E. hirta has a very high medicinal value. Ethnopharmacologically, E. hirta is used to cure respiratory and bronchial disorders (hay fever, bronchitis and asthma), conjunctivitis and gastrointestinal diseases such as intestinal parasitosis, dysentery and diarrhea. Furthermore, E. hirta shows significant tonic and hypotensive properties26. Stem sap of E. hirta is used to cure eyelid styes caused by bacterial infection, and leaves are used against boils and swellings by making their poultice. The plant as a whole is used by humans against different diseases, such as fresh herb decoction in the treatment of thrush by gargling, dry decoction to cure skin disorders and decoction of roots, which is implemented in snake bites and for milk production in nursing mothers27. Antispasmodic and antiamoebic activities have been shown for polyphenolic extracts of the plant28, 29. Furthermore, the E. hirta-isolated compound quercitrin has been reported to have remarkable antidiarrheal potential30, 31. It shows reflexive effects on cardiovascular systems in humans, such as the respiratory system32. The E. hirta plant alcoholic extracts show tranquilizing effects on the genitor-urinary tract and report hypoglycemic effects in rats33, 34. The isolated compounds and solvent extracts of E. hirta demonstrated substantial anticancer activities. E. hirta extracts exhibit inhibitory effects on prostaglandin release, including D2, E2 and I2. It has also been reported to produce protective effects against contamination caused by aflatoxin in mustard, rice, maize and wheat crops35. Methanolic extracts of E. hirta leaves have been shown to have strong antibacterial and antifungal properties. Itchy soles are treated by pounding, warming and rubbing the leaves of E. hirta with coconut oil and turmeric. Plant latex is used to cure eye sores by applying it to the surma on the lower eyelids. A number of the ethnopharmacological uses of E. hirta are listed in Table 2.

Table 1

No	Activity	Action
1	Anti-allergic activity	The ethanolic fraction of E. hirta induces inhibitive effects on the discharge of IL-6 and TNF-α in anti-DNP-HAS activated rat peritoneal mast cells.
2	Antibacterial activity	Different solvent extracts from E. hirta were evaluated for antibacterial effects Bacillus subtilis, Pseudomonas. aeruginosa, Staphylococcus aureus, and Escherichia coli. The results demonstrated outstanding antibacterial property of E. hirta against these pathogen bacteria.
3	Anti-diabetic activity	The solvent extracts of stem, flower and leaf of E. hirta showed lowering effects on overall blood glucose levels on administration to streptozotocin induced diabetic mice.
4	Anti-diarrheal activity	The leaves of E. hirta are rich in flavonoids content especially the quercitin molecule has been shown to exhibit anti-diarrheal effects through enhancement in the absorption of colonic fluid in presence of secretagogue compounds.
5	Antioxidant activity	Antioxidant activity of E. hirta was shown by performing FRAP and DPPH assay and outcomes demonstrated remarkable antioxidant potential of methanolic extract of E. hirta by acting against oxidative damage to protein.
6	Antitumor activity	Research has shown that the methanolic extract of E. hirta induce antiproliferative effects in Hep-2 cells isolated from human epithelioma of larynx. Hence, predicting antitumor potency of E. hirta.
7	Anxiolytic and sedative activity	The antagonists of the GABAA receptor-benzodiazepine receptor-Cl channel complex with E. hirta were used together, and anxiety in the EPM showed marked anti-anxiety activity in chronic immobilization stress
8	Diuretic activity	The E. hirta ethanolic extract on administration to rats augmented the total urine excretion thus improving diuresis.

Ethanolic extraction from E. hirta leaves has been tested for its antibacterial activities against Salmonella typhi, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. The extract showed strong inhibition of all these bacteria except Salmonella typhi. The minimum inhibitory values were calculated to be 74.61, 57.64, 22.55 and 54.09 mg/ml for Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli, respectively36. Unlike solvent extractions from the stem, bud and leaves of E. hirta, their antimicrobial effects against Staphylococcus aureus were evaluated using the disc-diffusion method. The methanolic extract from leaves and bud exhibited very strong activity against S. aureus, with a zone of inhibition score of 20 mm and a zone of inhibition area score of 471.00 mm² 37. Chloroform and aqueous fractions of E. hirta L. leaves have been reported to possess noncytotoxic but antibacterial effects against Klebsiella pneumonia38.

