Introduction

is frequently known as “Asthma plant” in English and “Dudhi” in Hindi. The plant is widely distributed throughout the globe, and in Asia, it is mainly found in Yemen, Oman, Palestine, Taiwan, Syria, Lebanon, India, Bhutan, Pakistan, Nepal, Myanmar, Thailand, Sri Lanka, Indonesia, Malaysia, Papua New Guinea and the Philippines1. The plant belongs to the genus Euphorbia family of Euphorbiaceae. The morphological features of include a slender stem with hair development and many branches arising from it from base to top. The plant is annual purple or reddish in color and attains a height of approximately 40 cm. The leaves of the plant grow oppositely and are elliptical-oblong to oblong-lanceolate in shape. The leaves measure up to 1 – 2.5 cm in length with green color on the top side and pale color on the bottom side. The fruits are three-celled, yellow, keeled capsules, hairy, 1 - 2 mm in diameter, containing four-sided, three brown, wrinkled, angular, seeds2, 3, 4, 5. The plant has long served humanity in the form of traditional and folk medicine. In addition to other species of the genus Euphorbia also show medicinal importance and are being used in traditional medicine. A milky juice comes out of all the species of Euphorbia upon breaking, and this juice is considered to be more/less toxic and hence was used on arrows for hunting purposes in old times6. is a high-value medicinal plant possessing significant antimalarial, antifungal, antifertility, antispasmodic, sedative, antiasthmatic, anthelmintic and antibacterial properties2. Additionally, the plant has been found to have significant anticancer effects against a variety of aggressive cancer cells.

This review aims to summarize the phytochemical compositions and pharmacological activities of and tries to bridge the possible role of in the management of COVID-19, a going on global pandemic. Respiratory tract exposure to the external environment leads to high communicability of the disease. SARS-CoV-2 patients differ in clinical symptoms some show evident symptoms, and some remain asymptotic7. Asymptomatic patients with SARS-CoV-2 viral loads are the most active transporters leading to the fast spread of the disease because these patients are not aware of the disease until advanced stages. The initial clinical symptoms involve chills, fever, fatigue, cough, diarrhea, shortness of breath and respiratory symptoms. The generation of potential vaccines or capable drugs against SARS-CoV-2 infection is the global emergency right now. Unfortunately, the development of vaccines or potential drugs may take a longer time. Therefore, intermediate treatment methodologies are needed to address this global health issue. The government of the Republic of China is currently emphasizing Traditional Chinese Medicine (TCM) in controlling SARS-CoV-2 infection8, 9. Several clinical trials have already been initiated to study the efficiency of TCM against SARS-CoV-2 infection. In certain cases, patients along with Western medicine were sidewise supplied with TCM. The results showed that TCM induced synergistic effects with Western medicine against SARS-CoV-210. Treatments with medicinal plants and herbs are mostly symptoms and sign based. Herbal medicines with potential efficacy against specified targets against viruses could be evaluated for their activity against SARS-CoV-2, reliant on signs and symptoms11, 12. The prime focus of this review was to summarize the phytochemical constituents and pharmacological and medicinal importance of along with assessing its possibility to be used against COVID-19.

. (Figure 1) is a small annual, branched herb that can grow to 70 cm in height, purple or reddish in color with copious amounts of latex, and covered with sprout hairs.

Leaves: The leaves are opposite, biculate and simple, the stipules are linear, the leaf blade is lanceolate, oblong serrate, long elliptic, tapering, 3 – 4 cm long and 1 – 1.4 cm wide, and its margin is smoothly serrated.

Flowers: The monoecious inflorescence, an axillary or terminal cluster of flowers, is known as a cyathium, in which several cyathia are arranged in a cyme. The male and female flowers are in a pod and both appellation. The flowers are unisexual, male flowers are sessile, prophylls are linear, fringed, perianth absent and have a stamen, female flowers have a small peduncle, the perianth is fringed, the ovary is covered with tiny hairs above, 3-celled, has 3 - Styles, small and the tip is double. The flowering period is usually year round.

Fruit: The fruit is allomorphic, pistillate, elongated, 3-lobed, obtuse base covered with shoot hairs.

Seeds: Seeds are oblong, 4-sided prismatic, wrinkled and brownish pink in color, capsule 3-seeded, green and covered with fleshy spines, seeds smooth, hard mottled crustal skin with a white caruncle at the top enclosing oily endosperm13, 14, 15, 16, 17, 18, 19.

Roots: The root is a distinct and developed primary root (taproot system).

Classification: . belongs to the Euphorbiaceae family, known as the Spurge family. It is the largest family, consisting of almost 300 genera and 5000 species. Euphorbia is the largest genus of the Euphorbiaceae family and includes approximately 1600 species.

