Ethnomedicinal Plants Traditionally Used for the Treatment of Jaundice (Icterus) in Himachal Pradesh in Western Himalaya—A Review

Ethnomedicinal plants have a significant role in the lives of people of rural and tribal areas. Thousands of medicinal plant species are used to treat various diseases, including jaundice, and are considered an important therapeutic resource to minimize these diseases. Jaundice (icterus) is a chronic disease that occurs when the amount of bilirubin in the blood increases. This review describes different ethnomedicinal plants used for curing jaundice by tribal and rural people of Himachal Pradesh. The study reveals 87 ethnomedicinal plant species belonging to 51 different families, which are used for treating jaundice in Himachal Pradesh. These plants are arranged in a systematic way, which includes a description of their common name, botanical name, along with its family, plant parts used, region, and mode of use in tabulated form. Some of the plant extracts have already been explored for their phytochemical and pharmacological significance and proved their potential in the preparation of new medicines or drugs against the treatment of jaundice. This review is an attempt to highlight the indigenous knowledge of medicinal plants, which are specifically used for the treatment of jaundice. The data mentioned in the present review is compiled from various sources like existing literature, books, Google Scholar, and Scopus publications. Among all the observed plant species, most used medicinal plants for the treatment of jaundice include Justicia adhatoda, Emblica officinalis, Ricinus communis, Saccharum officinarum, Terminalia chebula, Berberis aristata, Cuscuta reflexa, and Tinospora cordifolia. Plants that are mostly utilized for the treatment of jaundice need to be scientifically validated by pharmacological analysis and should be subsequently used for the preparation of new drugs, which may prove far more beneficial than the existing one.


