Silymarin is the main bioactive constituent found in the MT fruit oilseed cake (Vargas-Mendoza et al., 2014) (Table 2). It is a complex flavonolignan responsible for the plant’s hepatoprotective properties. Silymarin is a complex flavonolignan comprising silybin A and B, isosilybin A and B, silydianin, silychristin, isosilychristin, and taxifolin, a flavonoid precursor (Pradhan and Girish, 2006; Vargas-Mendoza et al., 2014). The silibinin, a mixture of silybins A and B, is also named silibinin. The ratio of flavonolignan isomers may differ depending on the region where MT was grown (Lee et al., 2007; Poppe and Petersen, 2016). Flavonolignan’s concentrations can also be influenced by oil extraction technology from MT fruits. The cold-pressed oil extraction preserves a unique combination and activity of bioactive constituents present in the plant fruits (Hou et al., 2010; Lee et al., 2013). The MT oilseed cake or seeds are the primary raw material used by the pharmaceutical and dietary supplement companies to prepare phytodrugs and dietary supplements.

The hepatoprotective properties of silibinin include blocking stabilizing liver cell membranes and blocking phosphodiesterase (Romanova and Krasavtsev, 2007). In addition, silibinin can bind radicals due to its phenolic structure, resulting in a significant increase in the reduced glutathione content in the liver. This reduction in glutathione increases the organ’s protection from oxidative stress, maintaining its normal detoxification function.

Silymarin reduces inflammation via downregulation of the expression of transcription factors [nuclear factor-kappa B (NF-kB) and signal transducer and activator of transcription 1 (STAT-1)] and inflammation-associated proteins. The downregulation of transcription factors led to a significant reduction of interleukin 1 alpha (IL1α) and tumor necrosis factor-alpha (TNFα) production (Lee et al., 2013) (Table 2). It has also been reported that silibinin may suppress melanoma cell growth by reducing the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. The reduction of ERK-1/2 resulted in downregulation of the MEK1/2 and reduced activity of NF-κB and STAT-3, followed by the cell-cycle arrest in the G1 (Lee et al., 2013). Interestingly, silymarin, but not silibinin, could attenuate ischemia-reperfusion-induced brain injury (Hou et al., 2010). Silibinin also reduced chemotherapeutic drug resistance in human bladder cancer cell lines via NF-kB dependent and independent pathways.

Bioactive flavonoids have been used to treat hepatobiliary system diseases (Flora et al., 1998; Pradhan and Girish, 2006; Abenavoli et al., 2010) (Table 1). Flavonolignans isolated from the fruit of MT prevail in this group of drugs. Studies have shown that the hepatoprotective effect of these phytodrugs are due to the presence of three flavonolignans: silibinin, silidianin, and silicristin (Abenavoli et al., 2010). Numerous preclinical studies were published demonstrating hepatoprotective properties of MT or MT extracts in animal models of liver injury. Only the PubMed database holds 311 articles, including review articles, published between 1989 and 2021. Several animal models of hepatotoxicity were used by investigators, including acetaminophen, alcohol, carbon tetrachloride, phenylhydrazine, and thioacetamide (Abenavoli et al., 2010; Kantah et al., 2011; Ahmed et al., 2020).

It has been reported that liver fibrosis in rats induced by the 8-weeks intragastric administration of carbon tetrachloride (CCl4) was successfully treated with a standardized extract of the MT (Tsai et al., 2008). The extract was administered at a 200 mg/kg dose four times per week for 3 weeks. The treatment has significantly decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the serum of experimental animals.

A study confirming the hepatoprotective activity of Silimar, an original phytodrug developed by the VILAR, was conducted on a model of experimental hepatitis in rats induced by a single subcutaneous administration of oil-based CCl₄ (Baginskaya et al., 2000; Sokol’skaya, 2000). Silimar at a dose of 100 mg/kg was administered 5 days before CCl₄ administration and continued 21 days after liver damage. The administration of CCl₄ resulted in a significant elevation of the γ-glutamyl transferase (GGT), ALP, ALT, and AST compared with healthy controls (Baginskaya et al., 2000). Following chronic administration of Silimar resulted in significantly reduced levels of GGT, ALT, AST. In an in vitro experiment, Silimar suppressed induced lipid peroxidation, evidenced by reducing the amount of malondialdehyde by 15–41% compared to the control (Baginskaya et al., 2000).

