Publications by authors named "Wei-Min Zhao"

61 Publications

Anomalous Superconducting Proximity Effect in Bi Se /FeSe Te Thin-Film Heterojunctions.

Adv Mater 2021 Nov 24:e2107799. Epub 2021 Nov 24.

National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China.

Superconducting proximity effect (SPE) induces superconductivity transition in the otherwise non superconducting thin-film in proximity with a superconductor. The SPE usually occurs in real space and decays exponentially with the film thickness. Herein, we unveiled an abnormal SPE in a topological insulator (TI)/superconductor heterostructure, which is attributed to the topologically protected surface state. Surprisingly, such abnormal SPE occurs in momentum space regardless the TI film thickness, as long as the topological surface states are robust and form a continuous conduction loop. Combining transport measurements and scanning tunneling microscopy/spectroscopy techniques, we explored the SPE in Bi Se /FeSe Te heterostructures, where Bi Se is an ideal three-dimensional topological insulator and FeSe Te a typical iron-based superconductor. As the thickness of the Bi Se thin-film exceeds 400 nanometers, there still exits SPE-induced superconductivity on the surface of Bi Se thin-film with a transition temperature T not less than 10 K. Such an extraordinary behavior is induced by the unique properties of topologically protected surface states of Bi Se . This research will deepen the understanding of important role of topologically protected surface states in the SPE. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202107799DOI Listing
November 2021

Minor immunosuppressive spiroorthoester group-containing pregnane glycosides from the root barks of Periploca sepium.

Bioorg Chem 2021 03 12;108:104641. Epub 2021 Jan 12.

Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, People's Republic of China. Electronic address:

LC-MS guided chemical investigation of the periploside-rich extract of the root barks of Periploca sepium afforded six new minor pregnane glycosides, named periplosides A1-A6 (1-6). Their structures were characterized on the basis of extensive spectroscopic analysis. Compounds 1-6 were evaluated for their inhibitory activities against the proliferation of T and B lymphocytes in vitro, among them, compound 5 exhibited significant inhibitory activities and the most favorite selective index (SI) values against the proliferation of T lymphocyte (IC = 0.30 μM, SI = 176) and B lymphocyte (IC = 0.55 μM, SI = 97).
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http://dx.doi.org/10.1016/j.bioorg.2021.104641DOI Listing
March 2021

Diterpenoids from the seeds of Euphorbia lathyris and their effects on microglial nitric oxide production.

Fitoterapia 2021 Apr 26;150:104834. Epub 2021 Jan 26.

Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, People's Republic of China. Electronic address:

Four new lathyrane-type diterpenoids (1-4) and a novel macrocyclic diterpenoid (5) featuring a 5/7/7/4-fused ring system, together with seventeen known ones (6-22), were isolated from the seeds of Euphorbia lathyris. Their structures were elucidated by extensive spectroscopic analyses and single crystal X-ray crystallography. These isolates were evaluated for their inhibition against nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells. As a result, the inhibitory rates of compounds 1, 3, 4, 6, 7, 9-11, 13-15, 20, and 21 on NO production were more than 40% with the cell viability more than 80% at their effective concentrations. In addition, compounds 6 and 11 markedly reduced the mRNA levels of pro-inflammatory cytokines IL-6 and IL-1β in LPS-stimulated BV-2 cells.
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http://dx.doi.org/10.1016/j.fitote.2021.104834DOI Listing
April 2021

Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis.

Neurochem Res 2021 Mar 3;46(3):686-698. Epub 2021 Jan 3.

Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.
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http://dx.doi.org/10.1007/s11064-020-03202-zDOI Listing
March 2021

Anti-nociceptive, anti-inflammatory and anti-arthritic activities of pregnane glycosides from the root bark of Periploca sepium Bunge.

J Ethnopharmacol 2021 Jan 3;265:113345. Epub 2020 Sep 3.

Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. Electronic address:

Ethnopharmacological Relevance: Periploca sepium Bunge (P. sepium) is used in traditional Chinese medicine (TCM) for the treatment of autoimmune diseases, particularly rheumatoid arthritis. Periploca sepium periplosides (PePs), isolated from the root bark of P. sepium, characterized as the cardiac glycosides-free pregnane glycosides fraction, is expected to possess therapeutic potential on inflammatory arthritis.

Aim Of The Study: The current study is designed to evaluate the anti-nociceptive, anti-inflammatory and anti-arthritic activities effects of the PePs.

Materials And Methods: The anti-nociceptive activity of PePs was examined in the writhing test and hot-plate test in mice. The anti-inflammatory activity of PePs was determined by the 2, 4-dinitro-1-fluorobenzene (DNFB)-induced ear edema model and the carrageenan induced paw edema model in mice. The anti-arthritic activity of PePs was investigated by evaluating the joint inflammation and arthritis pathology in rat adjuvant induced arthritis (AIA) and murine collagen induced arthritis (CIA). Phytohaemagglutinin M (PHA-M) -elicited human peripheral blood mononuclear cells (PBMCs) were further applied to assess the suppressive activity of PePs on IFN-γ and IL-17 production.

Results: PePs treatment markedly decreased the acetic acid-induced visceral nociceptive response and increased the hot-plate pain threshold. Further, oral administration of PePs exhibited anti-inflammatory activity by decreasing DNFB-induced ear edema in mice and carrageenan-induced paw edema in rats. Moreover, oral treatment of PePs ameliorated joint swelling and attenuated bone erosion in rodent arthritis, and the therapeutic benefits were partially attributed to the suppression of proinflammatory cytokines such IFN-γ and IL-17. Moreover, PePs suppressed the proliferation as well as IFN-γ and IL-17 secretion in PHA-M-elicited human PBMCs in a concentration dependent manner.

Conclusions: Taken together, our results justified the traditional use of Periploca sepium Bunge for the treatment of diseases associated with inflammation and pain.
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http://dx.doi.org/10.1016/j.jep.2020.113345DOI Listing
January 2021

Zhu et al. Reply.

Phys Rev Lett 2020 Aug;125(7):079702

National Laboratory of Solid State Microstructures and School of Physics, Nanjing University, Nanjing 210093, China.

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http://dx.doi.org/10.1103/PhysRevLett.125.079702DOI Listing
August 2020

Quasiparticle interference evidence of the topological Fermi arc states in chiral fermionic semimetal CoSi.

Sci Adv 2019 Dec 20;5(12):eaaw9485. Epub 2019 Dec 20.

National Laboratory of Solid State Microstructures, School of Physics, Nanjing University, Nanjing 210093, China.

Chiral fermions in solid state feature "Fermi arc" states, connecting the surface projections of the bulk chiral nodes. The surface Fermi arc is a signature of nontrivial bulk topology. Unconventional chiral fermions with an extensive Fermi arc traversing the whole Brillouin zone have been theoretically proposed in CoSi. Here, we use scanning tunneling microscopy/spectroscopy to investigate quasiparticle interference at various terminations of a CoSi single crystal. The observed surface states exhibit chiral fermion-originated characteristics. These reside on (001) and (011) but not (111) surfaces with p-rotation symmetry, spiral with energy, and disperse in a wide energy range from ~-200 to ~+400 mV. Owing to the high-energy and high-space resolution, a spin-orbit coupling-induced splitting of up to ~80 mV is identified. Our observations are corroborated by density functional theory and provide strong evidence that CoSi hosts the unconventional chiral fermions and the extensive Fermi arc states.
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http://dx.doi.org/10.1126/sciadv.aaw9485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989308PMC
December 2019

Realization of a Metallic State in 1T-TaS_{2} with Persisting Long-Range Order of a Charge Density Wave.

Phys Rev Lett 2019 Nov;123(20):206405

National Laboratory of Solid State Microstructures and School of Physics, Nanjing University, Nanjing 210093, China.

