CHAPTER 39
Beneficial Role of Chickpea (Cicer arietinum L.) Functional Factors in the Intervention of Metabolic Syndrome and Diabetes Mellitus Haji Akber Aisa*,†, Yanhua Gao*,†, Abulimiti Yili*,†, Qingling Ma*,†, Zhen Cheng*,† *
Key Laboratory of Chemistry of Plant Resources in Arid Regions, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China † Key Laboratory of Plants Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China
1. INTRODUCTION Diabetes is a serious, chronic disease that is now becoming globally prevalent. It has been estimated that 422 million adults were living with diabetes in 2014, compared to 108 million in 1980, rising from 4.7% to 8.5% in the adult population.1 Over the past two decades, the highest rates of diabetes increases are occurring in lower and upper-middle income countries, which undergoing transition to higher levels of human development are associated with changes in lifestyle, especially changes in diet and physical activity, as well as the population growth and aging.2 As the most populous country, the estimated prevalence of diabetes among a representative sample of Chinese adults was up to 113.9 million and 493.4 million people with prediabetes in 2010.3 Diabetes is increasingly becoming a burden on the public health, therefore, looking for risk factors for diabetes and investment in effective diabetes prevention and management has become necessary. Along with industrialization, socioeconomic development, and urbanization, many countries are undergoing various transitions, especially lifestyle such as communication, nutrition, and diet. Increased computerization and popularize use of automobiles, and improved transportation has caused many to reduce their physical activity and increase their sedentary time.4 With population growth came increased food production, causing a universal shift toward the increased consumption of processed foods—such as refined carbohydrates, sugary beverages, and animal source foods. These types of foods are linked with an excessive saturated fat, whole with high glycemic index, and glycemic load. In addition, traditional diets consisting of legumes, coarse grains, and other vegetables consumption were reduced. Decreased physical activity in combination with high-calorie diet intake increases the threat of susceptibility to a series of diseases involving Bioactive Food as Dietary Interventions for Diabetes https://doi.org/10.1016/B978-0-12-813822-9.00039-4
Copyright © 2019 Elsevier Inc. All rights reserved.
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hyperglycemia, dyslipidemia, insulin resistance, and so on. All of these mentioned symptoms are collectively described as metabolic syndrome, and are the strongest risk factors for impaired pancreatic β-cell function, which leads to type 2 diabetes.5 Emerging evidence from preventive medical studies and clinical trials indicates that an intensive diet and exercise program were effective in preventing type 2 diabetes.6, 7 Legumes are the staple food for a large part of the world population, especially in the developing countries, because their seeds provide valuable amounts of carbohydrates, proteins—which have an important composition of essential amino acids and vitamins.8 Pulses were considered a slow-glycemic index foods that are rich in bioactive properties such as dietary fiber, antioxidants, and phytochemicals, which were confirmed to have an effect on autoxidation, inhibitory α-glucosidase, improved dyslipidemia and reduced postprandial hyperglycemia.9 The genus cicer belongs to family leguminosae and comprises about 44 species.10 Chickpea (Cicer arietinum L.) was the most widely known species and the only cultivated plant in this genus from ancient times.11 Nowadays, chickpea is the world’s third most essential food legume and it is grown all over the five continents in around 50 countries, with 90% of its cultivates occurring in the developing countries.12 India is the largest producer of chickpea accounting for 67% (about 6.8million tons) of global production in 2013.13 As to records, Chickpea has been domesticated in Xinjiаng, China for over 2500 years,14 and now it is mainly cultivated in Mulei and Wushi counties in Xinjiang, the total planting areas of about 16,000 ha (no published data). In addition to its culinary usage, chickpea has been used as a traditional Uighur medicine for the treatment and prevention of many diseases, especially types 2 diabetes, hyperlipemia, bronchitis, and coprostasis.14 In the last several decades, legumes such as soybean, lentil, and chickpea have attracted considerable attention, as it was discovered that they possessed dietary origin hormones like diphenolic phytoestrogens (which include isoflavonoids). This may be the reason behind their ability to protect against hormone-dependent diseases such as breast, colorectal, and prostate cancer.15–17 Recently, large amount of investigations concentrated on bioactive components of chickpea involved the study of ingredients that be effective in correcting dyslipidemia or improving insulin resistance, adding chickpeas to foodstuff were able to increase nutritional value and also bulking of the fecal matter, and the mechanism of effects of chickpeas preventing diabetes.18 Given the voluminous reported the benefits of chickpeas, in this review we discuss the role of chickpea in the intervention of metabolic syndrome and type 2 diabetes.
