Alpinetin: anti-human gastric cancer potential and urease inhibition activity in vitro.

Introduction: Alpinetin is the bioactive component of a traditional Chinese medicine. This compound, one of the main constituents of the seeds of Alpinia katsumadai Hayata, is a member of the flavonoids, with anti-inflammatory, antibacterial, and other significant therapeutic activities of important potency and low systemic toxicity. Material and methods: In our study, the inhibitory effect of isoliquiritigenin on HMG-CoA reductase showed a lower value of IC50 = 21.86 ±1.44 µg/ml. A molecular docking study was performed as a complementary study to provide additional data about the biological activities of alpinetin in the presence of urease. The docking calculations revealed that alpinetin with a docking score of -5.097 (kcal/mol) has an acceptable binding affinity to the enzyme, and because of various hydrophobic contacts and hydrogen bonds created by this chemical compound, alpinetin could be considered as an adequate inhibitor of urease. Results: In the cellular and molecular part of the study, the cells treated with alpinetin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for 48 h as regards the cytotoxicity and anti-human gastric carcinoma properties towards normal (human umbilical vein endothelial cells (HUVECs)) and gastric carcinoma cell lines, i.e. SNU-1, Hs 746T, and KATO III. The IC50 values of alpinetin were 426, 586, and 424 µg/ml against SNU-1, Hs 746T, and KATO III cell lines, respectively. The viability of the malignant gastric cell line decreased dose-dependently in the presence of alpinetin. Conclusions: It seems that the anti-human gastric carcinoma effect of the investigated molecule is due to its antioxidant effects.

Real-time semi-quantitative assessment of anastomotic blood perfusion in mini­invasive rectal resections by Sidestream Dark Field (SDF) imaging technology: a prospective in vivo pilot study.

PURPOSE: Anastomotic leakage (AL) is one of the severe complications after rectal surgery, and anastomotic ischemia is one of the main factors. This prospective in vivo pilot study aimed to evaluate the effectiveness of Sidestream Dark Field (SDF) imaging in quantitative assessment of anastomotic microcirculation and to analyze its correlation with AL. METHODS: Thirty-three patients with rectal cancer who underwent laparoscopic low anterior resection from 2019 to 2020 were enrolled. Microcirculation was measured by SDF imaging at the descending colon, the mesocolon transection line (MTL), and 1 cm and 2 cm distal to the MTL. Anastomotic microcirculation was measured at the stapler anvil edge before anastomosis. Quantitative perfusion-related parameters were as follows: microcirculation flow index (MFI), perfused vessel density (PVD), proportion of perfused vessels (PPV), and total vessel density (TVD). RESULTS: All patients obtained stable microcirculation images. Functional microcirculation parameters (MFI, PPV, PVD) decreased successively from the descending colon, the colon at MTL, and 1 cm and 2 cm distal to the MTL (all P < 0.01). Extremely poor microcirculation was found at the intestinal segment 2 cm distal to the MTL. Micro-perfusion was significantly lower at the colonic limb of the anastomosis compared with the descending colon (all P < 0.001). Anastomotic leakage occurred in 3 patients (9.1%) whose anastomotic microcirculation was significantly lower than those without AL (all P < 0.01). Blood perfusion at the colonic limb of the anastomosis was significantly higher in patients with left colic artery preservation than in controls. CONCLUSION: SDF imaging is a promising technique for evaluating anastomotic microcirculation and has potential clinical significance for risk stratification of AL.

Eriocitrin, a dietary flavonoid suppressed cell proliferation, induced apoptosis through modulation of JAK2/STAT3 and JNK/p38 MAPKs signaling pathway in MCF-7 cells.

Eriocitrin, a lemons flavanone, exhibits several biological properties, antiproliferative, and proapoptotic effects. However, its molecular mechanical action is not entirely clarified. Oxidative stress causes abnormal stimulation of signal transducer and activator of transcription 3 (STAT3) and c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs) signaling has been strongly connected with the ruling of cell survival and apoptosis of cancer cells. Herein, we investigated an antiproliferative and proapoptotic effect that Eriocitrin modulates STAT3/MAPKs signaling activation in MCF-7 cells. We noticed that Eriocitrin strongly enhances reactive oxygen species (ROS) generation, alteration of mitochondrial outer membrane potential, and enhances apoptotic morphological changes. Furthermore, Eriocitrin suppressed STAT3 phosphorylation via inhibiting an upstream molecule of JAK2 and Src kinase activation, thereby blocking STAT3 nuclear translocation. Similarly, Eriocitrin causes oxidative stress-mediated JNK/p38 MAPK signaling activation. We confirmed that Eriocitrin induced ROS-mediated apoptosis inhibited by the antioxidant substance of N-acetylcysteine. Eriocitrin induced apoptosis via suppression of STAT3 signaling regulated proteins, activating proapoptotic factors Bax, caspase 7, 8, 9 and suppressing Bcl-2, Bcl-x expression in MCF-7 cells. Overall, these results evidenced that Eriocitrin can affect multiple signaling events associated with tumorigenesis. From this evidence, Eriocitrin, a novel chemotherapeutic agent, can be used to treat breast cancer.

Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats.

This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1ß], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.

Vicenin-2 Treatment Attenuated the Diethylnitrosamine-Induced Liver Carcinoma and Oxidative Stress through Increased Apoptotic Protein Expression in Experimental Rats.

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.