Metallization of 1T-TaS_{2} is generally initiated at the domain boundary of a charge density wave (CDW), at the expense of its long-range order. However, we demonstrate in this study that the metallization of 1T-TaS_{2} can be also realized without breaking the long-range CDW order upon surface alkali doping. By using scanning tunneling microscopy, we find the long-range CDW order is always persisting, and the metallization is instead associated with additional in-gap excitations. Interestingly, the in-gap excitation is near the top of the lower Hubbard band, in contrast to a conventional electron-doped Mott insulator where it is beneath the upper Hubbard band. In combination with the numerical calculations, we suggest that the appearance of the in-gap excitations near the lower Hubbard band is mainly due to the effectively reduced on-site Coulomb energy by the adsorbed alkali ions.
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http://dx.doi.org/10.1103/PhysRevLett.123.206405DOI Listing
November 2019

[Physiology and genetics research progress of teat traits in pigs].

Yi Chuan 2019 May;41(5):384-390

Jiangsu Germplasm Resources Protection and Utilization Platform, Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.

The pig teat traits are important indices of genetic improvement in pig breeding, which belong to reproductive traits and can directly affect the sows lactation rate and piglet survival rate. Understanding the genetic mechanism underlying the variation of teat traits is of immense value for the improvement of pig reproductive performance. However, the genetic mechanism underlying teat traits (including teat number, type, location distribution, and fluctuating asymmetry) remains elusive. In this review, we summarize the studies on physiology and genetics of teat traits in pigs, including the development process of the mammary gland, the QTL mapping, and candidate gene researches. This review aims to provide a new perspective for the identification of causal mutations and major genes affecting the teat traits and revealing the complex genetic mechanism of the differences in teat number, type and location distribution during embryonic development in pigs.
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http://dx.doi.org/10.16288/j.yczz.18-336DOI Listing
May 2019

Potential hypoglycemic effect of acetophenones from the root bark of .

Nat Prod Res 2019 Aug 25;33(16):2314-2321. Epub 2018 Feb 25.

b School of Pharmacy , Nantong University , Nantong , People's Republic of China.

Three new acetophenones, named cynwilforones A-C (-), together with cynandione A () were isolated from the root bark of (Maxim.) Hemsl. Their structures were deduced based on spectroscopic analysis and chemical methods. Compounds and exhibited potential hypoglycemic effects through inhibition of hepatic gluconeogenesis by down-regulating the expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. This is the first report that acetophenones from the root bark of possesses potential hypoglycemic activity .
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http://dx.doi.org/10.1080/14786419.2018.1443100DOI Listing
August 2019

Spiroorthoester group-containing pregnane glycosides from the root barks of Periploca chrysantha and their inhibitory activities against the proliferation of B and T lymphocytes.

Bioorg Med Chem Lett 2018 02 21;28(3):330-333. Epub 2017 Dec 21.

Department of Natural Products Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. Electronic address:

Phytochemical investigation of the root barks of Periploca chrysantha D. S. Yao, X. C. Chen et J. W. Ren (Asclepiadaceae) led to the elucidation of four new spiroorthoester group-containing pregnane glycosides (1-4), named periplosides W-Y and 3-O-formyl-periploside F. Their structures were elucidated on the basis of extensive spectroscopic analysis. The four new pregnane glycosides (1-4) were found to exhibit significantly inhibitory activities against the proliferation of B and T lymphocytes and favorable selective index comparable to those of cyclosporin A.
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http://dx.doi.org/10.1016/j.bmcl.2017.12.045DOI Listing
February 2018

C-steroidal glycosides and sesquiterpenes from the roots of Cynanchum bungei and their inhibitory activities against the proliferation of B and T lymphocytes.

Fitoterapia 2018 Jan 14;124:193-199. Epub 2017 Nov 14.

Department of Natural Products Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. Electronic address:

Phytochemical investigation of the roots of Cynanchum bungei Decne (Asclepiadaceae) led to the elucidation of seven C-steroidal glycosides (1-7) including three new compounds (1-3), named cynabungosides A-C, one new eudesmane-type sesquiterpene (8), named cynabungone, and one new humulane-type sesquiterpene (9), named cynabungolide. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations of 8 and 9 were defined unequivocally by ECD analysis and X-ray crystallography, respectively. A putative biosynthetic pathway of humulane-type sesquiterpenes 9 and 10 is proposed.
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http://dx.doi.org/10.1016/j.fitote.2017.11.014DOI Listing
January 2018

Effect of inhibiting Beclin-1 expression on autophagy, proliferation and apoptosis in colorectal cancer.

