed Chicken Broiler |
Fruits |
TC, TG, LDL, HDL, VLDL |
10 g/kg diet |
↓TC 47 mg/dL (31%) ↓TG 5 mg/dL (9,6%) ↓VLDL 3,4 mg/dL (28%) ↑HDL 7,6 mg/dL (31%) |
(Golzadeh et al., 2012) [37] |
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Streptozocidn-Induced Diabetic Type 2 |
Seeds |
TC, TG, LDL, HDL, VLDL |
400 mg/kg BW |
↓TC 69,7 mg/dL (38%) ↓LDL 61,36 mg/dL (43%) ↓VLDL 12,71 mg/dL (38%) |
(Anwer, 2012) [38] |
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Nicotinamide-Streptozotocin-Induced Type In Diabetic Male Mice |
Seeds |
TC, TG, LDL, HDL, VLDL |
300 mg/kg BW |
↓TC 24,02 mg/dL (28%) ↓TG 29,6 mg/dL (23%) ↓LDL 12,82 mg/dL (73%) ↓VLDL 5,92 mg/dL (23%) ↑HDL 14,89 mg/dL (84%) |
(Ahangarpour et al., 2017) [40] |
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High Fat Diet-Induced Hepatic Steatosis in Rats |
Fruits |
TC, TG, LDL, HDL |
250 mg/kg BW |
↓TC 5,8 mg/dL (7%) ↓TG 47 mg/dL (49%) ↓LDL 9,6 mg/dL (33%) ↑HDL 14,5 mg/dL (43%) |
(Pasavei et al., 2018) [39] |
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Rhus mysurensis Heyne |
Streptozotocin Induced Diabetes in Wistar Male Rats |
Roots |
TC, TG, LDL, HDL |
800 mg/kg BB |
↓TC 76,87 mg/dL (45,6%) ↓TG 41,73 mg/dL (29,6%) ↓LDL 78,73 mg/dL (65%) ↑HDL 10,08 mg/dL (51,6%) |
(Lamba et al., 2014) [41] |
|
|
Rhus verniciflua |
Diet-Induced Hyperlipidemia in Mice |
Rhus verniciflua Stokes (RVS) |
TC, HDL, LDL, Hepatic Cholesterol and Hepatic bile-acids |
1000 mg/kg BW |
↓TC 30 mg/dL (16,7%) ↓LDL 2 mg/dL (22,2%) ↓Hepatic Cholesterol 10 mg/dL (8,3%) ↑Hepatic bile-acids 75 µmol/g (37,5%) |
(Jeong et al., 2015) [42] |
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Schinus terebinthifolius |
Atherogenic Diet-Induced Obese Rats |
Fruits |
TC, TG, LDL, HDL |
50 mg/kg BW |
↓TC 40,3 mg/dL (32,4%) ↓TG 37,4 mg/dL (26,8%) ↓LDL 31 mg/dL (41,9%) ↑HDL 4,9 mg/dL (20,6%) |
(Feriani et al., 2021) [43] |
|
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Semecarpun anacardium |
Streptozocin-Induced Type 2 Diabetic Rat Model |
Nuts |
HDL, LDL, TC, TG |
200 mg/kg BW |
↓TC 94 mg/dL (42,5%) ↓TG 40 mg/dL (32%) ↓LDL 32 mg/dL (56,1%) ↑HDL 29 mg/dL (138%) |
(Khan et al., 2012) [44] |
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Hyperlipidemic Wistar Albino Rats |
Fruits |
TC, TG, VLDL |
45 mg/kg BW |
↓TC 17 mg/dL (22%) ↓TG 106 mg/dL (60.2%) ↓VLDL 20 mg/dL (56.8%) |
(Dwivedi et al., 2018) [45] |
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Spondias pinnata |
Streptozocin-Induced Diabetic Rats |
Barks |
TC, TG, LDL, HDL, VLDL |
1000 mg/kg BW |
↓TC 20,36 mg/dL (19,5%) ↓TG 9,37 mg/dL (24,3%) ↓LDL 19,64 mg/dL (25,5%) ↓VLDL 1,98 mg/dL (25,6%) ↑HDL 1,26 mg/dL (6,4%) |
(Attanayake et al., 2014) [46] |
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Alloxan-Induced Hyperglycemic Rats |
Fruits |
TC, TG, LDL, HDL, VLDL |
1000 mg/kg BW |
↓TC 7,67 mg/dL (14,7%) ↓TG 34,34 mg/dL (37,5%) ↓LDL 5,67 mg/dL (42,4%) ↓VLDL 6,86 mg/dL (37,4%) ↑HDL 4,86 mg/dL (23,7%) |
(Sutradhar et al., 2018) [47] |
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Notes: ↓ = decrease; ↑ increase
Abbreviations: TC= total cholesterol; TG= triglyceride; LDL= low-density lipoprotein; HDL= high-density lipoprotein; VLDL= very-low-density lipoprotein; TL = Total Lipid
Lipid profile
All species of the Anacardiaceae family possess promising antidyslipidemic activity characterized by improvement in lipid profile. Abnormalities of lipid profile including TC, TG, LDL, VLDL, and HDL are signs of dyslipidemia. It can be seen in Table 1. that most Anacardiaceae species exhibit the lowering effect of TC, TG, LDL, VLDL levels, and higher levels of HDL. Therefore, species from the Anacardiaceae family can cure abnormal lipid profiles in dyslipidemia, as described below.
