Swertia bimaculata moderated liver damage in mice by regulating intestine microbiota.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

Protection of Oxygen Glucose Deprivation-Induced Human Brain Vascular Pericyte Injury: Beneficial Effects of Bellidifolin in Cellular Pyroptosis.

Pericytes play critical roles in the maintenance of brain vascular homeostasis. However, very little is currently known about how pericytes regulate ischemic stroke-induced brain injury. Inflammation is a key event in the pathobiology of stroke, in which the nod-like receptor protein-3 (NLRP3) inflammasome is involved in, triggering sterile inflammatory responses and pyroptosis. In the current study, an immortalized cell line derived from human brain vascular pericytes (HBVPs) was constructed, and it showed that HBVPs challenged with oxygen glucose deprivation (OGD) displays pronounced cellular excretion of LDH, IL-1ß, IL-18 and increased PI positive staining. Mechanistically, upon OGD treatment, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein, containing a caspase recruitment domain (ASC) and caspase-1, manifested as much more co-stainings of NLRP3, ASC and Caspase-1 in HBVPs, accompanied by the increased protein levels of NLRP3, ASC, caspase-1 as well as the pyroptosis-associated protein gasdermin D (GSDMD). Intriguingly, GSDMD-N shuttled to the mitochondrial membrane triggered by OGD exposure, which promoted massive mitochondria-derived ROS generation. Importantly, the invention value of the specific targets was evaluated by treatment with bellidifolin, a kind of ketone compound derived from Swertia chirayita in traditional Tibetan medicine. It showed that bellidifolin exerts beneficial effects and attenuates the formation of NLRP3/ASC/Caspase-1 complex, thereby impeding GSDMD-N shuttling and resultant ROS generation, protecting against OGD-induced HBVPs pyroptosis. Overall, these findings unravel the potential mechanisms of pericyte injury induced by OGD and indicate that bellidifolin may exert its beneficial effects on pyroptosis, thus providing new therapeutic insights into stroke.

Rubioncolin C, a natural naphthohydroquinone dimer isolated from Rubia yunnanensis, inhibits the proliferation and metastasis by inducing ROS-mediated apoptotic and autophagic cell death in triple-negative breast cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubia yunnanensis Diels is a traditional Chinese medicine that has diverse pharmacological activities, including antituberculosis, antirheumatism and anticancers. Rubioncolin C (RC), a natural naphthohydroquinone dimer isolated from the roots and rhizomes of R. yunnanensis Diels, has shown potent antitumor activity. However, the antitumor activity and its potential mechanism of RC in triple-negative breast cancer (TNBC) cell lines remained unclear. AIM OF THE STUDY: This study was aim to investigate the anti-proliferation and anti-metastasis activity as well as the potential mechanism of RC on triple-negative breast cancer cells in vitro and in vivo. MATERIALS AND METHODS: The sulforhodamine B assay, colony formation assay and cell cycle analysis were used to determine the anti-proliferative activity of RC on TNBC. The anti-metastatic activity in vitro of RC was detected through the scratch wound assay, cell migration and invasion assays and gelatin zymography. The flow cytometry, JC-1, GFP-LC3B plasmid transfection, MDC, Lysotracker red and Carboxy-H2DCFDA, DHE, and MitoSOX™ Red staining were performed to investigate the effect of RC on apoptosis, autophagy and ROS level. The apoptosis inhibitor, autophagy inhibitors and ROS inhibitors were used to further verify the antitumor mechanism of RC. The protein levels related with cell cycle, apoptosis, and autophagy were examined with western blotting. In addition, the anti-tumor activity of RC in vivo was assessed in an experimental metastatic model. RESULTS: In the present study, RC suppressed the proliferation of TNBC cells in a time- and dose-dependent manner via regulating cell cycle. Further experiments showed that RC inhibited the migration and invasion of TNBC cells by downregulating MMPs and inhibiting EMT. Moreover, we demonstrated that RC induced obviously apoptotic and autophagic cell death, activated MAPK signaling pathway and inhibited mTOR/Akt/p70S6K and NF-κB signaling pathways. Furthermore, the excessive ROS was produced after treatment with RC. The antioxygen NAC and GSH could rescue the cell viability and reestablish the ability of cell metastasis, and inhibit the RC-induced apoptosis and autophagy. In a mice lung metastasis model of breast cancer, RC inhibited lung metastasis, and induced autophagy and apoptosis. CONCLUSION: These findings clarified the antitumor mechanism of RC on TNBC cell lines and suggested that RC is a key active ingredient for the cancer treatment of R. yunnanensis, which would help RC develop as a new potential chemotherapeutic agent for TNBC treatment.

Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-ß-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial.

BACKGROUND: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. OBJECTIVE: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. METHODS: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-ß peptide (Aß) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. RESULTS: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (-6.51, -10.57 to -2.45) compared to placebo. DHA lower the Aß40 levels (-40.57, -79.79 to -1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aß42 (-95.59, -150.76 to -40.43) and Aß40 levels (-45.75, -84.67 to -6.84) more than DHA (p < 0.05). CONCLUSION: Folic acid and DHA improve cognitive function and reduce blood Aß production in MCI patients. Combination therapy may be more beneficial in reducing blood Aß-related biomarkers.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis through Bcl-2/Bax Proteins Expression.

BACKGROUND: Deoxypodophyllotoxin, isolated from the Traditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant anti-tumor activity with strong toxicity in vitro and in vivo. OBJECTIVE: In this article, a series of deoxypodophyllotoxin derivatives were synthesized and their anti-tumor effectiveness was evaluated. METHODS: The anti-tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT assay method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. RESULTS: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29, and MG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. CONCLUSION: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Yan-Hou-Qing formula attenuates ammonia-induced acute pharyngitis in rats via inhibition of NF-κB and COX-2.

BACKGROUND: Yan Hou Qing (YHQ) is a Chinese medicinal formula designed to alleviate sore throat symptoms, but underlying mechanism of YHQ treatment for pharyngitis is poorly defined up to now. METHODS: In this study, the modulation of YHQ on pharyngitis is investigated in ammonia-induced acute pharyngitis rat models. After treatment with YHQ or dexamethasone respectively for five consecutive days, all rats were sacrificed for biomolecular and histopathologic study. Protein expressions of MAPKs, NF-κB, COX-2 and 5-LOX in pharyngitis tissue were evaluated by western blot analysis and the levels of TNF-α, IL-6, prostaglandin (PG) E2, leukotrienes (LT)-B4 and LT-D4 in pharyngeal tissue were measured via ELISA assay. Evans blue (EB) dye exudation test was performed parallelly to assess the integrity of pharyngeal tissue. RESULTS: Compared with normal control group, EB dye exudation, and inflammatory cytokines in the model group were significantly increased, and the pharynx tissue was obviously infiltrated by inflammatory cells. YHQ treatment improved the inflammatory infiltrate in pharyngeal tissue, and reduced EB dye exudation in AP rat models. The up-regulated TNF-α and IL-6 in pharyngeal tissue of AP were significantly reduced by YHQ through inhibition of phosphorylation of p38, Erk and NF-κB. YHQ treatment also reversed the increased level of PGE2 through down-regulation of COX-2. CONCLUSIONS: YHQ formula attenuated the pharyngitis related symptoms via suppression of COX-2 and phosphorylation of p38, Erk and NF-κB (p65).

Therapeutic assessment of fractions of Gastrodiae Rhizoma on chronic atrophic gastritis by 1H NMR-based metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

[UPLC-Q-TOF-MS analysis on chemical constituents of classical prescription Huangqi Guizhi Wuwu Tang standard decoction].

UPLC-Q-TOF-MS technology was used to analyze the chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction. Acquity HSS T3 column(2.1 mm × 100 mm, 1.8 µm) was used as the chromatographic column, with 0.1% formic acid solution-0.1% formic acid acetonitrile as the mobile phase for gradient elution. The volume flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry data of Huangqi Guizhi Wuwu Tang standard decoction were collected in positive and negative ion modes. The chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction were analyzed and identified by Masslynx 4.1 software combined with SciFinder database, comparison with reference mate-rials, mass spectrometry data analysis and reference to relevant literature. A total of 110 compounds were analyzed and identified, including 33 flavonoids, 14 monoterpene glycosides, 8 triterpenoids, 8 gingerols, 17 phenylpropanoids, 12 organic acids, 7 amino acids and 11 other compounds. The results of this study provide an experimental basis for the further research on the substance basis and quality control of Huangqi Guizhi Wuwu Tang standard decoction.

Bioactive constituents from Salacia cochinchinensis.

