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Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus , acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1 β ) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1 β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.

A study was designed to determine the effect of the consumption of the nutritive sweetener aspartame on non-insulin-dependent diabetics. Forty-three adult diabetics between the ages of 21 and 70 completed a 90-day study; all were diabetics whose conditions were managed by diet and/or hypoglycemic agents. Participants in the blind study were instructed to continue their usual diet and to take two capsules of an assigned preparation three times daily with meals, either the aspartame or the placebo. The 1.8 g of aspartame administered is approximately three times the expected daily consumption of aspartame if used as a sweetener to replace sugar. Throughout the study subjects were examined for (1) symptoms of intolerance, (2) fasting plasma phenylalanine levels exceeding 4 mg/100 ml, and (3) deterioration of diabetic control. At the conclusion of the study subjects exhibited no symptoms that could be traced to the administration of aspartame or the placebo, and diabetic control was unaffected by the chronic administration of these substances. Aspartame seems to be well tolerated by non-insulin-dependent diabetics.

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