Total cholesterol (TC)
Total cholesterol is the total amount of cholesterol in the body, including LDL and HDL. The high amount of cholesterol resulting in a high risk of CVD, particularly atherosclerosis. High cholesterol can accumulate fat in blood cells, decrease blood flow, and caused heart attack or stroke [48]. Cholesterol-lowering agent needed to prevent morbidity and mortality of cardiovascular disease (CVD). As shown in Table 1, all species of Anacardiaceae have a cholesterol-lowering effect in an animal model with a percent reduction of 7%-75%. Meanwhile, the percent reduction of a potent agent of lowering cholesterol (statin) is 29-40% [49]. 19 of 26 in vivo experiments, including ten species of Anacardiaceae, show their cholesterol-lowering effects above 29% means these are comparable to statin. It could be concluded that these Anacardiaceae species potentially be the new cholesterol-lowering agent.
Fruits extract of Anacardium occidentale show highest percent reduction of total cholesterol with 75,6% (231,44 mg/dL) at 400 mg/kg BW dose [20]. The main bioactive compound of Anacardium occidentale is a polyunsaturated fatty acid that contributes to lipid metabolisms. 9,12-octadecadienoic acid, 9,12-octadecadienoyl chloride, and 15-hydroxy-pentadecanoic acid are reported to be in this species. Potential mechanisms of polyunsaturated fatty acid in lowering cholesterol are by modifying the secretion of TG and cholesterol esterase, also increasing function of LDL receptor. These prevent the development of atherosclerosis, although the HDL level is low due to poor production and high catabolism of Apo A-l [50]. The molecular experiment of this species is still lacking. Further trial for the precise mechanism of action should be needed.
Triglyceride (TG)
Triglyceride (TG) is an ester derived from glycerol and three fatty acids. It is the major component of body fat in humans, along with vegetable fat. Plasma TGs are formed by exogenous, which is from the diet, and endogenous, which is from the liver carried in VLDL particles. It is correlated with several in vivo studies that are used a high-fat diet to induce dyslipidemia resulting in high TG levels [45]. High TG levels cause hypertriglyceridemia that concluded in dyslipidemia. TG levels are a secondary target for dyslipidemia therapy. Several prospective epidemiological studies have indicated elevated TG levels correlated with a high risk of heart disease [51]. Based on Table 1, the percent reduction of lipid profile by 15 species of Anacardiaceae family show varied with 9-66%. Compared to fibrate as a potent lipid-lowering agent that possesses reduction of TG levels 40-60% [52], 8 of 16 Anacardiaceae species elicit a percent reduction of more than 40%. This finding shows that Anacardiaceae species have the lipid-lowering effect comparable to potent agents, making it possible to improve the previous triglyceride-lowering agent with some side effects.
Among all the species, the Fatty oil of Pistacia lentiscus exhibit superior TG reduction with 66% and 80 mg/dL. This fatty oil reported as monounsaturated fatty oil, which is consists of high oleic acid. Monounsaturated fatty acid (MUFA) possesses lipid-lowering activity that leads to CVD protection [53]. Besides that, the fatty oil of Pistacia lentiscus consists of palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, gadoleic acid, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA). Djerrou et al., 2014) reported that a good PUFA/SFA ratio contributes to the lowering effect of this fatty oil. It could be accomplished by α-tocopherol and squalene that consist in the unsaponifiable fraction [32].
Low-density lipoprotein (LDL)
Low-density lipoprotein (LDL) is an influential lipoproteins group that delivers all fat molecules around the body to cells. LDL is oxidized when it is defected by free radicals in the arterial walls and leads to atherosclerosis [54]. LDLs are small dense fat molecules consist of high cholesterol esters that are formed by transporting the TG. This process involves a lipoprotein lipase enzyme (LPL) that carries TG from VLDL. Elevated LDL levels are indicated as familial hypercholesterolemia that causes the development of atherosclerosis CVD [55]. Fifteen species of Anacardiaceae reported has LDL-lowering activities with a percent reduction of 22-80%. This effect is comparable to a statin, which reduces LDL levels up to 60% [56]. Moreover, five species exhibit a percent reduction of 60% and more which are Anacardium occidentale (fruit), Lennea edulis (leave), Pistacia lentiscus (leave), Rhus coriaria L. (seed), and Rhus mysurensis Heyne (root) [20, 23, 33, 40, 41]. With this practical LDL-lowering effect, Anacardiaceae species could be a future better agent of controlling lipid profile in dyslipidemia.