Two new isopimarane diterpenoids, named 1α-hydroxy-7-oxoisopimara-8, 15-diene (1), 11ß-hydroxy-7-oxoisopimara-8(14), 15-diene (2), together with six known compounds (3-8), were isolated from the medicinal plant Salacia cochinchinensis. All isolates were assayed for their cytotoxicity and α-glucosidase inhibitory activity. Results suggested compounds 1, 3 possessed significant cytotoxic activity against HepG2, HL60, and Hela cell lines with IC50 values ranging from 0.23 to 0.35 µM, and compounds 7, 8 exhibited noticeable α-glucosidase inhibitory ability with IC50 values of 0.25 and 0.31 µM, respectively.

Bioactive glycosides from Salacia cochinchinensis.

Four new triterpene glycosides, named salaciacochinosides A-D (1-4) were isolated from the 90% ethanol extract of Salacia cochinchinensis, together with five known compounds 2α,3ß,23-trihydroxyurs-12,18-dien-28-oic acid 28-O-ß-d-glucopyranoside (5), racemiside (6), alangiplatanoside (7), acantrifoside E (8), and syringin (9). The structures of the four new triterpenoids were characterized by chemical methods and MS, IR, 1D and 2D NMR spectral analyses. The α-glucosidase inhibitory activities of the nine compounds were assessed, compounds 6 and 7 showed remarkable α-glucosidase inhibitory activities, with IC50 values of 0.44 and 0.75 µM, respectively. Compounds 1-5 exhibited moderate α-glucosidase inhibitory activities, and compounds 8 and 9 showed none α-glucosidase inhibitory activity in our current experiments.

[A new phenolic glycoside from honey-fried Eriobotrya japonica].

A total of twelve compounds were isolated from the ethyl acetate of the water extract of honey-fried Eriobotrya japonica through column chromatography over silica gel,Sephadex LH-20,RP-18,and preparative HPLC. Their structures were established by MS,1 D NMR and 2 D NMR data as japonicanoside A( 1),nerolidol-3-O-α-L-rhamnopyranosyl-( 1→2)-ß-D-glucopyranoside( 2),nerolidol-3-O-α-L-rhamnopyranosyl-( l→4)-α-L-rhamnopyranosyl-( 1 → 2)-[α-L-( 4-trans-feruloyl)-rhamnopyranosyl-( 1 → 6) ]-ß-D-glucopyranoside( 3),( +)-catechin( 4),(-)-epicatechin( 5),kaempferol 3-O-α-L-rhamnopyranoside( 6),quercitrin( 7),quercetin-3-O-ß-D-galactopyranoside( 8),quercetin-3-O-ß-glucopyranoside( 9),vanillin( 10),protocatechuic aldehyde( 11),and maltol( 12). Among them,1 is a new phenolic glycoside.

[Chemical constituent analysis for seeds of Celosia argentea by UPLC-ESI-Q-TOF-MS].

This Paper aimed to analyze and identify the chemical constituents from the seeds of Celosia argentea by UPLC-ESI-Q-TOF-MS. The analysis was performed on an ACQUITY HSS T3 reverse phase column(2.1 mm ×100 mm, 1.8 µm). The mobile phase consisting of 0.1% formic acid acetonitrile and 0.1% aqueous formic acid was used for gradient elution, and the flow rate was 0.4 mL·min~(-1). Mass spectrometry was applied for the qualitative analysis under positive and negative ionization modes and ESI ion source. Data was analyzed by Masslynx 4.1 software, literatures in SciFinder database, and standards. A total of 49 compounds, including 14 triterpenoids, 17 flavonoids, 11 cyclic peptides, 2 phenols, 2 organic acids, and 3 steroids were putatively identified. Among them, 19 compounds were firstly reported from this species. In-depth chemical constituent analysis for the seeds of C. argentea were accomplished here, and the findings could lay a good foundation for its quality control and clarifying the material basis of its efficacy.

Anti-inflammation action of xanthones from Swertia chirayita by regulating COX-2/NF-κB/MAPKs/Akt signaling pathways in RAW 264.7 macrophage cells.

