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Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia and steatohepatitis in rats

September 2019
Journal of Food Biochemistry 43(5)

DOI:10.1111/jfbc.12986

Project: Natural products on liver damage

Authors:

Eduardo Fernandez-Martinez

Autonomous University of Hidalgo

Raquel Cariño

Autonomous University of Hidalgo

Show all 6 authorsHide

Chia seeds (Salvia hispanica L.) are rich in omega fatty acids. Dyslipidemia and steatohepatitis are diseases that require effective treatments in obese and non‐obese patients. The aim was to evaluate the effect of chia intake on acute tyloxapol (TI)‐induced dyslipidemia, on acute carbon tetrachloride (TC)‐induced steatohepatitis, and on mixed damage (TC+TI) in non‐obese rats. Four experimental groups were fed for 4 weeks a diet with established rodent food (DE), and four groups were fed a diet with 15% added chia (DC). Plasma samples were analyzed for total cholesterol, triglycerides, glucose, biochemical liver damage markers, and tumor necrosis factor‐α (TNF‐α). Liver samples were used to quantify glycogen, catalase, lipid peroxidation, and TNF‐α. A histopathological analysis was performed. DC intake partially or totally prevented steatohepatitis, and reduced lipids in the dyslipidemic groups. The hypolipidemic and hepatoprotective effects of chia may be correlated to its high content of α‐linolenic acid (omega‐3) and phenolics. Practical applications Metabolic syndrome is associated with non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH), which are currently the most common causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. Dyslipidemia is a significant risk factor for NAFLD and NASH. Non‐obese patients may have NAFLD or NASH. Metabolic syndrome and dyslipidemia are more strongly associated with NAFLD in non‐obese than in obese patients. This is the first study evaluating the hypolipidemic and hepatoprotective effects of chia seed intake on acute dyslipidemia and/or steatohepatitis caused by the individual or combined administration of the inducers tyloxapol and carbon tetrachloride, respectively, in non‐obese rats. The pharmacological effects of dietary chia are correlated to its high content of omega‐3 and omega‐6 (1:1), protein, dietary fiber, and phenolics. The results suggest that inclusion of chia in diets of non‐obese patients with dyslipidemia and/or NAFLD/NASH may improve their health state and preventing cirrhosis or HCC.

Experimental design: groups were fed the diet of established rat pellets (DE) or the diet added with chia (DC). After 4 weeks of diets intake, animals were administered on the last day with vehicles, or tyloxapol (TI 400 mg/kg in saline i.p.) to induce dyslipidemia, or CCl4 (TC 2.5 ml/kg in mineral oil p.o.) to produce steatohepatitis, or both compounds to provoke a mixed damage, dyslipidemic and steatohepatitic group. After 24 hr the rats were sacrificed and samples of plasma and liver were taken for further biochemical, immunological, and histopathological analises

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Plasma cholestasis markers: (a) alkaline phosphatase (AP) and (b) γ‐glutamyl transpeptidase (GGTP) enzyme activities and (c) total bilirubins (TB) concentrations from rats fed established (DE) or chia (DC) diets and treated with vehicles, tyloxapol (TI), carbon tetrachloride (TC), or combined damage (TI+TC). Each bar represents the mean value of experiments performed in duplicate with samples from at least four animals ± SEM. (†) Different versus DE, (‡) different versus TI, (§) different versus TC, (¶) different versus TI+TC, p < 0.05. Student–Newman–Keuls test

…

Necrosis, functionality and inflammation indicators: (a) plasma alanine aminotransferase (ALT) enzyme activity, (b) hepatic glycogen, (c) plasma, and (d) hepatic TNF‐α levels from rats fed established (DE) or chia (DC) diets and treated with vehicles, tyloxapol (TI), carbon tetrachloride (TC), or combined damage (TI+TC). Each bar represents the mean value of experiments performed in duplicate with samples from at least four animals ± SEM. (†) Different versus DE, (‡) different versus TI, (§) different versus TC, (¶) different versus TI+TC, p < 0.05. Student–Newman–Keuls test

