Antibacterial activity of the structurally novel ocotillol-type lactone and its analogues.

A novel series of ocotillol-type lactone derivatives were designed and synthesized in order to study their antibacterial activity and structure-activity relationships. Among which, compounds 4j and 4 m were found to be the most active with minimum inhibitory concentrations (MICs) of 1-4 µg/mL against Gram-positive bacteria and showed low cytotoxicity against MCF-7, HEK-293 and HK-2 cells at their MICs. The antibacterial effect of compound 4 m was characterized further by scanning electron microscopy, cytoplasmic ß-galactosidase leakage assay and UV-visible analysis. The results showed that 4 m may exert its antibacterial effect by damaging bacterial cell membranes and disrupting the function of DNA, both of which could lead to rapid cell death.

Novel 3-substituted ocotillol-type triterpenoid derivatives as antibacterial candidates.

Plant-derived triterpenoid saponins are involved in the plant defense system by targeting bacterial membranes. A series of ocotillol-type triterpenoid derivatives were synthesized starting from PPD, one of the main components of Panax ginseng and their antibacterial activity against several representative bacteria were evaluated. Compounds 5 and 11 exhibited excellent antibacterial activity with MIC values of 1 µg/mL against Staphylococcus aureus and 8 µg/mL and 4 µg/mL against Bacillus subtilis, respectively. Furthermore, when compounds 5 and 11 were combined with two commercial antibiotics kanamycin and chloramphenicol, they showed strong synergistic activity at sub-MIC levels against S. aureus USA300 and B. subtilis 168. Moreover, chloramphenicol turned from a bacteriostatic to a bactericidal agent when combined with compound 11 against B. subtilis 168.

Tetrahydroxystilbene glucoside improves the learning and memory of amyloid-ß(1₋42)-injected rats and may be connected to synaptic changes in the hippocampus.

The aim of this study was to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on learning/memory deficits in Alzheimer's disease (AD). We randomly divided 24 male Sprague-Dawley rats among 4 groups: (i) the sham-operated group (control); (ii) sham-operated group also treated with TSG (sham+TSG); (iii) beta amyloid treated group (Aß); and (iv) Aß treatment group also treated with TSG (Aß+TSG). Rats in the Aß and Aß+TSG groups were treated with Aß1₋42 intracerebroventricularly, whereas the control and sham+TSG groups were given phosphate-buffered saline. Rats in the sham+TSG and Aß+TSG groups were then treated intragastrically with TSG (50 mg·(kg body mass)⁻¹·day⁻¹) for 4 weeks, and rats in the Aß and control groups were treated with saline. The results from Morris water maze tests, electron microscopy, real-time polymerase chain reaction, and Western blotting demonstrated that Aß1₋42 induced impairment in learning and memory, degeneration in synaptic structures, and downregulation of Src and NR2B at the gene and protein level, respectively. These alterations were reversed by the administration of TSG, suggesting that TSG exerts anti-AD properties by protecting synaptic structure and function. TSG-induced upregulation of Src and NR2B may be responsible for this process.

Anti-hyperglycemic effect of Potentilla discolor decoction on obese-diabetic (Ob-db) mice and its chemical composition.

Potentilla discolor is used as an ethnomedicine in treatments of diabetes mellitus in China for years. In the present study, the anti-hyperglycemic effects of a clinical active extract (decoction) from P. discolor were investigated in Ob-db mice. Four week's treatment of P. discolor decoction ameliorated the development of hyperlipidemia, lipid peroxidation and hyperglycemia associated with hyperphagia and polydypsia in Ob-db mice. P. discolor significantly attenuated the increase of blood glucose and cholesterol levels in Ob-db mice. These findings clearly provided evidences regarding the anti-hyperglycemic potentials of P. discolor decoction. High-resolution liquid chromatography-mass spectrometry/mass spectrometry (HR-LC-MS/MS) was used to analyze the phytochemicals in P. discolor decoction. In an comprehensive analysis of phytochemicals in P. discolor, thirty-five components were identified or characterized in P. discolor decoction and only sixteen of them have been reported in P. discolor previously. There are five major components identified in P. discolor decoction. One of the major components is a flavonoid sulfate, and this is the first evidence for the presences of sulfated flavonoid in P. discolor. Sulfated flavonoids have been reported to improve the complications of diabetes mellitus by inhibition of the aldose reductase in both experimental animals and clinical trials. Therefore, the sulfated flavonoid in P. discolor decoction may in part contribute to the anti-hyperglycemic effect of P. discolor.