Leaves extract of Lennea edulis has the highest percent reduction of LDL levels in an animal study with 80% and 179,23 mg/dL. These lipid-lowering effects could be associated with their secondary metabolites content. As reported by Banda et al., 2018, Lennea edulis contains flavonoids, saponins, tannins, alkaloids, cardiac glycosides, and steroids. Possible mechanisms of its effect are due to saponin content that previously reported inhibit the absorption of cholesterol and induce the secretion of cholesterol by excreting the bile acids [57]. Future trials to examine the molecular mechanisms of these effects should be needed.
Very-low density lipoprotein (VLDL)
VLDL is synthesized in the liver and released into the bloodstream carrying TG to body tissues. VLDL and LDL can cause plaque that is formed of fat, cholesterol, calcium, and other particles in the blood. The accumulation of fat results in reduced oxygen in the blood, leading to heart disease, especially in the arteries [58]. That means high levels of VLDL are abnormalities of a lipid profile that has to be cured. In the present study of Anacardiaceae family species, as shown in Table 1, 6 of 15 species possess a lowering effect of VLDL level with a percent reduction of 20-70%. Those species are Anacardium occidentale (nut and fruit), Lennea edulis (leave), Pistacia Atlantica, Rhus coriaria L. (seed), and Spondias pinnata (bark and fruit) [17, 20, 23, 29, 38, 40, 46, 47]. Atorvastatin as an antidyslipidemic agent has a percent reduction of VLDL levels as much as 60% [20] making these lipid-lowering effects of these species is comparable to atorvastatin.
Sumac (Anacardium occidentale) shows tremendous potential to be an alternative antidyslipidemic to improve the previous antidyslipidemic agent that still has disadvantage effects with a 74% reduction of VLDL levels. As reported by Dwivedi et al., 2018, the possible mechanism of the VLDL-lowering effect of sumac is by inhibiting the absorption of exogenous fat. In this process, there are two enzymes involved: pancreatic cholesterol esterase and acyl Co-A cholesterol acyltransferase enzyme (ACAT) Furthermore, sumac may inhibit these enzymes to elicits its lipid-lowering effect. Besides that, sumac is reported to contain numerous secondary metabolites that are ω-7 fatty acids, steroids, flavonoids, and polyphenolic compounds [59]. These compounds may contribute to the sumac lipid-lowering effect by several mechanisms. However, the precise molecular mechanisms of sumac still lack future trials to determine the mechanisms of action in this species that could be needed.
High-density lipoprotein (HDL)
HDL is composed of high protein and be the most heterogeneous lipoprotein. In addition, protein is the essential part of HDL particles that determine their function and structure. HDL plays a role in cholesterol efflux from peripheral cells and transports cholesterol to the liver. HDL level is used to calculate cardiovascular risk and is inversely associated with CVD and coronary death, independently from other traditional risk factors [60]. In dyslipidemia, HDL levels are lower than the normal range of a healthy person. Therefore, elevating HDL is the key to improve the abnormalities lipid profile of dyslipidemia. All Anacardiaceae species, as described in Table 1, except Mangifera indica and Rhus verniciflua show their effects on increasing the HDL levels with percent increasing 12-152% or almost twofold of normal levels. Compared to the potent agent, niacin, which can increase HDL level up to 20% [61], species Anacardiaceae show promising superior effects. It could be the new candidate for improvement antidyslipidemic, mainly focused on elevating HDL levels.
The highest increase is found in Pistacia atlantica extract with 152%. It has been reported that the primary chemical compound of this species is a flavonoid and phenolic compound. Phenolic compounds are well known to have inhibitory activity of HMG-CoA reductase (HMGR), the rate-limiting enzymes of cholesterol biosynthesis. HMGR is responsible for converting HMG-CoA to mevalonate, clear this enzyme is the initial precursor of cholesterol biosynthesis [62]. Inhibition of HMG-CoA reductase leads to an increase of peroxisome proliferator-activated receptor alpha (PPARα) expression and increases Apolipoprotein A-1 (Apo A-1) synthesis in the liver. This results in an enhancing effect on the formation of HDL precursors [63].
In vitro evaluation
Some of in vitro evaluation of anacardiaceae family species are described in Table 2 below. In this review, we explored the methods, result of study, and the mechanisms of action of these species.
