A Literature Review on Urtica dioica: An Ordinary Creature with Extraordinary Features

Urtica dioica Linn is a popular medicinal plant that is native to Europe and is very commonly found in Temperate Asia, Western and Northern Africa, America and New Zealand. It is a traditional medicine used widely in various kind of treatment as was believed to be galactagogue – a substance that promotes lactation. It is well recognized in Ayurveda due to its multidimensional pharmacological and therapeutic effects as the compress of nettle help to revive Rheumatoid arthritis, Muscle pain, Sciatic and as Rasaan tonic as it constitutes various beneficial phytochemicals. It is popularly known for its stinging action. Its chemical compounds are highly irritating mainly histamine. Traditionally, the leaves and roots are used as a blood purifier, emmenagogue, nasal hemorrhage, eczema and diarrhea.


INTRODUCTION
Medicinal plants are well known due to their useful action whether therapeutic or other purposes like cosmetic or diagnosis. Urtica dioica is as Kuksha, and Bichu or you can commonly call it Bichu Butti. It is broadly described and used in Ayurveda. It grows at a height up to 2-4 meters and it produces pointed leaves and flowers that are white to yellow and it belongs to Review Article the family Urticaceae [1]. It is well known for its edible leaves but these leaves when coming in contact as raw form they cause an irritation to the skin like itching and redness or a burning like sensation. The origin of its name is derived from the Latin verb "urere" which means burn and dioica means "two houses" so urere is because of the stinging action of the hairs and two houses because it either contains male or female flowers [2]. It is a herbaceous, perennial and flowering plant. As its pharmacological and therapeutic actions are well defined in Ayurveda it is a traditional plant known as Vrisckali in the Sanskrit language. It does have yellow creeping rhizomes, toothed leaves and stems are covered with numerous the stinging part and trichomes also [3]. For a good pharmacological activity, a plant needs chemical constituents filled with therapeutic efficacy and nutrition. It possesses alkaloids, tannins, flavonoids and it is also a medicinal plant that consists of various secondary metabolites that have various pharmacological effects on the body. U. dioica is not very popular but is a very useful medicinal plant [4]. It is also known as chronic or acute or even degenerative can be prevented. This genus is a large group of the plants that comprises of almost 2,625 species in the Urticaceae family. By this plant a wide range of diseases or problems can be cured [2]. and [4].

Fig. 1. Leaves of Urtica dioica
It is just an ordinary plant which can be used for other purposes for example it is used in Yarn making and it is also used as a galactagogue for cow by rural people [1].

Habitat
Urtica dioica L. is a small, evergreen and perennial plant. It is native to cold regions of Europe and is abundantly available in Northern India and now it grows worldwide. It is abundantly found in cooler temperate regions of the world -Africa, Asia, America and Europe. It is widely distributed in Northern regions of Europe and many regions of Asia but less in Southern Europe and North America. It is widely distributed in the USA and Canada, where it is found in other states but not in Hawaii and also in Northernmost Mexico. In Pacific Northernmost it grows at abundance and especially in the regions where annual rainfall is high. The distribution of U. dioica is also found in Europe and Britain and also in Faroe Islands, Iceland, Sweden, Greenland and Bulgaria. It grows in Himachal Pradesh at an elevation of 3,000 meters. Additionally, these species are found in America, Nepal and other Asian countries [5]. It grows very well in soil rich in Nitrogen. It blooms in the month of June to September every year. This plant is green and erect and the leaves are in opposite manner, heart-shaped at its base, oblong or ovate. The color of its flowers can be reddish-brown to greenish-white. It occurs as racemes in the axils of the upper leaves, the plant possesses either male or female flower [6].

Morphological Characteristics
If we will talk about its appearance Urtica dioica is an erect, herbaceous plant. And it is widely known for its painful and unpleasant stinging hair on the surface of its leaves and stem. Its sex identification can be done by its appearance that as if the flowers are yellow or purple then it's the male parts and if it is green or white it's the female part of the plant [7].

