Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection

The majority of patients with hepatocellular carcinoma (HCC) undergoing curative resection experience tumor recurrence. To examine the association between preoperative serum sorbitol dehydrogenase (SORD), a liver-derived enzyme that reflects liver damage, and recurrence of HCC after curative resection, 92 patients were randomly selected who underwent curative resection for HCC between 2011 and 2012 from a prospective registry. Recurrence-free survival (RFS) was compared based on serum SORD levels. Cox proportional hazard models were used to investigate prognostic factors for RFS. During a median follow-up duration of 57.1 months, 43 patients experienced HCC recurrence. Patients with serum SORD ≥15 ng/mL (HR, 3.46; 95% CI, 1.76–6.81; p < 0.001) had worse RFS compared with patients with serum SORD <15 ng/mL. Serum AFP and SORD levels were two independent prognostic factors for RFS. When patients were stratified by baseline serum SORD and AFP levels, patients with serum AFP levels ≥400 ng/mL and serum SORD levels ≥15 ng/mL had a distinctly poor prognosis with the lowest RFS rates (HR, 22.08; 95% CI, 6.91–70.50; p < 0.001). Baseline serum SORD is an effective prognostic factor for HCC after resection. It may help guide patient selection for surgery, especially when combined with serum AFP levels.

Ameliorative effects of Coccinia grandis leaf extract on Diabetes-Induced alterations of glucose metabolism, Cox activity and histological changes in Brain of Wistar Rats

Coccinia grandis has been used in tribal populations of India both as food and medicine, but it has been not reported to be a neuroprotective agent yet. The present study was designed to evaluate the protective effects of Coccinia grandis leaf extract on diabetes induced brain damage of Wistar rats. This study reports the protective effect of methanolic leaf extract of Coccinia grandis against STZ induced diabetes in rats. Metformin (150mg/kg body wt.) was used as a reference drug. The enzymes of the polyol pathway and its related substrates were studied in the brain tissue. The effect of Coccinia on Cyclooxygenase (COX) and Prostaglandin peroxidise (PG) was also studied. Diabetes induced rats showed a significantly increased activity of Aldose reductase, Sorbitol dehydrogenase, Glucose-6-phosphodehydrogenase, whereas the decreased activity of Hexokinase. The content of Glucose, Sorbitol significantly increased in rat brain. Sodium potassium ATPase activity was also decreased in diabetic rats. COX, PG peroxidase was increased. Histological alternations were induced in the hippocampus of STZ treated diabetic rats. Oral administration of Coccinia leaf extract (200mg/kg) of body weight to diabetic rats for 21 days efficiently attenuated the parameters studied. A decreased activity of brain AR, sorbitol dehydrogenase, glucose-6-dehydrogenase was observed along with the increase in Hexokinase and Sodium potassium ATPase activity. It also showed decreased content of glucose and Sorbitol. Diabetes induced brain damage in the hippocampus and cerebral cortex was restored with Coccinia treatment. Decreased COX and PG peroxidase suggest its protection against inflammation. The current results suggest that Coccinia grandis leaf extract exerts the potential ability to reverse the progression of hyperglycemia and its concomitant induced brain damage.

Inhibitory Potentials of Hunteria umbellata Seed Extracts on Some Key Enzymes of Diabetes Mellitus with Profiling of its Phenolic Constituents

Background: The seeds of Hunteria umbellatais a common folkloric plant used in the management of Diabetes mellitus in Nigeria. Though there are many reports on its antidiabetic potential, there is a scarcity of information on its mechanisms of antidiabetic action. This study was designed to investigate the mechanism of antidiabetic action of H. umbellata seed by evaluating the inhibitory effect of its extracts on enzymes that are targeted in the management of diabetes mellitus. Methods: Dried seeds of H. umbellata were powdered and extracted separately in water and ethanol. Alpha-amylase, α-glucosidase, and sorbitol dehydrogenase inhibitory activities of the concentrated extracts were determined spectrophotometrically. Furthermore, the phenolic profile of the seed was determined using HPLC-UV analysis. Results: The inhibitory effect of both ethanol and aqueous extracts H. umbellataon the selected enzymes were similar with IC50 value of 40.36 ± 2.92 and 40.25 ± 4.53 mg/mL for α-amylase, 45.42 ±2.44 and 39.32 ± 3.46 mg/mL for α-glucosidase, and 36.25 ± 2.31 and 32.35 ± 1.53 mg/mL for sorbitol dehydrogenase, respectively. Kinetic studies showed that α-amylase was inhibited competitively, while both α-glucosidase and sorbitol dehydrogenase were inhibited in a non-competitive manner. The phenolic compounds identified in the H. umbellata seed were gallic acid, catechin, p-coumaric acid, rutin, and ferulic acid. Conclusion: The H. umbellata seed extract’s antidiabetic action may be by inhibiting the activities of α-amylase, α-glucosidase, and sorbitol dehydrogenase. This inhibition could be due to the presence of phytochemicals such as phenolic compounds in the plant.

Laurus nobilis Linn. Inhibits Polyol Pathway Enzymes: Strategy for Managing Diabetic Complications

Background: The rising incidence of diabetic complications necessitate the continuous search for safer, cheaper and effective pharmacological agents. Polyol pathway is an underlying process implicated in the pathogenesis of diabetic complications. Inhibition of enzymes in the polyol pathway is a veritable means of ameliorating diabetic complications. Objective: This study evaluated the inhibitory potential of some spicy plants on the activities of polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase). Method: Aqueous extracts of Laurus nobilis (bay), Cinnamomum zeylanicum (cinnamon), Murraya koenigii (curry), Thymus vulgaris (thyme) and Curcuma longa (turmeric) were incubated with appropriate enzymes and substrates, and percentages inhibition determined. Results: Results showed that bay extract had effective IC50 for inhibition of both aldose reductase (174.87 µg/mL) and sorbitol dehydrogenase (37.08 µg/mL). It also revealed that bay extract inhibited aldose reductase and sorbitol dehydrogenase in a non-competitive and competitive manner respectively. Conclusion: It is therefore concluded that bay extract effectively inhibited activities of polyol pathway enzymes, and may contribute to the amelioration of diabetic complications.