BACKGROUND: Swertia chirayita, has been commonly used under the name "Zang-yin-chen" for the treatment of liver infections, inflammation, abdominal pain, and bacterial infection in traditional Tibetan medicine. However, the bioactive components with anti-inflammatory activities and underlying mechanisms remain poorly evaluated. STUDY DESIGN/METHODS: Repeated column chromatography yielded two main xanthones from petroleum ether (PE) and ethyl acetate fractions of whole plants of S. chirayita, and their structures were determined as bellidifolin (1) and swerchirin (2) on the basis of spectroscopic data and literature analysis. The anti-inflammatory activities and mechanisms of anti-inflammation of these two isolated xanthones were determined via enzyme-linked immunosorbent assay (ELISA) and western blot in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages in vitro. RESULTS: Anti-inflammation assay demonstrated that 1 and 2 inhibit the production of the pro-inflammatory cytokines interleukin-6 (IL-6) and TNF-α in LPS-stimulated RAW 264.7 macrophages. Xanthone 1 also potently inhibited the production of prostaglandin E2 (PGE2) by suppressing the protein expression of cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Western blot showed that the phosphorylation of c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPKs were remarkably attenuated by 1 in a concentration-dependent manner. Particularly, Compound 1 suppressed the phosphorylation of the inhibitor κB kinase-ß (IKK-ß), Akt, and p65 subunit of nuclear factor-kappaB (NF-κB). CONCLUSION: The potent suppressive effects of 1 from S. chirayita on inflammatory mediators by blocking the expression of COX-2 and phosphorylation of Akt, IKK-ß, MAPK and NF-κB, activation in LPS-stimulated macrophages suggest that 1 can be a preventive therapeutic candidate for the management of inflammatory-mediated immune disorders.

NF-κB and JNK mediated apoptosis and G0/G1 arrest of HeLa cells induced by rubiarbonol G, an arborinane-type triterpenoid from Rubia yunnanensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubia yunnanensis is a medicinal plant mainly grown in Yunnan province in Southwest China, and its root named "Xiaohongshen" has been used as a herb in Yunnan for the treatment of cancers. Three major types of chemical components, Rubiaceae-type cyclopeptides, quinones, and triterpenoids, were identified from R. yunnanensis, in which some of compounds including rubiarbonol G (RG), a unique arboriane-type triterpenoid, showed cytotoxicity on cancer cells. But the cytotoxic mechanism of RG has not been reported. AIM OF THE STUDY: To investigate the cytotoxic mechanism of RG on cancer cells. MATERIALS AND METHODS: RG was evaluated its cytotoxicity on 7 cancer cell lines by the SRB assay, and detected the effect on apoptosis and cell cycle arrest by Annexin V-FITC/PI apoptosis assay and DNA contents analysis. The expression and activity of apoptosis and cell cycle related proteins were also investigated by western blot and caspase activity assay. Furthermore, the effect of RG on NF-κB signaling was also tested by luciferase assay, western blot, and immunofluorescence staining. RESULTS: RG showed potent cytotoxicity on 7 human cancer cell lines, whose activity was attributed to apoptosis induction and G0/G1 arrest in HeLa cells. Results from the mechanism study showed that RG promoted the activation of ERK1/2 and JNK pathway in MAPK family, which in turn increased the expression of p53, thereby triggering the G0/G1 arrest through p53/p21/cyclin D1 signaling. Moreover, RG-mediated JNK activation down-regulated the expression of the anti-apoptotic protein Bcl-2, which caused the release of cytochrome c to the cytosol and activated the cleavage of caspase cascade and poly(ADP-ribose) polymerase, thereby inducing apoptosis in HeLa cells. In addition, RG was also found to inhibit the activation of NF-κB signaling by down-regulating the expression and attenuating the translocation to nucleus of NF-κB p65, by which the down-stream p53, cyclin D1, Bcl-2, and caspases were regulated, thereby triggering apoptosis and G0/G1 arrest in HeLa cells. CONCLUSION: These results indicated that RG induces mitochondria-mediated apoptosis and G0/G1 cell cycle arrest by activation of JNK signaling as well as inactivation of NF-κB pathway in HeLa cells, which suggests that RG is one of the key active ingredients accounting for the anti-tumor effect of R. yunnanensis.

[Chemical constituents from petroleum ether fraction of Swertia chirayita and their activities in vitro].

The present work is to study the chemical constituents from petroleum ether fraction of Tibetan medicine Swertia chirayita by column chromatography and recrystallization. The structures were identified by physical and chemical properties and spectral data as swerchirin (1), decussatin (2), 1,8-dihydroxy-3,5,7-trimethoxyxanthone (3), 1-hydroxy-3,5,7,8-tetramethoxyxanthone (4), bellidifolin (5), 1-hydroxy-3, 7-dimethoxyxanthone (6), methylswertianin (7), 1-hydroxy-3,5-dimethoxyxanthone (8), erythrodiol (9), oleanolic acid (10), gnetiolactone (11), scopoletin (12), sinapaldehyde (13), syringaldehyde (14), and ß-sitosterol (15). Compounds 3, 4, 9, 11-14 were isolated from S. chirayita for the first time. Compounds 9 and 12 were firstly isolated from the genus Swertia. The cytotoxic activities of compounds 1, 2, 5, 7 and 8 against human pancreatic cancer cell lines SW1990 and BxPC-3,and the protective effects of these compounds against hydrogen peroxide (H2O2)-induced oxidative stress in human endothelium-derived EA.hy926 were investigated in vitro. The results showed no obvious effect at the high concentration of 50 µmol•L⁻¹.