It appears that MT extracts have low bioavailability (El-Gazayerly et al., 2014; Mukhtar et al., 2021). The treatment of rats receiving CCl₄ with silymarin incorporated into phytosomes significantly decreased superoxide dismutase activities and glutamic pyruvic transaminase compared to the plant extract free of phytosomes (El-Gazayerly et al., 2014). Additionally, the treatment with encapsulated silymarin inhibited liver fibrosis induced in rats by administering 2 mg/kg acetaminophen for 2 weeks (Mukhtar et al., 2021). The treatment significantly decreased levels of ALT, AST, and ALP.

Several investigators have studied the pharmacokinetics of MT in healthy volunteers and patients with various liver diseases. The study published by Calani et al. investigated the bioavailability and metabolism of flavonolignans after a single administration of the water-soluble MT extract (Calani et al., 2012). After overnight fasting, the healthy volunteers consumed 8 g of the extract dissolved in the water in this study. The study showed that MT flavonolignans have low bioavailability (0.45%). Urinary excretion was studied following 48 h. Thirty-one metabolites of flavonolignans have been found in the urine. The most common metabolites were monoglucuronides followed by sulfate–glucuronides and diglucuronides. Zhu et al. investigated the pharmacokinetics of individual flavonolignans in humans following single or chronic administration of MT extract (Zhu et al., 2013). The authors determined that all investigated flavonolignans were rapidly absorbed and eliminated by the organism. Flavonolignan exposure was dose-dependent. The most prevalent flavonolignans detected in volunteers were silybin A and silybin B, followed by isosilybin B and isosilybin A. The pharmacokinetics of MT flavonolignans was significantly altered in patients infected with Hepatitis C virus and patients with non-alcoholic fatty liver disease (Abenavoli et al., 2018). High exposure to bioactive flavonolignans was observed in patients with live cirrhosis.

Several MT phytodrugs are marketed under different brand names (e.g., Silymarin, Legalon, Carsil, and Silibor). Legalon is a standardized phytodrug containing 70–140 mg silymarin (calculated as silibinin) in 86–186 mg of dry extract of the fruit (European OTC medicines and devices., 2020). The phytodrug is intended to treat acute and chronic hepatitis and cirrhosis. Legalon at a 25 mg/kg dose reduced lipid peroxidation and increased superoxide dismutase activity in hepatic tissues (Batakov, 2001). It has been reported that workers chronically exposed to toluene and/or xylene vapors receiving oral Legalon for 30 days had significant improvements in liver function and platelet counts compared with workers that did not receive this treatment (Szilard et al., 1988). Legalon-SIL^® has been used for intravenous treatment of patients infected with hepatitis C virus (HCV) and not responding to pegylated interferon/ribavirin treatment (Rutter et al., 2011). Most of the patients (85%) had undetectable HCV ribonucleic acid (RNA) after a 14-days course of Legalon-SIL^®.

Many clinical trials were conducted to find the efficacy of MT extracts in humans with various liver diseases. The first trial that we were able to find was conducted in 1980 and investigated the effectiveness of the MT derivatives for the treatment of chronic hepatopathies (De Martiis et al., 1980). The first randomized placebo-controlled trial was performed in 1989 and investigated the efficacy of silymarin in patients with liver cirrhosis (Ferenci et al., 1989). The patients in this trial received 140 mg of silymarin three times a day for an extended period. It has been determined that the 4-years survival rate in the treatment group was significantly higher compared with patients receiving placebo. Another double-blind placebo-controlled clinical trial proved the efficacy of milk thistle for treating patients with acute hepatitis (El-Kamary et al., 2009). The therapy reduced symptoms of biliary retention such as jaundice and scleral icterus. Interestingly, unlike in animal experiments, the reduction of ALT and AST in human subjects was not significant (El-Kamary et al., 2009). The evaluation of the efficacy of silymarin for treatment of non-alcoholic steatohepatitis has shown that patients receiving 700 mg of silymarin for 48-weeks had comparable to control non-alcoholic fatty liver disease activity scores; however, silymarin-treated patients had significantly lower liver fibrosis (Wah Kheong et al., 2017).

