Tryptanthrin

JOURNAL/nrgr/04.03/01300535-202511000-00031/figure1/v/2025-09-25T165316Z/r/image-tiff The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress–related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia–derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Wrightia dubia and Wrightia pubescens are traditionally used to treat malaria, yet their phytochemical and pharmacological profiles remain underexplored. A preliminary screening of the plant extracts showed promising antiplasmodial activity, warranting further investigation. Thus, this study aims to investigate their phytochemical constituents and their antiplasmodial, cytotoxic, and hemolytic activities. Of the ten extracts screened, three dichloromethane extracts of W. dubia wood, W. dubia twig, and W. pubescens twig demonstrated significant antiplasmodial activity with the IC₅₀ values of 1.89 ± 0.06 μg/mL, 6.38 ± 0.04 μg/mL, and 1.79 ± 0.03 μg/mL, respectively. LC-MS analysis of the active extracts tentatively identified 38 compounds. Exhaustive chromatographic procedures yielded a new natural product, 2-(2'-hydroxyphenyl)quinazolin-4(3H)-one, along with nine known compounds. Tryptanthrin demonstrated significant antiplasmodial activity against the Plasmodium falciparum 3D7 and Dd2 strains, with the IC₅₀ values of 2.50 ± 0.05 μM and 3.14 ± 0.023 μM, respectively. All active extracts (CC₅₀ > 30 μg/mL) and their isolated compounds (CC₅₀ > 10 μM) were non-toxic to HepG2 cell lines. None of the tested samples induced erythrocyte hemolysis at 100 μg/mL. These findings support further in vivo evaluation of tryptanthrin as lead candidate for antimalarial drug development.