Scorpion Venom Heat-Resistant Synthesized Peptide Increases Stress Resistance and Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1-Like Signal Pathway.

Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect Caenorhabditis elegans (C. elegans) against ß-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat-resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used C. elegans as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP in vivo. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation in vivo. Using gene-specific mutation of C. elegans, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.

Hydroxysafflor Yellow A Attenuates Lipopolysaccharide-Induced Neurotoxicity and Neuroinflammation in Primary Mesencephalic Cultures.

Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson's disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius. The purpose of this study was to investigate whether HSYA could attenuate LPS-induced neurotoxicity and neuroinflammation in primary mesencephalic cultures. Cell viability was measured by MTT and LDH assays. The number of tyrosine hydroxylase (TH) positive neuron was observed by immunohistochemistry. NF-κB p65 and iNOS expressions were evaluated with western blotting method. Pro-inflammatory cytokines including IL-1ß and TNF-α were determined by ELISA kits. Nitric oxide (NO) content in the culture medium was assayed. The results showed that HSYA treatment significantly attenuated the LPS-induced dopaminergic neurons damage. HSYA partially inhibited the expressions of NF-κB p65 and iNOS. Furthermore, HSYA decreased the content of IL-1ß, TNF-α and NO in the supernatants. Taken together, these results suggest that HSYA exerts protective effects on LPS-induced neurotoxicity in dopaminergic neurons and the mechanisms may be associated with the inhibition of inflammatory response.

Effects of the oligostilbenes from Iris lactea Pall. var. chinensis (Fisch.) Koidz on the adipocytes differentiation of 3T3-L1 cells.

The dried seeds of Iris lactea Pall. var. chinensis (Fisch.) Koidz, an important traditional Chinese medicine, are regarded to have effects of clearing heat, eliminating dampness and pharyngitis and so on. It has been used in the treatment of jaundice, diarrhea, leucorrhea and carbuncles. Previous phytochemical studies of Iris species showed the presence of flavones, isoflavones, triterpenes and stilbenes. In our previous research, we isolated five known oligostilbenes, vitisin A, vitisin B, vitisin C, vitisin D, and cis-vitisin A were successfully isolated from Iris lactea for the first time. The aim of this study was to assess the effects of these oligostilbenes on the differentiation and adipogenes in 3T3-L1 cells. Our results showed that vitisin A, vitisin B, cis-vitisin A significantly inhibited adipocytes differentiation and reduced lipid accumulation in 3T3-L1 cells. In addition, vitisin A, vitisin B, cis-vitisin A strongly suppressed the expression levels of adipocyte-specific genes including peroxisome proliferator activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα) and adipocyte fatty acid binding protein 4 (FABP4). In contrast, vitisin C and vitisin D significantly promoted adipogenesis and increased intracellular lipid accumulation, while the two oligostilbenes markedly increased the expression of adipocyte marker genes. In the present study, we found that vitisin A, vitisin B and cis-vitisin A inhibit the adipogenesis and adipocytes differentiation by their influence on the expression of PPARγ, which leads to subsequenet downregulation of PPARγ mediated adipocyte-specific gene during adipogenesis.

Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated ß-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.

Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 µmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated ß-catenin (p-ß-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-ß-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).

Two new flavonoid glycosides from the halophyte Limonium franchetii.

Two new flavonoid glycosides, named quercetin-3-O-(2″-O-tigloyl)-α-L-rhamnopyranoside (1) and quercetin-3-O-(3″-O-tigloyl)-α-L-rhamnopyranoside (2), together with 10 known flavonoids (3-12), were isolated from the whole plant of the halophyte Limonium franchetii. Their structures were elucidated on the basis of extensive spectroscopic analysis including 2D NMR and HR-EI-MS. In addition, primary bioassays showed that compound 1 had moderate cytotoxic activity against rat C6 glioma cell lines.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

Cardioprotective Effects of 20(S)-Ginsenoside Rh2 against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin (DOX) is considered as one of the best antineoplastic agents. However, its clinical use is restricted by its associated cardiotoxicity, which is mediated by the production of reactive oxygen species. In this study, 20(S)-ginsenoside Rh2 (Rh2) was explored whether it had protective effects against DOX-induced cardiotoxicity. In vitro study on H9C2 cell line, as well as in vivo investigation in one mouse and one rat model of DOX-induced cardiomyopathy, was carried out. The results showed that pretreatment with Rh2 significantly increased the viability of DOX-injured H9C2 cells. In the mouse model, Rh2 could suppress the DOX-induced release of the cardiac enzymes into serum and improved the occurred pathological changes through ameliorating the decreased antioxidant biomolecules and the cumulated lipid peroxidation malondialdehyde in heart tissues. In the rat model, Rh2 could attenuate the change of ECG resulting from DOX administration. Furthermore, Rh2 enhanced the antitumor activity of DOX in A549 cells. Our findings thus demonstrated that Rh2 pretreatment could effectively alleviate heart injury induced by DOX, and Rh2 might act as a novel protective agent in the clinical usefulness of DOX.