2. PHYTOCHEMICALS, THE SECONDARY METABOLITES ISOLATED FROM CHICKPEA 2.1 The Content of Total Saponins and Its Structures As reported, saponins and isoflavones are considered to be important bioactive components contributing to the beneficial health effects of pulse consumptions are major types of constitutive plant secondary metabolites in edible legumes. Saponins derive their
Beneficial Role of Chickpea (Cicer arietinum L.) Functional Factors
name from their ability to form stable, soap-like foams in aqueous solutions. The results showed that the total saponins content of different varieties of chickpea varied greatly in different places, from 1%19 to 3.7%20 and another study observed a higher saponin content in chickpea (5.6%) than in other pulses such as soybean (4.3%), green beans (1.3%), red kidney beans (1.6%), and lentil (4.6%).21 In the earlier studies, the saponins preparation from chickpea was identified by the high-performance liquid chromatography (HPLC) analysis presence of two saponins, and were considered poorly resolved.22 Similar results have been observed in the investigation of saponins profiles in nine different legume seeds. The author using ultra-performance liquid chromatography (UPLC)-photodiodide array (PDA)-electrospray ionization (ESI)/mass spectrometry (MS) technique showed that chickpea contains mainly two saponins, soyasaponin Bb and soyasaponinβg(2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one conjugated group B soysaponin).23 The DDMP moiety is easily lost when it is treated with heat during extraction procedures. Recently, the studies showed more group B soysaponins (see from Fig. 1) isolated from chickpea that produced in Xinjiang, China.24
2.2 Isoflavones, Increased in Germination and Its Structures Isoflavones are the second bioactive phytochemistry components which were found in chickpea. The major isoflavonoids in chickpea are formononetin (40 -O-methyl ether of daidzein), biochanin A (40 -O-methyl ether of genistein), ononin (formononetin-7-O-glucoside), and sissotri (biochanin A-7-O-glucoside), and the minor are genistein, calycosin, and trifolirhizin.25 In addition, one dihydroxy flavanol and one isoflavane glycoside called cicerarietinuoside A are two new compounds, which maybe inducible plant natural products, were isolated from chickpea (see from Fig. 1).26, 27 The amount of isoflavone in chickpea varies according to the type of chickpea, geographic area of cultivation, and harvest year.28 It is reported that the total contents of isoflavoned in chickpea range from 0.016% to 0.06%, but after several days sprouted its was dramatically increased, from 2.4 0.11 to 4.86 0.14 mg/g during days 2 and 4, and the maximum amount (8.14 0.21 mg/g) of total isoflavones was obtained on day 8.29 Therefore, sprouting is effective method enrich contents of isoflavones in chickpea.
3. CHEMICAL COMPOSITIONS FROM CHICKPEAS 3.1 Total Protein and Peptides Legumes are rich sources of protein that enhance the protein content of cereal-based diets. Chickpeas have high-protein content, 17%–22% and 25.3%–28.9%, before and after dehulling, respectively.30 They are consumed as a meat substitute, particularly by vegetarians in the developing countries. The storage proteins of chickpea seed have been
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HO
HO
O
OH
HO
O
HO
O
O
O
OCH3
OCH3
OH
Biochanin A
Genistein
Daidzein HO
HO HO HO
O
O O
O
HO HO
HO
OH
OO
O
HO
O
O
OCH3
OCH3
Sissotrin OH O
O
H
OH
Formononetin
H H
OH
OH
H O
O
O
HO HO
H
O
OH
OH OCH3
H
O
OH
OH
2¢,4¢-dihydroxy-6,7-methlenedioxyflavanol
Cicerarietinuoside A
OH OH O O
HO OH O O O
H 3C HO
OH
HO OH
HO
HO CH2OH
O
OH
HO
OH
Chickpeaditerpenoid glycoside A
HO HO
Chickpeasaponin B1
Fig. 1 Chemical structures of the compounds isolated from Cicer arietinum L.
