Biliverdin

Biliverdin, produced through the oxidation of bilirubin, can also be synthesized through a non-protoporphyrin pathway in Corynebacterium glutamicum . Biliverdin is investigated in biochemical and microbial research contexts focused on heme degradation pathways, oxidative stress response systems, microbial metabolic engineering, and bile pigment–associated cellular signaling mechanisms.

Methods：The metabolic pathway of biliverdin production was summarized. Combined with in vitro assays, its mechanisms regulating immunity, vascular physiology, inflammatory response and oxidative stress were explored.
Results：
1.Biliverdin is a degradation product of heme. Heme released from ruptured erythrocytes is catalyzed by heme oxygenase to generate biliverdin IX-α, carbon monoxide and ferrous iron. Biliverdin IX-α is further converted into bilirubin IX-α by NADPH-dependent biliverdin reductase .
2.Biliverdin accumulation elevates biliverdin reductase activity, thereby modulating innate immune function . It inhibits vascular smooth muscle proliferation, exerts vascular antioxidant effects, and suppresses intimal hyperplasia and angiogenesis .
3.Biliverdin downregulates pro-inflammatory factors such as TLR-4 and upregulates anti-inflammatory factor IL-10, effectively alleviating inflammation [1]. It scavenges hydroxyl peroxides, inhibits mitochondrial superoxide production at concentrations of 0.1–1 μM, and reduces systemic oxidative stress [1-2].

Methods：Rat balloon angioplasty and vascular graft injury models, as well as mouse graft injury model were established. Biliverdin was intraperitoneally injected at 50 μmol/kg for 2 consecutive weeks. Vascular intimal hyperplasia, immune cell infiltration and splenocyte proliferation were observed.
Results：Biliverdin markedly inhibited intimal hyperplasia after angioplasty and vascular transplantation, and reduced neointimal formation induced by balloon injury [1,3]. Drug treatment decreased immune cell infiltration in graft tissues and suppressed proliferative activity of mouse splenocytes [3].

DMSO: 2.4 mg/mL (4.12 mM), Sonication and heating are recommended.