“Lightest” lignin fraction tames type 2 diabetes in rats

Pulp-mill waste could be converted into a powerful diabetes drug, new animal data suggest. Scientists separated kraft lignin into three molecular-weight fractions by sequential 95 % and 80 % ethanol extraction and tested their ability to rescue insulin-resistant cells and diabetic rats. The lightest cut, F3 (Mn ≈ 1 900 Da), packed the highest density of phenolic –OH and –COOH groups and the strongest radical-scavenging capacity. In insulin-resistant 3T3-L1 adipocytes and HepG2 liver cells, 50 µg mL⁻¹ F3 raised glucose consumption 1.3-fold, cut triglyceride accumulation 31 % and slashed ROS and pro-inflammatory IL-6/TNF-α levels to match the clinical drug rosiglitazone. Confocal imaging and JC-1 staining showed F3 restored mitochondrial membrane potential and ATP synthesis, indicating repaired energy metabolism.

Encouraged by the cell data, the team injected male Sprague-Dawley rats that had developed type 2 diabetes after four weeks of high-fat feeding plus low-dose streptozotocin. Twice-weekly tail-vein doses of 50 mg kg⁻¹ F3 for four weeks reduced fasting blood glucose from 22.8 mmol L⁻¹ to 8.95 mmol L⁻¹—outperforming rosiglitazone (16.3 mmol L⁻¹) and approaching healthy controls (5.5 mmol L⁻¹). During intraperitoneal insulin-tolerance tests, the area under the glucose curve fell 66 % after F3 treatment versus only 12 % with the drug, confirming heightened insulin sensitivity. Western blots of liver tissue revealed F3 doubled IRS1, quadrupled PI3K and tripled phosphorylated AKT and AMPK, while the glucose transporter GLUT4 jumped 189 %. Parallel histology and serum chemistry showed F3 reversed hepatic steatosis, lowered serum IL-6, TNF-α, triglycerides and cholesterol, and restored liver glycogen and antioxidant enzymes without damaging heart, kidney, spleen or lung.

Gut-microbiome sequencing offered a further mechanism: F3 enriched short-chain-fatty-acid producers such as Lachnospiraceae NK4A136 group and Lactobacillus and suppressed pro-inflammatory Enterobacteriaceae and Escherichia–Shigella, correlating with higher fecal butyrate and propionate. The researchers say the fractionation process is simple, scalable and uses only food-grade ethanol, giving F3 a cost advantage over synthetic antidiabetics. Because lignin is already generated in millions of tonnes by kraft pulping, the work positions the lowest-molecular, highest-phenol fraction as a renewable, non-toxic active ingredient for functional foods, nutraceuticals or injectable therapies against type 2 diabetes.

See the article:

DOI

https://doi.org/10.1016/j.jobab.2025.10.001

Original Source URL

https://www.sciencedirect.com/science/article/pii/S2369969825000660

Journal

Journal of Bioresources and Bioproducts