Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis

Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenosides (PDG) from Panax ginseng. Although anti-diabetic activity of CK have been reported with genetic mouse models (db/db mice) in recent years, the therapeutic usefulness of CK and PDG in type 2 diabetes, a more prevalent form of diabetes, remains unclear. In the present investigation, we developed a mouse of non-insulin-dependent diabetes mellitus that closely simulated the metabolic abnormalities of the human disease. For this purpose, type 2 diabetes was induced in male ICR mice by combining of streptozotocin. The male ICR mice fed with HFD for 4 weeks received 100 mg/kg of STZ injected intraperitoneally. After 4 weeks, mice with fasting (12 h) blood glucose levels (FBG) above 7.8 mmol/L were divided into 3 groups (n = 12) and treated with vehicle (diabetes model, DM), 300 mg/kg/day of PDG and 30 mg/kg/day of CK for 4 weeks while continuing on the high-fat diet. Hypoglycemic effects of CK and PDG were consistently demonstrated by FBG levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing (OGTT). Moreover, the mechanism of hypoglycemic effect in type 2 diabetic mice was examined. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in two treatment groups with CK showing greater effects. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of CK on type 2 diabetes induced by HFD/STZ via down-regulation of PEPCK and G6Pase expression in liver.     

Identification of chicoric acid as a hypoglycemic agent from Ocimum gratissimum leaf extract in a biomonitoring in vivo study

Ocimum gratissimum L. is popularly used to treat diabetes mellitus. The hypoglycemic activity of this medicinal species has been confirmed by in vivo studies. The present study conducted a chemical investigation of a leaf decoction (10% p/v) of O. gratissimum monitored by in vivo hypoglycemic activity assays. Four phenolic substances were identified: l-caftaric acid (1), l-chicoric acid (2), eugenyl-β-d-glucopyranoside (3) and vicenin-2 (4). The acute hypoglycemic activity of the O. gratissimum decoction fractions Og1-S (300 mg/kg), Og1-A (240 mg/kg) and Og1-B (80 mg/kg) was evaluated intraperitoneally in normal and streptozotocin-induced diabetic mice. They reduced glycemia by 63%, 76% and 60% (in 120 min), respectively, in the diabetic mice. Subfractions of Og1-A were also evaluated under the same conditions: Og1-AS (200 mg/kg) and Og1-AP (40 mg/kg) produced a decrease of only 37% and 39%, respectively. Among the major phenolic substances, only chicoric acid (2; 3 mg/kg) reduced significantly the glycemic levels of diabetic mice by 53%, 120 min after treatment. This is the first study describing the hypoglycemic activity of chicoric acid in an animal model of diabetes mellitus. In addition, we suggest that there may be other substances contributing to this activity. Thus, for the first time, a correlation is established between the hypoglycemic activity of O. gratissimum and its chemical composition.     

Anti-diabetic effects of emodin involved in the activation of PPARγ on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice

Rheum palmatum Linn has been widely applied in the clinical treatment of diabetes mellitus. It has been found that emodin as the major bioactive component of R. palmatum L exhibits the competency to activate peroxisomal proliferator-activated receptor-γ (PPARγ) in vitro. So the aim of this study was to evaluate the anti-diabetic effects of emodin through the activation of PPARγ on high-fat diet-fed and low dose of streptozotocin (STZ)-induced diabetic mice. The diabetic mice were intraperitoneally injected with emodin for three weeks. No changes of food consumption and the body weight in emodin-treated mice were monitored daily during the entire experiment. At the end of experiment, the levels of blood glucose, triglyceride and total cholesterol in serum were significantly decreased after emodin treatment. However, serum high-density lipoprotein cholesterol (HDLc) concentration was significantly elevated. The glucose tolerance and insulin sensitivity in emodin-treated group were significantly improved. Furthermore, the results of quantitative RT-PCR analysis showed that emodin significantly elevated the mRNA expression level of PPARγ and regulated the mRNA expressions of LPL, FAT/CD36, resistin and FABPs (ap2) in liver and adipocyte tissues. No effects on the mRNA expressions of PPARα and PPARα-target genes were observed. Taken together, the results suggested that the activation of PPARγ and the modulation of metabolism-related genes were likely involved in the anti-diabetic effects of emodin.     

