The liver is a very important organ with a lot of functions for the host to survive. Dietary components are essential for and can be beneficial or detrimental to the healthy or diseased liver. Plants food is an essential part of the human diet and comprises various compounds which are closely related to liver health. Selected food plants can provide nutritional and medicinal support for liver disease. At the present, the knowledge of the effects of plants on the liver is still incomplete. The most urgent task at the present time is to find the best dietary and medicinal plants for liver health in an endless list of candidates. This review article updates the knowledge about the effects of plants consumption on the health of the liver, putting particular emphasis on the potential beneficial and harmful impact of dietary and medicinal plants on liver function.
1. Introduction
As a proverb goes, “a closed mouth catches no flies.” Selecting the best food for the mouth is essential for good health, especially the health of the liver. The liver is the largest digestive gland in the body playing a major role in metabolism of various substances. The liver is also under the great load of conducting various functions for the survival of the host, including detoxification, breakdown of red blood cells and substances, synthesis of proteins and hormones, and storing glycogen, as well as holding a reservoir of blood [1, 2]. Any damage that weakens the functioning of the liver is called liver disease including liver cancer [3, 4]. Currently food of plant origin is consumed more frequently for human health and leafy plants or plant parts are eaten usually as vegetables [5]. Generally speaking, all the plants, plant parts, and their ingredients which we ingest are related to the health of the liver because of the existence of enterohepatic circulation and hepatic detoxification [6].
Dietary and medicinal prevention or treatment of liver disease by plant-based stuff is an essential constituent of complementary and alternative medicine [7]. Human has a long history of consuming edible plants for food and survival and now still consumes a wide variety of wild and semidomesticated food plants, domesticated crops, vegetables, fruits, and plant food supplements, as well as plants for medicinal use [8–11]. In spite of the long history and wide distribution of use, the knowledge of the impact of these plants on the liver remains incomplete [12]. In addition, the known knowledge of botany-hepatology as a discipline can be used to learn new knowledge in the era of molecular medicine, and many of the traditional views and opinions gained through experience need to be confirmed by modern technology on the basis of evidence [13–16]. In a tremendous body of countless plants, finding the best ones with edible or potable elements for liver health presents too much a challenge to the researchers of liver disease. Based on the most recent literatures in the area, this paper reviews the impact of plants consumption on the health of the liver, with special emphasis on the positive and negative influence of dietary and medicinal plants on liver function.
2. Wild and Semidomesticated Food Plants Good for Liver
There is a very long history of consumption of domesticated and cultivated food plants including crops, fruits, and vegetables. People should have gained a lot of knowledge about the effects of these foods on human health. For example, the earliest domestication of common millet in East Asia can be dated to the Neolithic era 10,000 years ago [8]. However, both animal and human studies on many of these plants, like berries, carrot, grapes, ginger, green tea, pistachio, pomegranate, tomato, and wheat, have yielded conflicting results; thus, it is now still very hard to recommend what is the best estimate of the amount of these plants a person consumes for liver health [1, 3, 4].
The wild and semidomesticated food plants are now consumed as supplements to the domesticated foods and as main foods to suppress hunger at times of food shortage in underdeveloped world [10]. For example, the Northeast region of Thailand is regarded as the largest and poorest portion of the country. In anthropogenic areas there, wild food plants are a fundamental part of the diet for vulnerable farmer households and acquisition of wild food plants improves the readiness of seasonal crop throughout the year [17]. Forms of wild food plants include aquatic herb, bamboo, climber, rattan, terrestrial herb and tree, and edible parts of these plants cover shoot, flower, fruit, whole plant, leaves, cladode, seed, tuber, rhizome, stalk of flower, and stem [17, 18].
Reduction-oxydation (redox) state represents a crucial background of various liver disorders. There is always the paradox of oxygen use in metabolism for the existence of life. On one hand, oxygen is fundamental for the organism to survive. On the other hand, oxygen as a strong reactive molecule devastates the organism by generating reactive oxygen species. The organism in turn develops an antioxidant network to prevent this damage. Oxidation reaction can generate free radicals which can damage cell membranes and cause diseases. The imbalance between production of reactive oxygen species and the system’s defense represents oxidative stress which is one of the essential pathogenic factors in numerous liver diseases including inflammatory, metabolic and proliferative ones and antioxidants are chemicals rich in many food plants and can be used as prevention and treatment of such diseases [19]. Almost all chronic liver diseases are under the background of elevated oxidative stress. The organism maintains various systems of antioxidants which could be simply divided into enzymatic and nonenzymatic categories (Table 1).
Simple grouping of antioxidants for liver health.
Group
Name
Characteristics
Effective in liver disease
Enzymatic
Catalase
Very common antioxidant
Alcoholic liver disease
Superoxide dismutase
Both endo- and exogenous
Chronic liver injury
Peroxidases
Neutralizing hepatotoxins
Hepatotoxicity
Nonenzymatic
Reduced glutathione
Neutralizing hepatotoxins
Hepatotoxicity
Melatonin
Power very strong, versatile
Nonalcoholic fatty liver disease
Ebselen
Glutathione peroxidase analog
Alcoholic liver disease
Vitamin C
Cofactor in enzyme reactions
Viral hepatitis, cirrhosis
Vitamin A
Enhancing immunity
Cirrhosis, steatohepatitis
Vitamin E
Richest in flaxseed oil
Hepatitis B, nonalcoholic fatty liver disease
4-Hydroxynonenal
Cell signal transduction
Alcoholic liver disease
Malondialdehyde
Potentially mutagenic
Acute liver cell injury
Great sources of essential antioxidants are foods rich in vitamin C, vitamin E, and trace element selenium [1]. Some nonessential substances from plant food origin also have antioxidant activity, such as ascorbic acid, β-carotene, coenzyme Q10, curcumin, dong quai (Angelica sinensis), ebselen, ellagic acid, epigallocatechin gallate, lipoic acid, lycopene, mitoquinone, N-acetyl cysteine, quercetin, and resveratrol [20–23]. Minor dietary nonnutrients in plant foods also have notable activity in cancer prevention by their effects of suppression or block or both on carcinogenesis. Inhibitors with suppressing effect prevent development of tumorigenesis in cells that would become cancerous under other circumstances while those with blocking effect prevent cancer-causing agents from contacting or responding with all-important target sites [3, 24].
