Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease.

As a progressive neurological disease with increased morbidity and mortality, Alzheimer Disease (AD) is characterized by neuron damage that controls memory and mental functions. Enicostema axillare (EA), an herb with a history of combativeness and effectiveness in treating Rheumatoid Arthritis, Cancer, and Diabetes, is used in Indian folk medicine from a holistic point of view. Though the herb is used for many illnesses, the molecular mechanism of its bioactive on AD has not been deciphered by intricate research. A unique pharmacology approach based on ADME drug screening and targeting, pathway enrichment (GO and KEGG), and network pharmacology, was established to explore the molecular mechanisms of E. axillare (EA) bioactive compounds for the treatment of AD. In brief, we bring to light the three active compounds of EA and seven potential molecular targets of AD, which are mainly implicated in four signaling pathways, i.e., MAPK, Apoptosis, neurodegeneration, and the TNF pathway. Moreover, the network analysis of the active compounds, molecular targets, and their pathways reveals the pharmacological nature of the compounds. Further, molecular docking studies were carried out to explore the interactions between the EA bioactive compounds and the targets and examine the binding affinity. The outcome of the work reflects the potential therapeutic effects of the compounds for treating AD through the modulation of the key proteins, which further corroborates the reliability of our network pharmacology analysis. This study not only helps in understanding the molecular mechanism of the drugs but also helps in finding and sorting new drugs for the treatment of AD, and other complex diseases through modern medicine.

In vitro and in silico screening of novel typhoid drugs from endangered herb (Enicostema axillare).

In the present study, antibacterial activity of swertiamarin from Enicostema axillare (Lam) was checked against three different human gram-negative pathogens namely Salmonella typhi, Klebsiella pneumoniae and Shigella flexneri. Minimum inhibitory concentration assay revealed low dose and efficient activity of swertiamarin on the above said pathogens. Though swertiamarin is a well-studied and characterized compound, there is no experimental proof available for its antibacterial activity. To gain more insight about the antibacterial efficiency of swertiamarin against typhoid causing S. typhi, a comparative molecular docking of S. typhi OmpF (3NSG) was performed with swertiamarin and other typhoid drugs available in the market which exposed better activity strength of swertiamarin compared with that of the other drugs. Further, molecular dynamics of S. typhi OmpF-swertiamarin shows good flexibility and stability at 100 ns. The outcome of this work will definitely provide an idea of using very low dose of swertiamarin as a potent and promising drug against typhoid fever.Communicated by Ramaswamy H. Sarma.

Effect of novel therapeutic medicine swertiamarin from Enicostema axillare in zebrafish infected with Salmonella typhi.

Herbal treatments have been practiced by humans over centuries and therefore possess time-proven safety. However, it is crucial to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic drugs. Use of laboratory animals such as mice, rat, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more controversial. As a possible alternative model involving lower vertebrates such as zebra fish were introduced. Hence in the present study, swertiamain compound isolated from E. axillare was assessed for it antimicrobial activity in zebra fish larvae againt S. typhi. The cumulative mortality rate and bacterial localization in zebra fish larvae were studied. Biochemical markers assays were performed to find the preventive role of the compound during the typhoid infection. The results showed that zebra fish can be successfully used as a model to study typhoid infection and the anti-bacterial compound swertiamarin used in this study clears the bacterial load and pathogenic symptoms to a great extent.

Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio).

A secoiridoid glycoside called swertiamarin has been widely used as a herbal medicine for many decades. In particular, swertiamarin from the Enicostema axillare herb has been used as a multipurpose drug to treat innumerable health problems. As this medicine is consumed orally, its toxicity level should be determined. To examine the safety of this compound, toxicology work was done in zebrafish, and this is the first report to describe swertiamarin toxicity in zebrafish. Zebrafish embryos were used in this swertiamarin toxicity study, and morphological changes were observed. Further, the compound was also studied in adult zebrafish to determine the impact of the compound on the fish liver. Enzyme profiling with superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione levels, glutathione S-transferase, lactate dehydrogenase, glutamic oxaloacetic transaminases, lipid peroxidation, Na+ /K+ -ATPase, and glutamic pyruvic transaminases) was evaluated (p ≤ 0.05). Results suggest that swertiamarin is a safe drug only at a low concentration (40 µM). This study also shows that even herbal medicinal compounds may be toxic to humans at higher dosages. Hence, irrespective of whether a drug is synthetic or natural, it needs to be tested for its toxicity before use in humans.

Selenium nanoparticle synthesis from endangered medicinal herb (Enicostema axillare).

Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of E. axillare leaf extract. This method is capable of producing SeNPs in a size range of around 56.23-98.18 nm, under ambient lab condition. The synthesized nanoparticles were characterized by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Energy-dispersive X-Ray (EDX). To check the potential hazards of nanotoxicity median lethal concentration (LC50) and Na + /K + -ATPase activity was assessed on zebra fish which showed the LC50 of 258.72 ppm for 96 h and Na + /K + -ATPase seems to significantly decrease with increase in SeNPs concentration. Antibactericidal activity explored the use of SeNPs against wide range of pathogens. Cytotoxicity of SeNPs was assayed against human lung cancer cells (A549) confirmed that SeNPs are able to inhibit the cell growth by dose-dependent manner. In conclusion, green synthesized selenium nanoparticles are less toxic and harmless. This is the first report on green synthesized selenium nanoparticles using E. axillare possessing anti-bacterial and anti-cancer activity.