Antidiabetic Effect of an Active Components Group from Ilex kudingcha and Its Chemical Composition.

The leaves of Ilex kudingcha are used as an ethnomedicine in the treatment of symptoms related with diabetes mellitus and obesity throughout the centuries in China. The present study investigated the antidiabetic activities of an active components group (ACG) obtained from Ilex kudingcha in alloxan-induced type 2 diabetic mice. ACG significantly reduced the elevated levels of serum glycaemic and lipids in type 2 diabetic mice. 3-Hydroxy-3-methylglutaryl coenzyme A reductase and glucokinase were upregulated significantly, while fatty acid synthetase, glucose-6-phosphatase catalytic enzyme was downregulated in diabetic mice after treatment of ACG. These findings clearly provided evidences regarding the antidiabetic potentials of ACG from Ilex kudingcha. Using LC-DAD/HR-ESI-TOF-MS, six major components were identified in ACG. They are three dicaffeoylquinic acids that have been reported previously, and three new triterpenoid saponins, which were the first time to be identified in Ilex kudingcha. It is reasonable to assume that antidiabetic activity of Ilex kudingcha against hyperglycemia resulted from these six major components. Also, synergistic effects among their compounds may exist in the antidiabetic activity of Ilex kudingcha.

Tetrahydroxystilbene glucoside improves learning and (or) memory ability of aged rats and may be connected to the APP pathway.

The aim of this study is to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) on learning and (or) memory deficit in aged rats, as well as to explore the possible connection between TSG and the ß-amyloid precursor protein (APP) pathway. Sprague-Dawley rats were randomly divided into a young control group (age, 4 months), an aged control group (age, 22 months), and a TSG-treated group (age, 22 months). TSG at doses of 50 mg·kg(-1)·day(-1) was intragastrically administered to 22-month-old rats for 4 weeks. The learning and (or) memory ability was measured using the Morris water maze (MWM) test, and the mRNA and protein expression of APP pathway proteins was measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. The aged rats exhibited obvious learning and (or) memory deficit when compared with the young rats, but TSG treatment significantly improved the learning and (or) memory ability in the aged rats, as noted from the MWM test. RT-PCR and Western blot analysis showed an increase in the expression of beta-site APP cleaving enzyme 1 (BACE1) and A Disintegrin And Metalloproteinase 17 (ADAM17) in aged rats, and a decrease in ADAM10; however, TSG treatment significantly increased the mRNA and protein expression of ADAM10 (p < 0.01, compared with aged control rats). These results provide solid evidence for the therapeutic effect of TSG on age-related cognitive impairment, especially spatial learning and memory deficit. TSG might exert this effect through the APP pathway, although further studies on the topic are required.

Hypolipidemic effects of Alismatis rhizome on lipid profile in mice fed high-fat diet.

OBJECTIVE: To investigate the effect of Alismatis rhizome (AR) extract on lipid profile in mice fed high-fat diet. METHODS: The study was performed in Key Laboratory of Chinese Medicine Resource and Compound Prescription (Hubei University of Chinese Medicine), Ministry of Education, Wuhan, China, between December 2009 and June 2010. Forty male Kunming mice (8-week-old) were randomly divided into 4 groups and were treated for 4 weeks: Group 1: normal control, Group 2: high-fat control, Group 3: positive control and Group 4: AR 2.26 g/kg. The hypolipidemic effects of AR were evaluated by serum lipids, liver lipids, and reverse transcriptase polymerase chain reaction. Serum aminotransferases and histopathological changes were also measured. RESULTS: Alismatis rhizome treatment resulted in an obvious decrease in serum and liver cholesterol, triglyceride along with elevated serum high-density lipoprotein cholesterol in hyperlipidemic mice. The histopathological results showed that adipose vacuoles in AR treated mice liver were almost identical to those of normal control mice. Serum alanine transaminase, aspartate aminotransferase and the relative liver weight in AR treated mice were decreased significantly. Alismatis rhizome substantially decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr), while the expressions of sterol regulatory element binding factor 2 (Srebf2) and cholesterol 7alpha-hydroxylase (Cyp7a1) were marginally affected. CONCLUSION: These results confirmed the efficacy of AR in the treatment of hyperlipidemia. Alismatis rhizome may act by decreasing the liver synthesis of cholesterol, rather than by increasing the cholesterol catabolism.