ECLIPTA ALBA (BHRINGRAJ): A PROMISING HEPATOPROTECTIVE AND HAIR GROWTH STIMULATING HERB.

Plants are the primary source of food, shelter, and various remedial approaches. They are being in use for treating various kinds of human ailments across the world since the ancient times. One of such important plants is alba hassk ( Asteraceae ) which is commonly known as Bhringraj and false daisy . This plant is known for its extra-ordinary therapeutic properties. It is one of most widely used plant in traditional systems of medicines such as Ayurvedic, Unani, Sidha, homeopathy, Chinese, and folk. Each part of this medicinal plant contains many important phytochemical constituents such as coumestans, triterpenes, flavonoids, steroids, polypeptides, and saponins. It is majorly used for enhancing the growth, strength, and blackening of hair. It is used as the main ingredient in many hair oils. It significantly treats problems related to hair such as hair fall, dandruff, premature greying, and baldness. E. alba exhibits many other important biological properties such as anticancer, anti-bacterial, anti-viral, anti-stress, and immunomodulatory. Thus, this medicinal plant is playing a vital role in the medical field and cosmetic industry. The present review is a summary of phytomedicinal importance of E. in Ayurveda as well as folk medicine system.


INTRODUCTION
Nature is the primary source of numerous medicines for thousands of years [1,2]. Among plants, medicinal plants are of great significance. Medicinal plants are those plants whose one or more than one part possess substances which are medically important and are used for the synthesis of new drugs [3,4]. Kingdom plantae is considered as the treasure house of many important drugs. It has been a culture of using medicinal plants [5]. Initially most of the medicinal preparations were obtained from the plants only either in the simpler form or in the complex form [6]. Drugs derived from plants are named as herbal drugs, botanical drugs, botanicals, phytomedicines, traditional medicines, herbal medicines, traditional Chinese medicines (TCMs), traditional herbal medicinal products, natural health products, or plant food supplements. These phytomedicines have advantages over synthetic drugs such as they are easily available, less expensive, safe, and efficient and have negligible side effects [7][8][9][10]. Even most of the modern drugs are derived from the natural sources like plants. As per the data resources, quarter of the medicines used in the present times in industrialized countries has been derived from tropical plants directly or indirectly [11][12][13]. Medicinal plants have a very rich history of their utilization to treat variety of diseases. The practice of using plants to treat diseases and get relief from physical sufferings is as old as the origin of mankind [14,15]. As per the estimated reports of the WHO, in developed nations around 80% of the total population rely majorly on the phytomedicines for maintaining their health and fulfilling basic requirements [16][17][18][19]. India comes under the category of world biodiversity centers which is blessed with the rich medicinal plant history having more than 45,000 diverse species of plants; therefore, it is considered as Botanical garden of the world [20,21]. Indian medicinal plants are used in many traditional systems of medicine such as Ayurveda, Siddha, Unani Folk system, and as well as allopathy [22]. Ayurveda is the most ancient traditional medicine system. There are almost 600 medicinal plants and their formulations are being in use in Ayurvedic practices for the treatment of several diseases [23]. In U.K. around 25% of population use phytomedicines in their day-today routine. Phytomedicines are used in each and every corner of the world. Medicinal herbs are used for the healing purpose by African population [24]. In Africa, traditional medicines are being in use since 4000 years. These medicines served as the primary health-care system in the absence of modern medicines [25,26]. More than 1000 species of plants are mentioned in the compendium of Materia Medica which is an ancient encyclopedia of TCM [27]. In China, medicinal plants are being in therapeutic use in dietary therapy for numerous years and thus maintaining the health [28,29]. As per the reported data, 60 out of 104 global drugs that are used for last 37 years have been derived from the TCM plants [30]. In countries like West Africa modern drugs are not affordable by many people thus people rely on phytomedicines for cure and heal purpose [31]. About 85% of Swazis and Nigerians use traditional medicine as a health-care system [32,33]. Approximately 27% of South African population uses traditional medicines as its main health care system. Eclipta alba (L.) ( Fig. 1) is one of most well-known and valuable medicinal plants in India. It is commonly named as false daisy and Bhringaraj and Karisilakanni. Genus Eclipta originated from the Greek word "Deficient" which means absence of the bristles and awns on the fruits [34,35]. E. alba (L.) belongs to the family Asteraceae. This medicinal plant has rich ethnomedicinal history. E. alba and its therapeutic value has also been mentioned in classical text "Bhavaprakash" [36]. In Ayurveda, it is named as "bhringoraaja", in Unani system; it is named as "bhangra" whereas in Siddha it is named as "karissalaankanni" [37]. E. alba is categorized into three categories on the basis of the color of the flowers/fruits which are white-flowering, the yellow-flowering, and the black-fruiting. Each type is found in marshes, rivers, and lakes or on the foothills of the Himalayas in India [33]. This medicinal plant is mostly used in tropical and sub-tropical regions as a traditional medicine. It is also utilized as a functional food [38]. It is a very famous hepatoprotective drug and popularly called as "King of hair" [39]. The extracts of this medicinal herb are used as preventive measure or as an anti-venom against snakebite. It is used to treat issues related to gastro-intestinal tract, respiratory issues, to heal cut and wounds, inflammation, and many more diseases [40][41][42][43][44]. Wedelolactone, demethylwedelolactone, desmethyl-Wedelolactone, furanocoumarins, oleanane and taraxastane glycosides, and 7glucoside are the primary coumestan derivatives present in E. alba [45,46]. Ecliptal, ß-amyrin, luteolin-7-O-glucoside, hentriacontanol, heptacosanol, stigmasterol are other principle phytochemical constituents of E. alba. Each part of this
Eclalbatin, dasyscyphin C is present in the roots which are associated with the properties such as anticancer, antiviral, and antioxidant activity [75].