…

Hepatic oxidative stress markers: (a) lipid peroxidation (LP) degree and (b) catalase (CAT) enzyme activity from rats fed established (DE) or chia (DC) diets and treated with vehicles, tyloxapol (TI), carbon tetrachloride (TC), or combined damage (TI+TC). Each bar represents the mean value of experiments performed in duplicate with samples from at least four animals ± SEM. (†) Different versus DE, (‡) different versus TI, (§) different versus TC, (¶) different versus TI+TC, p < 0.05. Student–Newman–Keuls test

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Plasma dyslipidemia and metabolism indicators: (a) triglycerides (TG), (b) total cholesterol (CHOL), and (c) glucose (GLU) concentrations from rats fed established (DE) or chia (DC) diets and treated with vehicles, tyloxapol (TI), carbon tetrachloride (TC), or combined damage (TI+TC). Each bar represents the mean value of experiments performed in duplicate with samples from at least four animals ± SEM. (†) Different versus DE, (‡) different versus TI, (§) different versus TC, (¶) different versus TI+TC, p < 0.05. Student–Newman–Keuls test

…

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J Food Biochem. 2019;43:e12986. wileyonlinelibrary.com/journal/jfbc 

1 of 17

https://doi.org/10.1111/jc.12986

Received:11March2019

Revised:27J une2019

Accepted:30June2019

DOI: 10.1111/jfbc .12986

FULL ARTICLE

Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia

and steatohepatitis in rats

Eduardo Fernández‐Martínez1 | Ivet G. Lira‐Islas1 | Raquel Cariño‐Cortés1 |

Luis E. Soria‐Jasso1 | Elizabeth Pérez‐Hernández2 | Nury Pérez‐Hernández3

1Laboratory of Medicinal Chemistr y and

Pharmacology, Centro de Investigación

en Biología de la Reproducción, Área

AcadémicadeMedicina,Institutode

CienciasdelaSalud,UniversidadAutónoma

delEstadodeHidalgo,Pachuca,México

2Hospital de Ortopedia “Dr. Victorio de la

FuenteNar váez”,IMSS,CiudaddeMéxico,

México

3Programa Institucional de Biomedicina

Molecular, Escuela Nacional de Medicina y

Homeopatía,InstitutoPolitécnicoNacional,

CiudaddeMéxico,México

Correspondence

Eduardo Fernández‐Martínez, Laboratory

of Medicinal Chemistry and Pharmacology.

Centro de Investigación en Biología de la

Reproducción,ÁreaAcadémicadeMedicina,

Instituto de Ciencias de la Salud, Universidad

AutónomadelEstadodeHidalgo.C alleDr.

Eliseo Ramírez Ulloa no. 400, Col. Doctores,

PachucaHidalgo,42090,México.

Emails:efernan@uaeh.edu.mx,tomedyfm@

hotmail.com

Funding information

UniversidadAutónomadelEstadode

Hidalgo,Grant/AwardNumber:PAI-UAEH,

keyDI-IC SA-MED-SF-046,projectnumber3

Abstract

Chia seeds (Salvia hispanica L.) are rich in omega fatty acids. Dyslipidemia and

steatohepatitis are diseases that require effective treatments in obese and non‐obese

patients.Theaimwas toevaluatetheeffectofchiaintakeon acutetyloxapol(TI)-

induced dyslipidemia, on acute carbon tetrachloride (TC)‐induced steatohepatitis,

andonmixeddamage(TC+TI)innon-obeserats.Fourexperimentalgroupswerefed

for 4 weeks a diet with established rodent food (DE), and four groups were fed a

diet with 15% added chia (DC). Plasma samples were analyzed for total cholesterol,

triglycerides, glucose, biochemical liver damage markers, and tumor necrosis factor‐α

(TNF‐α).Liversampleswereusedtoquantify glycogen,catalase,lipidperoxidation,

and TNF‐α. A histopathological analysis was performed. DC intake partially or

totally prevented steatohepatitis, and reduced lipids in the dyslipidemic groups. The

hypolipidemic and hepatoprotective effects of chia may be correlated to its high

content of α‐linolenic acid (omega‐3) and phenolics.