A more detailed analysis of available clinical data confirming hepatoprotective properties of MT is available in the recently published articles by Abenavoli et al. (Abenavoli et al., 2018) and Marmouzi et al. (Marmouzi et al., 2021). The literature analysis led us to conclude that MT standardized extracts can improve liver function following several hepatic disorders, including chronic exposure to toxic chemicals, viral hepatitis, liver cirrhosis, and non-alcoholic liver steatosis. However, this treatment cannot cure the disease. In our opinion, this treatment can be combined with the standard of care therapies, especially when there is no improvement following conventional treatment.

MT oil, oilseed cake, or seeds could fortify bakery products (Semenkina, 2010; Ataei Nukabadi et al., 2021) (Table 1). MT fruits contain a complex of biologically active substances (vitamins, minerals, flavonoids, a significant amount of dietary fiber, and amino acids) (Semenkina, 2010). The MT seed oil is enriched with omega-6 and omega-3 fatty acids, tocopherols, and carotenoids. The addition of MT in bakery products may increase the nutritional value by supplying extra proteins, linoleic acid, vitamin E, and calcium. The presence of flavonolignans in the MT oilseed cake could supply additional support for liver function. MT flavonolignans may help increase bone calcium absorption when added to bakery products combined with fat-free milk (Semenkina, 2010; Nekrasova and Popov, 2020). The addition of nettle leaf and MT seed powder to sponge cakes could reduce blood sugar levels (Ataei Nukabadi et al., 2021) and improve liver functions.

Andrzejewska with colleague suggested that whole MT plant can be used as food and cosmetics (Andrzejewska et al., 2015). According to the Edible Wild Food resource, “the young stalks, leaves, roots and flowers can be eaten” (Edible Wild Food., 2021). Mediterranean communities have been using MT young stems as food for centuries (Andrzejewska et al., 2015). Spanish natives have been adding aerial parts to salads or eating them cooked (Andrzejewska et al., 2015). Unfortunately, the reports on the use of MT as food or functional food for humans are limited and primarily focused on the use of plant fruit, not aerial parts, potentially due to the presence of spikes on the leaves. MT may be an active ingredient of the cream intended to treat melasma (Nofal et al., 2019).

The MT can also be used as a part of functional food for farm animals (Table 1). MT oilseed cake is enriched in crude proteins, dietary fiber, and fat (Stastnik et al., 2020). The seed cake contains ∼4% of flavonolignans (Stastnik et al., 2020). It has been reported that the addition of MT oilseed cake in the diet of lactating dairy cows in the amount of 25% of the required digestible protein increased the protein and fat content in the milk, improved its amino acid composition, and augmented the average daily milk yield (Chabaev et al., 2011). The administration of MT oilseed cake at a dose of 44 mg/kg/day to Ayrshire heifers during the first twenty-first months of their lives reduced the number of diseases caused by impaired liver function and metabolic processes by ∼35% and prevented mortality of the livestock from the first month of cattle life to the end first lactation (Kravainis et al., 2014). The supplementation of the sow diet with MT at the dose 100 mg/kg/day starting from 88 days of gestation to farrowing positively affected the fetal formation and the weight of newborn piglets (Kolesnyk and Bankovska, 2008). The addition of MT to the sow fodders prevented suckling pig’s mortality and increased the average daily gain by ∼19% (Kolesnyk et al., 2009). Chickens receiving MT extract at doses of 0.1; 1.0; 1.5 and 2.0 mg/kg had the average daily body weight gain during the rearing period by 1.1–5.3%, the European productivity index increased 2.4–10.2%, and feed consumption per 1 kg of the weight gain increased 1.6–4.8% compared to the control group (Bagno et al., 2020). Feeding MT oilseed cake in combination with ascorbic acid to broiler chickens reduced the concentration of lead and cadmium in meat by 2.72 and 2.08 times and increased its biological value (Mildzikhov et al., 2013). Adding oilseed cake to the hens’ feed increased egg production and egg size (Stastnik et al., 2020). Some studies reported no effect on chicken wellbeing (Stastnik et al., 2020). As shown above, the fortification of farm animals’ fodder with the MT oilseed cake has significantly improved animals’ survival.

It has been hypothesized that the aerial part of the plant can also be used to fortify farm animal feed (Andrzejewska et al., 2015). It has been reported that MT can be used as supplemental food in cattle and chicken (Bagno et al., 2020; Shemuranova and Garifullina, 2020). Unfortunately, the nutritional value of the MT areal part is lower than barley (Stastnik et al., 2020).