Bioactive secondary metabolites from

Plants are a source of highly active biological principles, making them helpful to humanity in regard to tackling key issues, including health20, 21. The plant bears a wide variety of phytochemicals, including reducing sugars, alkaloids, terpenoids, flavonoids, tannins, steroids, fats, proteins, gums, oils, mucilage, saponins, glycosides, cardiac glycosides, coumarins, anthraquinones and phenolic compounds22. Some of the important phytochemical constituents are summarized in Figure 2. The methanolic extract of has been identified with ten compounds, including palmitic acid, chloromorpholin-4-ium, S-methyl-L-cysteine, nicotinic acid, methyl 14-methylpentadecanoate, 2,3,5-trimethyl-1 H-pyrrole, 5-methyl-1,3-oxazolidin-2-one, 2-amino-3-sulfanylpropanoic acid, 17-carboxyheptadec-9-en-1-ylium and 4-amino-4-oxobut-2-enoic acid23. Six compounds were identified and isolated from leaves: 3,4-di--galloylquinic acid, gallic acid, myricitriu, quercitrin, 1,2,3,4,6-penta--galloyl-beta--glucose and 2,4,6-tri-O-galloyl-D-glucose24. Aerial parts of the plant were identified with quercitrin, afzelin, 1,3,4,6-tetra-O-galloyl-β-d-glucose, 2,4,6-tri-O-galloyl-β-d-glucose, euphorbins A-D (Figure 3), myricitrin, kaempferol, rutin, quercetin, gallic acid, and protocatechuic acid25. Furthermore, 11α,12α-oxidotaraxerol, α-amyrin, β-amyrin, taraxerone, β-amyrin acetate, taxerol, tannins and taraxerone have been reported from plants. Moreover, β-sitosterol, α-amyrin, 24-methylencycloartenol, camphol, leucocyanidol, euphorbianin and euphorbins A-E have also been isolated from the plant.

Medicinal property of

Different parts of have shown numerous pharmacological and biological properties. The high biological value of the plant is primarily attributed to its high diversity in phytochemical content. Some of the biological activities are represented in Figure 4.

Possible role of against SARS-CoV-2

Unfortunately, communicability and COVID-19 infection are growing rapidly each day, causing huge human and economic losses globally65. The common clinical symptoms identified among COVID-19 patients include cough, shortness of breath, fever, and respiratory symptoms (such as inflammation caused by allergy to the pathogen). is an important medicinal plant involved in the global traditional medicine core, including Ayurvedic medicine and Traditional Chinese Medicine66. The lyophilized aqueous extract of revealed potential antipyretic, anti-inflammatory and analgesic actions in xenografted mice and rat models. The antipyretic effects of were evaluated via yeast-induced hyperthermia and showed potential activity at 100-400 mg/kg67. Furthermore, writhing and hot plate tests showed anti-analgesic activity in a dose-dependent manner at 20 mg/kg and 25 mg/kg, respectively. Additionally, strong anti-inflammatory activity of was observed in carrageenan-induced edema test rats at 100 mg/kg68. A clinical study in dengue patients performed by S. D Pareera at Sir Ganga Ram Hospital Lahore revealed that the administration of an aqueous extract of orally enhanced the total leucocyte count and platelets in patients aged 30-55 years. Moreover, 70% of the patients showed a response of lowering flu symptoms and fever. Moreover, the ethanolic extract of demonstrated significant inhibition of dengue virus stereotypes 1 and 269. is also known as an asthma plant and possesses remarkable activity against asthma70. Diarrhea is a key symptom commonly identified in COVID-19 patients. plant has been used against several gastrointestinal disorders, including diarrhea and ulcers. The methanolic extract of has been identified with rich flavonol glucoside content, including afzelin, myrcitrin and quercitin. The antimicrobial analysis of these compounds yielded IC values of 1.1, 5.4 and 4.1 against malarial parasites, respectively51. Furthermore, the plant has been reported to have high free radical scavenging properties. The maximum DPPH scavenging activity was reported by leaves, followed by flowers, roots and stems (72.96 ± 0.78%, 52.45 ± 0.66%, 48.59 ± 0.97%, and 44.42 ± 0.94%)71. Furthermore, has been reported to induce potential nonspecific immune responses, such as phagocytic ratio and lysozyme activity pathogen-infected fish model72. At higher concentrations, the plant was successful in eliminating Aeromonas hydrophila from the kidney and blood and enhanced the numbers of WBCs, RBCs and hemoglobin in test fish. Additionally, leaf extract enhanced the fabrication of log antibodies73. also showed potential immunomodulatory effects against animal models. The maximum inhibition was recorded at 100 and 200 mg/kg, wherein it remarkably blocks the generation of cell-mediated immune responses (IL-2, TNF-α, IFN-γ, CD3, CD4 and CD8)74.