Redox state activates the innate immune system and elevates the discharge of proinflammatory cytokines and other mediators for the establishment of alcoholic liver disease and nonalcoholic fatty liver disease. And oxidative stress also encourages the progression from steatosis to steatohepatitis [25]. Redox state impacts on brain function in hepatic encephalopathy by overproduction of reactive oxygen and nitrogen oxide species [26]. Fibroproliferative liver diseases can result from disturbance of redox homeostasis by activation of myofibroblast-like, hepatic stellate cells, and other profibrogenic cells [27]. Animal and human studies have shown that both hepatitis B virus (HBV) and hepatitis C virus (HCV) stimulate oxidative stress in liver cells with elevated oxidative DNA damage. In addition, both viruses disturb the response of liver cells to oxidative DNA damage with consequent genome instability and cancer formation [28]. Several RNA viruses including HCV are reported to induce oxidative stress with changes in host defense modulated by antioxidants [29].
Phytoestrogens are dietary plant estrogens that are not produced in the endocrine system but obtained by consuming phytoestrogenic plants. These nonsteroidal plant compounds are naturally occurring and similar in structure to estradiol with estrogenic and/or nonestrogenic effects exerted by binding to estrogen receptors. A group of phytoestrogens in the Coumestan family has been proved to be anti-HCV agents by inhibiting viral RNA replication [30]. One of the phytoestrogens that is called genistein falls into the category of isoflavones and has been demonstrated at the molecular level to have similar therapeutic effect to interferon-α on HBV infection [31].
Plant foods richest in phytoestrogens are oilseeds and nuts. The most frequently encountered sources of phytoestrogens are the plants of the legume family [32]. Such plant foods from wild and semidomesticated origin include alfalfa, anise, chaste-tree berry, Dunbaria villosa, fennel, fenugreek, ginkgo, ginseng, hops, kava, kudzu, lentil, licorice root, lupine, mint, psoralea, red clover, saw palmetto, and wild yam [33, 34]. Nevertheless, evidence is lacking for therapeutic use of these plants, and clinical trials are needed with concerns for long-term safety and efficacy.
Other hepatoprotective plant foods from wild and semidomesticated origin consist of amaranth, Aralia elata Seem, asparagus, balloonflower root (Platycodon grandiflorus), buckwheat, capillary wormwood, celery, chestnut, Chinese chive, Chinese small iris (Iris lactea), Chinese toon, heartleaf (Cordate houttuynia), cress, dandelion, daylily, devil’s tongue (Lilium brownii), hawthorn, hazelnut, kelp, kiwi fruit, longan, longstamen onion bulb, lotus root, mango, Manyflower Gueldenstaedtid herb (Herba Gueldenstaedtiae), olive, papaya, philippine violet herb (Herba violae), purslane, red date, rivier (Rhizoma amorphophalli), shepherd purse, sow thistle, spring bamboo shoots, summer squash, tangerine, tzu tsai (Porphyra haitanensis), wild bracken, and yam [35–39]. The list is still growing and in-depth studies on different phytonutrients are warranted for rationale consumption of these plant foods to improve liver health. Well-designed randomized clinical trials are needed.
3. Wild and Semidomesticated Food Plants Harmful to Liver
Phytoestrogens are now used for estrogen replacement as complementary and alternative therapy of several conditions. For example, black cohosh is widely advertised as bust-enhancing product and prescribed for menopausal symptoms and pain relief. However, this product has been associated with liver toxicity [40]. Many of the dietary plants associated with phytoestrogens are substrates for a genus of fungi called Fusarium to produce zearalenone which is a potent estrogen and has strong genotoxicity and liver toxicity [34, 40]. Excessive phytoestrogens have adverse effects not only on the reproductive system but also on the liver [41]. Use of food containing phytoestrogens is generally safe. However, estrogen-like effects are observed and increased with prolonged use [42]. A safety study on a phytoestrogen called genistein in Wistar rats demonstrated that very slight proliferation of bile duct, increased gamma glutamyl transferase, and hypertrophy of liver cells were observed at repeated doses of 500 mg/kg/day [43]. Another study of genistein effects on Wistar rats found that the phytoestrogen has strong impact on hepatic gene expression [44]. Phytoestrogens also have been shown to induce gene activation in human liver hepatocellular carcinoma cell line HepG2 cells [45]. So, researches are needed to acquire knowledge of avoiding particular components of plant-based foods for liver health.
Pesticide residue in wild plant foods is highly hepatotoxic and leads to change in metabolism and oxidative balance in the liver [46]. Fumigated or grilled foods are also harmful. A study showed that fumigation residues bound on seeds were highly bioavailable to experimentally fed animals with resultant hepatic injury [47]. Animals that were fed on a diet consisting of grilled foods showed with elevated serum levels of cholesterol, aspartate transaminase, creatinine, and urea and many kinds of chromosomal aberrations in examined cells [48]. Foods can go bad easily in summer. Deteriorated and rotten foods are full of molds and fungi and are dangerous to eat. One study examined the effects of decayed foods on the liver in rats. Male Wistar rats were fed with a diet containing gluten thermally processed with oil spontaneously for 11 weeks and damage in the liver occurred subsequently [49]. Rotten ginger is strongly poisonous. Rotting ginger produces a highly toxic substance safrole known as natural hepatoxin which leads to liver cell degeneration and necrosis and may induce liver cancer as tumorigenic effects in the liver were shown after long-term exposure of animals to other plants [50, 51]. Rotten potatoes as well as other food plants also have potent toxic effects on the liver through the intake of mycotoxins because rotting plants are frequently infected with Fusarium spp. [33, 40, 52].
Cassava is a woody shrub and is widely consumed for its starchy tuberous root as food in Latin American, Caribbean, African, and Asian countries. It is the third major source of dietary carbohydrates in the tropical zone, following rice and maize. However, people consume cassava excessively or incorrectly are at risk of poisoning. Goats fed with cassava leaves for 30 consecutive days showed toxic effects of cyanogenic glycosides with vacuolation of periportal hepatocytes [53]. Liver cancer has also been associated with this food plant [54, 55].
Currently literature is limited about liver damage induced by food plants but evidence will continue to accumulate for the effects of dietary components on the liver. The potential hazards of nightshades to liver health are described in the next section.