Practical applications

Metabolicsyndromeisassociatedwithnon-alcoholicfattyliverdisease(NAFLD)and

non-alcoholicsteatohepatitis(NASH),whicharecurrentlythemost common causes

of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide.

Dyslipidemia is a significant risk factor forNAFLD and NASH. Non-obese patients

mayhaveNAFLDorNASH.Metabolicsyndromeanddyslipidemiaaremorestrongly

associatedwith NAFLD innon-obese thanin obesepatients.This is the first study

evaluating the hypolipidemic and hepatoprotective effects of chia seed intake on

acute dyslipidemia and/or steatohepatitis caused by the individual or combined

administration of the inducers tyloxapol and carbon tetrachloride, respectively, in

non‐obese rats. The pharmacological effects of dietary chia are correlated to its high

content of omega‐3 and omega‐6 (1:1), protein, dietary fiber, and phenolics. The results

suggest that inclusion of chia in diets of non‐obese patients with dyslipidemia and/or

NAFLD/NASHmayimprovetheirhealthstateandpreventingcirrhosisorHCC.

KEYWORDS

chia, dyslipidemia, fatty acids, fatty liver, omega‐3, steatohepatitis

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Jun 2018
PLANT FOOD HUM NUTR

In previous studies, it has not been reported that protein isolated from chia interferes favorably with antibacterial activity, and reduces cholesterol synthesis. The objective of this study was to determine whether commonly used commercial microbial proteases can be utilized to generate chia protein-based antibacterial and hypocholesterolemic hydrolysates/peptides, considering the effects of protein extraction method. Alcalase, Flavourzyme and sequential Alcalase-Flavourzyme were used to produce hydrolysates from chia protein (CF), protein-rich fraction (PRF) and chia protein concentrates (CPC1 and CPC2). These hydrolysates were evaluated for their antimicrobial activity against Gram-positive (G⁺) and Gram-negative (G⁻) microorganisms. The protein hydrolysates were purified by ultrafiltration through a membrane with 3 kDa nominal molecular weight, for evaluation of hypocholesterolemic activity. An inhibition zone was observed when the hydrolysate was tested against S. aureus, and minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were obtained. Peptides from chia protein with molecular mass lower than 3 kDa reduced up to 80.7% of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) enzymatic reaction velocity. It was also observed that, independent of the method used to obtain chia proteins, the fractions showed relevant bioactivity. Moreover, the intensity of the bioactivity varied with the method for obtaining the protein and with the enzyme used in the hydrolysis process. This is the first report to demonstrate that chia peptides are able to inhibit cholesterol homeostasis.

The Effect of Chia Seeds ( Salvia hispanica L.) Addition on Quality and Nutritional Value of Wheat Bread

Article

Full-text available

Dec 2017
J FOOD QUALITY

The aim of the study was to analyze and characterize the influence of chia seeds (CS) addition (0, 2, 4, 6, and 8%) on wheat bread properties. Bread properties that underwent evaluation included chemical composition, fatty acid composition, total phenolics content, volume, baking losses, crumb texture, and color and sensory analysis. The addition of CS decreased baking losses and the volume of bread. The color of the crumb with CS was much darker as compared with the control sample. The texture analysis showed that the CS caused a decrease in the hardness of the crumb. Most importantly, the addition of CS increased the nutritional value of the bread. Bread with CS contained more dietary fiber and mineral components. Moreover, it has been observed that in comparison to the control product bread with CS was characterized by a rich fatty acids composition and higher level of phenolic compounds. Most importantly, the results showed that the substitution of wheat flour with chia seeds up to 6% did not negatively affect the final product acceptance.

