Affiliations 

  • 1 Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu, 603203, Tamil Nadu, India
  • 2 Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu, 603203, Tamil Nadu, India; Department of Pharmacology, Faculty of Medicine, Mahsa University, Bandar Sanjana Putra Selangor, 42610, Malaysia. Electronic address: tamilant@srmist.edu.in
  • 3 Department of Pharmacology, MNR College of Pharmacy, Sangareddy, 502294, Telangana, India
Neuroscience, 2025 Jan 26;565:232-246.
PMID: 39643234 DOI: 10.1016/j.neuroscience.2024.12.006

Abstract

Neuroinflammation can be directly linked to the imbalance in the Kynurenine-tryptophan Pathway (KP) metabolism. Under inflammatory circumstances, the KP is activated, resulting in a rise in the KP metabolite L-kynurenine (KYN) in the peripheral and central nervous systems (CNS). Increased amounts of KYN in the brain may lead to neurotoxic KYN metabolites, mostly due to breakdown by Kynurenine-3-monooxygenase (KMO). Tetrahydrocoptisine (also known as stylopine) is an alkaloid isolated from Corydalis impatiens. Molecular docking with specific proteins involved in the Neuroinflammation mechanism was studied. LPS-induced neuroinflammation to mice. After 7 days of acclimatization, the animals in groups II, III, and IV were given 5 mg/kg i.p. of the endotoxin LPS. Groups III and IV were subsequently given daily intraperitoneal doses of 18.4 mg/kg and 36.8 mg/kg of our test medication Tetrahydrocoptisine, while group II was used as a disease control. On the 15th day, all groups were assessed neuro-behaviorally. On the 16th day, the mice were slaughtered for histopathology, lipid peroxidation, and nitrite studies. The neurobehavioural assessment involving elevated plus-maze, sucrose preference test, line crossing, and actophotometer revealed that the test drug is capable of decreasing LPS-induced anxiety, depression, and anhedonia at both low and high doses respectively. The histopathological analysis indicated that the neurodegeneration is attenuated at high doses of Tetrahydrocoptisine. A test drug demonstrated potency in inhibiting Kynurenine monooxygenase (KMO) expression in the brain, leading to reduced levels of nitric oxide and lipid peroxidation compared to a control group.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.