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Table 2. In Vitro Experiments of Anacardiaceae Family On Lipid Profile |
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Species |
Part of Plant |
Methods |
Results |
Mechanism of Action |
Reference |
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Anacardium occidentale L. |
Leaves |
An in-cell western assay using Hep G2 cell line |
↑the concentration of Apo A-1, LCAT, SR-B1, ABCA1 and HL |
involve in reverse cholesterol transport process to reduce cholesterol metabolism in Hep G2 cell |
(Hasan et al., 2015) [21] |
|
Mangifera indica Linn. |
Leaves |
AMPK and PI3K/AKT signaling pathways |
↑AMPK ↓ACC (2.8-fold) ↓HSL (1.6-fold) ↓FAS (1.8-fold) ↓PPAR-c (4.0-fold). |
up-regulated AMPK and down-regulated expression of adipogenic genes (ACC, FAS, HSL) |
(Zhang et al., 2013) [26] |
|
Leaves |
Cholesterol esterase inhibition |
IC50 0.86 µg/ml |
inhibit the absorption of dietary cholesterol esters in the intestinal lumen |
(Gururaja et al., 2015) [25] |
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|
Leaves |
Adipogenic differentiation using 3T3-L1 cells |
inhibit lipid accumulation |
Increased HO-1 and PPAR-α expression |
(Sferrazzo et al., 2019) [27] |
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|
Protorhus longifolia |
Stem bark |
Pancreatic lipase and cholesterol esterase inhibitory assay |
IC50 = 0.04 – 0.31 mg/dL Percentage of adsorption ability on bile acid = ±60% ↓ lipid accumulation ±25% |
Inhibited lipid digestive enzymes and lipolysis, and binding bile acid |
(Mosa et al., 2014) [35] |
Notes: ↓ = decrease; ↑ increase
Abbreviations: Apo A-1 = apolipoprotein A-1; LCAT = lecithin cholesteryl acyl transferase; SR-B1 = scavenger receptor class B type 1; ABCA-1 = ATP binding cassette transporter A1; HL = hepatic lipase; AMPK = AMP-activated protein kinase; ACC= acetyl-CoA carboxylase; HSL= hormone sensitive lipase; FAS = fatty acid synthase; PPAR-γ= peroxisome proliferator-activated receptor γ; HO-1 = heme oxygenase-1
Reverse cholesterol transport (RCT) pathway
RCT is a mechanism of transporting the excess cholesterols from peripheral tissues back to the liver when cells are not used. HDL transports cholesterol from atherosclerotic plaques or other lipids back to the liver to be excreted within the RCT process. The cholesterol is ingested into HDL particles, esterified with a long-chain fatty acid by LCAT. Afterward, cholesterol is taken up within the liver and excreted in bile. This RCT is directed by a few proteins and enzymes such as Apo A-I, LCAT, SR-B1, HL, and LDL receptor (LDLR) [64]. As can be seen in Table 2, leaves extract of Anacardium occidentale reported elicits elevating the concentration of molecules that contribute in RCT pathway including Apo A-1, LCAT, SRB-1 ABCA-1, and HL [21]. Apo A-I is essential for nascent HDL formation, while high secretion of Apo A-1 is desired to increase the RCT. Other than that, LDLR correlates with HL, which is HL activates VLDL to form into LDL then undertaken by LDLR from plasma. Two more molecules involved in the RCT pathway are SRB-1, which removes cholesteryl esterase (CE) and carries out free cholesterol to be broken down in the liver, and ABCA-1, which is responsible for decreasing plaque atheroma formation [65]. These results suggested that Anacardium occidentale potentially as anticholesterol by increasing molecules involving in the RCT pathway.
AMPK and PI3K/AKT signaling pathways
TG metabolism involves various signaling pathways, including free fatty acids (FFA), phosphoinositide 3-kinases (PI3K), PPAR, adipocytokines, mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK) [66]. As demonstrated in Table 2, leaves extract of Mangifera indica significantly lowered the adipogenic genes expression, such as ACC, HSL, and FAS. AMPK activation via suppression of SREBP-1c and inhibition of enzymes involved in TG synthesis has been found in several previous studies [67]. This indicates a potential involvement of PI3 K/AKT and AMPK signaling pathway in the mechanism of this action.
Cholesterol esterase inhibitor
Cholesterol esterase works to hydrolyze long-chain fatty acid esters into cholesterol and fatty acids, which are then excreted in the intestinal lumen. This process is carried out because esters from cholesterol cannot be absorbed directly by intestinal epithelial cells, so they must be hydrolyzed into simpler molecules. If the enzyme cholesterol esterase is inhibited, cholesterol esters from food cannot be absorbed [68]. Gururaja et al., 2015 reported that leaves extract of Mangifera indica has an inhibitory activity of cholesterol esterase; thus, this extract exhibits hypolipidemic activity. In this study, a bioactive compound isolated from Mangifera indica is 3 β-taraxerol that showed cholesterol esterase inhibition with IC50 8,7 µg/mL [25]. 3 β-taraxerol is a sterol that competes with cholesterol within the mixed micelles, required for cholesterol absorption by the small intestine. Moreover, it leads to decreased cholesterol absorption from diet or even bile acid resulting in reduced cholesterol levels in blood [28].
