A new series of chromone and furochromone-based sulfonamide Schiff\'s base derivatives 3-12 were synthesized and evaluated for their antimicrobial activity against S. aureus, E. coli, C. albicans, and A. niger using agar diffusion method. Compound 3a demonstrated potent antimicrobial activities with MIC values of 9.76 and 19.53 μg/mL against S. aureus, E. coli and C. albicans, which is 2-fold and 4-fold more potent than neomycin (MIC = 19.53, 39.06 μg/mL respectively). To improve the effectiveness of 3a, it was encapsulated into chitosan nanoparticles (CS-3aNPs). The CS-3aNPs size was 32.01 nm, as observed by transmission electron microscope (TEM) images and the zeta potential value was 14.1 ± 3.07 mV. Encapsulation efficiency (EE) and loading capacity (LC) were 91.5 % and 1.6 %, respectively as indicated by spectral analysis. The CS-3aNPs extremely inhibited bacterial growth utilizing the colony-forming units (CFU). The ability of CS-3aNPs to protect skin wounds was evaluated in vivo. CS-3aNPs showed complete wound re-epithelialization, hyperplasia of the epidermis, well-organized granulation tissue formation, and reduced signs of wound infection, as seen through histological assessment which showed minimal inflammatory cells in comparison with untreated wound. Overall, these findings suggest that CS-3aNPs has a positive impact on protecting skin wounds from infection due to their antimicrobial activity.

Doxorubicin (DOX), a cornerstone of cancer chemotherapy, is marred by its dose-dependent cardiotoxicity, leading to cardiomyopathy and heart failure. The epidemiology of DOX-related cardiotoxicity highlights its cumulative, progressive nature, with a significant impact on the health of patients. The pathophysiological mechanisms involve mitochondrial dysfunction, oxidative stress and disrupted calcium homeostasis in cardiomyocytes. Despite the search for effective cardioprotective strategies, current treatments offer limited efficacy. Visnagin emerges as a potential solution, known for its vasodilatory and anti-inflammatory properties, and recent studies suggest its cardioprotective efficacy against DOX-induced cardiotoxicity through mitochondrial protection, the modulation of key signaling pathways and the inhibition of apoptosis. The present review aimed to provide a comprehensive overview of the mechanisms of action of visnagin, as well as to provide experimental evidence, and potential integration into cancer treatment regimens, highlighting its promise as a novel therapeutic agent for managing cardiotoxicity in patients undergoing anthracycline chemotherapy.

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.

Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

Khellin and visnagin furanochromones were recently reported as potential new bioherbicides with phytotoxic activities comparable to those of some commercially available herbicides. In this study, we examined the effect of O-alkylation and O-arylalkylation of both khellin and visnagin on its effect on herbicidal and antifungal activity. Synthetic analogues included O-demethyl khellin and visnagin, acetylated O-demethyl khellin and visnagin, O-benzylated demethyl khellin and visnagin, four O-demethyl alkylated khellin analogues, and six O-demethyl alkylated visnagin analogues, many of which are reported here for the first time. Both acetate analogues of khellin and visnagin indicated more activity as herbicides on Lemna pausicostata than visnagin, with IC50 values of 71.7 and 77.6 μM, respectively. Complete loss of activity for all O-alkyl analogues with a carbon chain length of greater than 14 carbons was observed. The O-demethyl butylated visnagin analogue was the most active compound with an IC50 of 47.2 μM against L. pausicostata. O-Demethyl ethylated analogues of both khellin and visnagin were as effective as khellin. In the antifungal bioautography bioassay against Colletotrichum fragariae at 100 μg, the only active O-alkyl and O-arylalkyl analogues were O-ethylated, O-butylated, and O-benzylated visnagin analogues with zones of inhibition of 10, 9, and 9 mm, respectively, an effect comparable to that of visnagin and khellin.

Pain management has been a severe public health issue throughout the world. Acute pain if not treated at the appropriate time can lead to chronic pain that can cause psychological and social distress. Nothing can be more rewarding than treating pain successfully for a physician. However, the use of chemical NSAIDs and opiate drugs has taken a toll on the patients with their unavoidable side effects. This study intends to explore the potential to treat pain by inhibiting nociception and inflammation with a safer, non-addictive, effective, and low-cost alternative agent from a natural source, visnagin. In vivo studies have been conducted using male Swiss albino mice as models for this research. Nociception was induced using different chemical and thermal stimuli such as acetic acid, glutamate, capsaicin, and formalin. To check for the anti-inflammatory properties, carrageenan was used to induce inflammation and the activity was assayed using peritoneal cavity leukocyte infiltration analysis and pro-inflammatory cytokine level comparison with the supplementation of visnagin at three different dosages. The findings of this study revealed that the visnagin treatment effectively attenuated the acetic acid-induced writhing response, glutamate-induced paw licking numbers, capsaicin-induced pain response, and formalin-induced biphasic licking incidences in the experimental mice models. Furthermore, the visnagin treatment remarkably suppressed the carrageenan-induced inflammation in mice, which is evident from the decreased leukocytes, mononuclear, and polymorphonuclear cell numbers in the mice. The levels of cytokines such as TNF-α, IL-1β, and IL-6 were effectively reduced by the visnagin treatment in the experimental mice. The results of open field test proved that the visnagin showed a better locomotor movement in the experimental mice. These results provided evidence for the potential activity of the visnagin against inflammatory and nociceptive responses in the mice.

