[Research progress in gut-skin axis and its association with traditional Chinese medicine theory].

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.

Kudzu Resistant Starch: An Effective Regulator of Type 2 Diabetes Mellitus.

Kudzu is a traditional medicinal dietary supplement, and recent research has shown its significant benefits in the prevention/treatment of type 2 diabetes mellitus (T2DM). Starch is one of the main substances in Kudzu that contribute decisively to the treatment of T2DM. However, the underlying mechanism of the hypoglycemic activity is not clear. In this study, the effect of Kudzu resistant starch supplementation on the insulin resistance, gut physical barrier, and gut microbiota was investigated in T2DM mice. The result showed that Kudzu resistant starch could significantly decrease the value of fasting blood glucose and the levels of total cholesterol, total triglyceride, and high-density lipoprotein, as well as low-density lipoprotein, in the blood of T2DM mice. The insulin signaling sensitivity in liver tissue was analyzed; the result indicated that intake of different doses of Kudzu resistant starch can help restore the expression of IRS-1, p-PI3K, p-Akt, and Glut4 and thus enhance the efficiency of insulin synthesis. Furthermore, the intestinal microorganism changes before and after ingestion of Kudzu resistant starch were also analyzed; the result revealed that supplementation of KRS helps to alleviate and improve the dysbiosis of the gut microbiota caused by T2DM. These results validated that Kudzu resistant starch could improve the glucose sensitivity of T2DM mice by modulating IRS-1/PI3K/AKT/Glut4 signaling transduction. Kudzu resistant starch can be used as a promising prebiotic, and it also has beneficial effects on the gut microbiota structure of T2DM mice.

Icariin ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting Nox2-containing NADPH oxidase activation.

Cerebrovascular smooth muscle cells (SMCs) hyperplasia is an important contributor to cerebrovascular remodeling during hypertension. The aim of present study was to investigate the effects of Icariin on cerebrovascular SMCs proliferation and remodeling and the underlying mechanisms. The results revealed that Icariin administration attenuated the enhanced basilar artery constriction in angiotensin II (AngII)-induced hypertension rat model, as well as the inhibition of basilar artery diameter reduction in response to AngII and phenylephrine. In addition, histological analyses showed that Icariin also significantly ameliorated basilar artery remodeling in AngII hypertensive rats. In human brain vascular SMCs (HBVSMCs), AngII-induced cell proliferation, migration and invasion were markedly inhibited by Icariin treatment. Moreover, Icariin treatment largely limited AngII-induced the increase of reactive oxygen species (ROS) production in HBVSMCs, which was closely associated with cell proliferation. Analysis of the mechanisms showed that Icariin decreased ROS production via inhibiting NADPH oxidase activity but not mitochondria-derived ROS production. Further, Icariin promoted Nox2 degradation and consequently reduced its protein expression. In conclusion, these findings demonstrate that Icariin attenuates cerebrovascular SMCs hyperplasia and subsequent remodeling through inhibiting Nox2-containing NADPH oxidase activation, suggesting Icariin may be a potential therapeutic agent to prevent the onset and progression of stroke.

Anti-hypoglycemic and hepatocyte-protective effects of hyperoside from Zanthoxylum bungeanum leaves in mice with high-carbohydrate/high-fat diet and alloxan-induced diabetes.

The development of diabetes mellitus (DM) is accompanied by hyperglycemia-induced oxidative stress. Hyperoside is a major bioactive component in Zanthoxylum bungeanum leaves (HZL) and is a natural antioxidant. However, the effects of HZL on DM and its mechanisms of action remain undefined. The present study evaluated the anti-hypoglycemic and hepatocyte-protective effects of HZL in mice with diabetes induced by a high-carbohydrate/high-fat diet (HFD) and alloxan. We also aimed to eludicate the underlying mechanisms. Our resutls demonstrated that the administration of HZL significantly reduced body weight gain, serum glucose levels and insulin levels in diabetic mice compared with the vehicle-treated mice. In addition, the levels of dyslipidemia markers including total cholesterol, triglyceride and low­density lipoprotein cholesterol in the HFD-treated mice were markedly decreased. Further experiments using hepatocytes from mice revealed that HZL significantly attenuated liver injury associated with DM compared with vehicle treatment, as evidenced by lower levels of alanine aminotransferase and aspartate aminotransferase in serum and by lower levels of lipid peroxidation, nitric oxide content and inducible nitric oxide synthase activity in liver tissues. Nuclear factor-κB (NF-κB) and mitogen-associated protein kinase (MAPK) signaling pathways were investigated to elucidate the molecular mechanisms responsible for the protective effects of HZL against diabetic liver injury. The results indicated that HZL inhibited the phosphorylation of p65/NF-κB, MAPK (including p38, JNK and ERK1/2) and activating transcription factor 3 protein expression, with an additional suppression of Bax, cytochrome c, caspase-9 and caspase-3 in the liver tissues of diabetic mice. Taken together, our findings suggest that HZL, which was effective in inhibiting oxidative stress-related pathways may be beneficial for use in the treatment of DM.

Quercetrin from Toona sinensis leaves induces cell cycle arrest and apoptosis via enhancement of oxidative stress in human colorectal cancer SW620 cells.