The artichoke plant has significant levels of polyphenols, sesquiterpene lactones, terpenoids, carotenoids, and chlorophylls (Turkiewicz et al., 2019; Zeaiter et al., 2019; Rocchetti et al., 2020) (Table 3). The artichoke is an excellent source of inulin, minerals (e.g., potassium and phosphorus), and vitamins (vitamins group B and vitamin C) (Bundy et al., 2008; Zeaiter et al., 2019). Levels of phytochemicals can vary significantly depending on the taxonomic variant, cultivar, or hybrid plant (Turkiewicz et al., 2019). The artichoke bracts have elevated levels of inulin and polyphenols (Turkiewicz et al., 2019). The analysis of phytochemicals in the seed-propagated artichoke hybrids revealed that leaves of artichoke contain >90 polyphenols and >120 sesquiterpene lactones (Rocchetti et al., 2020). Seven cultivars were investigated by Rocchetti and others (Rocchetti et al., 2020). The authors reported significant differences in the composition of bioactive compounds present in these cultivars. As proved by Turkiewicz and others, the health-promoting benefits of artichoke depended on the levels of bioactive phytochemicals present in cultivars and hybrids (Turkiewicz et al., 2019).

The preclinical studies investigating pharmacological properties of the artichoke leaf compounds have found that the hepatoprotective properties of the phenolic compounds (e.g., luteolin, chlorogenic and caffeic acids, cynarin and luteolin 7-O-glucoside) are associated with their ability to reduce plasma levels of malondialdehyde induced by t-BHP and as a result decrease of free radicals and hepatocyte damage (Ben Salem et al., 2015) (Table 3). The phenolic leaf compounds also prevent lipid peroxidation. Additionally, phenolic compounds may exhibit hypocholesterolemic, anti-cholestatic, and antimicrobial effects (Ben Salem et al., 2015). The treatment of volunteers with total plasma cholesterol levels 6.0–8.0 mmol/l with artichoke leaf extract (ALE) significantly decreased total cholesterol levels, but not low-density lipoprotein and high-density lipoprotein (Bundy et al., 2008). An in vitro study demonstrated that treatment of HT-29 and RKO tumor cells with cynaropicrin, caffeoylquinic acids, and chlorogenic acid-induced cell apoptosis suggests that ALEs could be potentially used as an effective tool chemotherapeutic agent (Villarini et al., 2021) (Table 3).

The hepatoprotective properties of the artichoke were actively studied in animal models of acute and chronic liver injury (Tables 1, 3). In 1987, Adzed and others showed that cynarine and caffeic acid possess cytoprotective properties in vitro experiments (Adzet et al., 1987). The ethanolic ALE was given to experimental rats for 60 days, and a high-fat diet was significantly reduced by high-fat diet levels of ALT, AST, and ALP (Ben Salem et al., 2019). Another study reported that the ALE treatment of rats with diazinon-induced liver injury reduced levels of ALT, AST, ALT, and TNFα gene expression in hepatocytes (Ahmadi et al., 2019). The treatment of rats with ALE for 2 weeks improved ALT and AST levels after CCl₄ hepatic injury and decreased DNA fragmentation and caspase 3 levels in liver tissues of CCl₄-exposed rats (Colak et al., 2016). While most of the studies evaluating the hepatoprotective properties of the artichoke were done using leaf extracts. Sumer and others investigated the hepatoprotective properties of artichoke stems and bracts in an animal model of acetaminophen-induced liver injury in rats (Sumer et al., 2020). They found that stem and bract extract also effectively reduced ALT and AST levels but not ALP. It appears that the intensity of hepatoprotective effects of artichoke extracts is associated with the levels of phenolic compounds present in the extract (Speroni et al., 2003).

Artichoke extracts are marketed as phytodrugs for the treatment of liver disorders (Lattanzio et al., 2009). A double-blind clinical trial in patients with non-alcoholic liver injury confirmed the results of preclinical studies. Patients receiving ALE 600 mg daily for 2 months had an increased hepatic vein flow, reduced portal vein diameter, and improved lipid and hepatic enzyme profiles (Panahi et al., 2018). Another trial investigated the efficacy of a standardized ALE in patients with chronic Hep C infection (Huber et al., 2009). Unfortunately, the treatment of patients for 12 weeks with ALE 3,200 mg/day did not improve hepatic enzymes levels while reducing the patient’s fatigue and joint problems.