fractionated into globulin (salt soluble; 56%), albumin (water soluble; 12%), prolamin (alcohol soluble; 2.8%), glutelin (acid/alkali soluble; 18.1%), and residual proteins.31 Globulins represent about 50% of chickpea seed proteins and are composed of two major groups: the 11S (legumin) and the 7S (vicilin). Chickpea seed protein is comprised of globulins (56.0%), glutelins (18.1%), albumins (12.0%), prolamin (2.8%), and residual proteins. Chickpea globulins consist of the 11S legumin (320–400 kDa) and the 7S vicilin (145–190 kDa).32 Chickpea is a good source of functional potential of plant proteins and peptides, because of its higher contents, well-balanced amino acid composition, and bioavailability.33
3.2 Dietary Fiber and Oligosaccharides The profile of dietary fiber in edible plants is a group of nondigestible carbohydrates that comprises insoluble and soluble carbohydrates including no starch polysaccharides
Beneficial Role of Chickpea (Cicer arietinum L.) Functional Factors
(NSP) such as cellulose, pectin, gums, hemicelluloses, β-glucans, and fibers contained in whole grains. Other dietary fiber components are those not recovered by alcohol precipitation such as inulin, oligosaccharides, and fructans, lignin, and some resistant starch.34, 35 Pulses, including beans, chickpeas, lentils, and dry peas are a rich source of both soluble and insoluble dietary fiber, in addition to resistant starch, and galacto-oligosaccharide. The total dietary fiber (TDF) contents in chickpea ranged from 18% to 22%, of which the contents of insoluble fiber and soluble fiber were 10%–18%, and 4%–8%, respectively.36 In a study, legumes have been showed to have a high value of TDF, varying from the lowest value of 17.2% for kidney beans to the highest value of 24.9% for chickpea contrast with barley (15%), wheat (8.3%), and tubers like potato (9.4%).37 Chickpea also showed the highest value of total starch content (60.3%) in legumes, with higher value of the amylose (32.3%) among total starch. After conventional boiling and pressure cooking process, the content resistant starch in chickpea is varied from 4.6% to 4.8%, higher than the value of resistant starch in tubers like cooked potato that have a higher content of total starch (85.5%) in its raw state. The reason may be due to amylose, which plays an important role in the formation and development of RS during heat processing.37 Oligosaccharides are widely distributed in the legume seeds, and are considered the components that can cause flatulence after the intake of pulses.38 The total contents of oligosaccharides in chickpeas varied from different cultivars, and ranged from 5.54% to 8.82%. It included ciceritol (2.04%– 5.26%), stachyose (1.54%–3.18%), raffinose (0.42%–0.86%), and a small amount verbascose (0.25%–0.73%).39
4. PREVENTING METABOLIC SYNDROME AND MANAGEMENT OF DIABETES 4.1 Modulating the Glycemic Response Epidemiological studies have shown that postprandial hyperglycemia and glycemic load are associated with a variety of diseases, especially since it is an important contributing factor to the development of atherosclerosis in nondiabetic and increasing risk of coronary heart disease (CHD) of obesity and type 2 diabetes patients.40, 41 Postprandial hyperglycemia refers to plasma glucose concentrations after eating and is determined by many factors involving the timing, quantity and composition of the meal, carbohydrate content and composition of the meal, insulin and glucagon secretion, etc.42 The threshold for unacceptable postprandial glycemia defined by the American Diabetes Association and the World Health Organization is 8.89 mmol/L ( >160 mg/dL) at any time after the meal.43 The concept of a glycemic index was developed to provide a numeric classification of carbohydrate containing foods according to the glycemic response which was first proposed by Jenkins et al. in 36 years ago.44 Mounting evidence suggests that high glycemic index
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foods produce an initial period of high blood glucose and insulin levels and increases risk for obesity, type 2 diabetes, and heart disease.45 In contrast, low glycemic index diets have been shown to lower urinary C-peptide excretion in healthy subjects, improve glycemic control in diabetic subjects, and reduce serum lipids in hyperlipidemic subjects.46 The metabolic effects mainly attributable to a reduced rate of glucose absorption in the small intestine after the consumption of low glycemic index carbohydrate foods will reduce the postprandial rise in gut hormones and insulin. Among international tables of glycemic index, dry beans elicit a low glycemic response relative to other high carbohydrate containing foods