Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats

Ethnopharmacological relevance

Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity.

Materials and methods

Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50 mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated.

Results

TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats.

Conclusion

The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.     

Astragalus polysaccharide improves insulin sensitivity in KKAy mice: Regulation of PKB/GLUT4 signaling in skeletal muscle

Ethnopharmacological relevance

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating diabetes.

Aim of the study

To study the mechanisms by which APS ameliorates diabetes, we examined whether treatment with APS improves insulin sensitivity in insulin-resistant mice and whether this is associated with an improvement of dysregulated protein kinase B and glucose transporter 4 expressions in skeletal muscle.

Methods

APS (700 mg kg⁻¹ day⁻¹) or vehicle was administered to 12-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Changes in body weight, blood glucose level, insulin resistance index, and oral glucose tolerance were routinely evaluated. The expressions of protein kinase B and glucose transporter 4 in skeletal muscle tissues were determined with Western blot.

Results

KKAy mice developed persistent hyperglycemia, impaired glucose tolerance and insulin resistance. Insulin-stimulated protein kinase B phosphorylation and glucose transporter 4 translocation were significantly decreased in KKAy compared to age-matched C57BL/6J mice. APS treatment ameliorated hyperglycemia and insulin resistance. Although the content of protein kinase B and glucose transporter 4 in KKAy skeletal muscle were not affected by APS, insulin-induced protein kinase B Ser-473 phosphorylation and glucose transporter 4 translocation in skeletal muscle were partially restored by APS treatment. In contrast, APS did not have any effect on C57BL/6J mice.

Conclusions

These results indicate that APS can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes.     

Inhibitory effect of total lignan from Fructus Arctii on aldose reductase

The potent inhibitory effect of the total lignan from the plant Fructus Arctii on aldose reductase was observed, suggesting its preventive potential on diabetic complications upon long term administration. Copyright © 2009 John Wiley & Sons, Ltd.     

Hypoglycemic effect of aqueous extract of seabuckthorn (Hippophae rhamnoides L.) seed residues in streptozotocin‐induced diabetic rats

An extract of seabuckthorn (Hippophae rhamnoides L.) seed residues has been shown to possess hypoglycemic and hypolipidemic properties in normal mice. The present study investigated the effects of an aqueous extract of seabuckthorn seed residues (ASSR) on serum glucose, lipid profiles and antioxidant parameters in streptozotocin‐induced diabetic rats. Male Sprague‐Dawley rats were divided into four groups: a normal control group; diabetic control group; diabetic groups supplemented with 5 mg/kg body weight glibenclamide (reference drug) and 400 mg/kg body weight ASSR. Diabetes in rats was induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight). Vehicle (distilled water), glibenclamide and ASSR were administered orally to normal and diabetic rats once a day lasting for 4 weeks. The data showed that administration of ASSR significantly lowered the serum glucose, triglyceride and nitric oxide levels in diabetic rats. Moreover, ASSR treatment also increased serum superoxide dismutase activity and glutathione level markedly. These results show that ASSR has hypoglycemic, hypotriglyceridemic and antioxidant effects in streptozotocin‐induced diabetic rats, suggesting that ASSR supplementation can be useful in preventing diabetic complications associated with hyperlipidemia and oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.     

Extracts of Scutellaria baicalensis Reduced Body Weight and Blood Triglyceride in db/db Mice

Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold. The present study was performed to investigate the anti‐obesity and anti‐dyslipidemia effect of Scutellaria baicalensis extracts (SBE) in type 2 diabetic db/db mice. Male db/db mice were divided into three groups (n = 5) and orally administrated vehicle (control), SBE 10, and 100 mg/kg body weight/day for 4 weeks everyday. Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice. In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels. In the livers of db/db mice, SBE promoted 5' AMP‐activated protein kinase activity and restored metabolic process and insulin signaling pathways. Our data demonstrate that SBE exerts potent anti‐obesity and anti‐hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia. Copyright © 2012 John Wiley & Sons, Ltd.     

