Since ancient times, people have searched for drugs in nature to cure their illnesses. There was no information concerning the cause of the disease or the medicinal plants, such as how to use them for treatment; everything was based on experience alone [1]. Many plants species from different parts of the world have been proposed for medicinal use as they are composed of various types of chemical compounds, such as secondary metabolites with different biochemical activities [2]. According to the World Health Organization (WHO) [3], almost 80% of the global population is still dependent upon the traditional system (Ayurvedic, Sidha, Tibetan, Unani, Rigpa, Sowa, Folk, Homeopathic, and Chinese) of medicines for the betterment and well-being of their lives. Most of the treatments include active components and extracts from the medicinal plants [4]. The difficulty in the formation of chemical-based drugs, along with increasing costs and health-related side effects, has led researchers to focus on medicinal plants [5]. The demand for naturally derived drugs has gained significant attention in both developed and developing countries because of their accessibility, preventive nature, diversity, affordability, and the safety of natural bioactive agents present in the plants [6].

Traditional medicinal systems have created a base of early medicines with chemical, pharmacological, and subsequent studies. Some of the well-known examples to date include salicin derived from the bark of Salix alba L., morphine isolated from Papaver somniferum, quinine isolated from Cinchona succirubra bark, pilocarpine derived from Pilocarpus jaborandi, etc., for the treatment of inflammation, congestive heart failure, fever, and chronic and acute glaucoma [7]. To hold a better position in both traditional and modern systems of medicine across the globe, the Euphorbia neriifolia Linn. plant needs to be characterized and its use standardized in terms of diversity and pharmacological activities [8]. The family Euphorbiaceae consists of approximately 800 species, 317 genera, and 49 tribes. A large number of species from the genus Euphorbia are under the snuk name and its synonym. Euphorbia neriifolia is a deciduous, large succulent medicinal plant with stipular thorns that is usually found throughout the Orissa and Deccan Peninsula in India [9]. This plant is widely known for its therapeutic activities, such as anti-viral, anti-convulsant, radioprotective, anti-arthritic, anti-asthmatic, anti-fertility, anti-diarrheal, and anti-ulcer activities [10]. Different types of diterpenoids with variable skeleton, such as eurifoloids A–R, eupnerias G–I, and eupnerias J–M, were isolated from E. neriifolia plants. Anti-HIV and cytotoxic activity against HepG2/Adr cell lines are the related pharmacological activities that were reported for these diterpenoids [11]. Some triterpenoidal compounds, such as neritroterpenols A–B, C, and D–G; turucallane triterpenes; and euphane from the stem of E. neriifolia are reported to have anti-proliferative and anti-inflammatory activities, respectively [12]. The research into natural compounds is relevant, and there are compounds used in clinical practice from natural sources. Furthermore, since plants have been used in treating various pathologies since ancient times, it is essential to validate these traditional applications and simultaneously study new compounds with relevant biological potential.

Classically, E. neriifolia is divided into the vagbhata, susruta, and caraka categories. The caraka exhibits the properties of rasa with tikta and katu actions, and susruta shows properties of virya with the action of usna. Guna expresses snigdha, tiksna, and laghu actions. Vipaka shows the action of katu, and karma exhibits recana, dipana, and kapha-vatahara actions. The caraka displays medoroga, kusta, arsas, sotha, sula, udara, gulma, and vatavyadhi indications ^[13][14][46,47].

The leaves are used for carminative, stomachic, and expectorant purposes ^[15][16][20,48]. Flavonoids isolated from E. neriifolia leaf are also utilized to treat various chronic diseases, whereas oil extracted from E. neriifolia and sesame is utilized to treat joint pain ^[17][49]. Coronavirus disease-2019 (COVID-19) has affected the health of a large population of people all across the world. This disease has different clinical presentations. Although different medicines have been repurposed to treat COVID-19, none of them were found to be particularly effective in the perspective of the global population. Thus, there is always a need to discover novel strategies to deal with this virus. A total of 60 patients in groups of four were analyzed properly. Approximately 66.66% of patients were below 40 years of age and approximately 68.33% were males. The patients complained of various symptoms at the commencement of therapy, such as diarrhea, red eye, loss of taste, headache, skin rash, chest pain, running nose, sore throat, difficult breathing, cough, body aches and pains, and weakness. The leaves of E. neriifolia were utilized for moderate and mild COVID-19 patients. The results showed the beneficent effect of E. neriifolia in the management of COVID-19, especially in resource-constrained and developing countries. In 15 mild COVID-19 patients, the p-value of the RBC variable was 0.5000 to 1.0000 from 1–7 days and 0.4493 to 0.8986 from 7–14 days; the WBC p-value varied from 0.0002 to 0.0004 from 1–7 days and 0.1976 to 0.3953 from 7–14 days; the neutrophil p-value varied from 0.0000 from 1–7 days and 0.0128 to 0.0257 on 7–14 days; the hemoglobin p-value varied from 0.0042 to 0.0085 from 1–7 days and 0.1032 to 0.2063 from 7–14 days; the platelet p-value varied from 0.0789 to 0.1578 from 1–7 days and 0.2380 to 0.4760 from 7–14 days; the d-dimer p-value varied from 0.0053 to 0.0105 from 1–7 days and 0.0067–0.0134 from 7–14 days; and the p-value of S-ferritin and oxygen saturation varied from 0.000 to 0.000 from 1–14 days. The discharge criterion was containment of COVID-19-associated symptoms so that the person can manage their health at home after being discharged from the hospital. A conclusion could not be made due to small sampling size. This plant is pertinent in the conditions of the spread of COVID-19, as the overload of CoV in infected individuals may be treated with the help of this plant without the need of hospitalization if direct connection is maintained between the physicians and the patients ^[18][50].

The latex of E. neriifolia is purgative, acrid, and results in dermatitis ^[19][32]. Burkill and Haniff ^[20][51] stated that E. neriifolia latex is a diuretic and vermifuge. The tribal people of Chattishgarh utilized the latex of E. neriifolia as an aphrodisiac mixture, and they treated cracks in their foot soles by boiling latex with castor oil, along with salt ^[21][52]. A chymotrypsin-like serine protease, neriifolin, was obtained from the E. neriifolia latex by gel filtration, cation exchange chromatography, and ammonium sulfate precipitation. The enzyme has an isoelectric point of pH 5.7 and a molecular mass of 35.24 kDa. A high ratio of proteolytic activity and stability against detergent additives, oxidizing agents, surfactants, temperature, and pH make neriifolin a suitable candidate for different applications related to industry ^[22][53]. Euphorbia neriifolia latex was utilized as an effective drug for rheumatism ^[23][24][27,54]. It was found to be useful in the treatment of the gaseous distension of the abdomen, paralysis, gout, and sciatica ^[24][25][26][54,55,56]. The bark was considered to be a poor stomach poison and good contact poison [9]. Other medicinal uses of E. neriifolia are listed in Table 1.