Trends in Euphorbia hirta Research: A 30-year Bibliometric Appraisal of the Present Realities

Euphorbia hirta L., is a common herb with global spread. Different parts of E. hirta are used in traditional medicine for the treatment of a variety of human and animal conditions, such as skin diseases, inflammation, digestive and respiratory disorders. This bibliometric study aimed to provide a panoramic view of the publication landscape in the last thirty years of Euphorbia hirta research. VOSviewer was used to analyze 603 documents retrieved from Scopus database during the period, 1992 to 2021. Dominant research themes in the last thirty years were centred on the application of crude extracts or isolated compounds from E. hirta against diabetes, oxidative stress, inflammation, tuberculosis, snake bite, gastro-intestinal disorders, respiratory infections, skin pathologies, bacterial, fungal and viral infections. Current paradigm shift in E. hirta research are targeted at improving the efficacy of phytomolecules against resistant bacterial pathogens and cancer cells via green synthesis of nanoparticles and the application of in silico technologies in predicting the activities of nano-phytomolecules against SARS-CoV-2 and the Dengue virus. This study recommends further research in the determination of the bioavailability of molecules in in vivo models. Researchers should carry out more preclinical investigations with the aim of establishing the pharmacokinetic and pharmacodynamic properties of phytocompounds instead of relying solely on in silico predictions.

Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti-SARS-CoV-2 Activity.

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC50 8.231±0.04 µg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.

Lagerstroemia, Euphorbia hirta, and Kleinhovia hospita as inhibitors of heptad repeat (HR) SARS-CoV-2 spike protein based on an in silico study

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-19 (COVID-19), has become a global health issue. Spike proteins from the virus have a vital role in infection. Herbal medicines such as Lagerstroemia, Euphorbia hirta, and Kleinhovia hospita have several pharmacological functions such as anticancer, antiviral, and antioxidant because of their bioactive compound content. Based on an in silico study, this research was conducted on the possibility of phytochemicals from herbal Lagerstroemia, E. hirta, and K. hospita to inhibit spike protein SARS-CoV-2. A three-dimensional (3D) compound structure of each herbal medicine was docked with HR protein using AutoDock Vina software. The docking result, which has the best binding energy value, is continued with the analysis of molecular dynamics simulation. Lagerine, rutin, and nicotiflorin compounds might bind to proteins with lower binding energy. Protein was unstable when complexed with compounds compared with control, as seen from the root-mean-square deviation (RMSD) value. Therefore, this research is pre-experimental to inhibit SARS-CoV-2 spike proteins by herbal medicines.

Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Euphorbia neriifolia Linn. against Infectious Diseases: A Comprehensive Review.

Medicinal plants have considerable potential as antimicrobial agents due to the presence of secondary metabolites. This comprehensive overview aims to summarize the classification, morphology, and ethnobotanical uses of Euphorbia neriifolia L. and its derived phytochemicals with the recent updates on the pharmacological properties against emerging infectious diseases, mainly focusing on bacterial, viral, fungal, and parasitic infections. The data were collected from electronic databases, including Google Scholar, PubMed, Semantic Scholar, ScienceDirect, and SpringerLink by utilizing several keywords like 'Euphorbia neriifolia', 'phytoconstituents', 'traditional uses', 'ethnopharmacological uses', 'infectious diseases', 'molecular mechanisms', 'COVID-19', 'bacterial infection', 'viral infection', etc. The results related to the antimicrobial actions of these plant extracts and their derived phytochemicals were carefully reviewed and summarized. Euphol, monohydroxy triterpene, nerifoliol, taraxerol, ß-amyrin, glut-5-(10)-en-1-one, neriifolione, and cycloartenol are the leading secondary metabolites reported in phytochemical investigations. These chemicals have been shown to possess a wide spectrum of biological functions. Different extracts of E. neriifolia exerted antimicrobial activities against various pathogens to different extents. Moreover, major phytoconstituents present in this plant, such as quercetin, rutin, friedelin, taraxerol, epitaraxerol, taraxeryl acetate, 3ß-friedelanol, 3ß-acetoxy friedelane, 3ß-simiarenol, afzelin, 24-methylene cycloarenol, ingenol triacetate, and ß-amyrin, showed significant antimicrobial activities against various pathogens that are responsible for emerging infectious diseases. This plant and the phytoconstituents, such as flavonoids, monoterpenoids, diterpenoids, triterpenoids, and alkaloids, have been found to have significant antimicrobial properties. The current evidence suggests that they might be used as leads in the development of more effective drugs to treat emerging infectious diseases, including the 2019 coronavirus disease (COVID-19).