Introduction
Himachal Pradesh is one of the Himalayan states of India, which has been regarded as the richest resource of biodiversity. The area is rich in medicinal plants, which are widely used by the people of different tribal and rural areas. The state is divided into 12 districts and 169 tehsils and sub-tehsils, covering a total area of 55,673 km 2 with altitude variation from 200-7000 m above sea level [1]. Geographically, the state shows three different zones or regions, known as the outer Himalaya, mid-hills, and the greater Himalaya. The outer Ethnomedicinal plants are generally used for curing various ailments like diabetes, dysentery, typhoid, and jaundice. Different parts of the plant, including roots, leaves, fruits, and flowers, are used for the treatment of jaundice. Furthermore, jaundice is not just a disease rather a sign of a disease that occurs in the liver, which indicates impairment of the liver functioning [14,15]. The foremost ancient literature says that "iecur" is a Latin word that was previously used to describe the term liver [16]. Basically, the term jaundice is taken from the french word "jaune", which means "yellowness" and is characterized by yellow pigmentation [17]. Pigmentation is generally shown by the skin and eyes. It occurs due to the exceeding level of bilirubin. Bilirubin is synthesized in the body and is a natural product that is produced because of hemolysis through the action of liver cells, which further in the presence of biliverdin reductase leads to the production of bilirubin or unconjugated bilirubin. The metabolism of bilirubin describes the pathophysiology of jaundice, as shown in Figure 1. Under normal circumstances, unconjugated bilirubin (lipid-soluble) in the presence of glucuronic acid gets converted into conjugated bilirubin (water-soluble), which is released in the small intestine. Removal of glucuronic acid in the presence of bacterial protease takes place in the small intestine, which further passes through the large intestine in the form of feces, and the remaining enters the kidney by the portal vein and passes out as urine, as shown in Figure 1 [15]. When this bilirubin accumulates in the blood, skin, sclera, and mucous membrane, it turns yellow in color. This yellowness of skin and other parts is generally called jaundice or icterus and is usually seen when the amount of plasma bilirubin is greater than its normal value, i.e., 2 mg/dL [18].
According to the pathophysiology of jaundice, it is mainly caused due to increased level of bilirubin and its overproduction in the liver, which may occur due to many reasons like acute or minor liver inflammation, obstruction of the bile duct, Gilbert's syndrome, cholestasis, and hemolytic anemia [15]. Jaundice is usually found much more effective and serious in adults rather than in new-born children (neonates), and sometimes it causes even death of the adult individual [19].
Jaundice shows three different stages or types based on its pathophysiology: prehepatic jaundice that is caused due to the hemolysis of red blood cells, also called erythrocytes. Hepatic jaundice occurs due to the abnormal metabolism of the liver or dysfunction of the liver, and post-hepatic jaundice is caused due to less liver functioning or any obstruction in the bile duct, as described in Figure 2. Under normal circumstances, unconjugated bilirubin (lipid-soluble) in the presence of glucuronic acid gets converted into conjugated bilirubin (water-soluble), which is released in the small intestine. Removal of glucuronic acid in the presence of bacterial protease takes place in the small intestine, which further passes through the large intestine in the form of feces, and the remaining enters the kidney by the portal vein and passes out as urine, as shown in Figure 1 [15]. When this bilirubin accumulates in the blood, skin, sclera, and mucous membrane, it turns yellow in color. This yellowness of skin and other parts is generally called jaundice or icterus and is usually seen when the amount of plasma bilirubin is greater than its normal value, i.e., 2 mg/dL [18].
According to the pathophysiology of jaundice, it is mainly caused due to increased level of bilirubin and its overproduction in the liver, which may occur due to many reasons like acute or minor liver inflammation, obstruction of the bile duct, Gilbert's syndrome, cholestasis, and hemolytic anemia [15]. Jaundice is usually found much more effective and serious in adults rather than in new-born children (neonates), and sometimes it causes even death of the adult individual [19].
Jaundice shows three different stages or types based on its pathophysiology: prehepatic jaundice that is caused due to the hemolysis of red blood cells, also called erythrocytes. Hepatic jaundice occurs due to the abnormal metabolism of the liver or dysfunction of the liver, and post-hepatic jaundice is caused due to less liver functioning or any obstruction in the bile duct, as described in Figure 2.
Jaundice can also be a viral disease, which can spread through contaminated water and food-related items or due to poor sanitization conditions or through several other diseases, such as hepatitis A, hepatitis B, hepatitis C, hepatitis D, liver cancer, and hemolytic Plants 2021, 10, 232 4 of 24 anemia, etc., which damage liver [14]. It has been estimated that more than two billion people worldwide are infected annually with the hepatitis B virus [20]. The history of jaundice is very long and shown in ancient Ayurveda and the Indian traditional system of medicines [21]. Jaundice is also known as Hariman disease in Rigveda (8000 BC). Herbal treatment is prescribed for jaundice because medicinal plants show a faster rate of reduction in cases when compared with western medicines [22]. This disease shows different kinds of symptoms like weakness, high fever, nausea, loss of appetite, vomiting, and the main symptom shown by this disease is the dark urine color. Sometimes, it also leads to serious conditions like coma, a sudden attack of illness or epileptic fits, psychosis (like having a severe mental disorder), and finally, death of the patient. Precautions or prevention for jaundice generally requires a low-fat diet, high water intake as much body requires, and mainly a healthy diet routine and proper nutrition [15]. Due to cultural or historical reasons and the high cost and side effects of allopathic medicines, traditional and herbal medicines have gained popularity for curing jaundice. So, numerous ethnomedicinal plants have been used by the people of different tribes and communities for treating jaundice based on their indigenous knowledge. Thus, this review is an attempt for the exploration of ethnomedicinal plants used for the treatment of jaundice, which can be cured by locally available plants or with the help of hermits.

Materials and Methods
All information regarding plants was collected through published data, including the botanical name of plants, family name, part used, and mode of use. The number of articles reviewed were available as published work on online databases (Science Direct, Pubmed, Web of Science, and Google Scholar) and were found using different key phrases (jaundice, ethnomedicinal plants, Himachal Pradesh, traditional uses, western Himalaya, and biological activity). The present study was revised from different scientific articles, including 108 research papers, 30 review papers, and 6 books from 1970 to the 2020 year. Botanical names of different plant species were validated from the online website (www.theplantlist.org).