Polypeptides
The main polypeptides present in E. alba are cystine, glutamic acid, phenyl alanine, tyrosine and methionine.

TRADITIONAL AND MODERN VIEW OF E. ALBA (BHRINGRAJA)
Ayurvedic view E. alba is called as Bhringaraja in Ayurveda. It is one of the most valuable plants in Ayurveda. This magical herb is associated with many biological properties which are being used in many Ayurvedic practices for the treatment of various human ailments. It significantly works on Pitta dosha (Fire and water component of the body) and Vatta dosha (air and space components of the body). It acts aa a rasayana. The extract obtained from the leaves is used as liver tonic, rejuvenative and beneficial for hair, eyes, edema, and phlegm [84]. It is mentioned in Dhanvantari Nighantu, Raj Nighantu, Kaiyyadev Nighantu for its use in pandu, shotha and kamala [85][86][87]. Rasapanchak of E. alba (Bhringraja) as per Ayurveda is shown in Table 3.

Sansthanic Karm-wahaya
It is topically used in cuts, wounds, and inflammation/swelling. It reduces headache when its oil is applied on head. It is used as eye/ear drop to reduce pain. It is also used in elephantiasis. It is very good for hair as it helps in growth, strengthening and blackening of hair. It is used in hair disorders such as premature greying, dandruff, hair fall, and baldness.

Abhyantar-nadi sansthan
It is used as pain killer.

Netra
It is beneficial for eyes.

Pachansansthan
It improves digestion and enhances appetite. It is good for liver. It helps in digestion of "ama" which means toxins and undigested food. It also acts as an anthelminthic. It is used in conditions such as anorexia, hepatomegaly, splenomegaly, jaundice, piles, and abdominal pain.

Rakatwahsansthan/Twacha
It helps in blood augmentation. It used in treating anemia. It induces sweating and helps to fight against skin disorders. It used in treatment of leprosy, psoriasis, eczema, and utricaria.

Swasansansthan
It has mucolytic property. It is used in cough and cold conditions.

Mootrawahsansthan
It has diuretic properties. It is used as a cure in burning micturition.

Prajnansansthan
It has aphrodisiac property.

Satmikaran
It enhances body strength.