4. Medicinal Use of Food Plants for Liver Health
For thousands of years people have the belief of food as medicine and medicine as food [56]. A commonest English axiom reads, “an apple a day keeps the doctor away.” Apples were one of the earliest foods that medical specialists accepted as beneficial and healthy. Apple polyphenol extract has been shown to have hepatoprotective effects on liver oxidative stress which was induced by aluminum chloride in the rat [57]. Tamoxifen is a nonsteroidal antiestrogen and has been used to induce oxidative stress in rats showing increase in aminotransferases. This effect was reduced significantly by a food product consisting of dried apple and mandarin juice [58]. Table 2 briefly lists medicinal use of common plant foods for liver health.
Medicinal use of common plant foods for liver health.
Category
Common name
Botanical name
Special active elements
Benefits to liver
Vegetables
Beets
Beta vulgaris
Betaine
Chloretic
Broccoli
Brassica oleracea
Diindolylmethane, glucoraphanin
Antiviral, anticancer
Carrots
Daucus carota
Beta carotene and other carotenoids
Antioxidative activity
Collard greens
Brassica oleracea
Diindolylmethane, sulforaphane
Anticancer, anti-inflammation
Kale
Brassica oleracea
A group of resins
Lowering cholesterol and fat
Sweet potato
Ipomoea batatas
Beta carotene, fiber
Attenuating liver injury
Yams
Dioscorea alata
Diosgenin
Inhibiting hepatomegaly
Cabbage
Brassica oleracea
Glucosinolates
Countering alcohol, hangover
Fruits
Avocado
Persea americana
Adiponectin
Hypolipidemic activity
Banana
Musa acuminata
Pectin
Relieving cirrhosis
Cherry
Prunus avium
Methyl jasmonate
Antioxidant activity
Fig
Moraceae ficus
Fumaric acid, ficin
Antifatty liver action
Lemon
Citrus limon
Naringin, citric acid
Decreasing liver damage
Papaya
Carica papaya
Lycopene, danielone
Antioxidative activity
Pomegranate
Punica granatum
Punicalagins (pomegranate ellagitannins)
Anticancer
Watermelon
Citrullus lanatus
Citrulline, lycopene
Antitoxic, hypoglycemic
Grains
Barley
Hordeum vulgare
Caffeic acid, p-coumaric acid
Antifatty liver action
Maize
Zea mays
Lutein, linolic acid
Antioxidative activity
Brown rice
Oryza sativa
Anthocyanins, tocopherols
Anti-inflammatory effects
Oat
Avena sativa
Ergothioneine
Antioxidative activity
Wheat
Triticum stivum
Alkylresorcinols, ferulic acid
Increasing lipid metabolism
Sorghum
Sorghum bicolor
p-Hydroxybenzaldehyde, methyl ferulate
Antioxidative activity
Green leaves are the best for liver health. There is the saying in traditional Chinese medicine: “the dark-green colored falls into liver meridian.” A flavone glucoside named as saponarin has been extracted from young green barley leaves. This flavonoid gives the typical green color to the leaves and demonstrates powerful antioxidant potencies with therapeutic effects on various cancers and inflammations [59]. In vivo studies proved that green tea leaves have strong inhibitory activity for liver cancer. Camella sinensis is a common Chinese green tea. Alcoholic extract of the leaves of this plant was prepared and given by gavage to Wistar rats bearing Walker-256 liver cancer. Strong antitumor activity was achieved in rats that received the treatment with the green tea extract [60].
Several categories of food plants have chemopreventive effects on carcinogen-induced neoplasia. They are cruciferous vegetables, citrus fruits, caraway (Carum carvi) seed oils, and Allium species [4, 61]. Cruciferous vegetables are green leafy veggies including bok choy, broccoli, cabbage, cauliflower, and cress. A large integrated series of case-control studies consisting of 1468 cancers presented supporting evidence of favorable effect of these food plants on several common cancers [62]. Citrus is the general name for many flowering plants cultivated since ancient time. The well-known citrus fruits are the grapefruit, lemons, limes, mandarins, and oranges. Citrus fruit oil was reported to improve hepatotoxicity in chickens fed with a diet containing aflatoxin, a potent hepatocarcinogen, showing reduced lesions of hydropic degeneration and bile duct hyperplasia in the liver [63]. Caraway is also called meridian fennel and has long been used as a valuable aromatic herb and a spice in food to enhance flavors. This plant shows a large range of antimicrobial activities especially distinct inhibitory effects on growth of fungi and aflatoxin production. Caraway seed oils are commonly employed as household medicine for many ailments including hepatobiliary complications [64]. Allium is the term for garlic in Latin language and represented unofficially as the onion genus. Food plants in the Allium genus include different chives, garlics, leeks, onions and scallions. They present various flavors and mouthfeels and are consumed either cooked or raw all over the world in different delicacies. A number of studies both in vitro and in vivo have been published reporting that allium-genus plants have potent hepatoprotective activity and distinct effects on various liver conditions such as hypercholesterolemia-induced oxidative stress, cadmium liver accumulation, liver fibrosis, liver fluke, and alcoholic fatty liver [65–69].
Patients with liver disease are advised to avoid nightshade plants which are the common name for the Solanaceae family that consists of more than 2800 plants. Well-known nightshades include eggplant, ground cherries (any of the genus Physalis), mandrake (Mandragora officinarum), peppers, pimentos (Capsicum annuum), potatoes, tobacco, tomatillos (Physalis ixocarpa), and tomatoes. Animal study of several nightshades resulted in the conclusion that the plants are hepatotoxic showing amyloidosis and moderate necrosis in liver [70]. Another nightshade plant (Solanum cernuum Vellozo) was also involved in hepatic toxicity when it was used in high dose and significant increase in the activities of alanine aminotransferase and aspartate aminotransferase was observed [71]. Jimson weed (Datura stramonium), also known as thorn apple, is a nightshade plant having spiny capsule fruits. Jimsonweed is ingested by some people to enjoy hallucinations that this plant can cause. However, jimsonweed is strongly poisonous and sometimes fatal. Jimsonweed intoxication can lead to fulminant hepatitis and acute liver failure requiring subsequent liver transplantation for salvage [72, 73].
