Delving into the Latest Updates on Visnagin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

NF-κB x NLRP3 x p38 MAPK

Action

inhibitors

Mechanism

NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), NLRP3 inhibitors(NACHT, LRR and PYD domains-containing protein 3 inhibitors), p38 MAPK inhibitors(P38 mitogen-activated protein kinase inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication

Acute Kidney Injury

Inactive Indication-

Originator Organization

Chung Shan Medical University Hospital

Active Organization

Chung Shan Medical University Hospital

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Sepsis-associated acute kidney injury (AKI) is a life-threatening complication marked by inflammation-driven renal dysfunction. Although advances have been made in supportive care, pharmacologic therapies targeting the underlying molecular mechanisms of sepsis-associated AKI are lacking. Visnagin, a furanochromone derivative with anti-inflammatory properties, has yet to be explored in treatment for sepsis-associated AKI.

EXPERIMENTAL APPROACH:

This study used a network pharmacology approach to identify visnagin targets associated with AKI. We conducted gene enrichment and protein-protein interaction analyses and performed molecular docking to predict binding affinities between visnagin and key inflammatory proteins. An in vivo murine model of LPS-induced AKI was established to evaluate the protection of visnagin. Renal function was assessed through serum creatinine and blood urea nitrogen levels. Additionally, histological injury, inflammatory cytokine expression, and molecular pathways were analysed.

KEY RESULTS:

Bioinformatics analyses identified MAPK1, MAPK14, NFKB1, and CASP1 as hub genes potentially targeted by visnagin. Molecular docking confirmed strong binding affinities between visnagin and these proteins that exceeded the binding affinity of dexamethasone in key inflammatory targets. In vivo, visnagin substantially reduced LPS-induced renal dysfunction and histopathological damage in a dose-dependent manner. Visnagin suppressed the phosphorylation of p38 MAPK and extracellular signal-related kinase, decreased NF-κB activation, and inhibited the generation of proinflammatory cytokines. Moreover, visnagin attenuated pyroptosis by inhibiting the NLRP3/apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain/caspase-1/Gasdermin-D axis.

CONCLUSION AND IMPLICATIONS:

Visnagin mitigates LPS-induced AKI by targeting multiple signalling pathways, particularly NF-κB-mediated inflammation and NLRP3 inflammasome-mediated pyroptosis. These findings suggest that visnagin is a promising multitarget candidate for treating sepsis-associated AKI.

01 Jun 2022·European review for medical and pharmacological sciences

Neuroprotective effects of visnagin on cerebral ischemia-reperfusion injury rats and the underlying mechanisms.

Article

Author: Huang, J ; Liu, L-L ; Rao, X-L ; Chen, J

OBJECTIVE:

Cerebral ischemia-reperfusion (I/R), caused by the treatments of ischemic stroke, usually leads to brain injury. Inflammation, oxidative stress, and autophagy play pivotal roles in the pathology. Visnagin presents a protective effect on I/R injured animal models of the heart, liver, kidney, and other organs. In our research, we identified the neuroprotective effects and the underlying mechanisms of visnagin in cerebral I/R injured models.

MATERIALS AND METHODS:

We constructed rat models of cerebral I/R injury and categorized them into 5 groups: sham operation group, I/R model group, and visnagin treatment I/R group (10, 30, 60 mg/kg). The neurological deficits of the rats were analyzed after 24 hours of reperfusion, then, the contents of glutathione peroxidase, malondialdehyde, superoxide dismutase catalase, caspase-3, nuclear factor kappa-B p65 unit, tumor necrosis factor-α, interleukin-1β, and interleukin6 were measured in rat models. The expressions of Bcl-2 and Bax were detected by Western blot analysis.

RESULTS:

Our results suggested that the administration of visnagin alleviated the cognitive dysfunction, reduced the activities of inflammatory factors, promoted the protein expression of Bcl-2, and downregulated the expression of Bax in the I/R injured rat model.

CONCLUSIONS:

Visnagin exerts a neuroprotective effect during I/R injury in rats, the underlying mechanisms may be the effect of attenuating neuroinflammation, anti-oxidative and inhibition of apoptosis.

01 Apr 2019·Molecular biology reportsQ4 · BIOLOGY

The anticancer activity of visnagin, isolated from Ammi visnaga L., against the human malignant melanoma cell lines, HT 144

Q4 · BIOLOGY

Article

Author: Aydoğmuş-Öztürk, Fatma ; Choudhary, Muhammad Iqbal ; Günaydın, Keriman ; Beyazit, Neslihan ; Jahan, Humera

Melanoma is a cancer of melanocyte cells and has the highest global incidence. There is a need to develop new drugs for the treatment of this deadly cancer, which is resistant to currently used treatment modalities. We investigated the anticancer activity of visnagin, a natural furanochromone derivative, isolated from Ammi visnaga L., against malignant melanoma (HT 144) cell lines. The singlet oxygen production capacity of visnagin was determined by the RNO bleaching method while cytotoxic activity by the MTT assay. Further, HT 144 cells treated with visnagin were also exposed to visible light (λ ≥ 400 nm) for 25 min to examine the illumination cytotoxic activity. The apoptosis was measured by flow cytometry with annexin V/PI dual staining technique. The effect of TNF-α secretion on apoptosis was also investigated. In standard MTT assay, visnagin (100 µg/mL) exhibited 80.93% inhibitory activity against HT 144 cancer cell lines, while in illuminated MTT assay at same concentration it showed lesser inhibitory activity (63.19%). Visnagin was induced apoptosis due to the intracellular generation of reactive oxygen species (ROS) and showed an apoptotic effect against HT 144 cell lines by 25.88%. However, it has no effect on TNF-α secretion. Our study indicates that visnagin can inhibit the proliferation of malignant melanoma, apparently by inducing the intracellular oxidative stress.

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