The reviewed literature confirmed that the artichoke extracts from leaves and other parts of the plant exhibit strong hepatoprotective properties (Table 1). More clinical trials are needed to verify the hepatoprotective properties of artichoke extracts in humans.

The artichoke was used as food from ancient times in Egypt, Greece, and Rome. Immature flowers and stems were used to prepare dishes, while mature flowers coagulate milk (Gostin and Waisundara, 2019) (Table 1). Modern-day artichoke flowers are exceedingly popular worldwide as a part of the everyday diet or delicatessen food. Immature flowers can be used fresh and canned or frozen for future use (Gostin and Waisundara, 2019). The artichoke was traditionally used in Mediterranean cuisine to prepare salads, dips, or soups (Barbosa et al., 2020). It can also be roasted with garlic and olive oil. The artichoke flowers and stigmas are used as a vegetable alternative to animal-driven rennet (Barbosa et al., 2020). The ability to clot milk is attributed to two enzymes mature artichoke flowers, cardosins A and B. The artichoke seed oil is enriched by linoleic, oleic, palmitic, and stearic fatty acids (Barbosa et al., 2020). The oil obtained from artichoke seeds is similar in composition to sunflower oil and can be used for human consumption and as a dietary supplement.

Artichoke is a rich source of non-digestible inulin, a heterogenous fructose polymer (Niness, 1999; Nwafor et al., 2017) and oligofructose, a shorter-chain oligomer, belonging to the inulin subgroup, which can be used as a part of dietary supplement blends or can be added to food to enhance its health benefits (Lattanzio et al., 2009). Inulin is well-known prebiotic that can support grows of a healthy intestinal microbiome. Antioxidant properties of phenolic compounds can be used in a functional food to support immune, endocrine, and cardiovascular systems (Table 3).

The biomass that is not used by the food industry could be a source of animal feed or feed supplement for farm animals, especially in areas of extensive artichoke cultivation. Silage artichoke (e.g., artichoke bracts and plants) has been investigated as an animal feed with generally positive results for animals and animal products (Meneses et al., 2007; Monllor et al., 2020) (Table 1). The analysis of artichoke foliage revealed that it is safe to use as animal feed.

A significant part of the artichoke is wasted after the food industry uses artichoke flowers. The alternative use of the artichoke aerial part is presented in Figure 1. It has been proposed to use remaining lignocellulosic biomass as solid biofuel for heating houses or energy generation (Fernández et al., 2006; Barbosa et al., 2020). Several studies evaluated the heating value and combustion of artichoke biomass (Fernández et al., 2006; Oliveira et al., 2012; Gominho et al., 2018). Artichoke biomass and oil can be used for biodiesel production (Fernández et al., 2006). A bioplastic prepared from a plant’s leaves can potentially replace slowly degrading plastic (Mirpoor et al., 2022). Gominho et al. suggested using artichoke stalks as a source for paper production (Gominho et al., 2001). It appears that the artichoke has good potential to be used from stem-to-stern in food, pharmaceutical, and bioenergetic industries. The use of waste by food industry by-products could have a significant impact on the environment.

The chicory plant contains numerous biologically active constituents, including inulin, sesquiterpene lactones (e.g., chicoroisides B and C, sonchuside C), flavonoids, alkaloids, caffeic acid derivatives (e.g., chicoric acid, chlorogenic acid), vitamins E, β-carotene, and minerals (calcium, phosphorus, magnesium, and potassium) (Al-Snafi, 2016; Perovic et al., 2021) (Table 4). The distinct parts of the plant may contain different amounts of bioactive constituents. Plant roots are enriched in inulin and tannins but contain low amounts of phenolic acids (Al-Snafi, 2016). Inulin comprises ∼70% of constituents present in the fresh chicory root (Nwafor et al., 2017). The leaves and seeds contain high levels of phenolic compounds and flavonoids and low levels of inulin (Al-Snafi, 2016). Both wild and cultivated chicory is used in the food and dietary supplement industries. The aerial part of the plant may be used as a raw material for hepatoprotective phytodrugs, while the food and dietary supplement industries use roots.

Chicory is reported to have several pharmacological properties, including antimicrobial, anthelmintic, antimalarial, anti-inflammatory, antioxidant, gastroprotective, and hepatoprotective (Street et al., 2013; Al-Snafi, 2016; Janda et al., 2021; Perovic et al., 2021) (Table 1). In addition, chicoric acid has hypoglycemic activity and antiviral effects (Zhang et al., 2014; Ferrare et al., 2018). Aqueous extracts from cultivated chicory possess antioxidant properties that were confirmed in animal models (Saybel', 2020). Hepatoprotective properties were reported for flavonoids isolated from Cichorium glandulosum Boiss. et Huet (Tong et al., 2015) (Table 4). Phenolic flavonoids extracted from leaves of chicory and artichoke also demonstrated hepatoprotective properties (Mohafrash and Mossa, 2020). The constituents present in the chicory extract are oxycoumarins: esculetin and cichoriin, hydroxycinnamic acids: chicory, chlorogenic, caftaric acids (Petropoulos et al., 2017; Saybel', 2020) (Table 4). These constituents have antioxidant and hepatoprotective properties. It is suggested that the complex biologically active constituents such as polyfructose, hydroxycinnamic acids, coumarins, and flavonoids, responsible for the plant’s hepatoprotective properties (Domitrovic and Potocnjak, 2016).

A double-blind, randomized controlled trial conducted in patients with chronic periodontitis has determined that treatment with 1 g of the chicory leaf extract decreases serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increased serum levels of high-density lipoprotein cholesterol, uric acid, and total antioxidant capacity (Babaei et al., 2018). Additionally, the authors reported that the treatment decreased periodontal pocket depth.

Several clinical trials were conducted to evaluate inulin or chicory coffee’s effects on various human organ and system functions (e.g., lipid profile, bowel movement, and platelet aggregation Schumacher et al., 2011; Grela et al., 2014; Buddington et al., 2017). One of these studies evaluated whether chicory coffee has any beneficial effects on the cardiovascular system (Schumacher et al., 2011). The consumption of chicory coffee for 1 week resulted in a significant decrease in whole blood, red blood cell deformability, plasma viscosity, and macrophage migration inhibitory factors. A more recent randomized crossover trial has determined that supplementation of diets with chicory inulin contacting snack bars of people with low fiber intake led to an increase of beneficial members of the human intestinal microbiome, Bifidobacterium genus (Reimer et al., 2020).

Cichorium intybus is a part of a phytodrug (Liv-52) introduced to the pharmaceutical market by the Himalaya Drug Company in 1955 (Himalaya Wellness Company., 2021b). Liv-52 includes Capparis spinosa, Cichorium intybus, Solanum nigrum, Cassia occidentalis, Terminalia arjuna, Achillea millefolium, and Tamarix gallica (Huseini et al., 2005; Himalaya Wellness Company., 2021b). Currently, Liv-52 and its modifications are widely used as dietary supplements in the United States and European countries. Liv-52 prevents the loss of functional integrity of the cell membrane, maintains cytochrome P-450 activity, and promotes hepatocellular regeneration (Himalaya Wellness Company., 2021b). The high hepatoprotective properties of this phytodrug were confirmed in patients with viral hepatitis, alcoholic and fatty liver, cirrhosis, anorexia (Sama et al., 1976; Huseini et al., 2005). Patients receiving Liv-52 for six consecutive months in a double-blind placebo-controlled trial had decreased ascites and significantly lower ALT and AST levels (Huseini et al., 2005). Huseini et al. attributed the hepatoprotective properties of the phytodrug to its antioxidant, anti-inflammatory, and immunomodulatory properties (Huseini et al., 2005). Recently, it has been proven that Liv-52 could treat ischemia reperfusion-induced liver damage in rats (Cimen et al., 2020).

Another clinical trial reported that supplementation of the diets of patients with non-alcoholic fatty liver disease for 12 weeks with a mixture of turmeric and chicory seeds resulted in a significant decrease of participants’ BMI and waist circumference and levels of serum alkaline phosphatase (Ghaffari et al., 2019).

We recently presented data demonstrating hepatoprotective properties of standardized dry extract obtained from the aerial part of wild chicory (Cichorium intybus L., DEC) (Bortnikova et al., 2021). DEC was developed at the VILAR. The analysis of the chemical composition revealed that the primary constituents present in DEC are phenol carboxylic acids [e.g., esters of caffeic, ferulic, coumaric acids with organic acids (quinic and tartaric)], flavonoids (isoquercetin, astragalin, rutin, luteolin, and kaempferol), and oxycoumarins (esculetin, cichoriin) (Saybel', 2020). The DEC contains 9.20 ± 0.43% of phenolic constituents calculated as chicoric acid.

