5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson’s Disease

Long-term administration of levodopa (L-DOPA) to patients with Parkinson’s disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor mani-festations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

Effects of natural raw meal (NRM) on high-fat diet and dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice

BACKGROUND/OBJECTIVES: Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS: Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-alpha, IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS: Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION: The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions.

Bioavailability of Aspartic Acid Chelated Calcium in Calcium Deficient Rats

Calcium (Ca) is an essential element to maintain body homeostasis. However, many factors disturb calcium absorption. Aspartic acid chelated calcium (AAC) was synthesized by new methods using calcium carbonate and aspartic acid. This study was carried out to investigate the bioavailability of AAC in Ca-deficient rats. The experimental groups were as follows: NC; normal diet control group, CD-C; untreated control group of Ca-deficient (CD) rats, CD-CaCO3; CaCO3 treated group of CD rats, CD-AAC; AAC treated group of CD rats, and CD-SWC; and seaweed-derived Ca treated group of CD rats. The Ca content of various types of Ca was held constant at 32 mg/day, and the four CD groups were fed for 7 days after randomized grouping. Ca content in serum, urine, and feces within feeding periods were analyzed to confirm Ca absorption. Serum Ca content was significantly higher in the CD-AAC (11.24 mg/dL) and CD-SWC (10.12 mg/dL) groups than that in the CD-C (8.6 mg/dL) group 2 hours following the first administration. The Ca content in feces was significantly lower in the CD-AAC (35.4 mg/3 days) and CD-SWC (71.1 mg/3 day) groups than that in the CD-CaCO3 (98.7 mg/3 days) group (p > 0.05). AAC had a 2.3-fold higher absorption rate of Ca than that of SWC. No differences in fibula length were observed in the NC and CD groups. The fibula weights of the CD-AAC (0.33 g) and CD-SWC (0.33 g) groups increased compared to those in the CD-C (0.27 g) group; however, no significant difference was observed between the CD groups. We conclude that bioavailability of AAC is higher than that of seaweed-derived Ca or inorganic Ca. Thus, these findings suggest the AAC has potential as a functional food material related to Ca metabolism.