because of their high fiber and high resistant starch content.47, 48 In humans, most dietary carbohydrates will be digested and converted into glucose and α-glucosidase, α-amylase, and lipase are the major enzymes involved in the hydrolysis of carbohydrates and fat.49 One of the therapeutic strategies to control postprandial hyperglycemia in diabetic is to inhibit carbohydrate-digesting key enzymes, α-glucosidase, and α-amylase enzymes, in order to slow down the intestinal absorption of glucose.50, 51 In one clinical trial, Volunteers consumed three different foods, white bread, wheat spaghetti, and wheatchickpea spaghetti, 2 h after eating, the blood was checked to evaluate the glycemic response. The result showed wheat-chickpea spaghetti reduced the hyperglycemia peak and the total hyperglycemia phase and this studies demonstrated that chickpea flour as one of the candidates for the low glycemic index was confirmed involved in more staple foods to low glycemic response.52 Similarly, in a later study by Moussou et al. which evaluated the quality of pulses flours such as chickpea, bean, and lentil changed in raw, toasted, and stored samples. The results showed inhibition of α-amylase in pulses flours was slightly augmented during processing. The results meaning content of undigested carbohydrates that reach the colon was increased, thus modulating the glycemic response.53 The inhibitory activities of chickpea on α-glucosidase, α-amylase, and lipase were evaluated and in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the α-glucosidase, α-amylase, and lipid activities. The tested chickpea showed inhibitory activity against α-glucosidase (IC50 2885 85.4 μg/ mL), α-amylase (IC50 167 6.12 μg/mL), and lipase were 9.74 1.09 μg/mL. This study demonstrates that chickpea may be a low-calorie food that can play a role in body weight management.54 The total saponin contents of chickpea are about 2.41%, and it has been reported to have beneficial effects toward diabetes complications in animal models. Hao et al. purified a proteinaceous α-amylase inhibitor from chickpea with the molecular mass was 25.947 kDa.55 The purified α-amylase inhibitor was classified as a legumins by analysis of the amino acid sequence of the polypeptide from it and the results of inhibiting activities experiments showed that purified α-amylase has the ability to inhibit α-amylase from plants and mammals, but incapable of inhibiting α-amylases from microbial. Hence, the protein from chickpea is a potential source in reduced postprandial blood glucose and weight loss.
Beneficial Role of Chickpea (Cicer arietinum L.) Functional Factors
4.2 Regulate Dyslipidemia The characteristic features of diabetic dyslipidemia including high plasma triglycerides (TGs) concentration, low lipoprotein cholesterol high-density lipoprotein cholesterol (HDL-C) concentration and increased concentration of small dense low-density lipoprotein cholesterol (LDL-C) particles.56 The combination of elevated serum TGs level and low HDL cholesterol level, commonly named atherogenic dyslipidemia which plays an important role in the risk of cardiovascular disease especially type 2 diabetic patients.57 The availability of multiple lipid-lowering natural products constitutes from plants had been demonstrated.58 The isolated chickpea saponins have been shown to prevent dietary hypercholesterolemia in the early studies.59 In the previous analysis, the main type of chickpea saponins belonged to group B soyasaponins and in a research study, the 20 hamsters were fed group B soyasaponins (containing no isoflavones), where after 4 weeks, it was shown the values of plasma total cholesterol (TC), nonHDL cholesterol, and TGs were lower by 20%, 33%, and 18%, respectively. The excretion of fecal bile acids and neutral sterols was significantly greater, so the mechanism of group B soyasaponin to lower plasma cholesterol levels may involve a greater excretion of fecal bile acids and neutral sterols.59 Isoflavones in chickpea suppressed 3T3-L1 adipocyte differentiation and lipid accumulation and stimulated glucose uptake the downregulation of PPARγ, C/EBP.60 In the experiment difference doses of biochanin A was administered to hyperlipidemia rats, after 30 days the levels of TC, TGs, LDL-C, HDL-C, and the whole blood viscosity and plasma viscosity were measured.61 The results showed that biochanin A can reduce the blood lipid levels, blood viscosity, and fibrinogen of hyperlipidemic in rats significantly. The legumin isolated from chickpea has been demonstrated to have the ability to regulate the lipid metabolism on hypercholesterolemic rats, in addition to its nutritional properties.62 The authors administered isolated 11S globulin from chickpea (300 mg/kg/day) and the simvastatin (50 mg/kg/day) by gavage to rats which were also fed a high-cholesterol (HC) diet to induce hypercholesterolemia separately, as compared to the normal diet and the only HC diet groups. After 28 days, analyses of TC, HDL-C, and TG in the plasma and TC and TG in the liver of animals. The results showed that the protein isolated from chickpea significantly reduced TC and TG in the liver relative to HC group, but the simvastatin has no effect. Nondigestible dietary fiber components such as oligosaccharides and resistant starch, caused a resistance to digestion in the human small intestine, allowing passage almost whole into the colon where they fermented by the intestinal microbiota to produce short-chain fatty acids (SCFAs), which including acetic, propionic, butyric, and valeric.63 Evidence demonstrated all SCFAs have antiinflammatory and antiproliferative properties, and increase viscosity of colonic mucosa.64 In addition, emerging studies demonstrate that diet significantly impacts the diversity of the intestinal microbiota, which subsequently influence the metabolome.35 Dai et al.65
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evaluated the effect of α-galactooligosaccharides from chickpea on the high-fat diet induced metabolic syndrome of mice, the results showed administration of α-GOS to model mice is able to positively regulate the intestinal microbiota such as incrassation of beneficial bifidobacterium and Lactobacillus composition, and lead to increased production of SCFAs, moreover, it also has significant effects on improved metabolic syndrome included regulate dyslipidemia and insulin resistance, and hypoglycemic.
4.3 Antioxidant Activity Reactive oxygen species (ROS), such as superoxide, hydroxyl radical, and hydrogen peroxide is produced by mitochondria and various enzymes. When ROS overproduction in vivo exceeds the buffering capacity of antioxidant enzymes and antioxidants, it leads to oxidative stress.66 ROS depletes cellular antioxidant defenses, reduce antioxidant enzyme activity, and alter membrane and protein structure, protein function.67 Glucose and its metabolites can react with hydrogen peroxide to form hydroxyl radical, so hyperglycemia induced oxidative stress.68 Overproduced oxidants also oxidized lipids, especially those containing polyunsaturated fatty acids to form reactive molecules such as malondialdehyde (MDA). A large number of studies have shown that induction of oxidative stress is a key process in the onset of diabetic complications.69 The total saponins that are prepared from chickpea were shown to improve type 2 diabetes mellitus rat models haslet antioxidant capacity.70 In the experiment, the activity of superoxide dismutase and hydrogen peroxidase from the rat’s liver, kidney, lung, muscle, and other tissues had been improved and the liver content of MDA was reduced significantly after the intake of the total saponins compared with the model group. The total saponins from chickpea showed has the capability of reducing blood glucose and repair the damaged pancreatic pathology on type 2 diabetes mellitus rats effectively.71 Germination of legume seeds is a process to produce sprouts and it was demonstrated nutritive value and contents of bioactive ingredients such as dietary fiber, free amino acids, and polyphenol compounds were raised during this process, meantime the capability of antioxidants was increased.72 In the study by Yili et al.,73 in which four antioxidant peptides were isolated from chickpea sprouts and with molecular weights of 1.148, 4.68, 5.41, and 9.086 kDa, respectively. That peptide with molecular weight 9.086 kDa was considered a new peptide rich in alanine by partial N-terminal amino acid sequences analysis and has antioxidant activity in vitro was IC50 156.2 μg mL1 (17.2 μmol L1) to the free radical of 2,20 -azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). Thus, the peptides that may be produced during chickpea germination were partially responsible for antioxidant activity of sprouts. Several studies showed chickpea protein hydrolysates contained bioactive peptides that possess biological activity include ace inhibitory, free radical scavenger, and ability of chelating metal ions.74 Kou et al.75 using alcalase and flavorzyme proteases, sequentially hydrolyzed
Beneficial Role of Chickpea (Cicer arietinum L.) Functional Factors