Interactive deciphering electron-shuttling characteristics of agricultural wastes with potential bioenergy-steered anti-COVID-19 activity via microbial fuel cells.

Background: This first-attempt study explored indigenous herbs from agricultural waste with bioenergy and biorefinery-stimulating potentials for possible anti-COVID-19 drug development. As prior novel study revealed, medicinal herbs abundant in ortho-dihydroxyl substituents and flavonoid-bearing chemicals were likely not only electron shuttle (ES)-steered, but also virus transmission-resisted. Methods: Herbal extract preparation from agricultural wastes were implemented via traditional Chinese medicine (TCM) decoction pot. After filtration and evaporation, a crude extract obtained was used for evaluation of bioenergy-stimulating and electron-mediating characteristics via microbial fuel cells (MFCs). Combined with cyclic voltammetric analysis, MFCs provided a novel platform to distinguish electron shuttles from antioxidants with electron-transfer steered antiviral potentials of herbal extracts. Significant findings: After 50 serial cyclic voltammogram traces, considerable ES activities of herbal extracts still stably remained, indicating that possible medication-associated capabilities could be persistent. This work also extended to explore bioenergy-stimulating herbs from agricultural waste recycling for bioenergy and biorefinery applications. Water extract of Coffea arabica was more biotoxic than ethanolic extract, resulting in its lower power-generating capability. The findings revealed that water extract of Trichodesma khasianum and Euphorbia hirta could exhibit considerable bioenergy-enhancing effects. For cradle-to-cradle circular economy, agricultural waste could be specifically screened for possible regeneration of value-added anti-COVID-19 drugs via bioenergy selection.

Philippine medicinal plants with potentialimmunomodulatory and anti-SARS-CoV-2 activities

Coronavirus disease 2019 (COVID-19) continues to devastate the world's health and economy, affecting all aspects of life leading to widespread social disruption. Even as several vaccines have been developed, their availability in developing countries is limited and their efficacy against the variants of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) needs to be continuously assessed. The World Health Organization (WHO) has acknowledged that vaccines alone will not overcome the global challenges of COVID-19. Medicinal plants may provide the needed support. Herein, we identify Philippine medicinal plants that possess phytochemicals with potential anti-SARS-CoV-2 activity and/or immunomodulatory properties that may strengthen one's immune system against COVID-19. These plants were selected from 100 of the best-studied Philippine medicinal plants with antiviral and immunomodulatory properties. The general antiviral and specific anti-SARS-CoV-2 activities and immunomodulatory properties of the phytochemicals that these plants contained were searched. While many compounds assessed individually using in vitro and in silico techniques suggest potential anti-SARS-CoV-2 or immunomodulatory effects, this review sought to identify the medicinal plants which contain these compounds and which, based on literature, have the best potential application against COVID-19. These plants are Allium spp. bulbs (bawang), Andrographis paniculata (Burm.f.) Nees leaves (sinta), Cocos nucifera L. oil (niyog), Euphorbia hirta L. leaves (tawa-tawa), Euphorbia neriifolia L. leaves (sorosoro), Moringa oleifera Lam. leaves (malunggay), Ocimum basilicum L. leaves (balanoy), Piper nigrum L. seeds (paminta), Vitex negundo L. leaves (lagundi), and Zingiber officinale Roscoe rhizome (luya). This review provides a shortlist that can guide research on possible solutions to COVID-19 using Philippine medicinal plants.

Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach.

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

Antimicrobial Triterpenoids and Ingol Diterpenes from Propolis of Semi-Arid Region of Morocco.

The chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were investigated. Fifteen compounds, including triterpenoids (1, 2, 7-12), macrocyclic diterpenes of ingol type (3-6) and aromatic derivatives (13-15), were isolated by various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and chiroptical methods. Compounds 1 and 3 are new natural compounds, and 2, 4-6, and 9-11 are newly isolated from propolis. Moreover, the full nuclear magnetic resonance (NMR) assignments of three of the known compounds (2, 4 and 5) were reported for the first time. Most of the compounds tested, especially the diterpenes 3, 4, and 6, exhibited very good activity against different strains of bacteria and fungi. Compound 3 showed the strongest activity with minimum inhibitory concentrations (MICs) in the range of 4-64 µg/mL. The combination of isolated triterpenoids and ingol diterpenes was found to be characteristic for Euphorbia spp., and Euphorbia officinarum subsp. echinus could be suggested as a probable and new plant source of propolis.

Euphorbia hirta as a gold mine of high-value phytochemicals: A comprehensive review of its pharmacological activities and possible role against SARS-CoV-2

Euphorbia hirta is a common medicinal plant in folk and traditional medicine systems. This plant has shown promising effects against several human ailments and infectious diseases. Therefore, it is important to summarize the medicinal activities and value of Euphorbia hirta. The main intent of this literature review was to summarize the phytochemical content and pharmacological applications of Euphorbia hirta. The literature review about the pharmacology and phytochemistry of Euphorbia hirta was collected from different global platforms, such as Scopus, ERIC, PubMed, and Web of Science. E. hirta has a rich phytochemistry and exhibits remarkable activity against respiratory diseases, gastrointestinal disorders and venereal diseases. Different extracts of this plant have shown significant preclinical anticancer propensity against an array of different cancer cell lines. It acts as a highly active antiviral agent and has shown pronounced activity against coxsackievirus, human immunodeficiency virus, dengue virus, poliovirus and simian immunodeficiency virus. A clinical study showed its inhibitory responses against flu and fever in dengue patients. Most importantly, the plant possesses remarkable inhibitory action on ACE, which aids SARS-CoV-2 entry into host cells. The multidimensional role of Euphorbia hirta as a potential antiviral agent suggests its possible application to control COVID-19 along with modern and Western medicinal strategies. In conclusion, the literature review regarding Euphorbia hirta showed its strong pharmacological applications, such as antimicrobial, antimalarial, anti-asthmatic, antioxidant, antiviral and anticancer activities. Further in-depth research is necessary to monitor its role in the management of viral diseases, especially COVID-19.

Phytochemicals of Euphorbia hirta L. and Their Inhibitory Potential Against SARS-CoV-2 Main Protease.

Euphorbia hirta L. is a medicinal plant widely used in the Philippines and across tropical Asia against various diseases, including respiratory disorders. In this study, the phytochemical components of E. hirta were investigated in silico for their potential to inhibit the severe acute respiratory syndrome-coronavirus-2 main protease (SARS-CoV-2 Mpro), a coronavirus disease 2019 (COVID-19) drug target that plays a critical role in the infection process of SARS-CoV-2. Phytochemical mining in tandem with virtual screening (PM-VS) was the strategy implemented in this study, which allows efficient preliminary in silico assessment of the COVID-19 therapeutic potential of the reported phytochemicals from the plant. The main rationale for considering E. hirta in the investigation was its reported efficacy against respiratory disorders. It is very promising to investigate the phytochemicals of E. hirta for their potential efficacy against diseases, such as COVID-19, that also target the respiratory system. A total of 298 E. hirta phytochemicals were comprehensively collected from the scientific literature. One hundred seventy of these phytochemicals were computed through molecular docking and were shown to have comparable or better binding properties (promising inhibitors) toward SARS-CoV-2 Mpro than known in vitro inhibitors. In connection to our previous work considering different medicinal plants, antiviral compounds were also rediscovered from the phytochemical composition of E. hirta. This finding provides additional basis for the potential of the plant (or its phytochemicals) as a COVID-19 therapeutic directly targeting drug targets such as SARS-CoV-2 Mpro and/or addressing respiratory-system-related symptoms. The study also highlights the utility of PM-VS, which can be efficiently implemented in the preliminary steps of drug discovery and development.