Oncol Lett 2017 Oct 28;14(4):4319-4324. Epub 2017 Jul 28.

Department of Abdominal Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.

The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay. The present study created 3 groups in the two cell lines, consisting of the targeting siRNA (TS) group, in which Beclin-1 was partially silenced, non-specific siRNA (NS) group and control group (CG; without transfection). By siRNA transfection, the mRNA and protein level of Beclin-1 in the TS group were significantly inhibited compared with the NS group and CG (P<0.05). After 0, 24, 48 and 72 h, the survival rate of the cells in the TS group was significantly decreased compared with the survival rate of the cells in the NS group and CG, as detected by CCK-8 methods (P<0.05). FCM and MTT results showed the apoptotic rate of the cells in the TS group was significantly decreased compared with the rate in the NS group and CG (P<0.05), and the proliferation of the cells in the NS group was evidently increased compared with the CG. In conclusion, Beclin-1 played an important role in regulating autophagy, proliferation and apoptosis in HCT116 and SW620 cells. The inhibition of Beclin-1 by RNAi suppressed the autophagic activity and proliferation, but promoted apoptosis in CRC cells. Beclin-1 was the new target of gene therapy for CRC.
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http://dx.doi.org/10.3892/ol.2017.6687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620484PMC
October 2017

Aromatic monoterpenoid glycosides from the seeds of Paeonia ostii.

J Asian Nat Prod Res 2017 Dec 5;19(12):1149-1154. Epub 2017 Apr 5.

a Department of Natural Product Chemistry , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 , China.

Phytochemical investigation into the seeds of Paeonia ostii T. Hong et J. X. Zhang (Paeoniaceae) led to the identification of three new aromatic monoterpenoid glycosides, named paeostisides A-C (1-3), along with one known compound. Their structures were identified by spectroscopic analysis and chemical method.
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http://dx.doi.org/10.1080/10286020.2017.1307191DOI Listing
December 2017

Absolute Configuration of Periplosides C and F and Isolation of Minor Spiro-orthoester Group-Containing Pregnane-type Steroidal Glycosides from Periploca sepium and Their T-Lymphocyte Proliferation Inhibitory Activities.

J Nat Prod 2017 04 15;80(4):1102-1109. Epub 2017 Mar 15.

Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.

Further phytochemical investigation of the root bark of Periploca sepium afforded nine new spiro-orthoester group-containing pregnane-type glycosides termed periplosides O-V and 3-O-formyl-periploside A. The structures of these glycosides along with the absolute configuration of the unique seven-membered formyl acetal-bridged spiro-orthoester function and the 4,6-dideoxy-3-O-methyl-Δ-2-hexosulosyl moiety were elucidated on the basis of spectroscopic data interpretation and chemical transformation. The absolute configurations of the major compounds periplosides C and F were established by single-crystal X-ray diffraction analysis. The isolated compounds were evaluated for their inhibitory activities against the proliferation of T-lymphocytes. As a result, periploside C, the most abundant glycoside containing a spiro-orthoester moiety found in the plant, exhibited the most favorite selective index value (SI = 82.5). The length and constitution of the saccharide chain in the periplosides were found to influence the inhibitory activity and the SI value.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00017DOI Listing
April 2017

Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation.

