Objective. Observe the protective effect of chlorogenic acid on dextran sulfate-induced ulcerative colitis in mice and explore the regulation of MAPK/ERK/JNK signaling pathway. Methods. Seventy C57BL/6 mice (half males and half females) were randomly divided into 7 groups, 10 in each group: control group (CON group), UC model group (UC group), and sulfasalazine-positive control group (SASP group), chlorogenic acid low dose group (CGA-L group), chlorogenic acid medium dose group (CGA-M group), chlorogenic acid high dose group (CGA-H group), and ERK inhibitor + chlorogenic acid group (E+CGA group). The effects of chlorogenic acid on UC were evaluated by colon mucosa damage index (CMDI), HE staining, immunohistochemistry, ELISA, and Western blot. The relationship between chlorogenic acid and MAPK/ERK/JNK signaling pathway was explored by adding ERK inhibitor. Results. The UC models were established successfully by drinking DSS water. Chlorogenic acid reduces DSS-induced colonic mucosal damage, inhibits DSS-induced inflammation, oxidative stress, and apoptosis in colon, and reduces ERK1/2, p -ERK, p38, p-p38, JNK, and p-JNK protein expression. ERK inhibitor U0126 reversed the protective effect of chlorogenic acid on colon tissue. Conclusion. Chlorogenic acid can alleviate DSS-induced ulcerative colitis in mice, which can significantly reduce tissue inflammation and apoptosis, and its mechanism is related to the MAPK/ERK/JNK signaling pathway.

The analogous β-carboline alkaloids, harmaline (HAL) and harmine (HAR), possess a variety of biological properties, including acetylcholinesterase (AChE) inhibitory activity, antioxidant, anti-inflammatory, and many others, and have great potential for treating Alzheimer’s disease (AD). However, studies have showed that the two compounds have similar structures and in vitro AChE inhibitory activities but with significant difference in bioavailability. The objective of this study was to comparatively investigate the effects of HAL and HAR in memory deficits of scopolamine-induced mice. In the present study, mice were pretreated with HAL (2, 5, and 10 mg/kg), HAR (10, 20, and 30 mg/kg) and donepezil (5 mg/kg) by intragastrically for 7 days, and were daily intraperitoneal injected with scopolamine (1 mg/kg) to induce memory deficits and then subjected to behavioral evaluation by Morris water maze. To further elucidate the underlying mechanisms of HAL and HAR in improving learning and memory, the levels of various biochemical factors and protein expressions related to cholinergic function, oxidative stress, and inflammation were examined. The results showed that HAL and HAR could effectively ameliorate memory deficits in scopolamine-induced mice. Both of them exhibited an enhancement in cholinergic function by inhibiting AChE and inducing choline acetyltransferase (ChAT) activities, and antioxidant defense via increasing the antioxidant enzymes activities of superoxide dismutase and glutathione peroxidase, and reducing maleic diadehyde production, and anti-inflammatory effects through suppressing myeloperoxidase, tumor necrosis factor α, and nitric oxide as well as modulation of critical neurotransmitters such as acetylcholine (ACh), choline (Ch), L-tryptophan (L-Trp), 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (γ-GABA), and L-glutamic acid (L-Glu). Furthermore, the regulations of HAL on cholinergic function, inflammation, and neurotransmitters were more striking than those of HAR, and HAL manifested a comparable antioxidant capacity to HAR. Remarkably, the effective dosage of HAL (2 mg/kg) was far lower than that of HAR (20 mg/kg), which probably due to the evidently differences in the bioavailability and metabolic stability of the two analogs. Taken together, all these results revealed that HAL may be a promising candidate compound with better anti-amnesic effects and pharmacokinetic characteristics for the treatments of AD and related diseases.