Therapeutic potential and pharmacological mechanism of visnagin.

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant, which is used to cure various ailments. Many investigations into the bioactive properties of visnagin have been studied to date. The literature on visnagin demonstrates its biological properties, including anti-inflammatory, anti-diabetic, and beneficial effects in cardiovascular and renal diseases. Moreover, visnagin improves sperm quality parameters, stimulates steroidogenesis, and increases serum gonadotropins and testosterone levels, while decreasing pro-inflammatory cytokines, oxidative damage, genomic instability, and it modulates apoptosis. Thus, visnagin has emerged as an exciting lead for further research, owing to its potential in various unmet clinical needs. The current review summarized its basic structure, pharmacokinetics, and pharmacological effects, focusing on its mechanisms of action. The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin's safe clinical use. Please cite this article as: Yadav P, Singh SK, Datta S, Verma S, Verma A, Rakshit A, Bali A, Bhatti JS, Khurana A, Navik U. Therapeutic potential and pharmacological mechanism of visnagin. J Integr Med. 2024; 22(4): 399-412.

ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine.

BACKGROUND: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. OBJECTIVE: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line. METHODS: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharmacology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. RESULTS: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dosedependent (0-500 µM) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 µΜ. The wound-healing assay showed that vincamine treatment (150 and 300 µM) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. CONCLUSION: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects.

Comparison of NICE Guideline CG149 and the Sepsis Risk Calculator for the Management of Early-Onset Sepsis on the Postnatal Ward.

INTRODUCTION: The NICE guideline CG149 has increased the number of well infants receiving antibiotics for suspected early-onset sepsis (EOS). The Kaiser Permanente sepsis risk calculator (SRC) has safely and dramatically reduced investigations and antibiotics for suspected EOS in the USA. This study evaluates the current management of suspected EOS against the NICE guideline CG149 and the SRC. METHODS: This study is a prospective, multicentre, observational study across 13 neonatal units in London. Infants were born between June and August 2019 at ≥34 weeks gestation and commenced on antibiotics for suspected EOS and cared for on postnatal/transitional care wards. Data were prospectively recorded: risk factors, clinical indicators, investigations, and results. Outcome measures included the following: (1) incidence of EOS and (2) proportion of infants recommended for antibiotics by NICE versus theoretical application of SRC. RESULTS: 1,066/8,856 (12%) infants on postnatal/transitional care wards received antibiotics, 7 of whom had a positive blood culture (group B Streptococcus = 6 and Escherichia coli = 1), making the EOS incidence 0.8/1,000 infants. Six hundred one infants had data for SRC analysis, which recommended "antibiotics" or "blood culture" for 130/601 (21.6%) infants using an EOS incidence of 0.5/1,000 versus 527/601 (87.7%) if NICE was applied. CONCLUSIONS: Currently, 12.0% of infants on postnatal/transitional care wards receive antibiotics for suspected EOS. The SRC could dramatically reduce antibiotic use, but further prospective studies are required to evaluate safety of SRC implementation.