Lunularin

Lunularin is an inhibitor of 11β-hydroxysteroid dehydrogenase 1, with an IC₅₀ of 45.44 μM and a K_i of 35.8 μM against human 11β-HSD1, and an IC₅₀ of 17.39 μM and a K_i of 10.31 μM against rat 11β-HSD1. Lunularin upregulates the transcription levels of Sirt1 and Hmox1 genes in the liver. Lunularin reduces food intake and body weight gain, and decreases blood glucose levels in mice fed a high-fat diet. Lunularin inhibits LPS-induced TLR4-mediated NF-κB pathway activation and nitric oxide production. Lunularin inhibits the proliferation and colony formation of renal cancer and colon cancer cells, and exhibits cancer cell-specific cytotoxicity. Lunularin binds to the steroid-binding site of human 11β-HSD1 and the steroid/NADPH-binding region of rat 11β-HSD1, but does not inhibit 11β-HSD2 or mouse 11β-HSD1. Lunularin can be used in research related to diet-induced obesity, renal cancer, colorectal cancer, inflammatory diseases and metabolic syndrome^[1][2][3][4]. In Vitro:Lunularin (0.5×-1.5×; 26.8-80.4 nmol/g) dose-dependently inhibits the proliferation of 786-O human renal adenocarcinoma cells, with greater activity than dihydroresveratrol alone at concentrations relevant to kidney tissue levels^[2].
Lunularin (0.5×-1.5×; 26.8-80.4 nmol/g) dose-dependently inhibits the proliferation of A498 human renal carcinoma cells, with greater activity than dihydroresveratrol alone at concentrations relevant to kidney tissue levels^[2].
Lunularin (1×; 53.6 nmol/g) significantly inhibits the clonogenic growth of 786-O human renal adenocarcinoma cells at concentrations relevant to kidney tissue levels, with enhanced activity when combined with dihydroresveratrol^[2].
Lunularin (1×10⁰; 53.6 nmol/g) significantly inhibits the clonogenic growth of A498 human renal carcinoma cells at concentrations relevant to kidney tissue levels, with enhanced activity when combined with dihydroresveratrol^[2].
Lunularin (0.5×-1.5×; 30.25-90.75 nmol/g) inhibits the proliferation of HCT-116 human colorectal carcinoma cells, with enhanced activity when combined with dihydroresveratrol at concentrations relevant to colonic tissue levels^[2].
Lunularin (1×; 60.5 nmol/g; 12 days) significantly inhibits the clonogenic growth of HT-29 human colon adenocarcinoma cells at concentrations relevant to colonic tissue levels, with enhanced activity when combined with dihydroresveratrol^[2].
Lunularin (0.5×-1.5×; 30.25-90.75 nmol/g) dose-dependently inhibits LPS-induced NO production in RAW264.7 mouse macrophages, with enhanced activity when combined with dihydroresveratrol at concentrations relevant to colonic tissue levels^[2].
Lunularin (0.5×-1.5×; 30.25-90.75 nmol/g) dose-dependently inhibits LPS-induced SEAP production in HEK-Blue mTLR-4 cells (targeting the TLR-4-mediated NF-κB pathway), with greater activity than resveratrol alone at concentrations relevant to colonic tissue levels^[2].
Lunularin (20-100 μM; 30 min to standard assay conditions) competitively inhibits human liver microsomal 11β-HSD1 with an IC₅₀ of 45.44 μM and a K_i of 35.8 μM by binding to the enzyme's steroid-binding site^[4].
Lunularin (12.5-100 μM; 30 min to standard assay conditions) acts as a mixed inhibitor of rat liver microsomal 11β-HSD1 with an IC₅₀ of 17.39 μM and a K_i of 10.31 μM by binding to the enzyme's combined NADPH and steroid-binding region^[4].
Lunularin does not inhibit mouse liver microsomal 11β-HSD1 activity^[4]. In Vivo:Lunularin (24 mg/kg; intraperitoneal injection; 3 times per week; 8 weeks) in ¹³-month-old C57BL/6JRj mice on a high fat, high sugar diet slightly reduces feed intake and body weight gain, lowers blood glucose levels, and increases hepatic Sirt1 and Hmox1 mRNA expression, but does not mimic the full metabolic effects of caloric restriction^[1].
Lunularin is a gut microbiota-derived metabolite of resveratrol, is highly abundant in mouse tissues, biological fluids, and gastrointestinal tract compared to resveratrol itself, and is eliminated when gut microbiota is depleted via antibiotics^[2].