The medicinal herb E. hirta has been reported to have remarkable anti-inflammatory effects. In a study, the aqueous and ethanolic extracts of E. hirta were evaluated for their anti-inflammatory activity against carrageenan-induced inflammation in rats. It has been shown that both extracts produced substantial anti-inflammatory effects against the reference drug diclofenac sodium (50 mg/kg)39. In a similar study, the lyophilized aqueous extract from E. hirta has been reported to suppress inflammation in carrageenan-induced rats starting from the concentrations of 100 mg/kg of body weight40. Furthermore, n-hexane extracts from E. hirta have been shown to inhibit inflammation in mouse models of phorbol acetate-induced ear inflammation41. The anti-inflammatory effects were found to be concentration-dependent. In another study, fractionated Euphorbia hirta aqueous extract showed in vitro anti‑inflammatory activity on rabbit synovial fibroblasts42.

E. hirta possesses strong antioxidant activities in both animal models and in vitro. It has been shown to have strong free radical scavenging potency in various experimental models using hydroxyl radical scavenging, ABTS, and DPPH assays. The free-radical scavenging ability of the methanolic extract of E. hirta was investigated. The results reported that the methanolic fraction of E. hirta leaf extract produced a tremendous DPPH inhibition of 71.96±0.78%. The increasing order of DPPH scavenging activity of E. hirta was stems (44.42±0.94%) < roots (48.59±0.97%) < flowers (52.45±0.66%) < leaves. The IC₅₀ values calculated for stems, roots, flowers and leaves were 1.358, 0.989, 0.972 and 0.803 mg/mL, respectively43. Another study carried out by S. Asha and coworkers reported significant antioxidant activity for E. hirta. They showed antioxidant activities for three types of extractions from E. hirta through superoxide, DPPH and hydroxyl radical scavenging assays. Out of the three extracts (ethanolic, methanolic and aqueous), the ethanolic extract exhibited the highest antioxidant propensity with a significant IC₅₀ value compared to the methanolic and aqueous extracts. Furthermore, a significant relationship was obtained between the phenolic content of the extracts and antioxidant activity, and the ethanolic extract showed a high phenolic content44. E. hirta showed maximum free radical scavenging and antioxidant activities at approximately 0.25 mg/ml.

Several traditionally used medicinal plants are thought to have preventive effects against different human malignancies, including cancer. These plants are rich in chemical contents that show modulatory effects on different physiological functions and target the proliferation of cancer cells. E. hirta has been reported to produce significant anticancer effects in vitro against acute myeloid leukemia HL-60 cells45. Furthermore, extracts from E. hirta have revealed anticancer effects against squamous cell carcinoma, Hep-2 and malignant melanoma46, 47. Shao-Ming Chi et al., 2012 isolated (1’R,5’R)-5-(5’carboxylmethyl-2’-oxocyclopentyl)-3Z-pentenyl acetate, a cyclopentanone derivative from Euphorbia hirta. The ethanolic extract was examined for cytotoxicity against the K562 and A549 cell lines. The outcome of the study revealed weak cytotoxicity against A549 cells (15.02 ± 11.60%) and remained almost inactive against K562 cells48. Sandeep et al. in 2011 evaluated the antitumor properties of E. hirta49. Aerial parts of E. hirta were extracted using different solvents, including chloroform, ethanol and petroleum ether, and showed positive results for the presence of alkaloids, tannins, saponins, and flavonoids. The ethanol and chloroform extracts were reported to maximize the mean survival and inhibit the growth of solid tumors in administered mice. This antitumor activity was attributed to the manifestation of flavonoids.