Ethnomedicinal Plants Used in the Treatment of Jaundice in Himachal Pradesh
It was observed that approximately 87 ethnomedicinal plants are used by the tribal and rural communities of Himachal Pradesh for curing jaundice, and this information is described in Table 1, where plant families are arranged in alphabetical order and include plant's botanical name, common name, family, and region (where these plants were reported). The study revealed that these 87 ethnomedicinal plants show variations among them and represent 51 different families of plants used for the treatment of jaundice in Himachal Pradesh. Most of these plant species used for treating jaundice were observed in different areas of Himachal Pradesh, including different districts, such as Kangra, Hamirpur, and Lahul and Spiti, as shown below in Figure 3. Among all these plant species, common medicinal plants belong to six major families, i.e., Asteraceae, Fabaceae, Euphorbiaceae, Gentianaceae, Lamiaceae, and Solanaceae. The plant species most frequently used for the treatment of jaundice include Justicia adhatoda, Emblica officinalis, Ricinus communis, Saccharum officinarum, Terminalia chebula, Berberis aristata, Cuscuta reflexa, and Tinospora cordifolia, and this shows the richness of information regarding medicinal plants used by the people of Himachal Pradesh. Medicinal plants like Aloe vera contains many bioactive compounds, which are responsible for many medicinal properties, such as antibacterial, antioxidants, and immunity-boosting property [18]. Various plant parts have been used for curing jaundice, including stem, leaves, roots, bark, fruits, flowers, seeds, and sometimes even whole plant (described in Table 2). This also strengthens the use of these plants by local people. All ethnomedicinal plants contain some phytochemical constituents, which may be effective in showing an impact on the disease and its cure. The ethnomedicinal significance of plants has been proved by a reassessment of their efficiency potential in different regions. In all the reported plants, there is variation in the usage of plant parts for treating jaundice, which is also shown in Figure 4. This is similar to the work performed in south-western Nigeria, which shows the data analysis of different plant parts used for the treatment of various ailments, including jaundice [8,43,44].

Aconitum rotundifolium
Whole plant Plant juice is taken orally along with an equal volume of water for five to seven days to cure jaundice. [31] Adiantum capillus Leaves A decoction of fresh leaves is taken two times for seven days to cure jaundice. [24] Aegle marmelos Leaves and fruit A decoction of leaves and unripe fruit is used to treat jaundice. [24] Ajania tibetica Leaves and flower Leaves and flowers are used to cure jaundice. [28]

Botanical Name Plant Part Used Mode of Use Reference
Aloe vera Fleshy leaves The pulp of the leaves is directly consumed by the patient for two weeks to cure jaundice. [23] Argemone mexicana Whole plant Yellow sap of the plant is used to treat jaundice. [24] Asparagus adscendens Roots A decoction of roots (10-15 mL) is given for eight to ten days to cure jaundice. [23] Aquilegia fragrans Seeds A decoction of seeds is used to treat jaundice. [34] Bauhinia variegata Leaves Leaves juice is taken for seven days for the treatment of jaundice. [23] Berberis aristata New leaves (twigs) and roots New leaves are directly consumed, and a decoction of ground roots (100 mL) is taken to cure jaundice. [23] Berberis ceratophylla Roots Fresh roots are cut into small pieces and further shade-dried to make pills. These pills are consumed with "Kujja-Mishri" with water to cure jaundice. [34] Berberis chitria Roots A decoction of roots is used to treat jaundice.
[27] Berberis lycium Roots A decoction of roots (80-100 mL) is given to cure jaundice. [23] Betula utilis Papery bark A decoction of the bark is given to the patient for ten to twelve days to cure jaundice. [23] Boerhavia diffusa Whole plant The whole plant is used to cure jaundice. [39] Cajanus cajan Leaves Leaf juice or leaf decoction is given with sugar (regularly in the morning) for about one month to cure jaundice. [40] Calotropis procera Flowers Flowers and betel leaf are taken with honey to treat jaundice. [26] Capparis spinosa Shoot Stem powder is taken with water at least for five to six days. [31] Capsella bursa-pastoris Stem The stem is used for the treatment of jaundice. [29] Capsicum annuum Leaves Boiled leaves are used as a vegetable (saag) and given for two to three days to cure jaundice. [23] Carica papaya Raw fruit Boiled vegetable of raw fruit is given to the patient to cure jaundice. [23] Carissa opaca Roots Roots are used for the treatment of jaundice. [25] Cassia fistula Seeds A decoction of seeds is consumed empty stomach for a week, daily in the morning. [34] Centella asiatica Whole plant (entire herb) The dried herb is crushed with kali mirch, and its paste (5-10 g is taken for seven days to cure jaundice. [23] Cicer microphyllum Seeds Seeds are used for the treatment of jaundice. [28] Colocacia antiquorum Corm Corm (cooked or pealed) is kept in open places overnight.
In the morning, chopped pieces are given with honey to the patient for five days. [23] Colocacia esculenta Bulb The dried bulb in the powder form is used for the treatment of jaundice. [24] Conyza japonica Leaves Leaf paste is used to cure jaundice. [29] Cucumis sativus Fruit Fresh fruit is cut into small pieces and taken thrice a day for three weeks to cure jaundice. [24] Cuscuta reflexa Whole plant A decoction of the whole plant is used to treat jaundice. [24] Crepis flexuosa Whole plant Whole plant juice is mixed with water in equal proportion and taken once a day to cure jaundice. [31] Datura stramonium Leaves and fruit Fruits and leaves are used to cure jaundice. [42] Emblica officinalis Roots A decoction of roots is recommended for two weeks to cure jaundice. [24] Elaeagnus rhamnoides Fruit Fruit juice is used to cure jaundice.
[31] Euphorbia hirta Stem and leaves Stem and leaf extract is used to cure jaundice.
[24] Euphorbia tirucalli Leaves A decoction of leaves is used for the treatment of jaundice. [39] Equisetum arvense Young branch Young branches are dipped in the water overnight, and juice is (mix a small quantity of Kujja-Mishri and two and a half kali mirch seeds) taken daily empty stomach at least for seven days to cure jaundice. [23] Flacourtia ramontchi Bark, fruits, and roots Bark, fruits, and roots are used to treat jaundice.