SARS-CoV-2 attaches to the host cell using the receptor-binding domain (RBD) in its spike protein75. The RBD recognizes the ACE2 binding ridge on the outer cell membrane of the host cell, which leads to smooth entrance. The SARS-CoV-2 RBD bears an ACE2-binding ridge with a more compact conformation. Moreover, two virus-binding hotspots at the RBD–ACE2 interface are stabilized by several residue changes. The methanolic extract of roots and leaves has been reported to possess substantial angiotensin converting enzyme (ACE) anti-dipsogenic and inhibition activities. The extract suppressed the activity of ACE 50% at 160 μg and 90% at 500 μg76. The possible inhibition of the interface between SARS-CoV-2 and human host cells is shown in Figure 5.

Future prospects

It is essential and needed of this era to continue the expansion of drug development and therapeutics based on plants and their chemical composition. Drugs and therapeutics based on plants are economical (cost effective) and are believed to be less toxic than synthetics. Cancer is a global health problem, making it difficult for scientists and researchers to overcome this ailment. Plants have assisted humanity against several malignancies in the past, and they are believed to do so currently and in the future as well. There are several drugs based on plants that have been approved for cancer chemotherapy, such as Taxol and paclitaxel. has a substantial potential to inhibit different cancers in humans due to its rich phytochemistry and active constituents. This plant bears a unique class of compounds called euphorbins, and they are complex in structure and active in nature. Therefore, it is believed to possess remarkable pharmacological potential, which needs to be explored.

It is highly recommended to push on progress in the field of potential antiviral therapeutics designed on natural products and their synthetic derivatives. Moreover, to look for therapeutics against coronaviruses, natural products have been the leading sources that have assisted human civilization in overcoming health hazards since the ages. The therapeutics designed on natural products have significant benefits over the synthetic ones, such as their cost effectiveness and miniscule or lack of side effects. Despite noteworthy developments in the field of vaccine development in this modern era, we lag behind in terms of developing breakthrough vaccines for several viruses, including SARS-CoV-2. Therefore, it seems to be a very difficult job to develop a potential treatment methodology for the management of such infectious viral diseases. However, plants such as and their bioactive phytochemicals have tremendous potential to serve humanity in overcoming these infectious diseases. Based on docking studies and the antiviral properties of phytochemicals, could also prove advantageous against coronaviruses. The rapid genomic mutations in SARS-CoV-2, HIV and HSV are the key drawbacks of antiviral therapeutics in targeting specific proteins and genes. The plant has huge potential against COVID-19, as it showed against different viruses, such as malaria, HSV and dengue. The plant has a strong antiviral property and has significant potential to target key sites, enzymes and replication of SARS-COV-2. Therefore, we recommend clinical investigations of against this lethal disease.

Conclusions

is a valuable medicinal plant used globally in different traditional systems of medicines. It has been reported to have various bioactivities against a wide array of human disorders. Most importantly, the plant as a whole bears a huge variety of chemical entities that enhance its therapeutic potential. The plant as a whole has been shown to have remarkable antiviral potential against HIV, DANV, HSV, etc. and enhancing immune responses against pathogens. It has great potency for free radical scavenging and ACE inhibition. Therefore, these features of may play an advantageous role throughout the management of highly infectious and deadly viral diseases such as COVID-19.

Abbreviations

SARS-CoV-2: Severe Acute Respiratory Syndrome Corona Virus-2, ACE: Angiotensin-converting enzyme, ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, CD: Cluster of differentiation, COVID-19: Corona Virus Disease 2019, DPPH: 2,2-diphenyl-1-picrylhydrazyl, DENV: Dengue Virus, HSV: Herpes Simplex Virus, HIV: Human Immunodeficiency Virus, IL-2: Interleukin-2, IFN-γ: Interferon gamma, MIC: Minimum inhibitory concentration, RBC: Red Blood cells, RBD: Receptor Binding Domain, WBC: White Blood Cells, TCM: Traditional Chinese Medicine, TNF-α: Tumor Necrosis Factor Alpha

Acknowledgments

Aadil Khursheed is highly thankful to Dr. Vikrant Jain and the whole Department of Chemistry, Madhyanchal Professional University, for providing academic guidance and platform.

Author’s contributions

All authors equally contributed to this work, read and approved the final manuscript.

Funding

None.

Availability of data and materials

Not applicable.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.