Reproduction
Urtica dioica plants reproduce by very popular way of reproduction in plants that is Wind Dispersal of Seeds and creeping rhizomes (horizontal underground stems) and it grows in dense clumps often forming large colonies [7]. This plant is also used for external purposes that is skin problems, sciatica, hemorrhoid, gout and also for hair purposes [10]. A large prostate gland can be a big problem but its roots can be very beneficial in such case. Roots can also be used in other problems like gout, chickenpox and rashes. It is externally applied to bruises [11]. So, let us recall some points of its history. In the first century, Pedanius Dioscorides a Greek Physician and Galen reported that the leaves of U. dioica consist of the diuretic as well as laxative properties. Other traditional uses include asthma treatment, spleen illness and pleurisy [10]. It is also used as a weight loss aid [12]. Nowadays in Germany this plant is being sold for prostate problems and as a diuretic [13]. Since, it is being used for the treatment of rheumatism, gout, arthritis, eczema, UTIs, kidney stone, hay fever, anemia and early stages of prostate enlargement for hundreds of years. The condition of prostate enlargement is known as Benign Prostatic Hyperplasia [13]. As this was being used for rheumatism for a long period of time in recent clinical studies it showed that this plant possesses possible anti-rheumatic properties [14]. According to that study it was reported by Riehemannet. Et al. that this plant possesses active chemical constituents that have the capability to inhibit Nuclear Factor Kappa Light Chain Enhancer of Activated B cells activation. Actually, this factor is a protein complex that controls DNA transcription and the production of cytokines [15]. Some other studies claim that as many as 80% of European Men with BPH were treated with the herbal remedy of this plant to control its symptoms including saw palmetto and roots. [16]. It was also mentioned that the roots can be very effective when used with other herbs and it was highlighted that better results can be found if given in combination with saw palmetto. It can be an effective treatment against BPH and treat urinary problems including a reduction in urinary flow, incomplete urine excretion; post urination dripping and also the constant urge to urinating.
Nettle also show different important pharmacological effects including Antiinflammatory effects and hypoglycemic effects in preclinical studies. The hydro alcoholic extract of this plant at 100 and 200 mg/kg can show a significant anti-diabetic effect against those suffering from fructose-induced diabetic patients [17]. It can also show other pharmacological significances including anti-viral, to treat hay fever and is also be used as an expectorant [18]. [7].

Phytochemical Constituents
There are a lot of plants in this world known for their appearance, fragrance, beauty and medicinal uses. When it comes to medicinal uses the great focus is always its secondary metabolites which are going to be used as a medicine and to prepare a formulation for any medicinal purpose. So, phytochemical screening can be performed to understand the phytochemicals [1]. As, phytochemicals directly affects the Pharmacological properties it is important for a research to know about the phytochemical compositions of a medicinal plant [25]. In the case of U. dioica it is also similar to other plants as its different parts have their own significance for their important chemical constituents [26]. But, this plant is more interesting than any other plant and the reason is of course it stinging action that is produced by its stinging hairs. So, the main cause of this stinging is the chemicals present in the leaves, stem or whole plant which causes irritation and burning to the skin. These chemicals are formic acid and histamine [1]. The leaves of the Urtica are popularly used as a herbal tea to treat and prevent various physiological abnormalities as mentioned above. It was reported that leaves constitute caffeic acid, high content of chlorophyll, chlorogenic acid and other pigments [26]. There are no reports published for the presence of alkaloids. Alguttin that is found in the rhizome is a series of long-chain amino acid linkage. [8]. The structure was also confirmed in the study as a member of the protein family as it

 GC-MS Analysis
In GC-MS analysis it was found that it contains derivatives of cinnamic acid, homovanilyl alcohol, coumarins and some phenolic compounds were found using trimethylsilyl ester. These phenolic compounds yielded 34 compounds and structure interpretation was done by Mass Fragmentation and then was compared with commercially available preparations. [11].
Other compounds found in GC-MS analysis are homovanilyl alcohol, vanillic acid, vanillin, (+) isolariciniresinol, (-) secolaricinresinol. By using methyl iodide, methylated derivatives of phenols and flavonoids from U. dioica with other plants were prepared by methyl iodide and analysis was done. In GC-MS analysis of U. dioica with methanolic leaf extract the presence of homo vanillic acid (3.0ng/mg), vanillic acid (2.5ng/mg) and Ferulic acid (574ng/mg) was found [27].

 HPLC Analysis
On preparative HPLC analysis using Sephadex column aqueous extract of U. dioica leaves yielded two fractions. One was found to contain the proteins (glycoproteins) & carbohydrates. In the study of Blumenthal et al. an experiment was attempted to study the link between proteins and carbohydrates by hydrolysis with NaOH and NaBH 4 and it was found that both are connected via serine and O-galactosidic linkages and methylation was also done with the help of which it was reported that glycoproteins were branched but unfortunately in this methylation the study on the second fraction was reported to be unsuccessful [32].
In HPLC studies it was also reported that roots showed the presence of trans-neo-olivil, a lignans glycoside [29].

Phytochemical Composition of Urtica dioica
There are a lot of factors that can affect the chemical composition of nettle plants like variety, climate, genotype, and vegetative stage, and soil, time of harvesting, processing, storage and treatment. This plant is a rich source of nutrients.

PHARMACOLOGICAL ACTION
Extract from Urtica dioica has a broad-spectrum pharmacological activity. It does have highly acting antioxidants this plant source is a rich antioxidant plant which has good activity as an antioxidant can prevent various free radicals induced problems in the body. It also acts as a

 Anti-diabetic Action
In the study of Korani et al. it was found that 250mg/kg hydro-alcoholic extract of the leaves of U. dioica was used to prevent the severity of diabetes in STZ induced diabetes in rats and it showed a reduction in complications like behavioral changes and cognitive dysfunction and oxidative stress. This plant also possess anti-diabetic mainly leaves possess this action. Leaf extract can help to decrease serum glucose levels. Its extract shows a significant increase in insulin secretion and hence decreases blood sugar level. In another study, it has been shown that the cold methanolic leaf extract (250mg/kg) can show anti-hyperglycemic action in Alloxaninduced diabetes [37].

