foods Review Bioactive Compounds and Biological Functions of Garlic (Allium sativum L.) Ao Shang 1, Shi-Yu Cao 1, Xiao-Yu Xu 1, Ren-You Gan 2,3,* , Guo-Yi Tang 1, Harold Corke 2, Vuyo Mavumengwana 4 and Hua-Bin Li 1,* 1 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China 2 Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China 3 Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China 4 DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, US/SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa * Correspondence: [email protected] (R.-Y.G.); [email protected] (H.-B.L.); Tel.: +86-21-3420-8517 (R.-Y.G.); +86-20-873-323-91 (H.-B.L.) Received: 27 May 2019; Accepted: 4 July 2019; Published: 5 July 2019 Abstract: Garlic (Allium sativum L.) is a widely consumed spice in the world. Garlic contains diverse bioactive compounds, such as allicin, alliin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, ajoene, and S-allyl-cysteine. Substantial studies have shown that garlic and its bioactive constituents exhibit antioxidant, anti-inflammatory, antibacterial, antifungal, immunomodulatory, cardiovascular protective, anticancer, hepatoprotective, digestive system protective, anti-diabetic, anti-obesity, neuroprotective, and renal protective properties. In this review, the main bioactive compounds and important biological functions of garlic are summarized, highlighting and discussing the relevant mechanisms of actions. Overall, garlic is an excellent natural source of bioactive sulfur-containing compounds and has promising applications in the development of functional foods or nutraceuticals for the prevention and management of certain diseases. Keywords: garlic; phytochemicals; organic sulfides; health benefits; antioxidant; anticancer; cardiovascular protection; antimicrobial 1. Introduction Garlic (Allium sativum L.) is a common spice with many health benefits, mainly due to its diverse bioactive compounds, such as organic sulfides, saponins, phenolic compounds, and polysaccharides [1–3]. Garlic is commonly consumed and has a long history of being utilized as a traditional medicine in China [4]. In recent decades, numerous studies have demonstrated the remarkable biological functions of garlic, including antioxidant, cardiovascular protective, anticancer, anti-inflammatory, immunomodulatory, anti-diabetic, anti-obesity, and antibacterial properties [5–11]. Investigations have increasingly focused on black garlic, a processed garlic product with increased polyphenol and flavonoid contents, as well as better antioxidant properties, compared to the fresh garlic [12]. In order to highlight the significance of garlic in human health, we searched high-quality studies from the last five years from the Web of Science Core Collection and reviewed the main bioactive compounds and biological functions of garlic, with special attention paid to the relevant mechanisms of actions. We hope that this review paper will attract more interest in garlic and provide updated scientific evidence for the better utilization of garlic in human health and disease management. Foods 2019, 8, 246; doi:10.3390/foods8070246 www.mdpi.com/journal/foods Foods 2019, 8, x FOR PEER REVIEW 2 of 30 paid to the relevant mechanisms of actions. We hope that this review paper will attract more interest in garlic and provide updated scientific evidence for the better utilization of garlic in human health and disease management. 2. Bioactive Compounds of Garlic Garlic has a variety of bioactive compounds, including organosulfur compounds, saponins, phenolic compounds, and polysaccharides [2,3,13,14]. The major active components of garlic (Figure 1) are its organosulfur compounds, such as diallyl thiosulfonate (allicin), diallyl sulfide Foods(DAS),2019 diallyl, 8, 246 disulfide (DADS), diallyl trisulfide (DATS), E/Z-ajoene, S-allyl-cysteine (SAC),2 ofand 31 S-allyl-cysteine sulfoxide (alliin) [15–18]. In general, organosulfur compounds in raw garlic have 2.higher Bioactive digestibility Compounds than those of Garlic in cooked garlic [19]. In addition, saponins were found to be more stable in the cooking process [20]. The total amount of saponin in purple garlic was almost 40 times higherGarlic than hasthat a in variety white garlic, of bioactive and several compounds, saponin including compounds organosulfur were only found compounds, to exist saponins,in purple phenolicgarlic, such compounds, as desgalactotigonin-rhamnose, and polysaccharides [2 ,3proto-desgalactotigonin,,13,14]. The major active proto-desgalactotigonin- components of garlic (Figurerhamnose,1) are voghieroside its organosulfur D1, sativoside compounds, B1-rhamnos such as diallyle, and thiosulfonate sativoside R1 (allicin), [2]. Moreover, diallyl sulfide garlic (DAS),contained diallyl more disulfide than 20 (DADS),phenolic compounds, diallyl trisulfide with (DATS), higher contents E/Z-ajoene, than S-allyl-cysteine many common (SAC), vegetables and S-allyl-cysteine[21]. The main phenolic sulfoxide compound (alliin) [15 was–18]. β-resorcylic In general, acid, organosulfur followed by compounds pyrogallol, in gallic raw garlicacid, rutin, have higherprotocatechuic digestibility acid, than as well those as in quercetin cooked garlic [22]. [19Fu].rthermore, In addition, garlic saponins polysaccharides were found were to be morereported stable to incontain the cooking 85% fructose, process 14% [20]. glucose, The total and amount 1% galactose of saponin [23]. in purple garlic was almost 40 times higher thanThe that effects in white of garlic,different and processing several saponin methods compounds on bioactive were components only found of to garlic exist in have purple been garlic, also suchstudied. as desgalactotigonin-rhamnose,For example, it was found proto-desgalactotigonin,that the 38 components proto-desgalactotigonin- of garlic changed after rhamnose, thermal voghierosidetreatment during D1, sativoside the processing B1-rhamnose, of black andgarlic sativoside [24]. In R1addition, [2]. Moreover, the polysaccharide garlic contained degraded more thanand 20the phenolic content compounds,of reducing withsugar higher increased contents during than th manye thermal common processing vegetables of [black21]. The garlic main [25]. phenolic Also, compoundincreasing temperature was β-resorcylic and decreasing acid, followed humidity by pyrogallol, enhance the gallic contents acid, rutin, of polyphenols protocatechuic and the acid, total as wellflavonoids as quercetin in black [22]. garlic Furthermore, [26,27]. garlic In the polysaccharides future, more were bioactive reported compounds to contain 85%produced fructose, in 14%the glucose,processing and of 1% garlic galactose should [23 be]. separated and identified. Figure 1. The chemical structures of the main organosulfur compounds in garlic. Figure 1. The chemical structures of the main organosulfur compounds in garlic. The effects of different processing methods on bioactive components of garlic have been also studied.3. Biological For example,functions it of was Garlic found that the 38 components of garlic changed after thermal treatment during the processing of black garlic [24]. In addition, the polysaccharide degraded and the content of3.1. reducing Antioxidant sugar Activity increased during the thermal processing of black garlic [25]. Also, increasing temperature and decreasing humidity enhance the contents of polyphenols and the total flavonoids The antioxidant activities of natural products have been widely evaluated, such as fruits, in black garlic [26,27]. In the future, more bioactive compounds produced in the processing of garlic vegetables, mushrooms, cereal, flowers, and wild fruits [28–34]. Accumulating studies have found should be separated and identified. that garlic has strong antioxidant properties. A study evaluated the antioxidant capacities of both 3. Biological functions of Garlic 3.1. Antioxidant Activity The antioxidant activities of natural products have been widely evaluated, such as fruits, vegetables, mushrooms, cereal, flowers, and wild fruits [28–34]. Accumulating studies have found that garlic has strong antioxidant properties. A study evaluated the antioxidant capacities of both raw and cooked garlic, and found that the raw garlic exhibited stronger antioxidant activity (by 1,1-diphenyl-2-picrilhydrazyl (DPPH) radical scavenging assay, 2,2’-Azino-bis(3-ethyl- Foods 2019, 8, 246 3 of 31 benzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay, and ferric ion reducing antioxidant power (FRAP) assay). Stir-fried garlic was also shown to have stronger antioxidant capacities (by β-carotene bleaching), indicating that the processing could affect the antioxidant property of garlic [35]. In another study, the results of DPPH and oxygen radical absorption capacity (ORAC) assays showed that the ethanolic extract of garlic sprouts exhibited stronger antioxidant activities than the ethanolic extract of raw garlic [36]. In addition, the antioxidant properties of aged garlic were found to be 2+ higher than fresh garlic by DPPH, ABTS, FRAP, H2O2 scavenging, and Fe chelating assays [37]. Compared with multi clove garlic extract, single