Manufacturers of dietary supplements usually cannot provide clinical data supporting their claims of safety or efficacy [16]. Physicians and the general public must take care of drug-food interactions and potential adverse effects when plant-based foods are used for medicinal purpose [74]. A physician must know as more as possible pharmacokinetic interactions of phytochemicals with drugs although currently our knowledge about nutrient-drug interactions is still limited and efforts to elucidate them should be reinforced [75]. Laxative plants can be used to clear the ingested toxins away from the digestive system. Such plants include aloe vera, dandelion, rhubarb rhizome and senna leaf [76]. The mung bean or moong bean is also known as green gram and is regarded as a detoxification agent for thousands of years in both in Traditional and folk Chinese medicine. Mung bean accelerates metabolism and transformation of toxins in food and drug by special enzymes which involve in the biosynthesis of phenolic compounds. Mung bean sprout produces several kinds of hepatoprotective compounds such as flavonoid and chlorogenic acid [77]. An aldehyde reductase has been extracted from mung bean that detoxifies fungal toxins [78]. Radish is in the Cruciferae family and also known as “Laifu” or “Luobo” in Chinese that has a history of being used for medicinal purpose for more than a thousand years. Spanish black radish comprises unique glucoraphasatin which has been proved to be a potent inducer of detoxification enzymes in liver cancer cell [79]. The degradation products of glucoraphasatin, such as sulforaphene, raphasatin and glucoraphenin, are also liver detoxification enzymes although not as potent as glucoraphasatin [80].
5. Liver Disease Herbs for Specific Therapy
Phyllanthus urinaria is an herbal medicine with potential antioxidative properties and has been proved to improve steatohepatitis both in cell cultures and in mice, perhaps via decreasing oxidative stress, relieving inflammation, and reducing lipid accumulation [14]. A trial of 1145 participants examined the effects of silymarin, an herbal product extracted from milk thistle (Silybum marianum), on patients with advanced chronic hepatitis C. The results showed that use of silymarin had no effects on hepatitis C virus RNA levels or serum alanine aminotransferase, but that better quality-of-life indices and fewer hepatic symptoms were observed in the silymarin users [15]. Curcuminoids have been proved to safeguard DNA against reactive oxygen species and protect liver cells in the time of liver damage and cirrhosis [81].
Simaroubaceae (Picrasma quassioides) is a family of tropical trees and shrubs and has been shown to be protective for carbon tetrachloride-induced liver injury and effective in treating liver cancer in moderate and late stage by comprehensive Chinese medicine with extended pain-relieving sustained time, improved quality-of-life, prolonged survival, and less adverse effects [82].
There are a great variety of live disease herbs all over the world and about 80% of the world population use herbal medicine. Elucidation of medicinal properties and hepatoprotective compounds of these herbs is of principal significance [83]. Herb induced adverse effects on liver functions are called herbal hepatotoxicity and there have been public concerns of the use of herbs. Although a large number of herbs and plant products have been involved in the causation of liver injury, the majority of the issues in causality is not yet validated and lack of enough evidence [13]. The establishment of the definite diagnosis for toxic liver disease needs hard evidence or at least sufficient supporting evidence. These reports often fall short of necessary diagnostic details and the methods for evaluating causality are nonspecific. Many external factors, such as difference in batches, adulterants, impurities, and misidentification of plant species, lead to the negative results of assessment [13]. The judgment system of herbal hepatotoxicity has to be improved for future research.
6. Amount and Methods of Consumption and Combination Use of Plants
It is of paramount importance to eat a well-balanced diet for liver health. A recent study conducted in Japan investigated the effects of well-balanced lunches on liver function. The lunch was low in animal protein and high in vegetables. This diet was provided to 10 subjects once a day for 1 month. At last, serum alanine aminotransferase status of the subjects reduced by 20.3% [84]. Although we are talking about plants consumption here, the role of animal protein and fat in improving liver health cannot be neglected and the amount of plant components in the food should be well regulated as a diet rich in sucrose was shown to cause inflammation and liver damage in mice [85]. The oxidative efficiency declines along with the age growth of the individual and consequently some chemical substances that need oxidation might accumulate to cause toxicity [86]. Simultaneous use of drugs with herbs may imitate, intensify, or counter the effect of drugs resulting in herb-drug interactions, and prediction and identification of such interactions present challenges for health professionals involved in the management of liver disease [50, 87].
Coleus forskohlii extract is a natural herbal product commonly used to offset obesity and induces hepatic drug metabolizing enzymes [12]. This induction is enhanced in mice by the amount of dietary starch, implying that the combination of coleus forskohlii extract and food rich in starch further increases enzyme activity of the liver. Hepatotoxicity of this plant is dose-related and hepatic cytochrome P450 enzyme is induced significantly [88].
The processing method of plant food is usually the key point for liver health [89]. For example, brown rice is well known as a healthy food. However, the therapeutic effect will be highly decreased when brown rice is simply steamed or cooked over for a patient with liver disease to take. The best way of processing it is preparing rice gruel, a very thin porridge that has been known as “congee” and applied in China for thousands of years to the treatment of digestive diseases. Brown rice congee is easy to digest and helpful for the liver to recover naturally [90]. But this procedure demands time, patience, and skill. Laba porridge, also known as babao gruel, is highly nutritious and famous meal eaten on the day that by folk legend Prince Siddhartha attained the top of enlightenment and became Buddha after eating this congee [91]. Babao means eight treasures and is made of eight elements. Today there are dozens of recipes for this dish using various nutritious and therapeutic ingredients such as glutinous rice, red bean, mung bean, black soybean, peanut kernel, sorghum, foxtail millet, brown rice, red date, Job’s tears, lotus seed, lily bulb, and raisin. Each of the components represents a different medicinal use and many of them have hepatoprotective activities [92, 93]. There are several different ways in which plants are prepared and used for therapeutic purpose like eating fresh raw plant, boiling, steaming, sauteing, pickling, oven curing, country curing, solar drying, shade drying and mechanical drying. There are remarkable differences between the methods of preparing plants in effects on liver health. For example, broccoli is best cooked by lightly steaming or stir-frying to preserve the most of its natural nutrients, while boiling or brewing will let the most important nutrients to come into the cooking fluid [21, 75, 89].
Although nightshades show antitumor activity, the mild hepatotoxicity is of concern as stated above. The effects of concomitant consumption of several nightshades on the liver need investigating. Poisoning by black nightshades is of particular concern because a recent investigation from New Zealand listed this plant as the commonest one in the 15 common poisonous plants [94].
The liver can be detoxified and cleansed by drinking more water. Good hydration is important for most basic physiological functions of the liver. Sufficient hydration is required to promote blood circulation and to dissolve nutrients. An adequate intake of water encourages metabolism and facilitates biliary secretion of bile, the process of digestion, absorption, and excretion of wastes to reduce the impairment of the liver by poisoning metabolites and toxins [95]. However, drinking too much water has negative impact on the liver and can be lethal. Acute hypoosmolarity leads to protein conservation related to impaired insulin sensitivity to glucose metabolism, increased lipid oxidation, lipolysis, and ketogenesis [96].