albumin derived from chickpea. After that, using chromatography methods to fractionate hydrolysate and obtain a purified peptide (named Fra.III) with molecular weight of 1155 Da. The results showed the Fra.III from chickpea albumin hydrolysates exhibited an excellent antioxidant activity through antioxidant ability and free radical scavenging activities assessment experiment in vitro, such as inhibition of hydroxyl radicals up to 74.56% at the concentration of 0.5 mg/mL, and the IC50 of against ABTS+ radicals was 0.97 mmol/L1. Li et al.76 prepared four peptide fractions isolates from chickpea protein by alcalase hydrolysis, in which fraction Fra.IV has been demonstrated with the antioxidant activity up to 81.13% in the linoleic acid oxidation system. Zhang et al.77 using consecutive chromatographic methods further purified this fraction and obtained an antioxidant peptide with a molecular weight of 717.37 Da. Antioxidant activity studies showed this peptide has the ability to quench the free radical sources such as DPPH, hydroxyl, and superoxide free radicals, chelating activities metal ions Cu2+ and Fe2+ were 76.92% and 63.08% at concentration of 50 μg mL1, and inhibit lipid peroxidation was greater than α-tocopherol. Moreover, it was demonstrated that the purified peptide has inhibition of the linoleic acid auto oxidation was up to 88.81% at the 8th day’s analysis. Chickpea protein hydrolysate displayed higher antioxidant than chickpea protein concentrate, in the support of studies that was also demonstrated by Ghribi et al.78 in which using alcalase enzymatic hydrolysis chickpea isolate protein and one fraction from hydrolysate exhibited the highest DPPH scavenging activity (54% at 1 mg mL1) after purified by size exclusion chromatography of Sephadex G-25. And then two new peptides were isolated and further purified using reversed-phase HPLC, the molecular masses, and amino acids sequences of the new peptides were determined by ESI-MS and ESIMS/MS, respectively. Their structures were identified as Asp-His-Gly and Val-Gly-Asp-Ile, the latter displayed the highest DPPH radical scavenging activity (67% at 200 μg mL1). The results suggest that the peptides from chickpea protein hydrolysate may be a potential antioxidant as functional food ingredients.
4.4 Improving Insulin Resistance Isoflavones belong to one class of phytoestrogens. Epidemiological surveys suggested that dietary phytoestrogens play a beneficial role in obesity and diabetes.79 Genistein and daidzein are the main isoflavones in soy and numerous evidences especially in animal models suggested that genistein has antidiabetic effects, such as protects pancreatic β-cells for damage and enhances proliferation, insulinotropic hormone, improved hyperglycemia and glucose tolerance, modulating hepatic glucose and lipid metabolism. The main form of isoflavones in chickpea is glycosides which could be converted to bioactive aglycones (genistein and daidzein) through bacterial β-glucosidases hydrolyzed in the intestines.80 Thus, the isoflavones in chickpea are one of the candidates associated with bioactive agents.
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5. CONCLUSIONS Chickpea may be considered as one of the functional foods needed to combat obesity prevalence in populations. Based on the above analysis, emerging evidences from animal models and in vitro experiments demonstrated that a wide variety of precursors of the biologically active compositions and phytochemicals from chickpea which have beneficial to prevent and management metabolic syndrome. The majority of total starch including slowly digestible starch, resistant starch, and amylose play an important role in mitigating postfeeding glucose excursions and slows glycemic response. The relative dietary fiber proportion constitute of carbohydrate in chickpea may reduce the risk of diabetes. Phytochemicals such as saponins and isoflavones are main secondary metabolites from chickpea, in which saponins been showed cause an increase in the fecal excretion of bile acids and isoflavones are critical for mediating the effects on β-cell proliferation, especially its structure has a hydroxyl group at C5 position. Chickpea protein hydrolysates may be potential free radical scavenger could be useful for improve immunity food products. Overall, chickpea plays a role in weight management and actions to address overweight and obesity are critical to prevent type 2 diabetes.
ACKNOWLEDGMENTS The studies were supported by “western young scholars program provided by CAS (No. CAS-LWC-2017-1),” and “the light of the western talent training plan (No. LHXZ-2014-01).”
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FURTHER READING 81. Gao Q, Wang W, Liu Y, et al. Isolation and identification of new diterpenoid from Cicer arierinum L. J Qingdao Univer (E&T). 2017;32(3):130–133. 82. Lee SO, Simons AL, Murphy PA, Hendrich S. Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters. Exp Biol Med. 2005;230(7):472–478.
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