Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice. AIM: To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes. RESULTS: A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time. CONCLUSION: These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.

Interactions Between Therapeutics for Metabolic Disease, Cardiovascular Risk Factors, and Gut Microbiota.

With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection.

The P2Y14 receptor in the trigeminal ganglion contributes to the maintenance of inflammatory pain.

P2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contribute to inflammatory and neuropathic pain. P2Y14 receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y14 receptor in the TG in inflammatory orofacial pain of Sprague-Dawley (SD) rats was investigated. Peripheral injection of complete Freund's adjuvant (CFA) induced mechanical hyperalgesia with the rapid upregulation of P2Y14 receptor, glial fibrillary acidic protein (GFAP), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), C-C chemokine CCL2, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated p38 (p-p38) proteins in the TG. Furthermore, immunofluorescence staining confirmed the CFA-induced upregulation of P2Y14 receptor. Double immunostaining showed that P2Y14 receptor colocalized with glutamine synthetase (GS) and neuronal nuclei (NeuN). Finally, trigeminal injection of a selective antagonist (PPTN) of P2Y14 receptor attenuated CFA-induced mechanical hyperalgesia. PPTN also decreased the upregulation of the GFAP, IL-1ß, TNF-α, CCL2, p-ERK1/2, and p-p38 proteins. Our findings showed that P2Y14 receptor in TG may contribute to orofacial inflammatory pain via regulating SGCs activation, releasing cytokines (IL-1ß, TNF-α, and CCL2), and phosphorylating ERK1/2 and p38.

P2Y14 receptor is functionally expressed in satellite glial cells and mediates interleukin-1ß and chemokine CCL2 secretion.

Satellite glial cells (SGCs) activation in the trigeminal ganglia (TG) is critical in various abnormal orofacial sensation in nerve injury and inflammatory conditions. SGCs express several subtypes of P2 purinergic receptors contributing to the initiation and maintenance of neuropathic pain. The P2Y14 receptor, a G-protein-coupled receptor activated by uridine diphosphate (UDP)-glucose and other UDP sugars, mediates various physiologic events such as immune, inflammation, and pain. However, the expression, distribution, and function of P2Y14 receptor in SGCs remains largely unexplored. Our study reported the expression and functional identification of P2Y14 receptor in SGCs. SGCs were isolated from TG of rat, and the P2Y14 receptor expression was examined using immunofluorescence technique. Cell proliferation and viability were examined via cell counting kit-8 experiment. Immunofluorescence demonstrated the presence of P2Y14 receptor in SGCs. Immunofluorescence and western blot showed that UDP-glucose treatment upregulated glial fibrillary acid protein, a common marker for glial activation. Extracellular UDP-glucose enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which were both abolished by the P2Y14 receptor inhibitor (PPTN). Furthermore, quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay demonstrated that extracellular UDP-glucose significantly enhanced interleukin-1ß (IL-1ß) and chemokine CCL2 (CCL2) release, which was abolished by PPTN and significantly decreased by inhibitors of MEK/ERK (U0126) and p38 (SB202190). Our findings directly proved the functional presence of P2Y14 receptor in SGCs. It was also verified that P2Y14 receptor activation was involved in activating SGCs, phosphorylating MAPKs, and promoting the secretion of IL-1ß and CCL2 via ERK and p38 pathway.

A new xanthatin analogue 1ß-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma.

1ß-hydroxyl-5α-chloro-8-epi-xanthatin (XTT), a sesquiterpene lactone isolated from Xanthium sibiricum, possessed potent cytotoxicity on cancer cells in vitro. The objective of this study was to investigate the anti-tumor effect and underlying mechanisms of XTT on human hepatocellular carcinoma (HCC). Firstly, XTT inhibited the cell growth and induced apoptosis in human HCC cells, which was associated with the induction of Bax and cleaved-caspase-3, inhibition of Bcl-2 and survivin expression. Importantly, XTT induced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), and depletion of glutathione (GSH) in HCC cells through covalently modification of GSH. Furthermore, XTT caused obvious activation of extracellular regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) and inactivation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) in HCC cells. ROS scavenger N-acetyl cysteine abrogated the effects of XTT on ERK/p38 MAPK activation and JAK2/STAT3 inhibition, and rescued HCC cells from XTT-induced apoptosis. Additionally, inhibitors of ERK/p38 MAPKs or activator of JAK2/STAT3 partially abolished XTT-mediated effect. In summary, XTT inhibited cell growth and induced apoptosis in HCC cells through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition by GSH depletion. These findings also show the therapeutic potential of XTT in HCC.