A well life-style is the best medicine. A balanced diet is necessary and binge overeating or frequent starvation should be avoided. Imbalanced food habits result in abnormal secretion of digestive juices and hepatic dysfunction [97]. Good sleep is also very important for liver health. Patients with cirrhosis often have sleep-wake abnormalities and they are observed sleeping significantly less well than healthy subjects [98]. A recent study from Seoul investigated the association of sleep quality and duration with nonalcoholic fatty liver disease in middle-aged males and females. Confounding factors such as alcohol drink and smoking were excluded from the cohort. Poor sleep quality and short sleep duration significantly increased the incidence of this liver disease [99]. Obstructive sleep apnea is now associated with liver injury that is caused by intermittent hypoxia. So sleep on the left or right side may be better for liver health than on the back [100]. Good temper is another great medicine for liver disease. The Traditional Chinese Medicine believes that anger leads to troubles of the liver. Acute stress showed significant impacts on gene expression and function of the liver in the rat, proving “raged impairing liver” [101]. Findings of rage experiences were obtained in HCV patients with evidence showing greater rage was in relation to poorer quality-of-life as negative feedback of the disease [102]. Patients with liver disease are suggested to take limited spicy food. Although curcumin is regarded as a great hepatoprotective product and has now been used in many countries as a supplement, and dietary spice turmeric has been consumed for medicative use for thousands of years, the natural turmeric has been found to contain up to 200 compounds of which the most are toxigenic. In addition, curcumin and its by-products may generate dose dependent hepatotoxicity [103].
7. Conclusions
First, do no harm. Various plants are consumed for dietary and medicinal use as wild, semidomesticated, and cultivated crops, vegetables, fruits, and herbs. It is necessary to increase availability of plants safety data to the general public and medical professionals. Safety concerns for plant consumption are rationale because of lack of evidence obtained from well-designed randomized clinical trials for long-term and large amount use. Herbal hepatotoxicity has been reported many a time involving a large number of herbs and plant products, but the most of the causal relationships are not confirmed and lack of convincing evidence.
A well-balanced diet is critically important for liver health. A healthy life-style includes additionally rejoicing with a merry mind, keeping smoke-free and alcohol-free, having good sleep, and drinking adequate water. The intake amount of a certain plant, method of consumption, and combination of plants could be either hepatoprotective or hepatotoxic. Older age should be considered as a risk factor for accumulated toxicity caused by plant chemicals. Concomitant use of drugs and herbs sometimes leads to herb-drug interactions.
Hepatoprotective plants contain substances with antioxidant activities. Plant sources of antioxidants are essential nutrients, such as vitamins and trace elements, and some nonessential substances. Plant-based antioxidants have preventive and therapeutic effects on various liver diseases including alcoholic liver disease, nonalcoholic fatty liver disease, fibroproliferative liver disease, viral hepatitis, and liver cancer. Cruciferous vegetables, citrus fruits, caraway seed oils, and Allium species are chemopreventive for liver cancer. Dietary plant estrogens are very effective in treating viral hepatitis but some of them are associated with liver toxicity caused by fungi contamination. Fumigated, grilled, pesticide-contaminated, or rotten plant foods should be avoided. Excessive or incorrect consumption of cassava is harmful. Nightshades show mild hepatotoxicity, and poisoning by black nightshades can be lethal and is of particular concern.
Nearly all the foods we consume are associated with the health of the liver. Diets rich in plant ingredients are getting popular now for human health and people are taking supplements from plant origin both in over-the-counter and in prescription form to detoxify and cleanse the liver. Prevention and treatment of liver disease by dietary or herbal method is one of the important components of complementary and alternative medicine. The knowledge of effects of various food plants on liver health is still insufficient. Traditional methods and experiences about use of food plants for treatment of liver disease must be validated by admissible evidence obtained on the basis of modern technology. The immediate challenge is to find the best dietary and medicinal plants for liver health in an infinite list of candidates. All of these topics require further assessment.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