Pancreatic lipase inhibitor
Enzymes involved in lipid digestion include pancreatic lipase and cholesterol esterase. If these enzymes are inhibited, the absorption of lipids from exogenous (food) will be reduced. As well as the inhibition of adipogenesis and lipolysis, through the inhibition of lipid-digesting enzymes is an effective means of treating hyperlipidemia and other related diseases [69]. Protorhus longifolia has been reported to contain triterpene, a bioactive compound that possesses many therapeutic effects. The triterpene isolated from this species is 3β-hydroxylanosta9,24-dien-21-oic acid and methyl-3β-hydroxylanosta-9,24-dien-21-oate show inhibitory activity against pancreatic lipase, CE, and HSL with IC50 0.04-0.31 mg/mL as presented in Table 1. These IC50 values are comparable to those of the positive controls used. Inhibitors of HSL are essential to drug targets in preventing hyperlipidemia and consequent peripheral insulin resistance [22]. Based on the results of this in vitro experiment, the triterpenes of Protorhus longifolia have inhibitory activity against pancreatic lipase and HSL. Therefore, it can be concluded that the two triterpenes have the potential to treat dyslipidemia through inhibition of exogenous fat and also lipolysis.
Conclusion
Various studies in animal (in vivo) and cell (in vitro) of 16 species of Anacardiaceae family selected in this review demonstrate their ability to improve the abnormalities lipid profile. Although their effects are varied, they depend on bioactive compounds that play a primary role in each activity. The polyphenolic compound of these species seems the most bioactive compound that exhibits many beneficial effects and possesses possible mechanisms of action. Four molecular mechanisms that have been reported to contribute to the antidyslipidemic activity of Anacardiaceae family species are inhibitory cholesterol esterase and pancreatic lipase, reverse cholesterol transport pathway, and AMPK PI3K/AKT signaling pathways. The lipid-lowering effect of improving lipid profile in dyslipidemia of these species shows a potent effect comparable to antidyslipidemic drugs such as statins, fibrates, and niacin. Therefore, the Anacardiaceae family species can be new drug candidates in the treatment of dyslipidemia.
Acknowledgments: We thank Universitas Padjadjaran for supporting the Author Processing Charge (APC) in this review article.
Conflict of interest: None
Financial support: None
Ethics statement: None
References
1. Fortes FS, Almeida AP De, Rosa C de OB, Silveira BKS, Reis N de A, Hermsdorff HHM. Dietary fat intake and its association with adiposity and inflammatory markers in individuals at cardiometabolic risk. Int J Cardiovasc Sci. 2020;33(5):447-56.
2. Warditiani NK, Susanti NMP. Antidyslipidemia activity of ethanol, methanol, and ethyl acetate extract of Zingiber montanum rhizome. Res J Pharm Technol. 2018;11(4):1381-5.
3. Nirwan R, Singh D. Distribution of lipids and prevalence of dyslipidemia among Indian expatriates in Qatar. J Lipids. 2021;2021.
4. Alanazi A, Alghanim MH, Alamer AJ, Alshaqaqiq MA, Al Busaeed MM, Alahmed AH, et al. Acute Myocardial Infarction Patients’ Knowledge Regarding the Modifiable Risk Factors of Heart Disease. Int J Pharm Res Allied Sci. 2020;9(2):210-6.
5. Permadi AW, Hartono S, Wahjuni ES, Lestari NK. The Combination of Physical Exercise Programs in Patients with Heart Failure. Int J Pharm Phytopharmacol Res. 2020;10(1):22-8.
6. Mohan V, Gayathri R, Jaacks LM, Lakshmipriya N, Anjana RM, Spiegelman D, et al. Cashew nut consumption increases HDL cholesterol and reduces systolic blood pressure in Asian Indians with type 2 diabetes: A 12-week randomized controlled trial. J Nutr. 2018;148(1):63-9.
7. Ebrahimi Y, Hasanvand A, Valibeik A, Ebrahimi F, Abbaszadeh S. Natural antioxidants and medicinal plants effective on hyperlipidemia. Res J Pharm Technol. 2019;12(3):1457-62.
8. Neves AM, Fontenelle RO dos S, Lopes FS, Mendes J de FS, Rodrigues ALM, Marinho MM, et al. Phenolic profile, antioxidant and antifungal activity of extracts from four medicinal plants of the Anacardiaceae family. Res Soc Dev. 2021;10(8):e44510817421.
9. Khalilpour S, Behnammanesh G, Suede F, Ezzat MO, Muniandy J, Tabana Y, et al. Neuroprotective and anti-inflammatory effects of Rhus coriaria extract in a mouse model of ischemic optic neuropathy. Biomedicines. 2018;6(2):1-13.
10. Nivedha K, Sivasakthi S, Prakash A, Devipriya N, Vadivel V. In vitro studies on antioxidant and cytoprotective activities of polyphenol-rich fraction isolated from Mangifera indica leaf. South African J Bot. 2020;130:396-406. doi:10.1016/j.sajb.2020.01.019
11. Arya D, Bhagour K, Sharma M, Gupta R. Phytochemical screening and antidiabetic activity of Mangifera indica (Seed kernels) in streptozotocin-induced diabetic rats. J Pharmacogn Phytochem. 2018;7(4):2521-7.