Green tea and incidence of colorectal cancer: evidence from prospective cohort studies.

A systematic meta-analysis of prospective cohort studies on green tea consumption and colorectal cancer was performed to determine whether green tea has a chemopreventive effect against colorectal cancer. Six eligible cohort studies involving 352,275 participants and 1675 cases of colorectal cancer were identified. Combined relative risk (RR) ratios for the highest vs. lowest and increment of 1 cup/day green tea consumption levels were calculated. The combined RR of 0.90 (95% CI: 0.72-1.08) was found comparing highest vs. lowest green tea consumption levels for colorectal cancer. No significant differences by cancer-site were found, but an inverse association between green tea and incidence of colorectal cancer (RR: 0.70; 95% CI: 0.55-0.85) and colon cancer (RR: 0.69; 95% CI: 0.48-0.98) was demonstrated in Shanghai population. Singapore men had a higher risk of colorectal cancer (RR: 1.36; 95% CI: 1.06-1.74). Furthermore, an increase in green tea consumption of 1 cup/day was not associated with incidence of colorectal cancer (RR: 0.97; 95% CI: 0.91-1.03). Despite the limited evidence from Shanghai studies in support of green tea as potential chemopreventive agents against colorectal cancer, available data from prospective cohort studies are insufficient to conclude that green tea may protect against colorectal cancer.

Tirucallane-type triterpenoids from Dysoxylum lenticellatum.

Ten new tirucallane-type triterpenoids, represented by a rearranged skeleton dysolenticin A (1), dysolenticin B (2), a rare trinortriterpenoid dysolenticin C (3), three tirucallane triterpenoid derivatives with a hemiketal moiety dysolenticins D-F (4-6), dysolenticins G-I (7, 9, 10), and the new alkaloid dysolenticin J (12), together with seven known analogues were isolated from the twigs and leaves of Dysoxylum lenticellatum. Their structures were elucidated by extensive spectroscopic methods, and those of compounds 1, 3, 4, 6, and 10 were confirmed by single-crystal X-ray diffraction experiments. Dysolenticin J (12) showed significant vasodilative effects on intact rat aortic rings with a diastolic degree of 87.4% at 10 µg/mL.

Study of the relationship between carotid intima-media thickness and traditional Chinese medicine syndrome of dyslipidemia.

OBJECTIVE: The study aimed to explore the relationship between the carotid intima-media thickness (IMT), lipids, high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy) and other indices of laboratory and the traditional Chinese medicine (TCM) syndrome of dyslipidemia. METHODS: A total of 152 dyslipidemia patients and 8 healthy people (taken as the control group) were recruited. According to the theory of the TCM syndrome, 152 dyslipidemia patients were assigned to 4 groups: the stagnation of phlegm (SP) group, the blood stasis blocking channels (BSBC) group, the stagnation of phlegm and blood (SPB) group and the non-stagnation of phlegm and blood (NSPB) group. The carotid ultrasonic test, hs-CRP, Hcy, blood rheology and blood lipids were examined for all the recruited patients. The relationships among carotid IMT, laboratory indices and TCM syndrome of dyslipidemia were analyzed by the methods of F test and multiple linear regressions. RESULTS: (1) Carotid IMT was significantly different among groups of healthy people and different TCM syndromes. The sequence from lowest to highest was: healthy group, NSPB group, SP group, SPB group and BSBC group. (2) Triglyceride (TG) and blood rheology were significantly different between the groups of healthy people and different TCM syndromes. Among different TCM syndrome groups, TG and blood rheology in the NSPB group were the lowest, but were the highest in SPB group. (3) Hcy, very low density lipoprotein and TG were correlated with atherosclerosis of the carotid. CONCLUSION: Carotid IMT, TG and blood rheology were closely correlated with the TCM syndrome of dyslipidemia. Atherosclerosis of the carotids would be prone to occur if one of these factors was heightened.

[Study on rules of TCM syndrome in patients with dyslipidemia and its objectization].