GlauertH. P.Calfee-MasonK.StemmD. N.TharappelJ. C.SpearB. T.Dietary antioxidants in the prevention of hepatocarcinogenesis: a review201054787589610.1002/mnfr.2009004822-s2.0-77954629491GlauertH. P.Role of NF-κB in hepatocarcinogenesis and its potential inhibition by dietary antioxidants2012129116011722-s2.0-84872504913WattenbergL. W.Inhibition of carcinogenesis by minor dietary constituents1992527supplement2085s2091s2-s2.0-0026590679WattenbergL. W.Inhibition of carcinogenesis by naturally-occurring and synthetic compounds1990521551662-s2.0-0025177898SkemieneL.UstinavicieneR.PiesineL.RadisauskasR.Peculiarities of medical students' nutrition20074321451522-s2.0-34247135075BengmarkS.Nutrition of the critically ill-emphasis on liver and pancreas2012112552DudhatraG. B.ModyS. K.AwaleM. M.PatelH. B.ModiC. M.KumarA.KamaniD. R.ChauhanB. N.A comprehensive review on pharmacotherapeutics of herbal bioenhancers201220123363795310.1100/2012/6379532-s2.0-84867758767LuH.ZhangJ.LiuK.-B.Earliest domestication of common millet (Panicum miliaceum) in East Asia extended to 10,000 years ago2009106187367737210.1073/pnas.09001581062-s2.0-66149153139Ali-ShtayehM. S.JamousR. M.Al-Shafie'J. H.Traditional knowledge of wild edible plants used in Palestine (Northern West Bank): a comparative study2008413TeklehaymanotT.GidayM.Ethnobotanical study of wild edible plants of Kara and Kwego semi-pastoralist people in Lower Omo River Valley, Debub Omo Zone, SNNPR, Ethiopia20106, article 2310.1186/1746-4269-6-232-s2.0-77955542649JuY.ZhuoJ.LiuB.LongC.Eating from the wild: diversity of wild edible plants used by Tibetans in Shangri-la region, Yunnan, China20139article 2810.1186/1746-4269-9-28YakotaniK.ChibaT.SatoY.NakanishiT.MurataM.UmegakiK.Influence of dietary macronutrients on induction of hepatic drug metabolizing enzymes by Coleus forskohlii extract in mice2013591374410.3177/jnsv.59.372-s2.0-84875682210TeschkeR.FrenzelC.GlassX.SchulzeJ.EickhoffA.Herbal hepatotoxicity: a critical review201375363063610.1111/j.1365-2125.2012.04395.x2-s2.0-84873481116ShenB.YuJ.WangS.Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo200847247348310.1002/hep.220392-s2.0-39549108872SeeffL. B.CurtoT. M.SzaboG.EversonG. T.BonkovskyH. L.DienstagJ. L.ShiftmanM. L.LindsayK. L.LokA. S. F.Di BisceglieA. M.LeeW. M.GhanyM. G.Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial200847260561210.1002/hep.220442-s2.0-39549094030HassD. J.LewisJ. D.Quality of manufacturer provided information on safety and efficacy claims for dietary supplements for colonic health200615857858610.1002/pds.12512-s2.0-33748341882Cruz-GarciaG. S.PriceL. L.Gathering of plants anthropogenic environments across the seasons: implications for poor and vulnerable farm households2014534363389CruzM. P.MedeirosP. M.CombarizaI. S.PeroniN.AlbuquerqueU. P.‘I eat the manofê so it is not forgotten’: local perceptions and consumption of native wild edible plants from seasonal dry forests in Brazil2014101, article 452-s2.0-8490160561810.1186/1746-4269-10-45CesarattoL.VascottoC.CalligarisS.TellG.The importance of redox state in liver damage20043386922-s2.0-21644436766MilnerJ. A.Diet and cancer: facts and controversies200656221622410.1207/s15327914nc5602_132-s2.0-33947209997BártaI.ŠmerákP.PolívkováZ.ŠestákováH.LangováM.TurekB.BártováJ.Current trends and perspectives in nutrition and cancer prevention200653119252-s2.0-32144462275BastianettoS.ZhengW.-H.QuirionR.The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C20007462268227710.1046/j.1471-4159.2000.0742268.x2-s2.0-0034122940PivettaL. A.PereiraR. P.FarinonM.De BemA. F.PerottoniJ.SoaresJ. C.DuarteM. M. F.ZeniG.RochaJ. B. T.FarinaM.Ethanol inhibits δ-aminolevulinate dehydratase and glutathione peroxidase activities in mice liver: protective effects of ebselen and N-acetylcysteine200621333834310.1016/j.etap.2005.10.0032-s2.0-33645240029SinghK. K.MridulaD.RehalJ.BarnwalP.Flaxseed: a potential source of food, feed and fiber201151321022210.1080/104083909035372412-s2.0-79952427799SakaguchiS.TakahashiS.SasakiT.KumagaiT.NagataK.Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress2011261304610.2133/dmpk.DMPK-10-RV-0872-s2.0-79952760290HäussingerD.SchliessF.Pathogenetic mechanisms of hepatic encephalopathy20085781156116510.1136/gut.2007.1221762-s2.0-48249105787NovoE.ParolaM.The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis201251, article S410.1186/1755-1536-5-S1-S42-s2.0-84881020384HiggsM. R.ChouteauP.LeratH.“Liver let die”: oxidative DNA damage and hepatotropic viruses201495599110042-s2.0-8489968982210.1099/vir.0.059485-0ReshiM. L.SuY.-C.HongJ.-R.RNA viruses: ROS-mediated cell death201420141646745210.1155/2014/4674522-s2.0-84901794462Kaushik-BasuN.Bopda-WaffoA.TaleleT. T.BasuA.CostaP. R. R.Da SilvaA. J. M.SarafianosS. G.NoëlF.Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors20083651482149610.1093/nar/gkm11782-s2.0-41149136756ZhangQ.WangY.WeiL.JiangD.WangJ. H.RaoH. Y.ZhuL.ChenH.FeiR.CongX.Role of ISGF3 in modulating the anti-hepatitis B virus activity of interferon-alpha in vitro200823111747176110.1111/j.1440-1746.2007.04985.x2-s2.0-56549120653WassermanM. D.Taylor-GuttA.RothmanJ. M.ChapmanC. A.MiltonK.LeitmanD. C.Estrogenic plant foods of red colobus monkeys and mountain gorillas in uganda20121481889710.1002/ajpa.220452-s2.0-84859917528Fugh-BermanA.“Bust enhancing” herbal products200310161345134910.1016/S0029-7844(03)00362-42-s2.0-0037532873HuX. J.SongW. R.GaoL. Y.NieS. P.EisenbrandG.XieM. Y.Assessment of dietary phytoestrogen intake via plant-derived foods in China201431813251335TiwariA. K.Revisiting “Vegetables” to combat modern epidemic of imbalanced glucose homeostasis201410supplement 2S207S213FardetA.ChardignyJ.-M.Plant-based foods as a source of lipotropes for human nutrition: a survey of in vivo studies201353653559010.1080/10408398.2010.5495962-s2.0-80052412182TrakaM. H.MithenR. F.Plant science and human nutrition: challenges in assessing health-promoting properties of phytochemicals2011237248324972-s2.0-8005193687610.1105/tpc.111.087916MartinC.ZhangY.TonelliC.PetroniK.Plants, diet, and health201364194610.1146/annurev-arplant-050312-1201422-s2.0-84874953186SmithH. A.KoenigR. L.McAuslaneH. J.McSorleyR.Effect of silver reflective mulch and a summer squash trap crop on densities of immature Bemisia argentifolii (Homoptera: Aleyrodidae) on organic bean200093372673110.1603/0022-0493-93.3.7262-s2.0-0034202657HeQ.