粉色果实花楸母本起源的分子证据

[目的]探讨河北驼梁山自然风景区内形态介于花楸树和北京花楸之间的粉色果实花楸的起源。[方法]本研究调查了花楸树、北京花楸和粉色果实花楸的海拔分布格局及生长状况,并通过叶绿体DNA序列分析3个类群的系统发育关系。[结果]北京花楸主要分布在海拔1 300 2 000 m,花楸树分布于1 500 2 200 m,粉果花楸出现在两者重叠分布区内;粉果花楸叶绿体单倍型有70%与北京花楸相同,10%与花楸树相同,其余20%为其特有。[结论]表明:粉色果实花楸是花楸树和北京花楸之间的天然杂交种,是多起源的类群,在自然分类系统中应作为独立的种来处理;花楸树和北京花楸均可作为母本。     

Comparative pharmacokinetics of baicalin in normal and the type 2 diabetic rats after oral administration of the Radix scutellariae extract

Radix scutellariae was used alone or in combination with other medicinal herbs in the treatment of type 2 diabetes mellitus in China. At present, the pharmacokinetics of baicalin in type 2 diabetic rats following oral administration of Radix scutellariae extract was investigated. The results showed that the pharmacokinetics (especially AUC) of baicalin in type 2 diabetic rats after oral administration of Radix scutellariae extract was remarkably different from that in normal rats. Then the mechanism which resulted in the increased AUC of baicalin in diabetic rats was investigated from system clearance and presystemic metabolism. And it was found that the increased AUC of baicalin in diabetic rats at least partly resulted from higher production of baicalein in the intestinal tract of type 2 diabetic rats. Moreover, the activity of β-glucuronidase in intestinal mucosa of type 2 diabetic rats was demonstrated to be higher than that in normal rats, which confirmed the results above. In conclusion, the pharmacokinetic behavior of baicalin was significantly altered in type 2 diabetic rats after orally administrated Radix scutellariae extract, which may partly result from the increased activity of intestinal β-glucuronidase under the pathological state of type 2 diabetes mellitus.     

Phytocomplexes from liquorice (Glycyrrhiza glabra L.) leaves--chemical characterization and evaluation of their antioxidant, anti-genotoxic and anti-inflammatory activity

Three extracts of different polarities of Glycyrrhiza glabra L. leaves were characterized and evaluated for their antioxidant, anti-genotoxic and anti-inflammatory activity. In total, thirty components have been identified and quantified through the use of liquid chromatography (LC) with ultraviolet-visible diode-array-detector (UV-vis-DAD) and mass spectrometry (MS). The main components belong to the polyphenols family, being flavonoid and dihydrostilbene derivatives. The extracts have been investigated for their antioxidant, anti-genotoxic and anti-inflammatory activities, which are fundamental requirements of efficacious chemo-preventive agents. The ethyl acetate extract proved to be the most valuable, evidently for the conspicuous presence of several polyphenols, namely flavonoids and dihydrostilbenes.     

Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase

This study investigated the urinary and biliary excretion of tectoridin, a major active isoflavonoid found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Using UHPLC/Q-TOFMS, seven glucuronides and/or sulfated metabolites and four Phase I metabolites were simultaneously quantified in rat urine after oral administration of tectoridin at 100 and 200 mg/kg. Over a 72-h period, 14.2% and 14.7% of the tectoridin were excreted as eleven metabolites in urine, among which, two major metabolites tectorigenin-7-O-β-D-glucuronide (Te-7G) and tectorigenin accounted for 5.5–5.5% and 4.3–4.4%. Furthermore, the cumulative excretion of four glucuronides and sulfated metabolites in bile accounted for 7.3% and 3.9% of the dose within 60 h, among which, Te-7G and tectorigenin-7-O-glucuronide-4′-O-sulfate (Te-7G-4′S) accounted for 2.3–3.0% and 1.4–3.9%, respectively. The results indicate that the urine was the primary elimination route, and glucuronidation after deglycosylation at C-7 position was the major metabolic pathway of tectoridin in vivo. Moreover, the inhibitory activities of tectoridin and its five metabolites on rat lens aldose reductase were confirmed (IC₅₀: 1.4–15.5 μM), whereas irisolidone-7-O-glucuronide (Ir-7G) and irisolidone showed little activity.     

Isolation and free radical scavenging activities of a novel biflavonoid from the shells of Camellia oleifera Abel.