Acta Pharmacol Sin 2017 Apr 20;38(4):459-468. Epub 2017 Feb 20.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 μmol/L) dose-dependently attenuated OGD- or HO-induced reduction of the viability of SH-SY5Y neuroblastoma cells. RABE pretreatment concurrently reduced the apoptotic cell rate, down-regulated the expression of the pro-apoptotic proteins Bax and p53, and up-regulated the expression of the anti-apoptotic protein phosphorylated death-associated protein kinase (DAPK). Furthermore, pretreatment with RABE (3 μmol/L) markedly inhibited lipopolysaccharide (LPS)-induced increases in the release of TNF-α, IL-1β, NO and PGE, and the expression levels of iNOS, and COX-2 in cultured rat microglial cells. In conclusion, these results reveal for the first time the potential anti-ischemic effects of RABE on neuronal and glial cells and elucidate the molecular mechanisms involved in its dual beneficial profiles in vitro. RABE may be a promising drug lead/candidate for the treatment of ischemic stroke.
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http://dx.doi.org/10.1038/aps.2016.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533207PMC
April 2017

Chlorogenic acid analogues from Gynura nepalensis protect H9c2 cardiomyoblasts against HO-induced apoptosis.

Acta Pharmacol Sin 2016 Nov 5;37(11):1413-1422. Epub 2016 Sep 5.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Aim: Chlorogenic acid has shown protective effect on cardiomyocytes against oxidative stress-induced damage. Herein, we evaluated nine caffeoylquinic acid analogues (1-9) isolated from the leaves of Gynura nepalensis for their protective effect against HO-induced H9c2 cardiomyoblast damage and explored the underlying mechanisms.

Methods: H9c2 cardiomyoblasts were exposed to HO (0.3 mmol/L) for 3 h, and cell viability was detected with MTT assay. Hoechst 33342 staining was performed to evaluate cell apoptosis. MMPs (mitochondrial membrane potentials) were measured using a JC-1 assay kit, and ROS (reactive oxygen species) generation was measured using CM-H DCFDA. The expression levels of relevant proteins were detected using Western blot analysis.

Results: Exposure to HO markedly decreased the viability of H9c2 cells and catalase activity, and increased LDH release and intracellular ROS production; accompanied by a loss of MMP and increased apoptotic rate. Among the 9 chlorogenic acid analogues as well as the positive control drug epigallocatechin gallate (EGCG) tested, compound 6 (3,5-dicaffeoylquinic acid ethyl ester) was the most effective in protecting H9c2 cells from HO-induced cell death. Pretreatment with compound 6 (1.56-100 μmol/L) dose-dependently alleviated all the HO-induced detrimental effects. Moreover, exposure to HO significantly increased the levels of Bax, p53, cleaved caspase-8, and cleaved caspase-9, and decreased the level of Bcl-2, resulting in cell apoptosis. Exposure to HO also significantly increased the phosphorylation of p38, JNK and ERK in the H9c2 cells. Pretreatment with compound 6 (12.5 and 25 μmol/L) dose-dependently inhibited the HO-induced increase in the level of cleaved caspase-9 but not of cleaved caspase-8. It also dose-dependently suppressed the HO-induced phosphorylation of JNK and ERK but not that of p38.

Conclusion: Compound 6 isolated from the leaves of Gynura nepalensis potently protects H9c2 cardiomyoblasts against HO-induced apoptosis, possibly by inhibiting intrinsic apoptosis and the ERK/JNK pathway.
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http://dx.doi.org/10.1038/aps.2016.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099414PMC
November 2016

Caffeoyl Triterpenoid Esters as Potential Anti-ischemic Stroke Agents from Celastrus orbiculatus.

J Nat Prod 2016 11 28;79(11):2774-2779. Epub 2016 Oct 28.

State Key Laboratory of Drug Research and ‡CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.

Three new triterpenoids, celastrusins A-C (1-3), together with 3-O-caffeoyl-α-amyrin (4) were isolated from the root bark of Celastrus orbiculatus. Their structures were identified by spectroscopic analysis, X-ray crystallography using Cu Kα radiation, and the comparison of both observed and reported spectroscopic data. An in vitro bioassay revealed that the caffeoyl triterpenoid esters 1, 3, and 4 possess neuroprotective effects against oxygen-glucose deprivation (OGD) induced SH-SY5Y cell damage. Further animal studies indicated that compound 1 significantly reduced brain infarction after transient middle cerebral artery occlusion (MCAO) in rats using a 10 mg/kg (i.v.) dose.
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http://dx.doi.org/10.1021/acs.jnatprod.6b00314DOI Listing
November 2016

Identification and Evaluation of Antiepileptic Activity of C21 Steroidal Glycosides from the Roots of Cynanchum wilfordii.

