甜菊苷及其衍生物的生物活性研究进展

甜菊苷是一种常用天然甜味剂,属于四环二萜糖苷类。药理学研究表明,甜菊苷及其水解产物甜菊醇、异甜菊醇和甜菊双糖苷等具有降血糖、降血压、抗炎、抗肿瘤、止泻、抗菌和免疫调节等多种生物活性。综述甜菊苷、甜菊醇、异甜菊醇、甜菊双糖苷及相关衍生物的生物活性研究进展。     

Stevioside protects against rhabdomyolysis‐induced acute kidney injury through PPAR‐γ agonism in rats

We explored the potential role of peroxisome proliferator activated receptor‐γ (PPAR‐γ) in stevioside‐mediated renoprotection using rhabdomyolysis‐induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol‐induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin–eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl‐2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR‐γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis‐induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside‐mediated renoprotection, which is suggestive of the involvement of PPAR‐γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis‐induced AKI, which may be attributed to modulation of PPAR‐γ expression.     

低糖蛇胆川贝液的研制

用新型甜味剂制成的低糖蛇胆川贝液不仅成本低,而且口感好,实验表明该制剂质量稳定,澄明度好。定性反应,薄层层析及生物碱含量测定结果均表明两者组分一致。     

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels

Recently, we showed that rebaudioside A potently stimulates the insulin secretion from isolated mouse islets in a dose-, glucose- and Ca(2+)-dependent manner. Little is known about the mechanisms underlying the insulinotropic action of rebaudioside A. The aim of this study was to define the signalling system by which, rebaudioside A acts. Isolated mouse islets were used in the cAMP[(125)I] scintillation proximity assay to measure total cAMP level, and in a luminometric method to measure intracellular ATP and ADP concentrations. Conventional and permeabilized whole-cell configuration of the patch-clamp technique was used to verify the effect of rebaudioside A on ATP-sensitive K(+)-channels from dispersed single beta cells from isolated mouse islets. Insulin was measured by radioimmunoassay from insulinoma MIN6 cells. In the presence of 16.7 mM glucose, the addition of the maximally effective concentration of rebaudioside A (10(-9) M) increased the ATP/ADP ratio significantly, while it did not change the intracellular cAMP level. Rebaudioside A (10(-9) M) and stevioside (10(-6) M) reduced the ATP-sensitive potassium channel (K(ATP)) conductance in a glucose-dependent manner. Moreover, rebaudioside A stimulated the insulin secretion from MIN6 cells in a dose- and glucose-dependent manner. In conclusion, the insulinotropic effect of rebaudioside A is mediated via inhibition of ATP-sensitive K(+)-channels and requires the presence of high glucose. The inhibition of ATP-sensitive K(+)-channels is probably induced by changes in the ATP/ADP ratio. The results indicate that rebaudioside A may offer a distinct therapeutic advantage over sulphonylureas because of less risk of causing hypoglycaemia.     

Antiamnesic effect of stevioside in scopolamine-treated rats

The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions.     

A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension

AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension. METHODS: A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean +/- s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27; mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and quality of life assessment showed no deterioration. CONCLUSIONS: This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.     

The low calorie natural sweetener stevioside: Nephrotoxicity and its relationship to urinary enzyme excretion in the rat

The relationships between urinary enzyme levels and changes in blood urea nitrogen (BUN) and plasma creatinine levels, along with simultaneous ultrastructural changes of the kidney, were studied in rats treated with stevioside. BUN levels increased at 3 h onward after subcutaneous injection (s.c.) with stevioside (1.5 g/kg BW). The maximum increases in BUN and creatinine were approximately 180% and 132% at 9 h after stevioside injection, respectively. At this time, stevioside also caused significant increases in glucosuria, alkaline phosphatase (AP) and γ-glutamyl transpeptidase (γ-GTP) but no significant changes in proteinuria, N-acetyl-β-D-glucuronidase (NAG) or glutathione-S-transferase (GSH-S-TF). Histopathological examination of the kidney induced by stevioside revealed degeneration of the proximal convoluted tubule cells but no relation to lipid peroxide formation was detected. These results suggest that stevioside induced nephrotoxicity at the proximal convoluted tubules rather than at the glomeruli and other tubules presumably by a defect of cell volume regulation due to depletion of intracellular ATP and disruption of microvilli, and nuclear dysfunction.     

Stevioside inhibits experimental fibrosis by down‐regulating profibrotic Smad pathways and blocking hepatic stellate cell activation

Liver cirrhosis is associated with increased morbidity and mortality with important health and social consequences; however, an effective treatment has not been found yet. Previous reports have shown some beneficial effects of stevioside (SVT) in different diseases, but the ability of SVT to inhibit liver cirrhosis has not been reported. Therefore, we studied the potential of this diterpenoid to inhibit liver cirrhosis induced by thioacetamide, a model that shares many similarities with the human disease, and investigated the possible underlying molecular mechanism using in vivo and in vitro approaches. Cirrhosis was induced in male Wistar rats by chronic thioacetamide administration (200 mg/kg) intraperitoneally three times per week. Rats received saline or SVT (20 mg/kg) two times daily intraperitoneally. In addition, co‐cultures were incubated with either lipopolysaccharide or ethanol. Liver fibrosis, hepatic stellate cells activation, metalloproteinases activity, canonical and non‐canonical Smads pathway and expression of several profibrogenic genes were evaluated. Thioacetamide activated hepatic stellate cells and distorted the liver parenchyma with the presence of abundant thick bands of collagen. In addition, thioacetamide up‐regulated the protein expression of α‐smooth muscle actin, transforming growth factor‐β1, metalloproteinases‐9,‐2 and ‐13 and overstimulate the canonical and non‐canonical Smad pathways. SVT administration inhibited all of these changes. In vitro, SVT inhibited the up‐regulation of several genes implicated in cirrhosis when cells were exposed to lipopolysaccharides or ethanol. We conclude that SVT inhibited liver damage by blocking hepatic stellate cells activation, down‐regulating canonical and non‐canonical profibrotic Smad pathways.     

Processing of a cowpea–groundnut blend into a miso-like product

A traditional salt-miso process was used to produce a miso-like product from a 50–50 mixture of cowpea and groundnuts in a 60-day fermentation process as part of a study to determine the suitability of local legumes as raw materials for the production of miso. The koji was freshly prepared from a locally obtained rice and Aspergillus oryzae spores obtained from Japan. An old miso sample also obtained from Japan was used as the source of lactic acid bacteria. The physico-chemical changes in the product associated with the fermentation and the functional and quality characteristics of the final product were determined. The study demonstrated the possibility of processing the legume blend into a miso-like product. The physico-chemical, functional and quality characteristics of the final product showed the suitability of the product for its intended use as a soup base. The product had a high protein and a moderately high lipid content (about 25% and 29%, respectively), which could contribute to the nutritional contents of diets.