DEC has significant hepatoprotective properties confirmed in a model of acute toxic hepatitis induced by a single subcutaneous injection of mercuric chloride (HgCl₂). Mercuric chloride is a potent thiol poison leading to protein structure damage and inhibition of thiol-containing antioxidants and liver damage caused by the development of oxidative stress (Deng et al., 2012).

Mercuric chloride intoxication led to increased relative liver weight in the HgCl₂ treated group (Bortnikova et al., 2021). Rats treated with HgCl₂ had a statistically significant increase in total protein, glucose, total cholesterol, total bilirubin, triglycerides, and the GGT, ALP, AST, and AST activities. The histological liver analysis showed the presence of hepatocyte dystrophy, characterized by hyaline droplet dystrophy. Treatment of rats with DEC in doses of 100 and 500 mg/kg for 3 weeks prevented a sharp decrease in the animals’ body weight and physical activity. The relative liver weight was lower than in animals treated with HgCl₂ (Bortnikova et al., 2021). The administration of the DEC resulted in a decrease in the activity of several liver enzymes characterizing the functional state of the liver and contributed to experimental rats’ fast recovery (Bortnikova et al., 2021). These changes were more noticeable in animals receiving the maximal DEC dose. Lipid, protein, glucose, and bilirubin levels decreased significantly in the DEC groups compared to the HgCl₂ group. The dystrophic changes in hepatocytes of rats treated with DEC 500 mg/kg were not visible. The comparison of hepatoprotective activity of DEC and Silimar indicates that the hepatoprotective effect of DEC at the dose 500 mg/kg was comparable with the effects observed in the group receiving 100 mg/kg of Silimar (Bortnikova et al., 2021). Preclinical data demonstrating DEC hepatoprotective properties in rats need to be confirmed in clinical studies.

Additionally, we have reported that DEC has immunomodulatory properties (Saybel', 2020). Oral administration of DEC to immunosuppressed mice at a 50 mg/kg dose for five consecutive days resulted in upregulation of innate, humoral, and cell-mediated immune responses. Similar upregulations were not observed in animals with normal immune responsiveness.

The food and dietary supplement industries actively use chicory roots (e.g., inulin and oligofructose) as a food substitute, dietary, functional, or food supplements (Wu and Cadwallader, 2019) (Table 1). Inulin is widely used as a prebiotic supporting the intestinal microbiome, specifically stimulating the development of the bifidobacteria in the colon (Niness, 1999). Additionally, inulin acts as dietary fiber (Niness, 1999). Therefore, inulin consumption may increase intestinal peristalsis and may help people experiencing constipation.

Overconsumption of fatty and sugary food has contributed to the disproportional increase in the number of people who are obese or have diabetes. Therefore, reducing fat and sugar in food products could help reduce this trend. Moreover, many people are interested in a healthy lifestyle and healthy eating habits. When dissolved in the water or milk, inulin forms a creamy texture and gives the food a fatty feel (Niness, 1999). Oligofructose has a sweet taste and can be used as a sugar substitute (Niness, 1999). Replacement of high-fat milk and sugar with inulin and oligofructose in milk products (e.g., ice cream) may significantly reduce fat and sugar consumption. At the same time, it will not compromise product taste. Significantly, inulin and oligofructose do not influence glucose levels and insulin secretion (Niness, 1999).

Lastly, the aerial part and root of chicory can be used as fodder and complementary treatment of livestock (Nwafor et al., 2017) (Table 1). It appears that chicory extracts or phytochemicals like inulin and volatile oils can eliminate or suppress the growth of intestinal worms and other parasites found in animals (Githiori et al., 2006). Therefore, fodder fortified by chicory foliage can promote overall livestock health and prevent intestinal parasite development. Adding 0.1% of chicory powder to the broiler’s diet increased body weight but significantly lower abdominal fat compared to control birds (Khoobani et al., 2020). The same study reported that adding probiotics or chicory to the diet improved the broiler’s ileal microbiome. When chicory is given in excessive amounts to farm animals, it can negatively affect the growth and performance of the livestock.