12. dos Santos GHF, Amaral A, da Silva EB. Antibacterial activity of irradiated extracts of Anacardium occidentale L. on multiresistant strains of Staphylococcus aureus. Appl Radiat Isot. 2018;140:327-32. doi:10.1016/j.apradiso.2018.07.035
13. Othman SOK, El-hashash MA, Hussein SAM, Amani MD, Rizk SA, Elabbar FA. Phenolic content as antioxidant and antimicrobial activities of Pistacia lentiscus Desf. (Anacardiaceae) extract from Libya. Egypt J Chem. 2019;62(1):21-8.
14. AB Z, CM da S, J BR, DR de M, J MS, M NE, et al. Extraction and assessment of oil and bioactive compounds from cashew nut (Anacardium occidentale) using pressurized n-propane and ethanol as cosolvent. J Supercrit Fluids. 2020;157:104686.
15. Alsamri H, Athamneh K, Pintus G, Eid AH, Iratni R. Pharmacological and antioxidant activities of Rhus coriaria L. (Sumac). Antioxidants. 2021;10(73):1-27.
16. Kulkarni VM, Rathod VK. Exploring the potential of Mangifera indica leaves extract versus mangiferin for therapeutic application. Agric Nat Resour. 2018;52(2):155-61. doi:10.1016/j.anres.2018.07.001
17. Batista KS, Alves AF, Lima MDS, Da Silva LA, Lins PP, De Sousa Gomes JA, et al. Beneficial effects of consumption of acerola, cashew or guava processing by-products on intestinal health and lipid metabolism in dyslipidaemic female Wistar rats. Br J Nutr. 2018;119(1):30-41.
18. Dias CCQ, Madruga MS, Pintado MME, Almeida GHO, Alves APV, Dantas FA, et al. Cashew nuts (Anacardium occidentale L.) decrease visceral fat, yet augment glucose in dyslipidemic rats. PLoS One. 2019;14(12):1-22.
19. Wattanathorn J, Thukham-Mee W, Muchimapura S, Wannanon P, Tong-Un T, Tiamkao S. Preventive effect of cashew-derived protein hydrolysate with high fiber on cerebral ischemia. Biomed Res Int. 2017;2017.
20. Jhansyrani T, Sujatha D, Bharathi K, Prasad K. Ethanolic extract of cashew apple inhibits lipid metabolism and ameliorates obesity in atherogenic diet-induced obese rats. Asian Pacific J Trop Biomed. 2019;9(10):405-14.
21. Hasan MKN, Kamarazaman IS, Arapoc DJ, Taza NZM, Amom ZH, Ali RM, et al. Anticholesterol activity of Anacardium occidentale linn. does it involve in reverse cholesterol transport? Sains Malaysiana. 2015;44(10):1501-10.
22. Sushma N, Venkata Smitha P, Venu Gopal Y, Vinay R, Srinivasa Reddy N, Murali Mohan C, et al. Antidiabetic, antihyperlipidemic and antioxidant activities of Buchanania lanzan spreng methanol leaf extract in streptozotocin-induced types I and II diabetic rats. Trop J Pharm Res. 2013;12(2):221-6.
23. Banda M, Nyirenda J, Muzandu K, Sijumbila G, Mudenda S. Antihyperglycemic and antihyperlipidemic effects of aqueous extracts of Lannea edulis in alloxan-induced diabetic rats. Front Pharmacol. 2018;9(September):1-8.
24. Sandoval-Gallegos EM, Ramírez-Moreno E, Lucio JG De, Arias-Rico J, Cruz-Cansino N, Ortiz MI, et al. In vitro bioaccessibility and effect of Mangifera indica (Ataulfo) leaf extract on induced dyslipidemia. J Med Food. 2017;21(1):47-56.
25. Gururaja GM, Mundkinajeddu D, Dethe SM, Sangli GK, Abhilash K, Agarwal A. Cholesterol esterase inhibitory activity of bioactives from leaves of Mangifera indica L. Pharmacognosy Res. 2015;7(4):355-62.
26. Zhang Y, Liu X, Han L, Gao X, Liu E, Wang T. Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/AKT signaling pathways. Food Chem. 2013;141(3):2896-905. doi:10.1016/j.foodchem.2013.05.121
27. Sferrazzo G, Palmeri R, Vanella L, Parafati L, Ronsisvalle S, Biondi A, et al. Mangifera indica l. Leaf extract induces adiponectin and regulates adipogenesis. Int J Mol Sci. 2019;20(13):3211.
28. Gururaja GM, Mundkinajeddu D, Kumar AS, Dethe SM, Allan JJ, Agarwal A. Evaluation of cholesterol-lowering activity of standardized extract of Mangifera indica in albino Wistar rats. Pharmacognosy Res. 2017;9(1):21-6.
29. Hosseini S, Nili-Ahmadabadi A, Mostafa Nachvak S, Dastan D, Moradi S, Abdollahzad H, et al. Antihyperlipidemic and antioxidative properties of Pistacia atlantica subsp. Kurdica in streptozotocin-induced diabetic mice. Diabetes, Metab Syndr Obes Targets Ther. 2020;13:1231-6.