Dalbergioidin Ameliorates Doxorubicin-Induced Renal Fibrosis by Suppressing the TGF-ß Signal Pathway.

We investigated the effect of Dalbergioidin (DAL), a well-known natural product extracted from Uraria crinita, on doxorubicin- (DXR-) induced renal fibrosis in mice. The mice were pretreated for 7 days with DAL followed by a single injection of DXR (10 mg/kg) via the tail vein. Renal function was analyzed 5 weeks after DXR treatment. DXR caused nephrotoxicity. The symptoms of nephrotic syndrome were greatly improved after DAL treatment. The indices of renal fibrosis, the phosphorylation of Smad3, and the expression of alpha-smooth muscle actin (α-SMA), fibronectin, collagen III (Col III), E-cadherin, TGF-ß, and Smad7 in response to DXR were all similarly modified by DAL. The present findings suggest that DAL improved the markers for kidney damage investigated in this model of DXR-induced experimental nephrotoxicity.

Apoptosis induction and G2/M arrest of 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone from Rubia yunnanensis in human cervical cancer Hela cells.

2-Methyl-1,3,6-trihydroxy-9,10-anthraquinone (MTA), one of the major components isolated from the traditional Chinese medicine Rubia yunnanensis, exhibited inhibitory activity on the proliferation of several human cancer cell lines. The results from an annexin V-FITC (fluoresein-5-isothiocyanate) apoptosis assay and DNA content analysis showed that MTA exerted cytotoxicity via apoptosis induction and G2/M cell cycle arrest in human cervical carcinoma HeLa cells. Further, MTA was found to induce apoptosis of HeLa cells through the mitochondria-mediated pathway. It caused the translocation of Bax to the mitochondria and release of cytochrome c into the cytosol, which caused the cleavage of caspase and poly(ADP-ribose) polymerase and finally triggered the apoptosis. Furthermore, the p53/p21/Cdc2-cyclin B1 signaling was found related to the G2/M arrest caused by MTA. The over-expression of p21 and down-expression of cyclin B1 caused by MTA inactivated the Cdc2-cyclin B1 complex of G2/M checkpoint and finally caused the G2/M arrest in HeLa cells. This study demonstrated that MTA is a potential anti-cancer component of R. yunnanensis, a folk anti-cancer herb used in Yunnan, China.

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction.

In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT.

[Cyclopeptides from Rubia schumanniana].

OBJECTIVE: To separate and identify cyclopeptides of tubers of Rubia schumanniana. METHOD: The 70% methanol extracts from tubers of Rubia schumanniana were separated and purified by silica gel, RP-18, Sephedax LH-20 and HPLC. Their structures were identified by spectral analysis. RESULT: Nine cyclopeptides were separated and identified as RA- II (1), RA-V (2), RA-VIII (3), rubiyunnanin C (4), RA-X (5), RY-II (6), RA- I (7), RA-XIII (8) and RA-XIII-OMe (9), respectively. CONCLUSION: All of nine cyclopeptides were separated from R. schumanniana for the first time.

Isolation, identification and antioxidative capacity of water-soluble phenylpropanoid compounds from Rhodiola crenulata.

Six water-soluble phenylpropanoid compounds obtained from Rhodiola crenulata (R. crenulata) were fractionated by high-speed counter-current chromatography (HSCCC), and purified by semi-preparative high-performance liquid chromatography (Semi-prep HPLC). The purities of the six compounds were all above 98.0% and their structures were identified by spectroscopic methods. Among them, a new compound, 2-(4-hydroxyphenyl)-ethyl-O-ß-D-glucopyranosyl-6-O-ß-D-glucopyranoside (1), together with two known phenylpropanoids, p-hydroxyphenacyl-ß-D-glucopyranoside (3) and picein (4) were isolated from R. crenulata for the first time. Meanwhile, the contents of six isolated ingredients from the crude extract of R. crenulata had been simultaneously detected, with satisfactory results. Furthermore, the antioxidant activities of the six compounds were accessed by measuring the radical scavenging activity against 2,2-diphenyl-1-picrylhydrazy (DPPH), and four compounds exhibited potent antioxidative activity.