Oil production from the seeds of Camellia oleifera Abel. causes a great waste of shells which contain a lot of bioactive components. The aim of this research was to isolate flavonoid from the shells of C. oleifera Abel. and evaluate its uses. The shells were extracted by 70% methanol, hydrolyzed by 2 M hydrochloric acid, and further crystallized in acetone, the corresponding yield of flavonoid was up to 2.1% (purity: 93.8%). The procedure is concise, quick and proper for industrial utilization of the shells. Flavonoid was identified as bimolecular kaempferol structure by UV, MS, ¹H NMR and ¹³C NMR spectra, which is a new biflavonoid and first found in C. oleifera Abel. It showed stronger scavenging activity of DPPH and ABTS radicals than kaempferol. MDA decreased, and SOD and GSH-Px activities increased significantly in serum (P < 0.01) and brain tissue (P < 0.05) of mice after intragastric administration of biflavonoid at 200 mg/kg/d for 30 d. Its effects in vivo are superior to vitamin C and similar to kaempferol. Thus biflavonoid can be used as a prospective antioxidant to protect brain cells against damage from free radicals.     

Genotypic variation in tree growth and selected flavonoids in leaves of Cyclocarya paliurus

Cyclocarya paliurus is a valuable medicinal tree species in China. However, limited information is available on its genotype selection and cultivation for improvement of growth and health-promoting phytochemicals. To contribute to improved knowledge of the potential use of the species, 33 families of C. paliurus were assessed with respect to genotype on growth and flavonoid content in the leaves, and the relationship between growth and flavonoid accumulation was examined. Growth and flavonoid content varied significantly among different families, and isoquercitrin was the main component of the individual flavonoids, followed by kaempferol and quercetin. Both total and individual flavonoids showed seasonal variation, with the mean highest contents of quercetin and isoquercitrin in July but the highest kaempferol content in October. Correlation analysis showed that tree height and diameter at breast height of C. paliurus were negatively correlated with the contents of quercetin and kaempferol in the leaves, whereas no significant correlation between tree growth and total flavonoid content was detected. Hierarchical cluster analysis based on the parameters of tree growth and leaf flavonoid contents indicated that 33 families of C. paliurus were classified into four distinct groups. Results from this study are valuable for identifying superior families for a specific site and provide a basis for C. paliurus breeding strategies for flavonoid production.     

Chemical composition,antioxidant and antibacterial activities of extracts from <Emphasis Type="Italic">Schinus molle</Emphasis> wood branch growing in Egypt

In the present work, for the first time, the chemical components of essential oils (EOs) and extracts from wood branch (WB) resulted from the tree pruning wastes of Schinus molle L. grown in Egypt were evaluated for their antioxidant and antibacterial activities. EOs, methanol (ME), dichloromethane (DCME) and water (WE) extracts as antioxidant and antibacterial activities were measured. Total phenolic and flavonoid contents as well as analysis of extracts by gas chromatography–mass spectrometry (GC–MS) were reported. The major components in EOs were α-elemol, β-pinene, and α-phellandrene, in ME were 6-(4-chlorophenyl)-3-cyano-4-(N-benzylpiperazino)-2H-pyran-2-one, and 2-naphthalene methanol, decahydro-α,α,4a-trimethyl-8-methylene, in DCME were 12-methyl-E,E-3,13-octadecadien-1-ol, and 1,2-benzenedicarboxylic acid, dioctyl ester, and in WE were β-eudesmol, and (Z,Z,Z)-9,12,15-octadecatrienoic acid, 2,3-dihydroxypropyl ester. The highest total antioxidant activity was found with EOs (90 ± 1.23 %) and WE (86.30 ± 1.40 %). The lowest IC₅₀ values of 13.11 ± 3.00, and 12.66 ± 2.15 μg/mL were found with WE and EOs, respectively. EOs and WE were observed to have good antibacterial activity against Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Escherichia coli, Sarcina lutea, Pseudomonas aeruginosa, and Micrococcus luteus. In conclusion, the Schinus molle L. WB EOs and extracts might, indeed, be used as a potential source for pharmaceutical or food industries.     

Chemical composition of the Lippia origanoides essential oils and their antigenotoxicity against bleomycin-induced DNA damage

The present work evaluated the chemical composition of the essential oils (EO) obtained from Lippia origanoides and their DNA protective effect against bleomycin-induced genotoxicity. L. origanoides EO chemical composition was determined by gas chromatography–mass spectrometry (GC–MS). The major compounds of the L. origanoides EOs were thymol (34–58%) and carvacrol (26%). The antigenotoxic effects of the EOs, major compounds and standard compound (epigallocatechin gallate) were assayed in co-incubation procedures using the SOS chromotest in Escherichia coli. Both EOs and their major compounds protected bacterial cells against bleomycin-induced genotoxicity indicating that these two compounds were principally responsible for the antigenotoxicity detected in the oils. Thymol and carvacrol antigenotoxicity was lower than those observed with epigallocatechin gallate. The results were discussed in relation to the chemopreventive potential of L. origanoides EOs and their major components, carvacrol and thymol.     