Botanical Name Plant Part Used Mode of Use Reference
Gentiana tubiflora Whole plant The whole plant is ground with lazi (salted curd) to form a paste and given for forty to forty-five days to cure jaundice. [30] Gentiana leucomelaena Gentianopsis detonsa Gentianopsis paludosa

Whole plant
Plants are crushed with a small proportion of petals of Polemonium caerulem, and this mixture is given with curd or cow milk empty stomach for fifteen to twenty-two days to cure jaundice. [30] Gentianella moorcroftiana Aerial plant part Juice of fresh extracted aerial plant part is taken empty stomach to cure jaundice. [31] Gernaium nepalenses Roots Root powder (2 g) is administered thrice a day to cure jaundice. [42] Geum elatum Wallich Leaves Leaves extract, mixed with cow milk or curd, is given for fifteen to twenty-two days to cure jaundice. [30] Hedera helix Leaves Crushed leaves' juice is used to cure jaundice. [27]

Hippophae tibetana
Fruit A decoction of the fruit is taken to cure jaundice. [31] Hordeum vulgare Seeds Dried seed powder is mixed with a sugar solution to cure jaundice. [37] Justicia adhatoda Roots A decoction of its roots is given to the patient for one month to cure jaundice. [24] Leucas cephalotes Entire herb Juice of the entire herb (10-15 mL) is given to the patient for eight to ten days. [23,36]

Mallotus philippinensis
Seeds Seed powder is given for the treatment of jaundice.

Mentha spicata Leaves
Fresh leaf juice is taken with Kujja-Mishri and given twice a day for two or more weeks. [23] Morus alba Fruit Fruit juice is used for treating jaundice. [24] Morus nigra Fruit Fresh fruit juice is given to the patients twice a day for two weeks. [24] Oroxylum indicum Bark of the stem Crushed bark is soaked in water overnight and given with a small amount of kapoor to cure jaundice. A decoction of the bark is also used for treating jaundice. [23] Persicaria amplexicaulis Whole plant A decoction of the whole plant is given orally to treat jaundice. [26] Picris hieracioides Whole plant Plant extract with salted curd is given to the patient for twenty to thirty days. [30] Pistacia integerrima Fruit Fresh fruit juice is given daily for seven days to curing jaundice. [24] Phyllanthus fraternus Whole plant, roots A decoction of the entire herb and juice of fresh roots is given for seven days to cure jaundice. [23] Picrorhiza kurroa Rhizome Rhizome powder is used to cure jaundice. [24] Polygonum tortuosum Whole plant A paste of the whole plant is mixed with curd (prepared from goat's milk) and given an empty stomach for fifteen to twenty-two days. [30] Podophyllum hexandrum Flower and leaves The juice of flowers and leaves is mixed with butter and taken orally to cure jaundice. [41] Prunus domestica Fruit The fruit extract is used for the treatment of jaundice. [24] Punica granatum Fruit and seeds Seeds and fruit powder is taken with water and sugar solution to cure jaundice. [24] Raphanus sativus Root and fleshy part A decoction of roots and juice of fleshy part is given to cure jaundice. [24] Ricinus communis Leaves Leaf juice is given with cow's milk early in the morning for seven days to treat jaundice. [23] Rosa webbiana Fruit Fruit powder is mixed with little quantity of water and taken daily to cure jaundice. [31] Rubia manjith Roots and stem Roots and stem paste is given to cure jaundice. [42]