30. Kamal F, Shahzad M, Ahmad T, Ahmed Z, Tareen RB, Naz R, et al. Antihyperlipidemic effect of Pistacia khinjuk. Biomed Pharmacother. 2017;96(July):695-9.
31. Georgiadis I, Karatzas T, Korou LM, Agrogiannis G, Vlachos IS, Pantopoulou A, et al. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice. J Med Food. 2013;17(3):393-9.
32. Djerrou Z. Anti-hypercholesterolemic effect of Pistacia lentiscus fatty oil in egg yolk-fed rabbits: A comparative study with simvastatin. Chin J Nat Med. 2014;12(8):561-6. doi:10.1016/S1875-5364(14)60086-8
33. Cherbal A, Kebieche M, Yilmaz EM, Aydoğmuş Z, Benzaouia L, Benguessoum M, et al. Antidiabetic and hypolipidemic activities of Algerian Pistachia lentiscus L. leaves extract in alloxan-induced diabetic rats. South African J Bot. 2017;108:157-62.
34. Said A. Antihyperglycaemic and antihyperlipidemic Activities of Pleiogynium timorense seeds and identification of bioactive compounds. Int J Biomed Eng Clin Sci. 2018;4(2):30-5.
35. Mosa RA, Naidoo JJ, Nkomo FS, Mazibuko SE, Muller CJF, Opoku AR. In vitro antihyperlipidemic potential of triterpenes from stem bark of Protorhus longifolia. Planta Med. 2014;80(18):1685-91.
36. Shafiei M, Nobakht M, Moazzam AA. Lipid-lowering effect of Rhus coriaria L. (sumac) fruit extract in hypercholesterolemic rats. Pharmazie. 2011;66(12):988-92.
37. Golzadeh M, Farhoomand P, Daneshyar M. Dietary Rhus coriaria L. powder reduces the blood cholesterol, VLDL-c, and glucose, but increases abdominal fat in broilers. South African J Anim Sci. 2012;42(4):398-405.
38. Anwer T. Antihyperglycemic, antidyslipidemic and antioxidant activity of Rhus coriaria in STZ-induced type 2 diabetic rats. African J Pharm Pharmacol. 2012;6(41):2851-5.
39. Ghaeni Pasavei A, Mohebbati R, Jalili-Nik M, Mollazadeh H, Ghorbani A, Nosrati Tirkani A, et al. Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats. Drug Chem Toxicol. 2021;44(1):75-83. doi:10.1080/01480545.2018.1533024
40. Ahangarpour A, Heidari H, Junghani MS, Absari R, Khoogar M, Ghaedi E. Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin-related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice. Res Pharm Sci. 2017;12(5):416-24.
41. Lamba SM, Sulakhiya K, Kumar P, Lahkar M, Barua CC, Bezbaruah B. Anti-diabetic, hypolipidemic and antioxidant activities of hydroethanolic root extract of Rhus mysurensis heyne in streptozotocin-induced diabetes in Wistar male rats. Pharmacogn J. 2014;6(3):62-71.
42. Jeong SJ, Park JG, Kim S, Kweon HY, Seo S, Na DS, et al. Extract of Rhus verniciflua stokes protects the diet-induced hyperlipidemia in mice. Arch Pharm Res. 2015;38(11):2049-58.
43. Feriani A, Contreras M del M, Tir M, Arafah M, G´Omez-Caravaca AM, Alwasel S, et al. Schinus terebinthifolius fruits intake ameliorates metabolic disorders, inflammation, oxidative stress, and related vascular dysfunction, in atherogenic diet-induced obese rats. Insight of their chemical characterization using HPLC-ESI-QTOF-MS / MS. J Ethnopharmacol. 2021;269:113701.
44. Khan HB, Vinayagam KS, Moorthy BT, Palanivelu S, Panchanatham S. Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a High fat diet: STZ-induced Type 2 diabetic rat model. Inflammopharmacology. 2013;21(1):37-46.
45. Dwivedi MK, Nariya M, Galib R, Prajapati PK. Anti-hyperlipidaemic effects of fresh and cured bhallataka kshaudra (Semecarpus anacardium L.) in animals. Indian J Nat Prod Resour. 2018;9(2):143-50.
46. Attanayake AP, Jayatilaka KAPW, Pathirana C, Mudduwa LKB. Antihyperglycaemic, antihyperlipidaemic and β cell regenerative effects of Spondias pinnata (Linn. f.) Kurz. bark extract on streptozotocin-induced diabetic rats. Eur J Integr Med. 2014;6(5):588-96. doi:10.1016/j.eujim.2014.03.010
47. Sutradhar A, Abu Saleh M, Binte Wahed T, Ahmed S, Kumar Kundu S, Prosun Sarkar A, et al. Investigation of antidiabetic and antilipidemic effect of fruit extract of Spondias pinnata (Amra) in alloxan-induced hyperglycemic rats. J Pharmacogn Phytochem. 2018;7(5):2785-9.