Transdermal behaviors comparisons among Evodia rutaecarpa extracts with different purity of evodiamine and rutaecarpine and the effect of topical formulation in vivo

Aim

Evodiamine (EVO) and rutaecapine (RUT), the major active components from Evodia rutaecarpa extract (EE), are recognized as a depended analgesic agent. This study was designed to investigate the effect of purity and chemical enhancers on the transdermal behavior of EVO and RUT, and the pharmacological effect of their topical cream in vivo.

Material and methods

Transdermal delivery across a full thickness pig abdominal skin was detected in vitro by Franz-type diffusion cell, with HPLC for quantification of the permeation of EVO and RUT. The activity of topical cream in vivo was evaluated by a mice pain model induced by formalin and hot plate.

Results

Transdermal characters of EVO and RUT showed a low transdermal rate, long lag time and low cumulative amount. The transdermal rate and cumulative amount could be promoted by lipophilic enhancers, whereas lag time was shortened by hydrophilic surfactant, but these permeation parameters were not markedly influenced by purity of EE (p > 0.05). The effect in vivo was confirmed by analgesic models in topical cream of EE, which produced a significant (p < 0.05) inhibitory effects on pain response in dose-dependent manner.

Conclusion

The purity of EVO and RUT from EE has no significant effect on their permeation through porcine skin, but oleic acid or nerolidol can markedly elevate the transdermal rate of EVO and RUT. High purity of EE is the best choice for topical preparation to increase the drug loading. The effect of EE in vivo is verified by formalin model and hot plate test.     

Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis

The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4 μg/ml. So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure–activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly.     

Geographical variations in life histories of Plutella xylostella in China

The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is one of the most important pests of crucifers worldwide. Susceptibility to insecticides and host plants of P. xylostella vary geographically. To investigate local adaptation, we measured the variation of the biology, life-histories and life-table parameters of P. xylostella populations from five widely ranging geographical regions in China, Beijing (BJ), Shandong (SD), Shaanxi (SX), Yunnan (YN), and Guangdong (GD), using the same variety of cabbage (Brassicae oleracea L. var. capitata; var. “Qingan 80”) as the food plant at the same temperature in the laboratory. Principal components analysis showed the life-history and life-table parameters of P. xylostella differed among the five geographical populations. The first component, including female fecundity and adult longevity and male adult longevity, accounted for the most variation among the five geographical regions, which can be classified into three groups: BJ–SX, YN–GD, and SD. The intrinsic rate of increase (r _m ) was greatest in BJ and SX, intermediate for GD and YN, and the lowest for SD, whereas mean generation time (T) was greatest in SD, intermediate for YN and GD, and the lowest for BJ and SX. These variations reflect the importance of local genetic adaptation and should be considered when planning management of P. xylostella in China.     

Anti-inflammatory activity of sulfate-containing phenolic compounds isolated from the leaves of Myrica rubra

Three sulfated phenolic compounds, juglanin B (11R)-O-sulfate (1), myricetin 3´-O-sulfate (2), and ampelopsin 3´-O-sulfate (3), were isolated from the leaves of Myrica rubra. Compound 1 was a new sulfated lignan, 2 was a new sulfated flavone, and 3 was a known sulfated flavone. The structures of the new compounds (1 and 2) were determined by acid hydrolysis and spectroscopic methods, including IR, FAB-MS, 1D and 2D NMR. The inhibitory activities of compounds 1–3 and their hydrolysates (1a–3a) against LPS-induced cytokine (TNF-α, IL-1β, and IL-6) production in macrophage RAW 264.7 cells were evaluated. The 2 new compounds (1 and 2) and their aglycones (1a and 2a) significantly reduced LPS-induced expression of iNOS and COX-2 proteins.     

Anti-diabetic effects of brown algae derived phlorotannins,marine polyphenols through diverse mechanisms

Marine algae are popular and abundant food ingredients mainly in Asian countries, and also well known for their health beneficial effects due to the presence of biologically active components. The marine algae have been studied for biologically active components and phlorotannins, marine polyphenols are among them. Among marine algae, brown algae have extensively studied for their potential anti-diabetic activities. Majority of the investigations on phlorotannins derived from brown algae have exhibited their various anti-diabetic mechanisms such as α-glucosidase and α-amylase inhibitory effect, glucose uptake effect in skeletal muscle, protein tyrosine phosphatase 1B (PTP 1B) enzyme inhibition, improvement of insulin sensitivity in type 2 diabetic db/db mice, and protective effect against diabetes complication. In this review, we have made an attempt to discuss the various anti-diabetic mechanisms associated with phlorotannins from brown algae that are confined to in vitro and in vivo.     