J Nat Prod 2016 Jan 30;79(1):89-97. Epub 2015 Dec 30.

Department of Natural Product Chemistry and ‡Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.

Nine new C21 steroidal glycosides, named cynawilfosides A-I (1-9), along with 12 known compounds were isolated from the roots of Cynanchum wilfordii. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The five major components, cynawilfoside A (1), cynauricoside A (11), wilfoside C1N (16), wilfoside K1N (17), and cyanoauriculoside G (18), exhibited significant protection activity in a maximal electroshock (MES)-induced mouse seizure model with ED50 values of 48.5, 95.3, 124.1, 72.3, and 88.1 mg/kg, respectively.
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http://dx.doi.org/10.1021/acs.jnatprod.5b00766DOI Listing
January 2016

Bioactive C21 Steroidal Glycosides from the Roots of Cynanchum otophyllum That Suppress the Seizure-like Locomotor Activity of Zebrafish Caused by Pentylenetetrazole.

J Nat Prod 2015 Jul 2;78(7):1548-55. Epub 2015 Jul 2.

†Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.

Six new C21 steroidal glycosides, cynotophyllosides A-F (1-6), together with 16 known compounds, were isolated from the roots of Cynanchum otophyllum. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The three major components, otophylloside F (15), otophylloside B (17), and rostratamine 3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (18), suppressed the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish. Preliminary structure-activity relation studies revealed that a pregnene skeleton with a C-12 ester group (ikemaoyl > cinnamoyl > hydroxy > p-hydroxybenzoyl) and a C-3 sugar chain consisting of three 2,6-dideoxysaccharide units is essential for this suppressive activity.
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http://dx.doi.org/10.1021/np501058bDOI Listing
July 2015

PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

Bioorg Med Chem Lett 2015 4;25(10):2028-32. Epub 2015 Apr 4.

Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.
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http://dx.doi.org/10.1016/j.bmcl.2015.04.003DOI Listing
February 2016

A novel caffeoyl triterpene attenuates cerebral ischemic injury with potent anti-inflammatory and hypothermic effects.

J Neurochem 2015 Apr 27;133(1):93-103. Epub 2015 Feb 27.

CAS Key Laboratory of Receptor Research, Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28-O-caffeoyl betulin (B-CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B-CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B-CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B-CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke.
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http://dx.doi.org/10.1111/jnc.13046DOI Listing
April 2015

Lithocarpic acids O-S, five homo-cycloartane derivatives from the cupules of Lithocarpus polystachyus.

Bioorg Med Chem Lett 2014 Dec;24(23):5395-8

Chemical investigation of the cupules of Lithocarpus polystachyus resulted in the identification of four 3,4-seco-homo-cycloartane and one homo-cycloartane derivatives named lithocarpic acids O-S. Their structures were determined based on extensive 1D/2D NMR, IR, MS spectroscopic analyses and chemical methods. Lithocarpic acid O (1) exhibited inhibitory activities on mouse and human isozymes of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) with IC₅₀ values of 0.49 and 1.1 μM, respectively.
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http://dx.doi.org/10.1016/j.bmcl.2014.10.036DOI Listing
December 2014

Four new triterpenoids isolated from the resin of Garcinia hanburyi.

J Asian Nat Prod Res 2014 Jan 7;16(1):20-8. Epub 2014 Jan 7.

a Department of Natural Products Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , 201203 , China.