Tapkram
Due to its sweat inducing and ama pachna property it acts as an antipyretic agent.

Some Ayurvedic formulations of E. alba (Bhringraja) [91-94]
Bhringraja is used in many Ayurvedic formulations. For example, Bhringraja taila is used for Khalitya (Hair fall or loss of hair). Another formulation of yakrit plihantak churna is used as an hepatoprotective. An important Ayurvedic cosmetological formulation of E. alba along with Vitex negundo, Sphaeranthus indicus and Carum copticum is used as a rejuvenator in the treatment of Kayakalpa.
Folk view E. alba (Bhringraja) is an important medicinal herb with rich history of its utilization in various folk systems around the world. It is used to treat numerous diseases. For instance, in Thailand, people use E. alba leaves against skin related problems and hair fall. They use stem to treat tuberculosis, asthma and as a blood tonic while E. alba roots exhibit antibacterial properties [95]. In Egypt, people administer plant juice to blacken the hair and beard [96]. In Philippines, people use this plant for hemoptysis and hematemesis. It is used in tea for treating sprains, furuncle and dermatitis. Dried for the herb is also use against dysentery and heamturia urine [97]. It is used as an emetic and purgative agent and in the treatment of cuts and wounds. People also use it in the treatment of jaundice in Eastern Nepal [98,99]. In many areas of India, leaf extract along with cow milk is used against the weakness of vision whereas leaves are also used to reduce wrinkles and heal wounds, palpitation, pimples, premature greying of hair, gingivitis, and alopecia. Whole plant is consumed in treating diarrhea and dysentery, fever, general weakness, jaundice, liver related problems, loss of appetite, and edema, whereas root extract is used against hemorrhoids [100]. In Himachal Pradesh India, people use leaf decoction of E. alba against headache. The extract obtained from the leaves is used against head lice, cold, and asthma [101]. E. alba is a common remedy for the upper respiratory infections and eye/ear infections in children. Bhringraj oil is used all over the India for good hair [102]. In Punjab, Pakistan leaves, roots, and flowers of E. alba are prescribed by herbal healers as a cure for liver disorders, hepatic, and spleen ailments. Leaves are used to enhance the digestion and appetite. The whole plant is used as hair tonic, whereas leaves are used to treat athlete's foot disease [103,104]. In Bahawalnagar District, Punjab, Pakistan, people use to chew E. alba leaves to improve their eye health and they treat hypertension using the extract of this plant [105]. In Bahawalpur, Pakistan, this plant is used as a blood purifier and hair tonic. It is also used against leprosy, itching, earache, jaundice, fevers and bleeding disorder, toothache and gum complaints, nausea, and vomiting [106]. In Odisha, India, leaves are used as an antibacterial agent [107]. The juice of E. alba is useful for the expulsion of worms in infants. Manipuri tribes use stem decoction of this plant against liver enlargement while use extracts of leaves in cough and fever. Toto tribe of India uses it as an antidote against scorpion sting. Some communities  [109]. In Javadhu Hills Tamil Nadu, E. alba leaves are used for treating diabetes [110]. Gujjars of Rajaji Tiger Reserve, Uttarakhand, treat liver problems with the leaves of this plant [111].
In some areas of Tamil Nadu, people use the paste made up of leaves of E. alba to prevent dandruff and to enhance the hair growth [112]. In some villages of Dakshin Dinajpur District, West Bengal, people use leaf and seed of this plant to treat problems related to stomach and liver, inflammation, digestion, and use it as a hair tonic [113]. In West Nimar district, Madhya Pradesh, people use oil extracted from the seeds of E. alba to enhance the hair growth [114]. In areas around the Dandeli Wild Life Sanctuary, people treat warts and leprosy by applying the E. alba leaf juice [115]. People of Warangal district of Andhra Pradesh, use this plant to avoid hair fall and provide strength to hair and to increase the appetite [116]. The people of Nandurbar tribe of Maharashtra use this plant as a remedy for menorrhagia [117]. The tribal people of Peth and Trimbakeshwar of Nashik District, Maharashtra, the leaves of E. alba are used for treating the injuries caused by mud [118]. In Chennai, people use whole plant as a liver tonic. Leaf juice along with honey is used to treat cough and watery nose in children. Furthermore, the leaves juice is used for hair growth [119]. In Karnataka, this plant is used as an antidote for scorpion bite while the paste made up of this plant is used to blacken and strengthen the hair [120]. In Chittagong Hill Tracts, Bangladesh, people use paste made up of stem, and leaves of E. alba against skin problems [121]. In Koikuri, Dinajpur, this plant is used to heal wounds and as a remedy for skin diseases [122]. In West Singhbhum districts of Jharkhand, people eat E. alba leaves used as a leafy vegetable as a cure to anemia [123]. The plant is administered as nasal or eye drop to get relief from pain and chronic headache in Bayelsa state of Nigeria [124].