Balancing Herbal Medicine and Functional Food for Prevention and Treatment of Cardiometabolic Diseases through Modulating Gut Microbiota

Article

Full-text available

Nov 2017

It has become apparent that gut microbiota is closely associated with cardiometabolic diseases (CMDs), and alteration in microbiome compositions is also linked to the host environment. Next generation sequencing (NGS) has facilitated in-depth studies on the effects of herbal medicine and functional food on gut microbiota. Both herbal medicine and functional food contain fiber, polyphenols and polysaccharides, exerting prebiotics-like activities in the prevention and treatment of CMDs. The administrations of herbal medicine and functional food lead to increased the abundance of phylum Bacteroidetes, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella, while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut. Both herbal medicine and functional food interact with gut microbiome and alter the microbial metabolites including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), which are now correlated with metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). In addition, trimethylamine (TMA)-N-oxide (TMAO) is recently linked to atherosclerosis (AS) and cardiovascular disease (CVD) risks. Moreover, gut-organs axes may serve as the potential strategy for treating CMDs with the intervention of herbal medicine and functional food. In summary, a balance between herbal medicine and functional food rich in fiber, polyphenols and polysaccharides plays a vital role in modulating gut microbiota (phylum Bacteroidetes, Firmicutes and Firmicutes/Bacteroidetes ratio, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella) through SCFAs, BAs, LPS and TMAO signaling regarding CMDs. Targeting gut-organs axes may serve as a new therapeutic strategy for CMDs by herbal medicine and functional food in the future. This review aims to summarize the balance between herbal medicine and functional food utilized for the prevention and treatment of CMDs through modulating gut microbiota.

Present and emerging pharmacotherapies for non-alcoholic steatohepatitis in adults

Article

Nov 2018

Introduction: Multiple parallel factors are implicated in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). Currently recommended therapies for NASH include vitamin E and pioglitazone, besides dietary and lifestyle changes. Areas covered: This review focuses on the clinical development of several emerging drugs for the treatment of NASH and the impact of these drugs on current treatment standards. Expert opinion: Four drug classes (FXR agonists, CCR2/CCR5 antagonists, ASK1 inhibitors, and PPARα/δ agonists) have moved into phase 3 trials for their investigation as NASH treatments. Results from phase 2 trials of other therapeutic agents with other pharmacological actions are also expected. The importance of combinational therapies with synergistic benefits engaging different targets, is now understood. Furthermore, studies have determined that the Mediterranean diet is beneficial for patients with NAFLD, while the traditional Okinawan diet is also considered useful. In the future, it will be important to establish new biomarkers to assess NAFLD activity, furthermore non-invasive diagnostic methods will promote the development of new drugs for NASH.

Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links

Article

Aug 2018

Metabolic syndrome (MetS), today a major global public health problem, is a cluster of clinical, metabolic, and biochemical abnormalities, such as central adiposity, hypertension, insulin resistance, and dyslipidemias. These MetS-related traits significantly increase the risk of type 2 diabetes mellitus, adverse cardiac events, stroke, and hepatic steatosis. The pathogenesis of MetS is multifactorial, with the interplay of environmental, nutritional, and genetic factors. Chronic low-grade inflammation together with visceral adipose tissue, adipocyte dysfunction, and insulin resistance plays a major role in the progression of the syndrome by impairing lipid and glucose homeostasis in insulin-sensitive tissues, such as the liver, muscle, and adipocytes. Adipose-derived inflammatory cytokines and non-esterified fatty acids establish the link between central obesity IR, inflammation, and atherogenesis. Various studies have reported an association between MetS and related traits with single-nucleotide polymorphisms of different susceptibility genes. Modulation of cytokine levels, pro-oxidants, and disturbed energy homeostasis, in relation to the genetic variations, is described in this review of the recent literature, which also provides updated data regarding the epidemiology, diagnostic criteria, and pathogenesis of MetS.

Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia and steatohepatitis in rats

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