Euphorbia hirta, an important medicinal herb, belongs to family Euphorbiacese. As a widely used local and traditional Chinese medicine ( TCM ) in clinical practice , the whole plant is commonly applied to cure various types diseases, especially gastrointestinal disorders (including intestinal parasites ,diarrhea peptic ulcers ,heartburn vomiting, and amoebic dysentery), affliction of the skin and mucous membranes ( including warts, scabies, tinea, thrush, aphthae, fungal, affections, and measles) and respiratory system disorders (including asthma , bronchitis, hay fever, laryngeal spasms, emphysema , coughs, and colds) [Zhong yao da ci dina ,1986, Zhong hua ben cao,1999] E. hirta is native to Central America. It was introduced into Southeast Asia a long time ago and has since spread throughout. It is a very common herb in the pan-tropic and partly subtropics areas worldwide, including China, India Philippines, Australia, Africa, Malaysia, and so on. In China, E hirta is naturally distributed in Fujian Guangdong Guangxi, Guizhou, Haimam, Hunan, Jiangxi, Sichuan, Taiwan and the Yunnan regions [Flora of China (Year) .Recently, modern Pharmacological investigations showed that E. hirta and its active components possessed wide pharmacological investigations showed that E. hirta and its active components possessed wide Pharmacological action, such as antic, action ,such as anti-inflammatory, antifungal, antibacterial, larvicdal,diuretic, and increases electrolytes. [Lanhers, 1990, Lanhers, 1991; Johnson, 1999; Euphorbiahirta L .Available : http://florabase.dec.wa.gov.au/profile.php/4629]. Most of its pharmacological action is in line with the traditional efficacy. On the other hand, E. hirta is used as livestock fodder worldwide. The chemical components of E. hirta along with its pharmacological action have been studies by various laboratories. Flavonoids, terpenoids, and phenols were isolated and identified as the main composition of E. hirta.
In the current study, an overview of the overall knowledge and information about E. hirta is presented fort the study of its ethno pharmacology, photochemistry, pharmacology, and toxicology.
Botany and ethnopharmacology
Botany
E. hirta is a small is annual, branched herb prostrate to ascending with branches reaching 70 cm in height, reddish or purplish in color with abundant latex covered with shot hairs. Its leaves are opposite, distichous, and simple; its obvious stipules are linear. The leaf blades are lanceolate-oblong, long elliptic,or ovate-lanceolate with assize of 1 cm to 4 cm 0.5 cm to 1 .3 cm base is unequal;cuneate, the other side is round; the apex almost acute, and margins are finely toothed, often with a purple blotch near the midvein. The inflorescence of E. hirta has a terminal or axillary cluster of flowers, called a ‘cyathuium’, with several cyathia densely clustered into a cyme. The flowers unisexual; the male flowers sessile, the bracteoles liner ,fringed , perianth absent , and possesses one stamen, whereas the female flowers have short pedicel ,the perianth rimmed, the ovary superior, covered with short hairs ,three-celled , possesses three styles ,minute ,and the apex is two-fid. Tge fruit of E. hirta is exserted ,acutely three-lobed capsule 1 mm to 1.5 mm, 1 mm to 1.5 mm base truncate, covered in chort hairs , and three- seeded. The seeds are oblong are , Four sided prismatic, 0.7 mm to 0. 9 mm 0.4 mm to 0.5 mm, slightly wrinkled, pinkish brown, and car uncle absen. Flowering duration of individual plant is usually throughout the year E. hirta oftion grows in cultivated areas in lowland, paddy fields, gardens, roadsides, and waste places. They prefer dry condition, from sea-level upn to 2000 m altitude.
Ethno pharmacology
E. hirta has a long history as a medicinal herb in China .Different formulations are used, including crude drug, decoction, infusion, lotion, and powders. E. hirta plays a very important role in TCM, especially in folk medicine because of its wide range of biological and pharmacological properties,.Considering the effects of E. hirta on curing skin ulcer and swelling of body, it was first recorded in “ Ling Nan Cai Yao Lu”.More than ten folk medicinal books in China also have recorded this plant [Yin,2008,; Lian et al. 2005 ;Zhu et al 2007 he et .,2006].The whole plant was officially recorded in a Chinese pharmacopoeia (1977;edition ).However, E. hirta had been removed from the 1958 to 2005 edition ,and have been re-listed as Feiyangcao in the pharmacopoeia edition of 2010. The pharmacopoeia stated the properties of E. hirta that cure fever, detoxify, promote dieresis, stop itching and induces prolactin. The clinical indications include pulmonary abscess, acute mastitis, diarrhea, eczema, furunculosis, pyogenic infections,and postpartum malik. The fresh whole plant or its crude powders were in also traditionally used as veterinary medicine for treating esoenteritus, gastritis, diarrhea in pig ,cattle ,horse ,sheep ,and fish [The State pharmacopoeia Commission of peoples Republic of Chine ,2010].