Modern view
In the modern era people are showing great interest in herbal medicines because these have several advantages over the modern synthetic drugs. The demand of herbal drugs in the market is increasing rapidly due to which the chances of their adulteration/contamination have also increased [125,126]. There are several factors which promote the degradation of the herbal products such as misidentification of species or plant parts, intentional adulteration, and contamination. Due to all these factors the quality and safety of herbal drugs is in question [127].
There are reported cases of misidentification of herbal plants that might happen due to similarities of morphology of the plants and sometimes due to conflict in the common as well scientific names of the plants. This is one of the primary reasons that lead to the degrading of the herbal products [128]. Another major factor of degradation of herbal products is intentional adulteration which is done in many ways such as by inducing either orthodox drugs or by substituting products of inferior quality or by introducing foreign particles or contaminants like sand, metals, soil etc. The main purpose behind intentional adulteration is to derive maximum profit [129][130][131]. Most commonly used contaminants in herbal products are heavy metals like mercury, arsenic, and lead, cadmium, copper and thallium. Other contaminants used are pesticides, microbes, and mycotoxins [132][133][134][135][136][137][138]. The most common forms of herbal drugs available in the market are powders, capsules, and extracts. Adulterants are often induced before processing stage or during the processing of herbal drugs. Proper quality analysis and standardization at these stages are required to avoid health risks [139][140][141]. Standardization of herbal drugs confirms the accurate quantity, quality and associated therapeutic properties with dosage [142]. Techniques like standard DNA barcode have proved to be important in detecting species misidentification [143].

PHARMACOLOGICAL AND THERAPEUTIC USES OF E. ALBA (BHRINGRAJA)
E. alba (Bhringraja) has variety of phytochemical constituents present in it which exhibit various therapeutic properties. Some of its reported therapeutic uses are summarized below.

Hepatoprotectivity
Singh et al. conducted a study on rats and mice models in which lung injury was induced artificially by carbon tetrachloride. It was found that alcoholic extract of E. alba (Bhringraja) exhibit hepatoprotective activity at a dosage of 62.5-500.0 mg/kg p.o. Extract restored all the changes induced by carbon tetrachloride [144]. The experimental study conducted by Naik et al., on albino rat models treated with high fatty diet to investigate the hepatoprotective activity of E. alba (Bhringraja) demonstrated that phytochemical constituents such as Wedelolactone, demethylwedelolactone, and saponins are associated with hepatoprotectivity. It was found that these phytochemicals significantly reduced the fat deposition, mononuclear infiltration, and necrotic foci. Regeneration of hepatocytes in the liver was also stimulated by these phytochemical constituents [145]. This activity was also investigated by Ahirwar and Saxena, on albino rat models. Models were artificially induced with hepatotoxicity by carbon tetrachloride. It was found that isolated fraction of E. alba had significant hepatoprotective potential at dosage of 200 mg/kg body weight. The protein levels were restored after the treatment with E. alba extract. [146]. This activity was also supported by a comparative study conducted by Kumar et al., on albino rat models. In this study paracetamol was used to induce hepatotoxicity in the models. Alcoholic and aqueous extracts were comparatively investigated. It was found that alcoholic extract of E. alba has more potent hepatoprotective activity [147]. Indhuleka and Jeyaraj performed an investigative study on animal models to find out the hepatoprotective nature of E. alba. Models were induced with hepatotoxicity by paracetamol. Study revealed that E. alba has potent hepatoprotective activity [148].