Euphorbia hirta has been reported to contain a pool of active phytochemicals that raise the medicinal value of the plant. Euphorbia hirta has been termed an “Asthma plant”. It shows depressant effects on the respiratory system and reflexive effects on brochial tubes32. Additionally, methanolic extraction from aerial parts of Euphorbia hirta by bioassay-guided fractionation has been evaluated for antiparasitic activity against P. falciparum. The key chromatographic fraction has been reported to show over 90% inhibition at 5 µg/ml against P. falciparum50.

Table 2

Family	Plant Species	Mode of Action	Plant Part	Origin
Acanthaceae	Andrographis paniculata	Antiviral	Leaves	India, Sri Lanka
Acanthaceae	Strobilanthes cusia	Inhibits HCoV-NL63 via tryptanthrin; anti-influenza virus activity; anti-inflammatory potential	Leaves, Whole plant	Tropical Asia, Madagascar
Adoxaceae	Sambucus nigra	Antiviral activity against HIV, HSV, influenza, hepatitis, and coxsackievirus	Whole plant	Europe and North America
Adoxaceae	Viburnum opulus	Immunomodulation; anti-inflammatory effects	Fruits	Western and eastern, Siberia Eastern Europe, Caucasus, and Central Asia
Alliaceae	Allium sativum	Inhibits avian coronavirus; antiviral, fungistatic	Bulb	Central Asia, Iran
Anacardiaceae	Rhus coriaria	Antiviral potential	Fruit	Mild Mediterranean climates of western Asia and southern Europe
Apiaceae	Ferula assa-foetida	Antiviral activity; great potency against H1N1; anti-inflammatory	Oleo-Gum-resin	Iran, Afghanistan
Apiaceae	Saposhnikovia divaricata	High antiviral activity against PEDV corona-virus	Whole plant	China
Apocynaceae	Aspidosperma sp.	Antiviral activity against avian metapneumovirus and other groups	Whole plant	South America
Apocynaceae	Gymnema sylvestre	Inhibition of viral DNA synthesis; immunomodulation	Leaves, Whole plant	Asia, Africa, Australia
Araliaceae	Oplopanax elatus	Immunomodulation and anti-inflammatory activities	Whole plant	North America, northeastern Asia
Asteraceae	Anthemis hyalina	Inhibits coronavirus replication and expression of transient receptor potential gene family	Whole plant	Mediterranean region, south-west Asia to Iran
Asteraceae	Artemisia sp. (Artemisia absinthium)	Reduces coronavirus replication; antibacterial, anti-inflammatory	Whole plant	Eurasia, north Africa, North America
Asteraceae	Cichorium intybus	Immunomodulation; antiviral action against adenovirus type and 5HSV-1	Whole plant, Roots	Eurasia, Mediterranean region
Asteraceae	Cynara scolymus	ACE inhibitor, antiviral	Flower heads	Mediterranean region
Asteraceae	Echinacea angustifolia	Antiviral activity against cold and flu viruses; inhibits discharge of pro-inflammatory cytokines and viral growth.	Flowers	North America
Asteraceae	Echinops sp.	Antiviral, cough suppressant	Trehala manna	Iran
Asteraceae	Inula helenium	Anti-inflammatory	Rhizomes, Roots	Caucasus, Eastern Europe, western Siberia, Central and Far East Asia
Asteraceae	Rhaponticum carthamoides	Immunomodulation	Roots	Southern Siberia, Kazakhstan, Altay region
Asteraceae	Sphaeranthus indicus	Antiviral activity against mouse coronavirus; anti-inflammatory and bronchodilation	Whole plant	Northern Australia, Indomalayan realm