-H.XuY.Advance in study on zearalenone's toxicity and determination20053445025042-s2.0-77955076049RussellL.HicksG. S.LowA. K.ShepherdJ. M.BrownC. A.Phytoestrogens: a viable option?2002324418518810.1097/00000441-200210000-000042-s2.0-0036789494GirardiA.PiccinniC.RaschiE.Use of phytoestrogens and effects perceived by postmenopausal women: result of a questionnaire-based survey2014141, article 26210.1186/1472-6882-14-262Michael McClainR.WolzE.DavidovichA.PfannkuchF.EdwardsJ. A.BauschJ.Acute, subchronic and chronic safety studies with genistein in rats200644156802-s2.0-2884449671910.1016/j.fct.2005.05.021DielP.HertrampfT.SeibelJ.Laudenbach-LeschowskyU.KolbaS.VollmerG.Combinatorial effects of the phytoestrogen genistein and of estradiol in uterus and liver of female Wistar rats20061021–5607010.1016/j.jsbmb.2006.09.0222-s2.0-33751216770SafeS. H.PallaroniL.YoonK.GaidoK.RossS.SavilleB.McDonnellD.Toxicology of environmental estrogens200113430731510.1071/RD001082-s2.0-0035214154WangP.WangH. P.XuM. Y.Combined subchronic toxicity of dichlorvos with malathion or pirimicarb in mice liver and serum: a metabonomic study20147022223010.1016/j.fct.2014.05.027MostafaI. Y.ZayedS. M. A. D.HazzaaN. I.HegaziB.Bioavailability to rats and toxicity of bound residues in bean seeds fumigated with 14C-methyl bromide199227440741710.1080/036012392093727912-s2.0-0026779933HassanG. M.MagdaR. A.AwadA. A.Nutritional, biochemical and cytogenotoxicity studies on wasted fat released from chicken during grilling process201048102675268110.1016/j.fct.2010.06.0392-s2.0-77956338540BurenjargalM.TotaniN.Cytotoxic compounds generated in heated oil and assimilation of oil in Wistar rats20095811710.5650/jos.58.12-s2.0-60049101038SinghD.GuptaR.SarafS. A.Herbs-are they safe enough? An overview2012521087689810.1080/10408398.2010.5124262-s2.0-84863550576DunnickJ. K.NyskaA.The toxicity and pathology of selected dietary herbal medicines201341237438610.1177/01926233124664512-s2.0-84875728723EllnerF. M.Mycotoxins in potato tubers infected by Fusarium sambucinum2002182576110.1007/BF029466972-s2.0-33646885946Soto-BlancoB.GórniakS. L.Toxic effects of prolonged administration of leaves of cassava (Manihot esculenta Crantz) to goats201062436136610.1016/j.etp.2009.05.0112-s2.0-77953613910UhegbuF. O.Dietary secondary amines and liver hepatoma in Port Harcourt, Nigeria199751325726310.1023/A:10079478150172-s2.0-0031430219BababunmiE. A.UwaifoA. O.BassirO.Hepatocarcinogens in Nigerian foodstuffs1978281882092-s2.0-0017831486LippiD.Chocolate in history: food, medicine, medi-food2013551573158410.3390/nu50515732-s2.0-84877858347ChengD.ZhuC.WangC.XuH.CaoJ.JiangW.Hepatoprotective effects of apple polyphenol extract on aluminum-induced liver oxidative stress in the rat201492210911610.1139/cjpp-2013-03662-s2.0-84893553932Codoñer-FranchP.BetoretE.López-JaénA. B.BetoretN.FitoP.Valls-BellésV.Dried apple enriched with mandarin juice counteracts tamoxifen-induced oxidative stress in rats201364781582110.3109/09637486.2013.7982672-s2.0-84885414613KamiyamaM.ShibamotoT.Flavonoids with potent antioxidant activity found in young green barley leaves201260256260626710.1021/jf301700j2-s2.0-84862859002PonteM. F.TarginoT. S. E. S.MotaM. A. D. L.LandimJ. S. P.RibeiroT. R.SoaresF. P.PereiraM. R. P.da SilvaS. L.da SilvaS. F. R.Growth inhibition of Walker carcinosarcoma 256 with alcoholic extract of green tea leaves (Camellia sinensis)201227963463810.1590/S0102-865020120009000082-s2.0-84865829849AvielloG.AbenavoliL.BorrelliF.Garlic: empiricism or science?2009412178517962-s2.0-77649267891BosettiC.FilomenoM.RisoP.Cruciferous vegetables and cancer risk in a network of case-control studies20122382198220310.1093/annonc/mdr6042-s2.0-84864929880OrtatatliM.OğuzH.HatipoǧluF.KaramanM.Evaluation of pathological changes in broilers during chronic aflatoxin (50 and 100 ppb) and clinoptilolite exposure2005781616810.1016/j.rvsc.2004.06.0062-s2.0-6444229796KahkhaM. R.AmanlooS.KaykhaiiM.Antiaflatoxigenic activity of Carum copticum essential oil20141212312342-s2.0-8489393173410.1007/s10311-013-0439-xOtunolaG. A.OloyedeO. B.OladijiA. T.AfolayanA. J.Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats20144715NwokochaC. R.Younger-ColemanN.NwokochaM.OwuD. U.IwualaM.Investigation of effects of time of measurement and modes of administration on cadmium accumulation in rat liver under some medicinal plants food supplemented diet20146324024510.4103/0974-8490.132604MahmoudM. F.ZakariaS.FahmyA.Aqueous garlic extract alleviates liver fibrosis and renal dysfunction in bile-duct-ligated rats2014693-413314110.5560/ZNC.2013-01122-s2.0-84901390460JeyathilakanN.MuraliK.AnandarajA.Abdul BasithS.In vitro evaluation of anthelmintic property of ethno-veterinary plant extracts against the liver fluke Fasciola gigantica2012361263010.1007/s12639-011-0064-12-s2.0-84860407604RaghuR.LiuC.-T.TsaiM.