Four new triterpenoids, 2-O-acetyl-3-O-(4'-O-acetyl)-α-l-arabinopyranosylmaslinic acid (1), 2-O-acetyl-3-O-(3'-O-acetyl)-α-l-arabinopyranosylmaslinic acid (2), 2-O-acetyl-3-O-(3',4'-O-diacetyl)-α-l-arabinopyranosylmaslinic acid (3), and 3-O-(3'-O-acetyl)-α-l-arabinopyranosyloleanolic acid (4), together with six known triterpenoids, 3-O-(4'-O-acetyl)-α-l-arabinopyranosyloleanolic acid (5), maslinic acid (6), 2-O-acetylmaslinic acid (7), 3-O-acetylmaslinic acid (8), betulinic acid (9), and 2α-hydroxy-3β-O-acetylbetulinic acid (10), were isolated from the EtOAc extract of Garcinia hanburyi resin. Their structures were elucidated by analysis of the spectroscopic data and chemical methods.
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http://dx.doi.org/10.1080/10286020.2013.875012DOI Listing
January 2014

Folate deficiency and aberrant expression of DNA methyltransferase 1 were associated with cervical cancerization.

Curr Pharm Des 2014 ;20(11):1639-46

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

DNA methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation. Aberrant DNA methylation is a recognized feature of human cancers and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also have suggested that folate deficiency was associated with many cancers. The aim of the present study was to evaluate the effect of folate deficiency and aberrant expression of DNA methyltransferase 1 (DNMT1) on cervical cancerization. The expression of DNMT1 protein and mRNA and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (NC,n = 53), cervical intraepithelial neoplasia (CIN I, n = 52; CIN II/III, n = 53), and squamous cell carcinoma of the cervix (SCC; n = 80). In addition, the expression of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate. Serum folate levels decreased and expression levels of DNMT1 protein and mRNA increased gradually with progressive severity of the cervix lesions (P<0.001). It was found that folate was able to reduce the viability of Caski or C33A cell (r=0.978, P=0.002; r=0.984, P<0.001) and regulated aberrant expression of DNMT1 protein (r=-0.859, P=0.01; r=-0.914, P<0.001) and mRNA (r=-0.297, P=0.159; r=0.433, P=0.034) in vitro. Our findings indicated that the low-level of serum folate and high-expression of DNMT1 protein or mRNA was significantly associated with cervical carcinogenesis. Folate deficiency and aberrant expression of DNA methyltransferase 1 had additive effect on cervical cancerization. Folate supplement and recovery of aberrant DNA methylation status may offer a new strategy for prevention and therapy of cancers.
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http://dx.doi.org/10.2174/13816128113199990543DOI Listing
December 2014

Promising effects on ameliorating mitochondrial function and enhancing Akt signaling in SH-SY5Y cells by (M)-bicelaphanol A, a novel dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus.

Phytomedicine 2013 Sep 6;20(12):1064-70. Epub 2013 Jun 6.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.

Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. In this study, we investigated the neuroprotective effects of (M)-bicelaphanol A, which has been the first dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus, against hydrogen peroxide (H2O2)-induced injury in human SH-SY5Y neuroblastoma cells. Our study showed that cells pretreated with (M)-bicelaphanol A significantly attenuated H2O2-induced cell viability reduction and cell apoptosis. These neuroprotective effects of (M)-bicelaphanol A were associated with a reduction of reactive oxygen species and an increase in the level of adenosine triphosphate. In addition, (M)-bicelaphanol A pretreatment markedly increased the phosphorylation level of Akt in SH-SY5Y cells. In conclusion, our results for the first time demonstrate that the protection of (M)-bicelaphanol A on SH-SY5Y cells against H2O2-induced oxidative stress may attribute, at least partially, to its attenuation of mitochondrial dysfunction and activation of Akt signaling pathway. Above results shed more light on the molecular mechanisms involved in the neuroprotective effects of (M)-bicelaphanol A, which could be a potential drug candidate for the treatment of oxidative stress-associated neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.phymed.2013.04.017DOI Listing
September 2013

(M)- and (P)-bicelaphanol A, dimeric trinorditerpenes with promising neuroprotective activity from Celastrus orbiculatus.

J Nat Prod 2013 Apr 19;76(4):745-9. Epub 2013 Feb 19.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.