Saccharum officinarum
Stem Stem juice is used to cure jaundice. [24]

Saxifraga flagellaris
Leaves and stem Leaves and stems are used to cure jaundice. [28] Scorzonera divaricata Leaves and shoot A decoction of leaves and shoots is taken orally to cure jaundice. [31]

Botanical Name Plant Part Used Mode of Use Reference
Sesamum indicum Leaves Powder made from fresh leaves is used to cure jaundice. [24] Solanum nigrum Leaves Tablets are made from crushed leaves and taken with imli (tamarind) or curd for treating jaundice. [23] Solanum surattense Fruit The fruit is directly consumed for the treatment of jaundice. [24] Tamarindus indica Fruit and root A decoction of its roots is used to treat jaundice. The fruit is also used to cure jaundice. [24] Taraxacum officinale Root and leaves and whole herb The entire herb in the crushed form (10 gm) is given to the patient for ten days to curing jaundice. [23] Terminalia bellirica Leaves A decoction of leaf powder is taken to cure jaundice. [36] Terminalia chebula Fruit rind Fruit powder is mixed with rock salt and taken with warm water for eight to ten days to cure jaundice. [23] Thalictrum foliolosum Roots A decoction of roots is used to treat jaundice. [27] Tinospora cordifolia Fresh stem The dried stem of the giloe is crushed with punarnava mool, and its juice is taken for seven to ten days. [23] Trigonella emodi Leaves and flower Leaves and flower powder is taken with water twice a day for seven to ten days. [31] Urtica dioica Whole plant The whole plant is used to treat jaundice. [42]

Vernonia anthelmintica
Seeds and leaves A decoction of seeds and leaves is given to cure jaundice. [27] Viola serpens Whole plant A decoction of dried plant is taken with sugar for more than fifteen days. [24] Woodfordia fruticosa Flowers Flower extract is used to cure jaundice.
[24] Youngia tenuifolia Leaves Leaves are used to treat jaundice. [28] 1 Figure 4. Analysis of the data showing a total estimation of plant parts used for the treatment of jaundice [8,44].

Mode of Plant Used for the Treatment of Jaundice in Himachal Pradesh
Traditionally, people of Himachal Pradesh use these plant species in appropriate dosages or amounts for curing jaundice. There are different methods of usage of these medicinal plants, like in district Hamirpur, bulb of Colocasia esculenta is cooked as a vegetable, the dried bulb is cut into pieces and then crushed to make powder and given orally to treat jaundice, and juice of fresh Pistacia integerrima is given daily to cure jaundice [24]. Uses of other ethnomedicinal plants are described in Table 2, which includes the plant's botanical name, plant part used, and mode of use (route of administration) of these plants for treating jaundice. In most cases, these plants are taken alone as a decoction or with a combination of the talmishri or kali mirch. On the other hand, some plants are also taken in combination with other plants, e.g., Emblica officinalis fruit is taken along with the Terminalia chebula and Terminalia bellirica fruits, grounded into powder form, and taken orally to cure jaundice [25].
The above pie-chart highlights the different plant parts commonly used for the treatment of jaundice, as analyzed from data in Table 2. It was observed that for jaundice treatment, leaves are highly utilized (31.03%), followed by fruits (20.68%), roots (19.54%), whole plant (19.54%), seeds (8.04%), stem (10.34%), flowers (5.74%), and bark (3.44%); the same pattern is also shown in Figure 3. This indicates that in most cases, the leaves of medicinal plants have more significance than any other plant part. Hence, it can be concluded that leaves are highly effective for curing jaundice, which may be due to more phytochemical accumulation in the plant leaves. However, fruits are the second most used to treat jaundice, root belongs to the third position for treating jaundice, and bark is utilized in the least cases.
Intake of these ethnomedicinal plant parts is suggested to be continued for a definite period or until full recovery. Thus, plants are suggested to be taken in the form of paste, decoction, extract, and dried powder form. Different plant parts contain various organic compounds within them, called secondary metabolites, which may be the reason behind the effectiveness of plant-based treatments and show various chemical and physiological actions against jaundice. These phytoconstituents include proteins, carbohydrates, steroids, terpenoids, alkaloids, saponins, phenols, flavonoids, vitamins, tannins, and essential oils, which show an inhibitory effect against hepatoprotective diseases, mainly against jaundice [45,46]. T. chebula contains a significant amount of phenolic and flavonoid compounds. The main constituents of the plant include 2,4-chebulyl-β-D-glucopyranose, ellagic acid, gallic acid, and chebulic ellagitannins. T. chebula is one of the main components of the important Ayurvedic formulation "Triphala" (infusion of three fruits, i.e., T. chebula, T. bellirica, and Emblica officinalis). Ayurveda prescribes this formulation to cure kidney and liver dysfunctions. T. chebula extract ensures hepatoprotection against liver diseases, such as jaundice, due to its antioxidant activity and bilirubin level lowering effect. The reduction in serum bilirubin level is the most important evidence, which supports the traditional use of the plant against jaundice [47].