Finding effective strategies against colorectal cancer (CRC) is still an emergent health problem. In the present study, we investigated the anticancer activity of quercetrin from Toona sinensis leaves (QTL) and explored the underlying mechanism in human CRC cell line SW620. The cells were treated with various concentrations of QTL and the cytotoxic effects of QTL were determined using the MTT assay. Apoptosis and cell cycle status were detected by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using DCF-DA and JC-1 fluorescence spectrophotometry, respectively. Western blot analysis was used to quantify the expression of apoptosis­related proteins. RT-PCR was applied to determine the mRNA levels of glutathione peroxidase (GPx) and catalase (CAT). QTL exhibited growth inhibitory effects and caused cell cycle arrest in the G2/M phase, which was accompanied by increased expression of p53 and p21 proteins. QTL promoted apoptosis which was consistent with the upregulated expression of Bax, cytochrome c, caspase-9, Apaf-1 and caspase-3. In addition, QTL induced the loss of mitochondrial membrane potential and triggered ROS generation, as revealed by the downregulated mRNA expression and enzymatic activity of GPx and CAT. Furthermore, both N­acetyl cysteine (NAC) and GSH attenuated the QTL-induced growth inhibition observed in SW620 cells along with the increase of ROS levels. These findings revealed that QTL inhibited the growth of CRC cells and facilitated apoptosis by enhancing oxidative stress. QTL may therefore have potential for use in CRC chemotherapy.

Flavonoids from persimmon (Diospyros kaki L.) leaves inhibit proliferation and induce apoptosis in PC-3 cells by activation of oxidative stress and mitochondrial apoptosis.

Persimmon (Diospyros kaki L.) leaves are extensively used in Chinese medicine and are also excellent source of dietary polyphenols. Here we investigated the antiproliferative and pro-apoptotic activity of the total flavonoids extracted from persimmon leaves (FPL) in PC-3 cells. After treating cells with different concentration of FPL, Quercetin or Rutin for 24 h, MTT and flow cytometry were used to measure the cytotoxicity, apoptotic rate and cell cycle arrest. Compared with Quercetin and Rutin, FPL showed higher cytotoxicity at 12.5 and 25 µg/ml concentrations and also presented lower IC50 in PC-3 cells. In addition, FPL induced PC-3 cells apoptosis by activation of oxidative stress, as detected by ROS, MDA, nitrite and iNOS activity, and increased mitochondrial membrane permeability. Morphological changes, inactivation of Bcl-2, upregulation of BAX, release of cytochrome c and activation of downstream apoptotic signaling in FPL-treated PC-3 cells also suggested apoptotic death. Meanwhile, FPL significantly inhibited migration of PC-3 cells. Therefore, FPL inhibited proliferation, migration and induced apoptosis of PC-3 cells by activation of oxidative stress and mitochondrial-related apoptosis.

Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with Myasthenia Gravis: A Systematic Review and Meta-Analysis.

BACKGROUND: The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has been used widely for treating myasthenia gravis (MG) in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing therapy as an adjunctive therapy in MG patients. METHODS: Seven electronic databases were searched through June 2016. Randomized controlled trials (RCTs) evaluating the add-on effect of Qi-supplementing therapy in MG patients were included. The outcome measures were the total effective rate, relapse rate, and adverse events. RESULTS: Twenty-three RCTs involving 1,691 MG patients were included. The included studies were of low-to-moderate quality. Meta-analysis showed that Qi-supplementing therapy combined with Western medicine (WM) significantly improved the total response rate and reduced the relapse risk during 6-24 months of follow-up. Subgroup analysis showed that Qi-supplementing therapy only affected the total response rate within the first 6 months of treatment. Moreover, the rate of adverse events was lower with the addition of Qi-supplementing therapy to WM than with WM only. CONCLUSIONS: Short-term Qi-supplementing therapy combined with WM appears to be superior to WM for improving the total response rate and reducing the relapse rate. However, more high-quality RCTs are warranted owing to methodological flaws of previous trials.

Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice.

The development of diabetes mellitus is related to oxidant stress induced by a high carbohydrate/high-fat diet (HFD). Quercetin, as a major bioactive component in Toona sinensis leaves (QTL), is a natural antioxidant. However, the exact mechanism by which QTL ameliorate diabetes mellitus is still unknown. In this study, we investigated the hypoglycemic effects and hepatocytes protection of QTL on HFD and alloxan induced diabetic mice. Intragastric administration of QTL significantly reduced body weight gain, serum glucose, insulin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase serum levels compared to those of diabetic mice. Furthermore, it significantly attenuated oxidative stress, as determined by lipid peroxidation, nitric oxide content, and inducible nitric oxide synthase activity and as a result attenuated liver injury. QTL also significantly suppressed the diabetes-induced activation of the p65/NF-κB and ERK1/2/MAPK pathways, as well as caspase-9 and caspase-3 levels in liver tissues of diabetic mice. Finally, micrograph analysis of liver samples showed decreased cellular organelle injury in hepatocytes of QTL treated mice. Taken together, QTL can be viewed as a promising dietary agent that can be used to reduce the risk of diabetes mellitus and its secondary complications by ameliorating oxidative stress in the liver.