48. Kopin L, Lowenstein CJ. Dyslipidemia. Ann Intern Med. 2018;10-1.
49. Adams SP, Sekhon SS, Wright JM. Lipid-lowering efficacy of rosuvastatin. Cochrane Database Syst Rev. 2014;2014(11):CD010254.
50. Drouin G, Rioux V, Legrand P. The n-3 docosapentaenoic acid (DPA): A new player in the n-3 long-chain polyunsaturated fatty acid family. Biochimie. 2019;159:36-48. doi:10.1016/j.biochi.2019.01.022
51. Chang Y, Robidoux J. Dyslipidemia management update. Curr Opin Pharmacol. 2017;33:47-55. doi:10.1016/j.coph.2017.04.005
52. Oh RC, Lanier JB. Management of hypertriglyceridemia. Am Fam Physician. 2007;75(9):1365-71.
53. Nameni RO, Woumbo CY, Kengne APN, Zokou R, Tekou FA, Nguekouo PT, et al. Effects of stifled cooking on the quality and lipid-lowering potential of oils extracted from two species of pumpkin seeds (Citrullus lanatus and Cucumeropsis mannii). Investig Med Chem Pharmacol. 2021;4(1):1-7.
54. Geng J, Xu H, Yu X, Xu G, Cao H, Lin G, et al. Rosuvastatin protects against oxidized low-density lipoprotein-induced endothelial cell injury of atherosclerosis in vitro. Mol Med Rep. 2019;19(1):432-40.
55. Nimonkar AV, Weldon S, Godbout K, Panza D, Hanrahan S, Cubbon R, et al. A lipoprotein lipase-GPI-anchored high-density lipoprotein- binding protein 1 fusion lowers triglycerides in mice: Implications for managing familial chylomicronemia syndrome. J Biol Chem. 2020;295(10):2900-12. doi:10.1074/jbc.RA119.011079
56. Edwards JE, Moore RA. Statins in hypercholesterolaemia: A dose-specific meta-analysis of lipid changes in randomized, double-blind trials. BMC Fam Pract. 2003;4:1-19.
57. Navarro del Hierro J, Herrera T, Fornari T, Reglero G, Martin D. The gastrointestinal behavior of saponins and its significance for their bioavailability and bioactivities. J Funct Foods. 2018;40(September 2017):484-97. doi:10.1016/j.jff.2017.11.032
58. Lee HC, Lin YH. The pathogenic role of very-low-density lipoprotein on atrial remodeling in the metabolic syndrome. Int J Mol Sci. 2020;21(3):1-14.
59. Girija K, Lakshman K. Anti-hyperlipidemic activity of methanol extracts of three plants of Amaranthus in triton-WR 1339 induced hyperlipidemic rats. Asian Pac J Trop Biomed. 2011;1(SUPPL. 1):S62-5. doi:10.1016/S2221-1691(11)60125-1
60. Femlak M, Gluba-Brzózka A, Ciałkowska-Rysz A, Rysz J. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017;16(1):1-9.
61. Gordon SM, Amar MJ, Jeiran K, Stagliano M, Staller E, Playford MP, et al. Effect of niacin monotherapy on high-density lipoprotein composition and function. Lipids Health Dis. 2020;19(1):1-10.
62. Son KH, Lee JY, Lee JS, Kang SS, Sohn HY, Kwon CS. Screening of phenolic compounds with inhibitory activities against HMG-CoA reductase. J Life Sci. 2017;27(3):325-33.
63. McTaggart F, Jones P. Effects of statins on high-density lipoproteins: A potential contribution to cardiovascular benefit. Cardiovasc Drugs Ther. 2008;22(4):321-38.
64. Trajkovska KT, Topuzovska S. High-density lipoprotein metabolism and reverse cholesterol transport: Strategies for raising HDL cholesterol. Anatol J Cardiol. 2017;18(2):149-54.
65. Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport: Basic mechanisms and their roles in vascular health and disease. Circ Res. 2019;124(10):1505-18.
66. Zhang C, Zhang Q, Huang Z, Jiang Q. Adropin inhibited tilapia hepatic glucose output and triglyceride accumulation via AMPK activation. J Endocrinol. 2020;246(2):109-22.
67. Wang C, Li Y, Hao M, Li W. Astragaloside IV inhibits triglyceride accumulation in insulin-resistant HepG2 cells via AMPK-induced SREBP-1c phosphorylation. Front Pharmacol. 2018;9(APR):1-12.
68. Zhang HL, Wu QX, Wei X, Qin XM. Pancreatic lipase and cholesterol esterase inhibitory effect of Camellia nitidissima Chi flower extracts in vitro and in vivo. Food Biosci. 2020;37(September 2019):100682. doi:10.1016/j.fbio.2020.100682
Les F, Arbonés-Mainar JM, Valero MS, López V. Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. J Ethnopharmacol. 2018;220(March):67-74. doi:10.1016/j.jep.2018.03.029
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