Hair growth
Begum et al. conducted a study on nude mice to evaluate the hair growth promoting activity of E. alba. Petroleum ether extract (PEE) along with other solvent fractions of E. alba was topically applied on the backs of nude mice. Prominent follicular hypertrophy was observed after the treatment with PEE. In the basal epidermal and matrix cells, follicular keratinocytes number was increased. These changes support E. alba use in the growth of hair [42]. Another study conducted by Begum et al., supported the use of E. alba for hair growth. The study was conducted on nude mice models which were genetically suffering from hair loss due to abnormal keratinization. It was revealed from the study that topical application of methanolic extract of E. alba had significant impact on the hair growth of mice models. It was observed that hair follicle number had increased after the treatment which shows that E. alba is a brilliant hair growth promoter [149].

Anti-cancer
An in vitro study was conducted by Chaudhary et al., to evaluate the anti-cancer potential of E. alba. The model systems used for the study were Human liver cancer cell line (HepG2), C6 glioma and A498 cell lines. It was found that hydroalcoholic extract of this plant caused inhibition of cell proliferation [150].

Antibacterial
An in vitro study conducted by Gurrapu (50,100,250, and 500 in µg/mL) while aqueous extract showed significantly less activity than the other extracts [152].

Anti-viral
A study conducted by Manvar et al., against Hepatitis C virus (HCV) showed that E. alba extract had significant inhibitory actions against RNA dependent RNA polymerase activity of HCV replicas in vitro whereas it caused inhibition of HCV replication in cell-culture system which showed its anti-viral potential [153].

Memory enhancer
Banji et al. examined the memory enhancing activity of E. alba. The suspension of E. alba extract in distilled water was administered to rat models. They evaluated the transfer latency of models on an elevated plus maze. The study revealed that E. alba is associated with memory enhancing activities [154].

Immunomodulatory
Syed et al. evaluated the immunomodulatory behavior of E. alba in an in-vitro study. It was found that coumestans such as Wedelolactone and demethylwedelolactone had inhibitory actions against trypsin which supports its use as an immunomodulatory agent [155].

Anti-stress
Chanu et al. studied anti-stress property of E. alba in Labeo calbasu fingerlings in stress was induced by acid. It was observed that ethanolic extract of the plant exhibited anti-stress activity by restoring the levels of stress hormones -serum cortisol, glucose, alanine amino transferase, aspartate amino transferase -and enzymes -lactate dehydrogenase, malate dehydrogenase, ATPase, superoxide dismutase, and catalase which showed its anti-stress activity [156].

CONCLUSION
E. alba (Bhringraj) is a wonder herb which is most commonly used in traditional systems of medicine for treating numerous human ailments. It is widely used for its extra-ordinary property of enhancing the hair growth and provides strength to hair. It possesses wide range of phytochemical constituents such as coumestans, saponins, and alkaloids which exhibit significant biological properties such as hepatoprotectivity, antibacterial, anti-viral, anti-stress, and immunomodulatory. It is used in almost each culture and tribe of the world. It is also used as leafy vegetable in some cultures. In Ayurveda, it is used against diseases such as elephantiasis, anorexia, leprosy, eczema, psoriasis, jaundice, piles, cough, col, and splenomegaly. This small medicinal herb with multiple therapeutic applications can be a promising and reliable source of new drugs in future.

AUTHOR CONTRIBUTION
We declare that this work was done by the authors named in this article and all liabilities pertaining to claims relating to the content of this article will be borne by the authors.
Dr. Gitika Chaudhary drafted the article and contributed in writing Ayurvedic view of the article. Dr. Hemlata Kaurav contributed in drafting and writing pharmacological portion of plant. Isha Kumari contributed in data collection and writing the paper.