E. hirta has also been widely used in medicine among minority group including Yao. Zhuang ,Dai, Nazi and Yi, who lived in the southern area of China .The Yao people use the entire plant for the treatment of bronchitis, external usage for scald and burned, decoction of dry plant ,whereas as fresh crushed leaves are used to cure skin disease [Yin,2008]. For the of Zhuang people ,a decoction, infusion , or tincture of the plants is used to treat asthma, chronic bronchial disorders, and emphysema [Liang et al.; 2005] For Dai nationality, E. hirta ,commonly known as Yan an mo ,Is applied to stimulate milk secretion and to stopping cough [Zhu et al.; 2007 .Moreover .E hirta is used to cure gonorrhea and hematurai in Naxi people [He et ., 2006]. Therefore, E. hirta can be served clinically as potential hemostatic.
E. hirta is included in the African pharmacopoeia of the Organization of African Unity as dysentery medication .In South Africa ,E. hirta is commonly used for asthma treatment , which is one of the most common respiratory complaints [Ekpo et al ., 2007 In West Africa, E. hirta is used a livestock fodder. In the Gold coast, E, hirta was ground .Mixed with water, and used an enema for constipation. In traditional Indian medicinal systems, the leaves are used in the treatment of coryza, cough, asthma, bronchial infections, bowel complaints, helminthic infestions, wounds, kidney stone, and abscesses. In addition, it is used for the treatment of syphilis .The latex is applied to the eyes to treat conjunctivitis and corneal ulcerational .The tender shoots are used as famine food ,raw or steamed , but they may cause intestinal complaints . Moreover, E. hirta is used by nursing mothers with deficient milk supply. In the Philippines , Leaves are mixed with dature metel leaves and flowers in the preparation of “asthma-cigarettes’ The latex and fluid extract of the tincture are used in asthma , chronic bronchitis , emphysema ,as well as in pulmonary cardiac disease and angina pectoris and ringworm. The decoction is used to allay the dyspnea of asthmatics. The decoction of the root is used to aiiay vomiting, chronic diarrheas, and fevers. Root decoction is also used for snake bites, sores, wounds, and is beneficial for nursing mothers with deficient milk. The entire plant is prescribed as an antidote; it is considered haemostatic, sedative and soporific. In Australia, the most common use of E. hirta is to treat hypertension, asthma edemas, and pectoral complaints
Phytochemistry
E. hirta mainly contains Flavonoids, terpenoids, phenols, essential oil, and other compounds. The major chemical structures of these compounds are shown in Fig. 1.One type of the important constituents of E. hirta is flavonoids including quercetin, quercitrin, quercitol, and derivatives containing rhamnose, quercetin-rhamoside, a chlorophenolic acid, rutin, quercitol, and derivatives containing rhamnose, quercetin-rhamoside, a chlorophenolic acid, rut in, leucocyanidin, leucocyanidol, myricitrin 3,5-diglucoside, pelargonium 3, 5-diglucoside, and ,camphol. The flavonol glycoside xanthorhamni was also isolated from E; hirta.The steams contain the hydrocarbon hentriacontane and myricyl alcohol. The latex contains inositol, taraxerol, friedelin B –amyrin , friedelin , taraxerol, and its esterst: taraxerone, 11a 12a oxidotaraerol, cycloartenol, 24- methylene-cycloartnol, and euphorobol hexacosoate. The aerial part and roots of E. hirta also contain diterpene esters of the phorbol type and ingenol type, including 12-deoxyphorbol-13dodecanoate-20aceteate,12deoxyphorbol-13-phenylacteate-20acetate,ingenol triacetate ,as well as the highly toxic tinyatoxin ,a resiniferonol derivative.Some new ent-kaurane diterpenoid were isolated from the ethanol extract of E. hirta and idientified as 2-beta,16-alpha,19-trihydroxy-ent-kaurane,2-beta,16-alpha,-dihydroxy-ent-kaurane,2-beta,16-alpha,19-trihydroxy-ent-kaurane,[Yan et al.,2011].The other terpenoids isolated are sterols, including B-sitosterol, campesterol, cholesterol, and stigmasterol [ Hazimi et al., 2008., Baslas et al ,. 