Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates diabetic wound healing by the NRF2/COX2 axis.

BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. MATERIALS AND METHODS: With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. RESULTS: Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1ß), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-ß1 (TGF-ß1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. CONCLUSION: IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice.

Oolong tea consumption and its interactions with a novel composite index on esophageal squamous cell carcinoma.

BACKGROUND: No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index. METHODS: In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC. RESULTS: No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94-2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06-2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93-5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74-1.83). Drinking warm oolong tea did not influence the risk of ESCC. CONCLUSIONS: No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.

Development of LC-MS determination method and back-propagation ANN pharmacokinetic model of corynoxeine in rat.

Corynoxeine(CX), isolated from the extract of Uncaria rhynchophylla, is a useful and prospective compound in the prevention and treatment for vascular diseases. A simple and selective liquid chromatography mass spectrometry (LC-MS) method was developed to determine the concentration of CX in rat plasma. The chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 µm) column with acetonitrile-0.1% formic acid in water as mobile phase. Selective ion monitoring (SIM) mode was used for quantification using target ions m/z 383 for CX and m/z 237 for the carbamazepine (IS). After the LC-MS method was validated, it was applied to a back-propagation artificial neural network (BP-ANN) pharmacokinetic model study of CX in rats. The results showed that after intravenous administration of CX, it was mainly distributed in blood and eliminated quickly, t1/2 was less than 1h. The predicted concentrations generated by BP-ANN model had a high correlation coefficient (R>0.99) with experimental values. The developed BP-ANN pharmacokinetic model can be used to predict the concentration of CX in rats.

Genistein, a soybean isoflavone, reduces the production of pro-inflammatory and adhesion molecules induced by hemolysate in brain microvascular endothelial cells.

Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean that exhibits an anti-inflammatory effect. The present study was designed to examine the effects of genistein on expression levels of hemolysate-induced proinflammatory and adhesion molecules in SD rat brain microvascular endothelial cells (BMECs). Genistein treatment attenuated hemolysate-induced nuclear factor-kappa B (NF-kappaB) p65 translocation in BMECs. In addition, genistein suppressed the expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). The inhibitory rate of 50 pM genistein for TNF-alpha, MCP-1 and ICAM-1 was 65.4%, 60.5% and 54.9% respectively. These inhibitory effects of genistein on proinflammatory and adhesion molecules were not due to decreased BMEC viability as assessed by MTT test. Taken together the present study suggests that genistein suppresses expression levels of hemolysate-induced pro-inflammatory and adhesion molecules in cerebral endothelial cells.