Identification of bioactive phytoconstituents from the plant euphorbia hirta as potential inhibitor of sars-cov-2: An in-silico approach

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro;PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp;PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro . Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19. © 2021 by the authors.

Medicinal plants from West Africa for the management of respiratory diseases that may appear during the COVID-19

As part of contributing to the symptomatic management of respiratory conditions that may manifest during Covid-19, the current study was undertaken to identify African medicinal plants active against these manifestations. A bibliographic study was carried out to identify the plant species used in the management of respiratory diseases in West Africa. The frequency of citation and a convergence score for the use of the species were also calculated. A total of 318 recipes from 145 plant species were inventoried through various publications. Guiera senegalensis, Sterculia setigera, Bridelia ferruginea, Euphorbia hirta and Terminalia avicennioides were the most cited plants with the best usage convergence scores. Leaves from these species were most cited while the cough was more indicated. The results of this study could serve as a database of plant species used in the management of respiratory tract diseases in West Africa.

Herbal plants from Riau Province as inhibitors of COVID-19 binding to ACE2 receptor by computer aided molecular design an in-silico method

Corona Virus Disease (COVID-19) is announced as pandemic by World Health Organization (WHO) since 11th March 2020. Riau Province has many herbal plants e.g. Cheilocostus specious, Euphorbia hirta l, Cassia torra, Bryophyllum pinnatum, Daniella ensifollia, and Ziziphus mauritiana that can cure many diseases and there is not report yet focusing on in-silico method using SARS-CoV-2 protease (PDB ID:6LU7). This study aims to reveal the potential of compounds contained in Riau Herbal Plants as anti SARS-CoV-2 through its binding to protein receptors. The study was conducted by molecular docking using Autodock Vina 1.5.6 and drug ability studies using Swiss ADME. The docking results of six active compounds including diosgenin, tannin, triterpenoid, chrysophanol, flavone and phytosterol were -8,3;-7,5;-7,5;-7,2;-6,9;-6,9 respectively against the affinity result for natural ligand of COVID-19 (-6,1). This result indicates the stronger bond between ACE2 and inhibitors because the affinity value of active compounds are higher than natural ligand of COVID-19. The SwissADME results show that triterpenoid and tannin violate some Lipinski Rules that make their drug-likeness is low. In general, all the active compounds were potential as candidates of SARS-CoV-2 antiviral but the most potential one is diosgenin in Cheilocostus specious. © Published under licence by IOP Publishing Ltd.

Potential Medicinal Plants for the Treatment of Dengue Fever and Severe Acute Respiratory Syndrome-Coronavirus.

While dengue virus (DENV) infection imposes a serious challenge to the survival of humans worldwide, severe acute respiratory syndrome-coronavirus (SARS-CoV) remains the most devastating pandemic in human history. A significant number of studies have shown that plant-derived substances could serve as potential candidates for the development of safe and efficacious remedies for combating these diseases. Different scientific databases were used to source for literature on plants used against these infections. Thirty-five studies described the traditional use of 25 species from 20 families for treating DENV infection with Carica papaya and Euphorbia hirta were the most widely used across different regions. 13 in vivo studies, 32 in vitro studies, and eight clinical studies were conducted on 30 species from 25 families against different DENV serotypes, while plants from 13 families were reported to inhibit different forms of SARS-CoV, all of which were investigated through in vitro studies. Phytoconstituents belonging to various chemical classes were identified to show a wide range of antiviral activity against these infections. Extensive studies on the potentials of medicinal plants are needed to confirm their efficacy. This paper reveals the capabilities of medicinal plants and their phytochemicals in inhibiting DENV and SARS-CoV infections.