-H.Transcriptome analysis of garlic-induced hepatoprotection against alcoholic fatty liver2012604411104111192-s2.0-8486851534710.1021/jf303800pAguilar-SantamaríaL.Herrera-ArellanoA.ZamilpaA.Alonso-CortésD.Jiménez-FerrerE.TortorielloJ.Zúñiga-GonzálezG.Toxicology, genotoxicity, and cytotoxicity of three extracts of Solanum chrysotrichum2013150127527910.1016/j.jep.2013.08.0392-s2.0-84885423012AlmançaC. C.SaldanhaS. V.SousaD. R.et alToxicological evaluation of acute and sub-chronic ingestion of hydroalcoholic extract of Solanum cernuum Vell. in mice201113825085122-s2.0-8125515783210.1016/j.jep.2011.09.045ErtekinV.SelimoǧluM. A.AltinkaynakS.A combination of unusual presentations of Datura stramonium intoxication in a child: Rhabdomyolysis and fulminant hepatitius20052822272282-s2.0-1354427336710.1016/j.jemermed.2004.11.006AkmanS. A.CakirM.BaranM.ArikanC.YuksekkayaH. A.TumgorG.SazU. E.ZeytunluM.KilicM.AydogduS.Liver transplantation for acute liver failure due to toxic agent ingestion in children20091381034104010.1111/j.1399-3046.2008.01119.x2-s2.0-73349095029AndradeC.Potentially significant versus clinically significant drug interactions: pomegranate juice as a case in point2014754e292e29310.4088/JCP.14f091122-s2.0-84899721079Rodríguez-FragosoL.Martínez-ArismendiJ. L.Orozco-BustosD.Reyes-EsparzaJ.TorresE.BurchielS. W.Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters2011764R112R12410.1111/j.1750-3841.2011.02155.x2-s2.0-79955593489Rodriguez-FragosoL.Reyes-EsparzaJ.BurchielS. W.Herrera-RuizD.TorresE.Risks and benefits of commonly used herbal medicines in Mexico2008227112513510.1016/j.taap.2007.10.0052-s2.0-38749149580KojimaM.TakeuchiW.Detection and characterization of p-coumaric acid hydroxylase in mung bean, Vigna mungo, seedlings198910522652702-s2.0-0024616611ColratS.LatchéA.GuisM.PechJ.-C.BouzayenM.FallotJ.RoustanJ.-P.Purification and characterization of a NADPH-dependent aldehyde reductase from mung bean that detoxifies eutypine, a toxin from Eutypa lata11999119262162610.1104/pp.119.2.6212-s2.0-0032839496HanlonP. R.WebberD. M.BarnesD. M.Aqueous extract from Spanish black radish (Raphanus sativus L. Var. niger) induces detoxification enzymes in the HepG2 human hepatoma cell line200755166439644610.1021/jf070530f2-s2.0-34548033452SchollC.EshelmanB. D.BarnesD. M.HanlonP. R.Raphasatin is a more potent inducer of the detoxification enzymes than its degradation products2011763C504C5112-s2.0-7995504053310.1111/j.1750-3841.2011.02078.xBengmarkS.MesaM. D.Gil HernándezA.Plant-derived health: the effects of turmeric and curcuminoids20092432732812-s2.0-68049145089TianH.-Q.LiH.-L.WangB.LiangG.-W.HuangX.-Q.HuangZ.-Q.LangJ.-M.ZhangY.-P.ChenX.-Z.ChenY.-S.Treatment of middle/late stage primary hepatic carcinoma by Chinese medicine comprehensive therapy: a prospective randomized controlled study201016210210810.1007/s11655-010-0102-32-s2.0-77954486127Shamsi-BaghbananH.SharifianA.EsmaeiliS.MinaeiB.Hepatoprotective herbs, avicenna viewpoint2014161e12313IwamotoM.YagiK.YazumiK.KomineA.ShirouchiB.SatoM.Eating a healthy lunch improves serum alanine aminotransferase activity2013121, article 13410.1186/1476-511X-12-1342-s2.0-84883722805OliveiraL. S.SantosD. A.Barbosa-da-SilvaS.Mandarim-de-LacerdaC. A.AguilaM. B.The inflammatory profile and liver damage of a sucrose-rich diet in mice201425219320010.1016/j.jnutbio.2013.10.0062-s2.0-84892502707SousounisK.BaddourJ. A.TsonisP. A.Aging and regeneration in vertebrates201410821724610.1016/B978-0-12-391498-9.00008-52-s2.0-84893607356AlissaE. M.Medicinal herbs and therapeutic drugs interactions2014364413422VirgonaN.TakiY.YamadaS.UmegakiK.Dietary Coleus forskohlii extract generates dose-related hepatotoxicity in mice20133399249322-s2.0-8488069890110.1002/jat.2770MajewskiM.Allium sativum: facts and myths regarding human health201465118PattenG. S.BirdA. R.ToppingD. L.AbeywardenaM. Y.Effects of convenience rice congee supplemented diets on guinea pig whole animal and gut growth, caecal digesta SCFA and in vitro ileal contractility2004131921002-s2.0-3042736233JosephP. G.Serotonergic and tryptaminergic overstimulation on refeeding implicated in “enlightenment” experiences201279559860110.1016/j.mehy.2012.07.0292-s2.0-84867336664WangL.ChenJ.XieH.JuX.LiuR. H.Phytochemical profiles and antioxidant activity of adlay varieties201361215103511310.1021/jf400556s2-s2.0-84878388087SharmaS. K.SumanVasudevaN.Hepatoprotective activity of Vitis vinifera root extract against carbon tetrachloride-induced liver damage in rats20126959339372-s2.0-84865994300SlaughterR. J.BeasleyD. M. G.LambieB. S.WilkinsG. T.SchepL. J.Poisonous plants in New Zealand: a review of those that are most commonly enquired about to the national poisons centre20121251367871182-s2.0-84872770995Kullak-UblickG. A.StiegerB.HagenbuchB.MeierP. J.Hepatic transport of bile salts200020327329210.1055/s-2000-94262-s2.0-0033736448KellerU.SzinnaiG.BilzS.BerneisK.Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health200357supplement 2S69S7410.1038/sj.ejcn.16019042-s2.0-0742324407BiltonR.Averting comfortable lifestyle crises201396431936810.3184/003685013X137432921079152-s2.0-84888397517MontagneseS.MiddletonB.SkeneD. J.MorganM. Y.Sleep-wake patterns in patients with cirrhosis: all you need to know on a single sheet. A simple sleep questionnaire for clinical use200951469069510.1016/j.jhep.2009.06.0062-s2.0-69949174768KimC.-W.YunK. E.JungH.-S.ChangY.ChoiE.-S.KwonM.-J.LeeE.-H.WooE. J.KimN. H.ShinH.RyuS.Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses201359235135710.1016/j.jhep.2013.03.0352-s2.0-84880275199VeaseyS.Good soldier falls: the liver in sleep apnea2007102251351410.1152/japplphysiol.01371.20062-s2.0-33846885446GaoX.ZengY.LiuS.WangS.Acute stress show great influences on liver function and the expression of hepatic genes associated with lipid metabolism in rats2013121, article 11810.1186/1476-511X-12-1182-s2.0-84880881808DanA. A.CroneC.WiseT. N.MartinL. M.RamseyL.MageeS.SjogrenR.OngJ. P.YounossiZ. M.Anger experiences among hepatitis C patients: relationship to depressive symptoms and health-related quality of life200748322322910.1176/appi.psy.48.3.2232-s2.0-34248665273BalajiS.ChempakamB.Toxicity prediction of compounds from turmeric (Curcuma longa L)201048102951295910.1016/j.fct.2010.07.0322-s2.0-77956341395