BACKGROUND: Visnagin is a phenolic and natural compound in turmeric and fenugreek, and its anti-inflammatory effect has been indicated. Therefore, this study aimed to investigate and compare the anti-inflammatory properties of visnagin and its methoxy derivative khellin on human lymphocytes.
METHODS: Human lymphocytes were treated with khellin, visnagin (10, 30, and 100 µM), and dexamethasone (0.1 mM) in the presence of phytohemagglutinin (PHA). The levels of cell proliferation, nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA), and MDA/GSH ratio were measured using biochemistry methods. Furthermore, the mRNA levels of interferon-γ (IFN-γ), interleukin (IL)-4, and IL-10 were assessed using real-time PCR, while IFN-γ/IL-4(Th1/Th2), IFN-γ/IL-10(Th1/Treg), and IL-4/IL-10(Th2/Treg) ratios were made by dividing their exact values.
RESULTS: In the PHA-stimulated group, GSH and IFN-γ/IL-4 levels were markedly diminished, but other variables were significantly elevated compared to the control group. Khellin and visnagin significantly declined the levels of cell proliferation, MDA, MDA/GSH ratio, and NO production. Khellin and visnagin concentration-dependently diminished IFN-γ and IL-4 levels and increased IL-10 levels compared to the PHA-stimulated group. Two higher concentrations of khellin and visnagin (30 and 100 μM) considerably diminished the IFN-γ, IFN-γ/IL-10, and IL-4/IL-10 values compared to the PHA-stimulated group. However, 100 µM of khellin and visnagin significantly increased GSH level compared to the PHA-stimulated group.
CONCLUSIONS: In PHA-stimulated lymphocytes, representing Th2 dominant allergic diseases, khellin and visnagin provides more specific anti-oxidant, anti-inflammatory, and immunomodulatory functions than dexamethasone. In addition, the effects of khellin were more prominent than visnagin.

Khellin is the key furanocoumarin of Ammi visnaga L. (Lam.) that exhibits various biological properties. This unique natural product has inspired the discovery of two first-in-class drugs, amiodarone and sodium cromoglycate. A wide range of analytical methods were generated while translating khellin scaffold into clinically used drugs; however, they have never been reviewed and critically assessed. The present review aims to review and evaluate the analytical techniques for the natural products, khellin, visnagin, and their inspired drugs, amiodarone and sodium cromoglycate. High-performance liquid chromatography (HPLC) is the extensively used technique in most analytical methods reported for these compounds; however, other techniques including the fluorimetry, luminescence spectrophotometry, potentiometry, voltammetry, FT-Raman spectroscopy, and ELISA were also employed. The review will be helpful for further basic and translational research on furanochromone and related scaffolds.

Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weight and several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-κB p65, TNF-α, IL-6, and decreased glutathione and antioxidant enzymes in rats\' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-κB p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPARγ. Molecular docking simulations revealed the binding method of VIS to NF-κB, Keap1, and PPARγ. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPARγ mediates the cardioprotective effect of VIS.

BACKGROUND: Khella (Ammi visnaga Lam.) fruits (Apiaceae) are rich in furanochromones, mainly khellin and visnagin, and are thus incorporated in several pharmaceutical products used mainly for treatment of renal stones.
METHODS: The objective of this study was to compare the yield of khellin and visnagin obtained using different conventional solvents and supercritical fluid extraction (SCFE) with carbon dioxide (containing 5% methanol as co-solvent). Water, acetone and ethanol (30% and 95%) were selected as conventional solvents.
RESULTS: Highest extract yield was obtained from 30% ethanol (15.44%), while SCFE gave the lowest yield (4.50%). However, the percentage of furanochromones were highest in SCFE (30.1%), and lowest in boiling water extract (5.95%). HPLC analysis of conventional solvent extracts showed other coumarins that did not appear in supercritical fluid extraction chromatogram due to non-selectivity of solvent extraction. Ammi visnaga extracts as well as standard khellin and visnagin were tested for their cytotoxic activity using sulforhodamine B assay on breast cancer (MCF-7) and hepatocellular carcinoma (Hep G2) cell lines. Results revealed a strong cytotoxic activity (IC50 < 20 µg/mL) for the SCFE and standard compounds (khellin and visnagin) (IC50 ranging between 12.54 ± 0.57 and 17.53 ± 1.03 µg/mL). However, ethanol and acetone extracts had moderate cytotoxic activity (IC50 20-90 µg/mL) and aqueous extract had a weak activity (IC50 > 90 µg/mL).
CONCLUSIONS: Thus, supercritical fluid extraction is an efficient, relatively safe, and cheap technique that yielded a more selective purified extract with better cytotoxic activity.