1980].Tannins isolated from E. hirta include the dimeric hydrolysable dehydroellagitannins euphorbins A, B ,C, E, and techebin ,the monomeric hydrolysable tanning geraniin,2,4,6-tri-O-gallyl-b-D-glucose and 1,2,3,4,6-penta-O- gallyl-b-D-glucose and the easters 5-O-caffeoylquinic acid (neochlorogenic, gallic, tannic maleic and tartaric acids.The major components of the assential oil include 3, 7, 11, 15-teramethyl-2hexadecen-1-ol, 6,10,14-trimethly-2pentadecanone, hexadecanel, phytol,and n-hexadecanoic acid adding up to 61.01%. Minor constituents of E. hirta include 2=- butoxyethanol,tetradecane, phthalic ,butyl teradeceyl ester ,oeic,acid , butyl tetradecly easter, oleic acid, 13-heptadecyn-1-ol, 2-methly-1-hexadecanol, and 1,2-benzene dicarboxylic acid diisooctylester. The component in essential oil may be responsible in the treatment of asthma and function as a repellent against Anopheles species, and thus, is useful for the treatment of malaria [Ogunlesi et al., 2009]. The other compounds found in the dride leaves was: Ca 1.1% ,P 0.%, Fe 0.03 %,Mg 0.5 %,Mn 0.01 %, And Cu 0.002 %.Fresh leaves from E. hirta plants of Nigerian oring were found to contain high levels of Mn (189ppm), Cu (30.5ppm),Zn(152ppm), and NO3 (4600ppm).Varying proportions of of Fe, Mg, K Ca, and Na were also found .more recently, two novel butanol rhabnopyranosides ( 1 and 2), have been isolated from various non-polar and polar extracts of an Indian traditional herb, E. hirta . The structures of the new compounds were elucidated as n- buty-1-O—L rhamnopyranoside [Mallavadhani et al., 2009]
Pharmacological properties
Antibacterial/Antifungal activity
The antimicrobial activity of ethanol extracts of the aerial parts of the aerial parts of E. hirta was then investigated. A remarkable antimicrobial effect has been revealed against Escherichia coli (enteropathongen), Proteus vulgaris, pseudomonas aeruginosa, and Staphylococcus aureus.The diameters of inhibition zones were 21, 19,23, and 19 mm, respectively .The MIC values were 0.189,0.2,0. 166, and 0.216 mg/mL [Sudhakar et al., 2006 ] . The ethanol extract from the leaves of E. hirta was analyzed for antimicrobial activitily against S. aureus, B. cereus, S typhi, K pneumonia , P aeruginosa, and fungus specices A. niger ,A fumigates, A. Flavus, and R .oryzae Antimicrobal activity was attributed to tannins ,flavonoids ,alkaloids,glycosides,proteins,sterols and saponins .Moreover ,leaves collected from august to December showed more significant antimicrobial activities [Suresh et all., 2008].
Mohammed abu Basma Rajeh assessed the potential antimicrobial activity of E. hirta leaves , flower, stem and root ,extracts using abroad arrange of antimicrobial samples ,including four gram positive bacteria (S. aureus , Micrococcus sp., Bacillus, and Bacillus thuringengensis ), four gram negative bacteria (E. coli, K pneumonia, S typhi ,and .P. mirabilis), Candida albicans ).Inhibition Zones ranged between 16 mm to 29 mm. Leaf extract inhibited the growth of all tested all the bacteria except C. albicans .The most susceptible microbes to all extracts were S. aureus and Micrococcu sp. Root extract displayed larger inhibition zones against gram positive bacteria than gram negative bacteria, and had larger inhibition zones compared with the extract .The lowest MIC values were obtained for E. coli and C. albicans ( 3.12 mg/m
L, followed by S. aureus (12, 50 mg/ mL, and P. mirabilus (50.00 mg/mL). all other bacteria had MIC values of 100.00 Mg/mL [Mohammad et al., 2010]. The results support the use of E. hirta in Traditional medicine.