Phytochemical Constituents Present in the Ethnomedicinal Plants
The medicinal property of plants is mainly because of the formation or stimulation of various chemical compounds that occur naturally in the plants and hence used to cure jaundice and various other diseases. So, this review describes various phytochemical constituents present in the ethnomedicinal plants used by people of Himachal Pradesh for curing jaundice, and the data is taken from different sources. The plants are further used for the development of antimicrobial and antioxidant drugs [48], thus proving their medicinal worth. Plant like Justicia adhatoda consists of various organic [49] and bioactive compounds [50], which possess numerous biological activities, such as antitussive, abortifacient, cardiovascular protection, anti-inflammatory, and antimicrobial. Berberis lycium plant shows the presence of tannins, terpenoids, fats, resins, and many active alkaloids. The roots are the foremost important part of the Berberis species as they contain a variety of alkaloids, and the most prominent one is berberine. It has been found that the inhibitory activity of Berberis lycium is shown by the components present in its root extract [51]. Like this, many other plants are used in the treatment of jaundice, possessing various phytochemical constituents, out of which some predominant phytochemicals are described in Table 3. Table 3. Major phytochemicals present in ethnomedicinal plants used for curing jaundice in Himachal Pradesh.

Ethnopharmacological Evidence of Some Plant Species Used for the Treatment of Jaundice
As described in Table 3, the beneficial effects of medicinal plants are due to the presence of different bioactive compounds that are responsible for the treatment of jaundice. Ethnomedicinal studies combined with phytochemicals are one of the convincing approaches for ethnopharmacological studies [118]. The medicinal effect of different plant parts shows various hepatoprotective activities, including the curing of various liver diseases in which one of the major diseases is jaundice. Various ethnomedicinal plants are traditionally used for the treatment of jaundice, while some plants promote the discovery of active compounds, which further aids in the development of synthetic drugs against jaundice. Although some epidemiological studies are required for the practical implementation of the plants for jaundice treatment [47]. To assess the ethnomedicinal significance of the hepatoprotective plants used, particularly for treating jaundice, different plant species have been reported to be used in various in vivo experiments (Table 4). Table 4 includes various plant species, plant parts used/extracts taken, toxicant and its dose, experimental model (the animal model used for study), constituents that may be responsible for hepatoprotective activities, and their effectiveness against jaundice [15].
In vivo experimental studies with these plants (Table 4) have shown effective results in the treatment of jaundice and confer scientific evidence regarding plant use in the same. In most of the in vivo studies, hepatotoxicity is introduced with CCl 4 or with paracetamol; however, in few cases, gentamycin, thioacetamide, t-BHP, and ethanol are also used for the same. Phytochemicals observed for curing hepatotoxicity are phenolic and flavonoid compounds as a major factor in curing hepatotoxicity in most of the in vivo studies. In some cases, hepatotoxicity is reduced by the decrease in serum bilirubin level and an increase in the antioxidant defense system.  Ricinus communis Leaves (ethanolic extract/800 mg/kg) Paracetamol-induced cholestasis (2 g/kg)/adult Druckrey rats Ricinine and n-demethyl-ricinine [138] Solanum nigrum Whole plant (water or methanolic extract 500 mg/kg) CCl 4 -induced hepatotoxicity (0.2 mg/kg)/Wistar albino rat NA [139] Tamarindus Indica Stem bark (ethanolic extract/NA) Hepatic damage induced (100 to 200 mg/kg bw)/female SD rats NA [140] Terminalia chebula Fruit (aq. extract/NA) t-BHP-induced hepatotoxicity/(NA)/mice Phenolic compounds [47] Thalictrum foliolosum Roots (ethanolic extract (200 to 1000 mg/kg bw)) Paracetamol-induced hepatotoxicity (2 g/kg bw)/Wistar rat and male albino mice NA [141] Tinospora cordifolia Root, stem (petroleum ether/ethanol and aq. extract/400 mg/kg bw) CCl 4 -induced Flavonoids, alkaloids, and phenolics [15] liver toxicity/albino Wistar rat

