Anti-Colorectal Cancer Effects of Fucoidan Complex-Based Functional Beverage Through Retarding Proliferation, Cell Cycle and Epithelial-Mesenchymal Transition Signaling Pathways.

BACKGROUND: Fucus vesiculosus-derived fucoidan, a multifunctional bioactive polysaccharide sourced from marine organisms, exhibits a wide range of therapeutic properties, including its anti-tumor effects. While previous research has reported on its anti-cancer potential, limited studies have explored its synergistic capabilities when combined with other natural bioactive ingredients. In this current study, we present the development of an integrative functional beverage, denoted as VMW-FC, which is composed of a fucoidan complex (FC) along with a blend of various herbal components, including vegetables (V), mulberries and fruits (M), and spelt wheat (W). OBJECTIVE: Colorectal cancer (CRC) remains a significant cause of mortality, particularly in metastatic cases. Therefore, the urgent need for novel alternative medicines that comprehensively inhibit CRC persists. In this investigation, we assess the impact of VMW-FC on CRC cell proliferation, cell cycle dynamics, metastasis, in vivo tumorigenesis, and potential side effects. METHODS: Cell growth was assessed using MTT and colony formation assays, while metastatic potential was evaluated through wound healing and transwell migration assays. The underlying signaling mechanisms were elucidated through qPCR and western blot analysis. In vivo tumor formation and potential side effects were evaluated using a subcutaneous tumor-bearing NOD/SCID mouse model. RESULTS: Our findings demonstrate that VMW-FC significantly impedes CRC proliferation and migration in a dose- and time-dependent manner. Furthermore, it induces sub-G1 cell cycle arrest and an increase in apoptotic cell populations, as confirmed through flow-cytometric analysis. Notably, VMW-FC also suppresses xenograft tumor growth in NOD/SCID mice without causing renal or hepatic toxicity. CONCLUSION: The integrative herbal concoction VMW-FC presents a promising approach for inhibiting CRC by slowing proliferation and migration, inducing cell cycle arrest and apoptosis, and suppressing markers associated with proliferation (Ki-67, PCNA, and CDKs) and epithelial-mesenchymal transition (EMT) (Vimentin, N-cadherin, and ß-catenin).

L­carnitine alleviates oxidative stress­related damage via MAPK signaling in human lens epithelial cells exposed to H2O2.

L­carnitine (LC) is well known for its antioxidative properties. The present study aimed to evaluate the effects of LC on human lens epithelial cells (HLECs) and to analyze its regulatory mechanism in cataractogenesis. HLE B­3 cells were cultured with hydrogen peroxide (H2O2) and were pretreated with or without LC. The Cell Counting kit­8 assay was used to determine cell viability. Reactive oxygen species (ROS) assay kit was used to measure the cellular ROS production induced by H2O2 and LC. In addition, reverse transcription­quantitative PCR and western blot analysis were performed to detect the expression levels of oxidative damage markers and antioxidant enzymes. Notably, ROS overproduction was observed upon exposure to H2O2, whereas LC supplementation markedly decreased ROS levels through activation of the antioxidant enzymes forkhead box O1, peroxiredoxin 4 and catalase. Furthermore, LC suppressed the expression of apoptosis­associated genes (caspase-3) and inflammation­associated genes [interleukin (IL)1, IL6, IL8 and cyclooxygenase­2]. Conversely, LC promoted proliferating cell nuclear antigen, cyclin­dependent kinase (CDK)2 and CDK4 expression, which may increase proliferation of HLECs that were incubated with H2O2. In addition, epithelial­mesenchymal transition occurred upon ROS accumulation, whereas the effects of H2O2 on AQP1 and vimentin expression were reversed upon LC supplementation. Notably, this study revealed that LC restored the oxidant/antioxidant balance and protected against cell damage through the mitogen­activated protein kinase signaling pathway. In conclusion, LC may serve a protective role in curbing oxidative damage and therefore may be considered a potential therapeutic agent for the treatment of cataracts.

Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement.

BACKGROUND: The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San (DSS) is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. METHODS: A total of 36 rats were randomly divided into three groups: (1) Sham group (n = 12), rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment; (2) experimental tooth movement (ETM) group (n = 12), rats received saline treatment and ETM; (3) DSS + ETM (DETM) group (n = 12), rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Morris water maze test was evaluated; immunofluorescent histochemistry was used to identify astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. RESULTS: Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased compared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus (DG). CONCLUSIONS: Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG of hippocampus in the ETM group rats may be related with the decline of the ability of learning and memory. The ability to change the synaptic plasticity in hippocampus after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM treatment.

Danggui-shaoyao-san, a traditional Chinese medicine prescription, alleviates the orthodontic pain and inhibits neuronal and microglia activation.

BACKGROUND: The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. Danggui-shaoyao-san (DSS) is a traditional Chinese medicine (TCM) prescription which has long been used for pain treatment and possesses antioxidative, cognitive enhancing and antidepressant effects. We raise the hypothesis that DSS exerts analgesic effect for orthodontic pain via inhibiting the activations of neuron and microglia. METHODS: DSS was given twice a day from day 5 prior to experimental tooth movement (ETM). Directed face grooming and vacuous chewing movements (VCM) were evaluated. Immunofluorescent histochemistry and Western blot analysis were used to quantify the Iba-1 (microglia activation) and Fos (neuronal activation) expression levels in the trigeminal spinal nucleus caudalis (Vc). RESULTS: ETM significantly increased directed face grooming and VCM which reached the peak at post-operative day (POD) 1 and gradually decreased to the baseline at POD 7. However, a drastic peak increase of Fos expression in Vc was observed at 4 hours and gradually decreased to baseline at POD 7; while the increased Iba-1 level reached the peak at POD 1 and gradually decreased to baseline at POD 7. Furthermore, pre-treatment with DSS significantly attenuated the ETM induced directed face grooming and VCM as well as the Fos and Iba-1 levels at POD 1. CONCLUSION: Treatment with DSS had significant analgesic effects on ETM-induced pain, which was accompanied with inhibition of both neuronal and microglial activation.