Hydroethanolic Extract of L. Mediates the Anti-Inflammatory Activity in RAW 264.7 Murine Macrophages Through Induction of Heme Oxygenase-1 and Inhibition of Inducible Nitric Oxide Synthase.

Plants (Basel)

Herbal Medicine Research Division, Korea Institution of Oriental Medicine (KIOM), Daejeon 34054, Republic of Korea.

Published: November 2024

AI Article Synopsis

  • L. (PAL), or knotgrass, has been traditionally used in various cultures to treat inflammatory conditions like arthritis and airway inflammation, but its molecular mechanisms are not fully understood.
  • The study explores the role of the antioxidant enzyme heme oxygenase-1 (HO-1) in mediating the anti-inflammatory and antioxidative effects of PAL, specifically through its interactions with nuclear factor kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2).
  • Results indicate that PAL enhances HO-1 levels and reduces inflammatory markers in macrophages, but inhibiting HO-1 results in increased iNOS expression and nitric oxide production, highlighting the complex relationship between antioxidant and anti

Article Abstract

L. (PAL), commonly known as knotgrass, has been utilized as a traditional folk medicine across Asian, African, Latin American and Middle Eastern countries to treat various inflammatory diseases, including arthritis and airway inflammation. Numerous medicinal herbs exert anti-inflammatory and antioxidative effects that are mediated through the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of nuclear factor kappa B (NF-κB). However, the underlying molecular mechanisms linking the antioxidative and anti-inflammatory effects remain poorly understood. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that catalyzes heme degradation, ultimately leading to the production of carbon monoxide (CO). Elevated levels of CO have been correlated with the decreased level of inducible nitric oxide synthase (iNOS). In this study, we examined whether HO-1 plays a key role in the relationship between the antioxidative and anti-inflammatory properties of PAL. The anti-inflammatory and antioxidative activities of PAL in an in vitro system were evaluated by determining NF-κB activity, antioxidant response element (ARE) activity, pro-inflammatory cytokine and protein levels, as well as antioxidant protein levels. To examine whether HO-1 inhibition interfered with the anti-inflammatory effect of PAL, we measured nitrite, reactive oxygen species, iNOS, and HO-1 levels in RAW 264.7 murine macrophages pre-treated with Tin protoporphyrin (SnPP, an HO-1 inhibitor). Our results demonstrated that PAL increased ARE activity and the Nrf2-regulated HO-1 level, exerting antioxidative activities in RAW 264.7 macrophages. Additionally, PAL reduced cyclooxygenase-2 (COX-2) and iNOS protein levels by inactivating NF-κB in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Further investigation using the HO-1 inhibitor revealed that HO-1 inhibition promoted iNOS expression, subsequently elevating nitric oxide (NO) generation in LPS-activated RAW 264.7 macrophages treated with PAL compared to those in the macrophages without the HO-1 inhibitor. Overall, our findings suggest that HO-1 induction by PAL may exert anti-inflammatory effects through the reduction of the iNOS protein level. Hence, this study paves the way for further investigation to understand molecular mechanisms underlying the antioxidative and anti-inflammatory activities of medicinal herbs.

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Source
http://dx.doi.org/10.3390/plants13233314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11644326PMC

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