Bignoniaceae	Arrabidaea samydoides	Antiviral activity against HSV-1, vaccinia virus and murine encephalomyocarditis virus	Whole plant	South America
Bignoniaceae	Tabebuia sp.	Antiviral potential	Whole plant	South America
Boraginaceae	Echium amoenum	Antiviral	Flowers	Iran, Caucasus, Russia
Brassicaceae	Isatis tinctoria	Inhibits cleavage activity of SARS-3CLpro enzyme; anti-inflammatory and strong antioxidant potential	Roots extracts	Caucasus, Central Asia, eastern Siberia, western Asia
Cannabaceae	Humulus lupulus	Immunomodulation; antiviral activity against cold and influenza viruses, herpesvirus and hepatitis C; inhibition of virus replication	Inflorescences	North America, Europe, western Asia
Crassulaceae	Bryophyllum pinnatum	Anti-inflammatory, immunomodulator	Whole plant	Madagascar
Cupressaceae	Juniperus communis	Prevents replication, 3CLpro; antiseptic and anti-inflammatory	Fruits	Europe, North America, Asia
Cupressaceae	Thuja occidentalis	Immunostimulation; antiviral activity against acute common cold	Leaves Whole plant	Upper northeastern, North and Central United States and Eastern Canada
Elaeagnaceae	Hippophae rhamnoides	Anti-influenza activities and Immunomodulation	Fruits	Cold-temperate regions of Europe and Asia
Euphorbiaceae	Euphorbia sp.	Antiviral activity against SIVmac251, HSV-2, HIV-1 and HIV-2	Roots	North and South America, Southern Africa and Madagascar, Mediterranean region
Fabaceae	Acacia nilotica	Inhibits HIV protease; cytotoxic and antiviral	Whole plant	Indian subcontinent, Middle East and Africa
Fabaceae	Alhagi maurorum	Inhibits influenza and cold viruses; relieves cough, pectoral aches, fever, vomiting and thirst	Gum tragacanth	South-east Europe, south-west Asia
Fabaceae	Clitoria ternatea	Antiviral	Whole plant	Indian subcontinent, Southeast Asia
Fabaceae	Desmodium canadense	High antiviral activity toward coronaviruses	Whole plant	North America
Fabaceae	Glycyrrhiza glabra	Immunomodulation; antiviral activity against human cytomegalo-virus, Epstein–Barr virus, HSV-1, and RNA viruses including H1N1, influenza A, and H5N1	Roots	Mediterranean area, Iran-Turan, Azerbaijan
Geraniaceae	Pelargonium sidoides	Decreases rhinovirus infection through regulation of binding viral proteins in bronchial cells.	Leaves, Whole plant	South Africa
Hypericaceae	Hypericum connatum	High antiviral activity	Whole plant	North America, eastern Asia
Lamiaceae	Mentha piperita	High antiviral activity against coronavirus group	Whole plant	Europe, Middle East
Lamiaceae	Mosla sp.	Anti-influenza activity	Whole plant	Eastern and southeastern Asia, Himalayas
Lamiaceae	Ocimum kilimandscharicum	Antiviral activity against HIV-1, SARS-CoV-2	Whole plant	Central Africa, Southeast Asia
Lamiaceae	Origanum vulgare	Respiratory and antiviral activity	Leaves, Stems	Mediterranean region, Southwestern and Western Eurasia
Lamiaceae	Rosmarinus officinalis	Antiviral activity against human respiratory syncytial virus; immunomodu-lator; anti-inflammatory	Whole plant	Mediterranean region
Lamiaceae	Salvia officinalis	High binding to COVID-19 proteases; Inhibits HSV-1 and SARS-CoV replication	Whole plant	Mediterranean basin
Lamiaceae	Scutellaria baicalensis	Inhibit nsP13 by affecting the ATPase activity	Roots	China, Korea, Mongolia, Russian far east, Siberia
