Abstract: BACKGROUND: Gestational diabetes mellitus may cause embryonic dysplasia and fetal malformations, which seriously threaten the health of fetus and pregnant women; however, there is no perfect treatment measures. Andrographolide reduces blood glucose level, insulin resistance and oxidative stress, and attenuates nerve damage in diabetic rats.
OBJECTIVE: To investigate the effect of andrographolide on insulin resistance in gestational diabetes mellitus rats. 
METHODS: Fifty female Sprague-Dawley rats were enrolled. Animal models of gestational diabetes mellitus were established by high-fat feed combined with intraperitoneal injection of streptozotocin. Forty rats with successful modeling were selected and randomly divided into four intervention groups by using the randomized numerical table method: saline gavage was given to the model group (n=10), and 2.5 mg/kg andrographolide was given to the low-dose andrographolide group (n=10), and 5 mg/kg andrographolide was given to the high-dose andrographolide group (n=10), and intragastric injection of 5 mg/kg andrographolide and peritoneal injection of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway activator Colivelin were given to the high-dose andrographolide+Colivelin group (n=10). The administration was given once a day, for 2 continuous weeks. Another 10 pregnant Sprague-Dawley rats were taken as the control group and given saline by gavage once a day for 2 weeks. After administration, body mass, fasting blood glucose and insulin levels, insulin resistance index and serum inflammatory factors (interleukin 6, tumor necrosis factor α, interleukin 1β), blood lipid levels, pancreatic tissue superoxide dismutase, peroxidase and malondialdehyde levels were detected in each group. The morphology of pancreatic tissue was observed by hematoxylin-eosin staining. Western blot was used to detect Bcl-2, Bax, cysteine proteinase 3, JAK2/STAT3 signaling pathway protein expression in pancreatic tissue.
RESULTS AND CONCLUSION: (1) Compared with the control group, in the model group, the pancreatic tissue structure of rats was significantly damaged, and the body mass, fasting blood glucose and insulin levels, insulin resistance index, levels of serum inflammatory factors, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and malondialdehyde, and protein expression levels of Bax, cysteine protease 3, p-JAK2/JAK2, and p-STAT3/STAT3 increased, while the levels of serum high-density lipoprotein cholesterol and superoxide dismutase, peroxidase activity, and Bcl-2 protein expression decreased (P < 0.05). (2) Compared with the model group, the above indexes were significantly improved in both the high-and low-dose andrographolide groups, and the improvement was more significant in the high-dose andrographolide group. Peritoneal injection of Colivelin could partially reverse the improvement effect of andrographolide on insulin resistance of rats with gestational diabetes mellitus. To conclude, andrographolide can reduce blood glucose, insulin resistance, inflammation, and oxidative stress in rats with gestational diabetes mellitus, improve blood glucose metabolism and pancreatic tissue damage, which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Key words: andrographolide, JAK2/STAT3 signaling pathway, gestational diabetes mellitus, insulin resistance, fasting blood glucose, fasting insulin