OBJECTIVE: To explore the rules of TCM syndrome in patients with dyslipidemia and its relation with C-reactive protein (CRP), homocysteine (Hcy), carotid ultrasonic picture, blood lipids and blood viscosity. METHODS: From 152 recruited patients symptoms and physical signs (including figures of tongue and pulse) were selected and analyzed in grading and quantifying by factor analysis. At the same time, blood lipids, CRP, Hcy, carotid ultrasonic picture and blood viscosity were detected to conduct a canonical correlation analysis for exploring the relationship between different TCM syndromes and their corresponding physical and/or chemical indexes. RESULTS: Five types of TCM syndrome obtained by factor analysis were syndrome of Shen-yin deficiency (I), Pi-qi deficiency (II), turbid-phlegm impediment (III), blood stasis (IV), and phlegm-blood block (V). By canonical correlation analysis, they were characterized with: Type I, high levels of CRP and blood viscosity; Type II, high level of very low-density lipoprotein cholesterol (VLDL-C); Type III, high level of total cholesterol (TC) and low level of high-density lipoprotein cholesterol (HDL-C); and Type V, high level of Hcy. CONCLUSION: The five syndrome types frequently found in patients with dyslipidemia are syndrome of Shen-yin deficiency, Pi-qi deficiency, turbid-phlegm impediment, blood stasis, and phlegm-blood block. Different syndrome has its own correlation with some corresponding physical and/or chemical laboratory indexes, the issue provides new evidences for the objectification of TCM syndromes in patients with dyslipidemia.

[Study on tissue culture and plant regeneration of Nervilia fordii].

OBJECTIVE: Tissue culture of Nervilia fordii to get its regeneration. METHOD: Effects on indusement of rhizoma and plant regeneration of different implants, density of hormones, additives were studied. RESULT: The best implant was conn. Effect of 6-BA 2 mg x L(-1) were better than 6-BA 1 on rhizoma reducing. The coconut juice and active carbon could increase the growth of rhizoma. CONCLUSION: Bud could be induced on 1/2MS + 6-BA 2 mg x L(-1) by inoculating corm on culture mediem, and could grow lots of rhizoma after inoculating on the culture mediem containing 10% coconut juice and 1 per thousand active carbon. The white rhizoma could be induced to corms and regeneration plants on 1/2MS + 1 per thousand active carbon. The green rhizoma could be induced directerly to regeneration plants on 1/2MS + 6-BA 2 + NAA 2.

[Protective effect of hydroxysafflor yellow A on experimental cerebral ischemia in rats].

AIM: To investigate the protective effect of hydroxysafflor yellow A (HSYA), a soluble element extracted from Carthamus tinctorius L., on focal cerebral ischemia in rats. METHODS: Focal cerebral ischemia in male Wistar-Kyoto (WKY) rats were induced by permanent middle cerebral artery occlusion (MCAO). Three doses of 1.5, 3.0 and 6.0 mg x kg(-1) of HSYA were administrated to three groups of rats, separately, via sublingular vein injection 30 min after the onset of ischemia. 24 h after ischemia in rats, neurological deficit scores were evaluated and the infarction area of brain was assessed by quantitative image analysis. The in vitro neuroprotective effect of HSYA was tested in cultured fetal cortical neurons exposed to glutamate and sodium cyanide (NaCN). RESULTS: HSYA at doses of 3.0 and 6.0 mg x kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury as expressed by neurological deficit scores and reduced the infarct area as compared with saline group, and the potency of HSYA at dose of 6.0 mg x kg(-1) was similar to that of 0.2 mg x kg(-1) of nimodipine. In vitro studies, HSYA significantly inhibited neurons damage induced by exposure to glutamate and NaCN in cultured fetal cortical cells. CONCLUSION: HSYA has potential neuroprotective action against focal cerebral ischemia in rats and cultured rat fetal cortical neurons as well.

[Alkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium].

AIM: To study the alkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium L. METHODS: Isolation and purification were carried out on silica gel and HPLC; the structures of chemical constituents were elucidated by spectral analysis. RESULTS: From the alkaline-degradation products, nine compounds were identified as: 20 (S) -protopanaxadiol (I), 20 (S) -dammar-25 (26)-ene-3beta, 12beta, 20-triol (II), 24 (R) -ocotillol (III), 20 (S) -protopanaxatriol (IV), 20 (S) -dammar-25 (26)-ene-3beta, 6alpha, 12beta, 20-tetrol (V), dammar-20 (21), 24-diene-3beta, 12beta-diol (VI), dammar-20(21), 24-diene-3beta, 6alpha, 12beta-triol (VII), 20 (S), 24 (S) -dammar-25 (26) -ene-3beta, 6alpha, 12beta, 20, 24-pentanol (VIII), 20 (S) -dammar-23-ene-25-hydroperoxyl-3beta, 6alpha, 12beta, 20-tetrol (IX). CONCLUSION: The configuration of C20 position of ginsenosides was not changed by alkaline-degradation. The complete assignments of 1H and 13C NMR chemical shifts of four new compounds V, VII, VIII, IX, were acquired by means of 2D NMR spectra. Compound I showed antitumor effect on human colon carcinoma cells in vitro.