Lamiaceae	Stachys schtschegleevii	Antiviral, anti-inflammatory and anti-SARS-CoV-2	Leaves	Iran
Lamiaceae	Thymus vulgaris	High antiviral activity toward coronaviruses; antioxidant effects	Whole plant	Southern Europe
Lauraceae	Cinnamomum cassia	Antiviral, anti-inflammatory; inhibits attachment of human respiratory syncytial virus	Bark	Vietnam and eastern Himalayas, China
Lythraceae	Punica granatum	Inhibits viral glycoproteins; antiviral action against influenza virus and HSV-1	Fruits, Peel, Seeds	Iran to northern India, Mediterranean region
Malvaceae	Althaea officinalis	Anti-inflammatory in diseases of the upper respiratory tract; antitussive, chest emollient, immuno-modulator, antiviral	Whole plant	Western palearctic, boreal area, Europe, Asia and Africa
Malvaceae	Firmiana simplex	Immunomodulation; general tonic and adaptogenic drug	Leaves	South Japan, China and Indonesia
Menispermaceae	Stephania tetrandra	Inhibits expression of HCoV-OC43 nucleocapsid and spike proteins; anticancer and immunomodulatory potential	Roots	China, Taiwan
Plantaginaceae	Plantago major	Anti-inflammatory; antiviral activity against herpesviruses and adenoviruses	Leaves, Whole plant	Europe, Northern and central Asia
Ranunculaceae	Nigella sativa	Antiviral activity against avian influenza virus (H9N2), Immunomodulator, broncho-dilator and anti-inflammatory agent	Whole plant	Eastern Mediterranean, northern Africa, Indian Subcontinent, western Asia
Rhamnaceae	Ampelozizyphus amazonicus	Immunomodulation, anti-inflammatory	Whole plant	South America
Rhamnaceae	Ziziphus jujuba	Antiviral activity; potential therapeutic agent for treating influenza	Fruit	Southeastern Europe to China
Rosaceae	Rubus sp.	Antiviral effect against human influenza virus	Fruits, Flowers	Forest-steppe zones of Eurasia
Rosaceae	Rosa sp.	Immunomodulatory effects; antiviral activity against HIV and HSV	Completely matured fruits	Europe, North America, Northwestern Africa
Rutaceae	Citrus trifoliata	Antiviral against oseltamivir-resistant influenza virus	Seeds	Northern China and Korea
Sapindaceae	Litchi chinensis	The plant inhibit SARS-3CLpro, while the isolated terpenoids suppress HIV-1 protease	Seeds	Southeastern China
Saururaceae	Houttuynia cordata	Inhibits viral tRNA polymerase (RdRp) and SARS-3CLpro activity; activates IL-2 and IL-10 secretion	Whole plant	Southern Asia
Solanaceae	Hyoscyamus niger	Viral inhibition; bronchodilator; antiviral effect against human influenza virus A/WSN/33	Whole plant	Middle East, Asia, Continental Europe
Theaceae	Camellia japonica	Strong inhibition of a member of coronavirus family that is porcine epidemic diarrhea virus through suppression of important protein and gene synthesis during replication	Whole plant, Flowers	East Asia
Urticaceae	Urtica dioica	Inhibition of SARS coronavirus replication	Leaves	Europe, temperate Asia, and western North Africa
Verbenaceae	Vitex trifolia	Strongly antiviral against and mouse coronavirus HSV, anti-inflammatory effects on lungs, immunomodulatory	Whole plant	French Polynesia, Tropical East Africa
Zingiberaceae	Zingiber officinale	Inhibition of syncytial virus effecting human respiratory	Rhizome	Asia, Maritime Southeast
Zosteraceae	Zostera marina	Strongly antiviral against influenza A virus	Whole plant	North America, Europe, Asia