Mixture of five herbal extracts ameliorates pioglitazone-induced aggravation of hepatic steatosis via activating the adiponectin receptor 2/AMP-activated protein kinase signal pathway in diabetic KKAy mice

OBJECTIVE: To assess the effect of a mixture of five herbal extracts(FT-5) on insulin resistance, glucose/lipid metabolism, hepatic steatosis, and to investigate whether the combination of FT-5 and pioglitazone would provide a robust effect on diabetes treatment, while may minimize undesirable side-effects of pioglitazone in diabetic Ay gene(KKAy)mice.METHODS: Seven-week-old KKAy mice were randomly divided into five groups: control(CON)group, FT-5(2.0 g/kg) group, pioglitazone(20 mg/kg)(PIO) group, pioglitazone(20 mg/kg) + FT-5(2.0 g/kg)(P + F) group. Age-matched C57 BL/6 J micewere used as the control group. After seven weeks of continuous intragastric administration of medication, the glucose metabolism, insulin sensitivity and lipid metabolism of KKAy mice were evaluated by assessing the fasting blood glucose(FBG), oral glucose tolerance test(OGTT), fasting serum insulin(FINS), insulin tolerance test(ITT), homeostasis model of assessment-insulin resistance index(HOMA-IR), total cholesterol(TC), total triglycerides(TG), and free fatty acids(FFA) in plasma and liver.Plasma and hepatic adiponectin were measured via enzyme-linked immunosorbent assays. Genes related to adipogenesis and lipolysis in white adipose tissues(WAT) and liver were examined by real-time polymerase chain reaction. Lipid metabolism-related protein expression in the liver of KKAy mice were detected by Western blotting.RESULTS: PIO treatment remarkably improved insulin resistance. However, it also showed substantial side effects. FT-5 group exhibited no significant decrease in serum glucose. However, it reduced fasting plasma TG levels and improved hepatic steatosis of KKAy mice. P + F group showed improved insulin resistance and similar body weight gain, as compared with control group. The m RNA expression of genes related to fatty acid oxidation was markedly up-regulated in the liver of P + F group.Pioglitazone administration markedly decreased the phosphorylation levels of AMPK, as compared with all other groups. Besides, even though plasma adiponectin increased in PIO, FT-5, P + F group, adipo R2 gene expression significantly decreased in the liver of PIO group.CONCLUSION: FT-5 decreased plasma TG and alleviated aggravating hepatic steatosis induced by pioglitazone in KKAy mice. FT-5's mechanism might be associated with its ability to activate the Adipo R2/AMPK pathway.     

Cognitive Ameliorating Effect of Acanthopanax koreanum Against Scopolamine‐Induced Memory Impairment in Mice

Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade‐induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine‐induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y‐maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory‐associated signaling molecules, such as protein kinase B (Akt), Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII), and cAMP response element‐binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine‐induced cognitive impairment in the passive avoidance task, the Y‐maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two‐fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p < 0.05). Moreover, the phosphorylation level of CREB was also significantly increased compared with the control group by the administration of EEAK (200 mg/kg) (p < 0.05). The present study suggests that EEAK ameliorates the cognitive dysfunction induced by the cholinergic blockade, in part, via several memory‐associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.     

Chemoprotective effects of Ulva lactuca (green seaweed) aqueous‐ethanolic extract against subchronic exposure to benzo(a)pyrene by CYP1A1 inhibition in mice

The protective effect of the supplementation with an aqueous‐ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene‐induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL‐1β and TNF‐α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene‐exposed group. The benzo(a)pyrene‐induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract‐supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene‐induced‐toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.     

Hypoglycemic effects of malonyl‐ginsenosides extracted from roots of Panax ginseng on streptozotocin‐induced diabetic mice

Hypoglycemic effects of malonyl‐ginsenosides (MGR), extracted from roots of Panax ginseng, were examined in streptozotocin‐ (STZ‐) induced diabetic mice. Animals received daily intravenous injections of MGR in doses of 30, 60, 120 mg/kg. At a dose of 120 mg/kg, MGR reduced the fasting blood glucose level of diabetic mice by 77.8% (76.7 ± 8.5 mg/dl versus 345.2 ± 35.8 mg/dl, P < 0.01). The same dose also showed a marked improvement in glucose tolerance of 80% (75.3 ± 10.8 mg/dl versus 375.6 ± 43.3 mg/dl, P < 0.01) in diabetic mice after four days. The alkali hydrolysis productions of MGR, ginseng panaxadiol (PDS), malonic acid and a mixture of malonic acid with PDS, showed no effects on fasting blood glucose levels indicated the hypoglycemic effect of MGR relied on their unique esterified chemical structures. The findings from this study suggest that MGR extracted from Panax ginseng may be prescribed as adjunct to drug treatment for controlling diabetes mellitus. Copyright © 2009 John Wiley & Sons, Ltd.     

Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene on Testosterone Propionate‐Induced Prostatic Hyperplasia in Mice

The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate‐induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd.