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The present study investigated whether Shenqi-wan possesses a protective effect against hydrogen peroxide (H₂O₂)-induced apoptosis of the hippocampal cell line HiB5. Through morphological and biochemical analyses, it was demonstrated that HiB5 cells treated with H₂O₂ exhibited several apoptotic features, while cells pre-treated with Shenqi-wan prior to H₂O₂ exposure showed a decrease in the occurrence of apoptosis. In addition, a patch clamp study revealed that Shenqi-wan inhibited profoundly N-methyl-D-aspartic acid (NMDA) receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results suggest that Shenqi-wan may exert its protective effect against H₂O₂-induced apoptosis via inhibition of NMDA receptors in hippocampal neuronal cells.

Yukmijihwang-tang (YMJ), also known as Luweidihuang-tang in China, has been widely used as a general herbal tonic for hundreds of years in many Asian countries. This study examines whether YMJ derivatives (YMJd) enhance cognitive ability in normal human subjects and discusses its potential as treatment for dementia patients with deficient cognitive ability. Subjects were divided into two groups, the placebo-treated group (n=15) and the YMJd-treated group (n=20). K-WAIS tests, a Korean version of an individual intelligence quotient (IQ) test, and a P300 latency assessment of event-related potential (ERP) were conducted in order to measure changes in cognitive ability before and after 6 weeks of YMJd treatment. The K-WAIS mean scores of the group treated with YMJd were significantly higher than those of the placebo group (p<0.05), and their mean P300 latency was substantially shorter (p<0.005). These results suggest that YMJd treatment accelerates the speed of information processing and enhances cognitive ability. YMJd treatment may help dementia patients or the elderly recover from cognition deficiencies or degeneration in clinic.

Corni Fructus (Cornus officinalis Sieb. et Zucc.) is a traditional medicine exerting multifaceted protective effects against diabetes and its complications. In this study, to further identify the physiological effects of Corni Fructus against diabetes and its complications, we investigated α-glucosidase inhibitory activities in vitro and employed the sucrose tolerance test as an indicator of the control of the postprandial blood glucose level. In vitro assays showed that Corni Fructus extract has a higher inhibitory activity than its major components. Then, Corni Fructus extract was fractionated again to screen the fractions showing a strong inhibitory activity against α-glucosidase. Of the tested fractions, five showed a rate of α-glucosidase inhibition of over 80%. Next, the four abundant fractions were evaluated their IC₅₀ values, as well as the inhibition mode in vitro and plasma glucose level after sucrose loading in normal Wistar rats. As a result, the IC₅₀ values of these fractions were between 1.1–2.1 μg/ml. Among the four fractions, three showed mixed inhibition, while one (Fr. 4–9) showed the competition-independent inhibition of α-glucosidase. In addition, Fr. 4S-1 significantly inhibited the rise in the plasma glucose levels at a dose of 20 mg/kg body weight after sucrose loading. These results indicate that Fr. 4S-1 from Corni Fructus has a potential to control postprandial hyperglycemia by α-glucosidase inhibition.

Our previous studies have shown that the best compatibility of components in Corni Fructus (PC) had a protective effect on vascular endothelial cells. In this study, the effect of PC on WT1 expression in glomerular podocytes and the mechanism of PC on early nephropathy in type 2 diabetic rats have been investigated. Type 2 diabetic rats were generated by high-fat diet combined with intraperitoneal injection of 30 mg/kg streptozotocin (STZ), then fed aminoguanidine (100 mg/kg), glimepiride (0.4 mg/kg), low-dose (60 mg/kg) or high-dose (120 mg/kg) of PC once a day for 12 weeks. Fasting blood glucose (FBG) was examined regularly. Insulin (INS) was measured by a radioimmunoassay. Microalbuminuria (mALB) was measured by an ELISA assay. Urinary creatinine (UCr), blood urea nitrogen (BUN) and N-acetyl-β-D-glucosaminidase (NAG) were measured by colorimetric assays. Renal morphological changes were observed by optical microscopy. The expression index of Wilms tumor 1 (WT1EI) in glomeruli was examined by immunohistochemistry. The results showed that PC led to a decrease in FBG (p < 0.01), NAG (p < 0.05) and mALB (p < 0.05) and an increase in INS (p < 0.01) and WT1EI (p < 0.05) compared to the diabetic group. PC could improve renal damage and greatly reduce the renal morphology score (p < 0.05). These results suggested that PC had the protective effect on early nephropathy in type 2 diabetic rats, which was closely related to the regulation of podocytes.

The aim of the present study was to identify the selective therapeutic effects of Corni Fructus (Cornus officinalis Sieb. et Zucc.) on different organs in streptozotocin (STZ)-induced diabetic rats. Diabetes in rats was induced by intraperitonal injection with STZ at a dose of 30 mg/kg body weight (bw) for 3 days (once per a day). STZ-induced diabetic rats were orally administrated Corni Fructus (CF) extract at 300 mg/kg or metformin at 250 mg/kg daily for 4 weeks. Blood glucose and triglyceride (TG) in sera and urine total volume were measured. Histopathological changes of different organs, pancreas, liver, kidney, and lung tissues were observed by H&E staining. The expression of insulin and α-smooth muscle actin (α-SMA) was investigated in pancreas, and kidney by immunohistochemistry, respectively. The results revealed that CF extract significantly decreased the serum levels of blood glucose, and TG, and also urine total volume in STZ-induced diabetic rats. The histological examinations revealed amelioration of diabetes-induced pancreas injury including pathological changes of the Langerhans's islet and glomerular with their loss after the administration of CF extraction. Moreover, the administration of CF extract increased the numbers of insulin releasing beta cells in pancreas and also inhibited the expression of α-SMA in kidney of STZ-induced diabetic rats. On the other hand, CF extract showed no effect on the pathological damages of liver and lung in STZ-induced diabetic rats. These results demonstrated that CF extract may have a selective therapeutic potential through the control of hyperglycemia, and the protection of pancreas and kidney against diabetic damage.

Accumulating evidence suggests that gut microbiota plays a crucial role in the development of metabolic diseases, especially type 2 diabetes mellitus (T2DM). The nutrient-rich resource Cornus Fructus (CF) showed curative effects on diabetes mellitus. However, the mechanism underlying its hyperglycemic activity remains obscure. Herein, the antidiabetic potential of four extracts from CF, including saponin (CTS), iridoid glycoside (CIG), tannin (CT), and alcohol extract (CCA) was evaluated in vivo. The results showed that all four extracts could increase the body weight, decrease the blood glucose levels, and elevate the glucose tolerance. Moreover, insulin sensitivity and lipid profile were significantly improved in fed mice. In the $\alpha$-diversity index of samples, compared to the DM group, the diversity and richness of gut microbiota in mice to a certain extent were reduced in both CF extracts and Metformin (PC). Among them, there was statistical significance in PC (ACE, $p=0.01$) and CCA (ACE, $p=0.01$; chao1: $p=0.04$). Beta diversity showed the same trend as the UPGMA clustering trees, which revealed that CF extracts could improve intestinal homeostasis in T2DM mice. Also, CF extracts could elevate the production of short-chain fatty acids, as well as regulate the composition of gut microbiota. The key bacteria related to T2DM including Firmicutes, Bacteroides, Lactobacillus, and Clostridium were modulated by metformin and CF. Altogether, CF is a potential nutrient-rich candidate that can be used in functional foods for the treatment of T2DM, and the change of gut microbiota might be a novel mechanism underlying its hyperglycemic activity.