Pre-treatment of Syndrex® protects mice from becoming diabetic after streptozotocin injection

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to either insufficiency of insulin or inability of cells to respond to insulin. Many clinical and experimental evidence have suggested the strong association between hyperglycemia, oxidative stress and diabetic complications. Therefore, the antidiabetic drugs with antioxidant potential would have a higher therapeutic value. To check its antidiabetic and antioxidant properties in vivo, experiments were done wherein mice were fed with Syndrex^® in different schedules and/or made diabetic by intraperitoneal injection of streptozotocin. Animals fed with Syndrex^® prior to the induction of diabetes by streptozotocin injection showed resistance to an increase in blood glucose levels. This treatment increased the activities of antioxidant enzymes namely, catalase, glutathione reductase and superoxide dismutase and reduced serum triglyceride and cholesterol levels as compared to those found in uncontrolled diabetic mice. Among the three different schedules used for Syndrex^® treatment, the best effect was seen in the case of mice pretreated with Syndrex^® prior to STZ injection. In our opinion, Syndrex^® given along with insulin may reduce the amount of insulin dose required and because of its strong antioxidant activity would certainly help to reduce the development of diabetic complications.     

Effects of eugenol on hepatic glucose production and AMPK signaling pathway in hepatocytes and C57BL/6J mice

Eugenol is a phenylpropanoid with many pharmacological activities, but its anti-hyperglycemic activity is not yet fully explored. For in vitro study, HepG2 cells and primary rat hepatocytes were used, and glucose production was induced by adding 100 nM of glucagon in the presence of gluconeogenic substrates. In animal study, hyperglycemia was induced by high fat diet (HFD) in male C57BL/6J mice, and eugenol was orally administered at 20 or 40 mg per kg (E20, E40) for 15 weeks. Eugenol significantly inhibited glucagon-induced glucose production and phosphorylated AMPK in the HepG2 and primary rat hepatocytes, and these effects were reversed in the presence of compound C (an AMPK inhibitor) or STO-609 (a CAMKK inhibitor). In addition, the protein and gene expression levels of CREB, CRTC2 · CREB complex, PGC-1α, PEPCK and G6Pase were all significantly suppressed. Moreover, inhibition of AMPK by over-expression of dominant negative AMPK prevented eugenol from suppressions of gluconeogenic gene expression and hepatic glucose production. In animal study, plasma glucose and insulin levels of the E40 group were decreased by 31% and 63%, respectively, when compared to those of HFD control. In pyruvate tolerance tests, pyruvate-induced glucose excursions were decreased, indicating that the anti-hyperglycemic activity of eugenol is primarily due to the suppression of hepatic gluconeogenesis. In summary, eugenol effectively ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis via modulating CAMKK-AMPK-CREB signaling pathway. Eugenol or eugenol-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes.     

Anti-diabetic effect of American ginseng may not be linked to antioxidant activity: Comparison between American ginseng and Scutellaria baicalensis using an ob/ob mice model

Antioxidants have been considered as a useful remedy in diabetes therapeutics, and thus, herbal medicines with antioxidant properties may play major role in treating diabetes. In this report, we performed a comparative study using American ginseng and Scutellaria baicalensis to test whether the anti-diabetic effect of American ginseng is associated with its antioxidant activity. We used a simple water extraction procedure to prepare American ginseng root extract (AGE) and S. baicalensis extract (SbE), and utilized these two antioxidant herbs to evaluate their anti-diabetic effect in obese diabetic ob/ob mice. HPLC analysis was used to identify major constituents in the AGE and SbE. After 12 days of daily intraperitoneal injection, AGE at 300 mg/kg showed significant effects on fasting blood glucose levels (P < 0.01) and glucose tolerance test (P < 0.01) compared to vehicle-treated mice. Animal body weights also reduced significantly after 12-day treatment (P < 0.01). However, SbE, a very strong antioxidant extract, administered at 5–50 mg/kg (based on our previous studies without adverse events) for 12 days did not show any significant effects on blood glucose and body weight changes. No effects were shown when baicalein, an effective antioxidant constituent in SbE, was administered at 1–5 mg/kg. It appears that the anti-diabetic effect of American ginseng may not be linked to its antioxidant actions. The mechanisms of American ginseng's effects on reducing high blood glucose levels and body weight remain to be investigated in future experiments.