Medicinal and aromatic plants have been a rich reserve for antiviral agents since time immemorial. Some of the medicinal plants with antiviral activity are listed in Table 3. Euphorbia hirta is a medicinally as well as biologically important plant. It has been used to treat a wide variety of disorders since time immemorial52. Euphorbia hirta has been a foremost important constituent of traditional systems of medicines, including Ayurveda medicine and TCM. It is used for the management of respiratory diseases, gastrointestinal disorders, venereal diseases, sterility, menstrual problems, kidney stones, colds, coughs, emphysema, laryngeal spasms, hay fever, bronchitis, asthma, amoebic dysentery, vomiting, heartburn, peptic ulcers, diarrhea, and intestinal parasites53, 54, 55, 56, 57, 58. Gyuris et al. evaluated the Euphorbia hirta extract for its antiretroviral potency against T lymphocyte MT4 cells. The effects of aqueous and methanolic extracts of the plant on replication of human immunodeficiency virus-1 (HIV-1), simian immunodeficiency virus SIVmac251 and HIV-2 were determined. The results supported the remarkable antiviral activity of both fractions against all three viruses59. Moreover, the methanolic extract of Euphorbia hirta showed more efficacy than the aqueous extract.

In another study, the role of Euphorbia hirta against dengue was demonstrated. Dengue disease is a viral disease caused by four distinct serotypic members of the family Flaviviridae and genus Flavivirus, including DENV 1-460. The Euphorbia hirta plant has been regarded as a game changer in dengue management. Clinical investigation of Euphorbia hirta has been recorded against age group 30 - 35, which after the supplementation revealed an approximately 70% reduction in flu-like symptoms caused by dengue61. The in vitro analysis of the ethanolic extract of the plant showed remarkable inhibition of plaque formation up to 85% and 34.7% against DENV-1 and DENV-262, respectively. Some of the studies that have been carried out for the calculation of the anti-dengue property of Euphorbia hirta are listed in Table 4.

Table 3

Study	Results	Experimental model	Plant part(s)/extract
Apostol et al. 2012	The administration of E. hirta continuously for 14 days to rat’s exhibit enhancing effects on platelet count and reductive effects on clotting and bleeding time.	Rats induced thrombocytopenic by ethanol (i.p injection) (In vivo assay model)	Decoction of fresh whole plant
Arollado et al. 2013	The consecutive treatment of rats with E. hirta for 9 days increased mean platelet count by 80%.	Rats induced thrombocytopenic by Anagrelide (i.p injection) (In vivo assay model)	Water extract of leaves
Coloma et al. 2015	A surveillance study of questionnaire was executed in Agoo, La Union, Philippines demonstrated Tawa-Tawa is very high in demand against dengue. The thrombocytopenic rabbits fed with E. hirta juice showed remarkable increase in the platelet count with 24 h of time.	Descriptive ethnobotanical survey. Aspirin-induced thrombocytopenia rabbits (In vivo assay model)	Expressed juice of E. hirta. Expressed juice of E. hirta
de Guzman et al. 2016	The study showed very high percentage of women of 60-80 years of age have remarkable primary and secondary knowledge of using E. hirta against dengue.	Ethnopharmacological survey	Decoction of leaves or bark
Mir et al. 2012	Post 24 h of E. hirta administration over 70% patients showed promising platelet increase. Patients showed noticeable recovery in flu and fever like symptoms.	Clinical study, Sir Ganga Ram Hospital, Lahore using on admitted dengue patients.	Herbal water
Saptawati et al. 2017	Virus inhibition by 34.7%.	In vitro assay for DENV-2 serotype	Ethanol extract of leaves
Siva Ganesh et al. 2015	Quercetin molecule has been reported to possess extraordinary binding efficacy against dengue virus. The leaves of E. hirta are rich in quercetin and thus effective against dengue virus.	Molecular docking study using phytochemicals with 2P40-methyl transferase, and 2FOM-dengue proteases of dengue	Leaves
Tayone et al. 2014	Ethyl acetate fraction of dichloromethane and methanolic extracts of E. hirta inhibit the plaque formation by 85% in dengue virus serotype-1. The extract fraction resulted in the identification and isolation of Nine compounds.	In vitro assay	Ethyl acetate/methanol and ethyl acetate partitioning and tea of E. hirta.

Furthermore, Euphorbia hirta has been reported to have evident antiviral potency against herpes, coxsackie and polioviruses. Euphorbia hirta has also been reported to have selective antiviral activity against HSV-1 with an MIC value of 0.1 mg/ml63. The leaf extract of Euphorbia hirta plant has been reported to impart protective cover against potato virus X in both systemic and hypersensitive hosts. The active constituent actinomycin D was systemically sensitive toward the virus X64.