 Hepato-protective Action
In the study of Joshi B. et. al., the 150mg/kg extract of leaves of the plant show significant hepato-protection in isolated liver cells of rats (in vitro) lower down the chances of degeneration of hepatic cells and necrosis in CCl 4 induced hepatotoxicity. The ability of an agent or drug or a molecular entity to shoe action against liver damage are referred as hepato-protective. Again, leaves help to cure these kinds of damages tap liver. Leaf extract of U. dioica shows a very good hepato-protective action by decreasing levels of ALT (Alanine transaminase), AST (Aspartate phosphatase), ALP (Alkaline phosphatase) and MDA (Malon di-aldehyde). Another part of the plant that are seeds also show hepato-protection with ischemia-reperfusion and help to protect liver by increasing the activity of enzymes like aryl esterase and liver tissue catalase activity. [38].

 Anti-inflammatory Activity
In the study of Patel S. et al. it was reported that extract of Mt-OH extract seed oil of Urtica dioica at a dosage of 200mg/kg inhibit the twitches in the abdomen induced by acetic acid and 400mg/kg inhibit inflammation in paw edema induced by carrageenan and a positive result was found. It also possesses anti-inflammatory action. In a study it has been found that Mt-OH extract can show activity to inhibit acetic acidinduced model on rats. Actually, this can be caused due to the anti-inflammatory effect of the plant by inhibition of NF-kB activation. Actually, the hair in the leaves and stem of the plant consist of different kinds of chemicals that can lead to pain relief and show action against inflammation. Due to its action against inflammation, it can be used in Arthritis. Secondary metabolites are mainly responsible for anti-inflammatory action is Glycosides [39].

 Antiviral Activity
In the study of et al. they used U. dioica in combination with Sambucus nigra L. and used FIV (Ferine Immunodeficiency Virus) as a model and found that at some concentration it showed anti-viral activity against FIV as assayed by forming of syncytia using CrFK. As this plant can deal with so many physiological problems it has been found that it can also deal with viral infections. In some studies, it has been noticed that it can work against FIV, a virus that has been widely spread in domestic cats which can be similar to a very popular and lethal virus HIV (Human Immunodeficiency Virus) [41].

 Diuretic Activity
In a study by Dizaye K. et al. it was found that aqueous extract of the whole plant was administered at a dose of 4 mg/kg showed diuresis in rabbits and significant diuretic property was found. As U. dioica is a herbal plant so it can act as a natural diuretic due to some beneficial constituents. It has been found that it is a loop diuretic and then it can cause hypokalemia by the excess output of Potassium in urine. This plant has been reported for its remarkable diuretic action. A wide range of phytochemicals such as Alkaloids, Tannins and Phenols which possess the diuretic action are present in U. dioica. [42].

 Immunomodulatory Action
In the study of Beatriz S. et al. they malnourished Wistar rats for 21 days and then they were treated with extract of the leaves U. dioica at a dose of 0.2g/ml and was found to give a significant immuno-modulatory action.
Immuno-modulatory action of this plant is due to flavonoids. Mainly in those who were suffering from a deficiency and chronic granulomatous disease. For the management of HIV infection an oral immune-modulator has been reported that consists of flavonoids extracted from U. dioica. When it is used as an immune-modulator it can produce several allergic substances that can cause edema and also inflammation [43].

 Anti-cancer Activity
In the study by Kopytko Y et. al the extract of the aerial parts of the plant was used and it exhibited the highest cytotoxicity against breast infection and it was found that 85% of cells were dead at 500μg/ml and due to the phenolic content present and was observed to inhibit mutagenesis in humans. [46].

Sr. No. Part of the plant Phytochemical constituents
Pharmacological Activities
In today's world cancer has been one of the greatest lethal diseases and as his herb consist of the antioxidant property so it can be effective against free radical-induced Cancer. Several studies have been found that has demonstrated that U. dioica possess Anticancer activity particularly it works against colon, gastric, lungs, prostate and breast cancer [44].

STINGING ACTION OF NETTLE
As mentioned earlier in this review Nettle is well known for its stinging action, it causes inflammation on the skin mostly hands come in contact with U. dioica that can cause a burning sensation. This mechanism is known as Contact Urtica [61]. This contact of skin with leaves or stem or even whole body of the plant can lead to irritation, itching and pain by few biochemical presents in it. These active chemicals which produce this unpleasant sensation are -Histamine, Serotonin and Acetylcholine [62]. The solution to get rid of that pain is -Anti itching drugs as creams, these creams consist of Antihistaminic agents, Hydrocortisone that provides relief [63]. Cannabis leaves are also used to provide relief only by rubbing it on the affected region [64].

CONCLUSION
So, from above-mentioned information in this review article, it has been found that Urtica dioica do have both therapeutic as well as dietary potential. It has also been found out that this medicinal herb is mentioned in Traditional Indian Pharmacopeia Ayurveda. As it contains a huge number of phytochemicals that do have pharmacological potential and is very effective against so many physiological problems. Different pharmaceutical formulations are being used in different dosage forms depending upon the conventional route of administration.

DISCLAIMER
The products used for this research are commonly and predominantly use the products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by the personal efforts of the authors.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.