Woodfordia fruticosa
Flower (petroleum ether, chloroform, ethanolic/250 mg/kg bw) CCl 4 (1%)/albino Wistar rat NA [5] As few plants are evaluated with their experimental studies, so this study needs to be intensified more on those plant extracts, which are used extensively for jaundice treatment. Further, nano-formulation of plant extracts enhances their medicinal significance [143,144], so nano-formulation of herbal plants can also be used as an alternative for curing jaundice in the future. At the same time, farmers should be encouraged for the commercial production of important medicinal plants and should further have support from industry and government.

Conclusions
Ethnomedicinal knowledge is respected by rural people and has been shown to be useful in the treatment of various diseases and the production of medicines in the Western Himalaya from time to time. Traditional or folk-based plant medicines have shown great potential to form the basis of jaundice-curing drugs. The purpose of the present study was to record the ethnomedicinal knowledge of plants used for the treatment of jaundice by the rural and tribal communities of Himachal Pradesh in western Himalaya. The other aims of this research were to discuss the different important phytochemicals and active compounds present in these plants and to discuss the different in vivo studies performed in support of their medicinal uses, with specific reference to the treatment of jaundice. The outcome of this research showed that the rural people of Himachal Pradesh used 87 different plant species with 51 different families to treat jaundice and contribute to healthcare. These plants demonstrated the presence of several phytochemicals in them and displayed phenolic and flavonoid compounds with hepatoprotective properties in most of the experimental studies (in vivo) performed with these plants. With antioxidant potential, the phenolic and flavonoid compounds are recognized, and due to this property, these plants have been shown to be important in curing jaundice. Aloe vera, Bauhinia variegata, Berberis aristata, Emblica officinalis, and Terminalia chebula are some of these herbs, which suggest the ethnopharmacological approach to treating jaundice with the hepatoprotective operation.
There is a lot of knowledge in the latest literature on the use of various plants for treating jaundice. Nevertheless, very few studies are carried out on the scientific validation of medicinal plants by means of biochemical, clinical, and pharmacological screening to validate the jaundice healing folklore medicine. In the future, it is, therefore, very important to pursue steps that do not deviate from shifting the view of tribal people toward their indigenous belief in the treatment of jaundice to develop successful drugs or to discover new potential sources of drugs. In addition, nano-formulation of plant extracts also improves their therapeutic significance [143,144], and it is also possible to use nano-formulation of herbal plants as an alternative and refining conventional knowledge for the potential cure of jaundice.
Author Contributions: D.R., R.D. and A.S. wrote the first draft of the manuscript. R.D. and H.K. contributed to making the figures and providing the literature. R.V., D.K., M.V., K.K. and S.P. revised and improved the first draft. All authors have seen and agreed on the final submitted version of the manuscript.
Funding: It was supported by the UHK project VT2019-2021. This study was also partially supported by grants from the Ministry of Health of the Czech Republic (FN HK 00179906) and the Charles University in Prague, Czech Republic (PROGRES Q40).

Conflicts of Interest:
The authors declare no conflict of interest.