Anti-Allergic activity
The ethanolic extract of E. hirta was found to possess a prominent anti-anaphylactic activity. E. hirta inhibited passive cutaneous anaphylaxis( PAC) in rat active paw anaphylaxis in mice .The suppressive effect of E. hirta was observed on the release of TNF-a and IL -6 from anti DNP_HAS activated rat peritoneal mast cells. The findings of the current study prominently validate the traditional use of E. hirta as a herbal drug against Type I allergic disorders [Youssoyf et al. 2007].The current study demonstrated that 90% of the ethanolic extract from the whole aerial parts of E. hirta possessed, anti-inflammatory, and immunosuppressive properties. Moreover, the ethanolic extract of E. hirta can prevent and treat and rat anaphylactic [Yahossouf et al., 2007 Singh et al., 2006]
Antidiarrheal activity
The aqueous leaf extract of E. hirta significantly and –dependently decreased the gastrointestinal motility in normal rats and recreased the of castor oil-induced in mice [ Hore et al., 2006]. The antidiarrheal effect of the E. hirta herb decoction was studided in mie. It demonstrated an activity in modei s of diarrhea indced by castor oil, archidonic acid prostaglandin E 2.Quercitrin ,a flavonoids isolated from this drug contributed to the antidiarrrheal activity at dose of 50 mg/ kg ,against castor oil and prostaglandin E2-induced diarrhea in mice [Galvez et al .., 1993; Galvez et al . 1993] The water extract of E. hirta exhibited antidiarrheal ,antibacterial ,antiamoebic, and antitetanic properties. The polyphenolic extract of E. hirta inhibited the growth of Entamoeba histolytic with a minimum active concentration of less than 10 g/ mL [Tona et al, 2000]
Anti-inflammatory activity
In 1991, Lanhers MC et al ([Lanhers et al .., 1991]) has proved that the extract of E . hirta had significant and dose-dependent anit –inflammatory effect in carrageenan –induced edema test in rats (an acute inflammatory process ) From a Dose of 100 mg/kg]. Martinez Vet al. (1999) (Martinez et al., 1999]) evaluated the anti-informmatory effect of the N-hexane extract of the aerial parts of E. hirta and its main triterpene constituents .The results showed that the extract and chemicals reduced the effects in the model hyperalgia in a dose-dependent manner and displayed significant anti-inflammatory effects in the model of phorbol acetate-inuced ear inflammation in mice . In 2007, Ekpo O. E et al. evaluated the anti-inflammatory activity activity of the chemicals in E. hirta and concluded that the flavonoids quercitrin (converted to quercetin in the alimentary canal) and myricitrin, as well as the sterols 24-methlene-cycloartenol and -sitosterol, exert a noteworthy and dose –depends anti-inflammatory activity. Triterpene beta-amyrin also seems to exert a similar anti-inflammatory activity [Ekpo et al., 2007]. In 2010, Mei-Fen Shih elucidated the underlying pharmacological molecule mechanism of action in alleviating inflammation.
The aqueous extract of E. hirta demonstrated an antioxidant effect and a free radical scavenging effect in various in vitro in models , such as total antioxidant effect reducing power determination ,free radical-scavenging activity assay using ABTS,DPPH, and hydroxyl radical scavenging assays. The extravt showed maximum antioxidant and free radical scavenging activities,at the concentration of 0,25 mg/mL. The free radical scavenging effect on hydroxyi and DPPH was (73.36_+ 5.21) % and (68.80 _+ 5.21) %, respectively [Sharma et al., 2007]. The free radical scavenging effect of ethanolic extract and petroleum ether extract of flower of E. hirta was also evaluated through various in vitro antioxidant assays, including 1, 1-diphenyl-2-picryl hydrazyl free radical scavenging activity, superoxide anion radical scavenging, No scavenging, and reducing power assay. It was compared with standard antioxidant compounds, such as butylated hydroxyl anisole and ascorbic acid, All the extract showed antioxidant activity [ Kuar et al ., 2010].
Anti-Diabetic activity
The antidiabetic activity of the ethanol ethyl acetate extracts of E. hirta was assayed in vitro using the alpha glucosidase inhibitor method and confirmed through in vivo oral glucose tolerance test using various loading methods. Several mechanisms may be involved in the process, including the antioxidant activity, a- glucosidase inhibitory activity, and increasing the activity of insulin release from B cells of the Langerhans islets. The study of ethanolic extract of leaf flower, and stem of E. hirta on streptozotocin –induced diabetic mice showed significant reduction in blood glucose leaves. Biochemical effects showed significant decreases in serum cholesterol with the elevation of HDL [Widharna et al., 2010]. The ethanolic and petroleum ether extract of the flower of E. hirta also demonstrated potential antidiabetic mellitus activities in alloxan diabetic mice .A signification reduction in serum cholesterol, triglycreatinine ,urea and alkaline phosphatase leavels were pbserved after the administration of the extract .However ,high density lipoprotein levels and total proteins were found increase [ Kumar et al., 2010].
Other activities
Antihypertensive/ ACE Inhibition:
Angiotensin-converting enzyme inhibition and anti-dipsogenic activities of E. hirta extract: The current study showed that the extract from leaves and of E. hirta inhibited the activity of angiltensin-converting enzyme (ACE).
Anti-Malarial:
Study of the isolated flvonol glycosides afzelin, quercitrin. The three compounds showed inhibition of the proliferation of Plasmodium falcifarum at different concentrations [Koli et al., 2002].
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