(M)-Bicelaphanol A (1) and (P)-bicelaphanol A (2), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A (3), were isolated from the root bark of Celastrus orbiculatus. The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single-crystal X-ray diffraction analyses. Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide-induced cell viability decrease in PC12 cells at 1 μM, while compounds 2 and 3 showed such effects at 10 μM.
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http://dx.doi.org/10.1021/np3008182DOI Listing
April 2013

[Interaction of folate deficiency and aberrant profile of DNA methyltransferase 1 in the progression of cervix carcinogenesis].

Zhonghua Yu Fang Yi Xue Za Zhi 2012 Dec;46(12):1088-94

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

Objective: To explore the interaction of folate deficiency and aberration of DNA methyltransferase 1 (DNMT1) in the progression of cervix carcinogenesis.

Methods: All clinical samples were collected from 80 patients with cervix squamous cell carcinoma (SCC), 105 patients with cervical intraepithelial neoplasm (CINI, n = 52; CINII/III, n = 53) and 53 patients with cervix inflammation (CI). The participants were diagnosed by histology at Shanxi Province Tumor Hospital and Second Hospital of Shanxi Medical University during the period of September 2009 to May 2010. Meanwhile, cervical cancer cell lines Caski and C33A were treated with different concentration of folate. Radioimmunoassay (RIA), Western blotting and real-time PCR were used to detect the levels of serum folate, the expression of DNMT1 protein and mRNA, respectively. The data were analyzed by Student t test, ANOVA, chi-square test and Spearman correlation using SPSS statistical package. The correlation strength between factors and cervical canceration was calculated by OR and 95%CI value. Interaction effect was evaluated by the application of additive effect model.

Results: The levels of serum folate (median inter-quartile range) were (2.66 ± 1.82), (2.83 ± 2.23), (3.17 ± 1.91) and (3.21 ± 1.74) ng/ml, the levels of DNMT1 protein (x(-) ± s) were 2.28 ± 0.55, 1.84 ± 0.37, 1.33 ± 0.38 and 0.92 ± 0.29, the Ct-ratio (Ct value of DNMT1/Ct value of β-actin) of DNMT1 mRNA (x(-) ± s) were 1.26 ± 0.13, 1.27 ± 0.12, 1.27 ± 0.12 and 1.33 ± 0.11 in the group of SCC, CINII/III, CINIand CI, respectively. The results showed that the serum folate levels were descended, and the expression levels of DNMT1 protein (χ(2)(tend) = 50.80, P < 0.05) and mRNA (χ(2)(tend) = 17.63, P < 0.05) were increased steadily with the severity of the cervix lesions. Moreover, our results revealed that there was an additive interaction between folate deficiency and high-expression of DNMT1 protein related to the risk of CIN and SCC. And it showed that the relative excess risk of interaction (RERI), attributable proportion of interaction (API) and synergy index(S) was 0.27, 0.14 and 1.40 in CINI group, 0.47, 0.19, 1.46 in CINII/III group, 1.60, 0.31, 1.61 in SCC group, respectively. It was found that folate was able to reduce the proliferation of Caski and C33A cells (r values were 0.954 and 0.969, all P values < 0.05), with 11.4% and 13.6% of growth inhibition at the concentration of 10 µg/ml, 64.8% and 49.4% at 1000 µg/ml in Caski and C33A cells, respectively. The result showed there was an inverse correlation between the levels of folate and DNMT1 protein (r values were -0.859 and -0.914, all P values < 0.05), with 1.96 and 1.92 of expression levels at the concentration of 10 µg/ml, and 1.60 and 1.38 at 1000 µg/ml in Caski and C33A cells, respectively. At folate concentration of 1000 µg/ml, the expression of DNMT1 protein or mRNA was higher in Caski cell than in C33A cell (t values were -4.22 and 3.50, all P values < 0.05).

Conclusion: Our finding indicated that the low levels of serum folate and high-expression of DNMT1 protein or mRNA seemed to be associated with high risk of cervical cancer and cervix precancerous lesion. Sufficient folate is able to effectively inhibit the growth of cervical cancer cells in vitro, and would counteract transcriptional and posttranscriptional aberration of DNMT1. It suggested that there might be a synergistic action between folate deficiency and aberration of DNMT1 in the progression of cervix carcinogenesis.
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December 2012
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