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Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

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Objective:To study the antitumor mechanism of W40,a monomer purified from Wedelia prostrate (Hook.et Arn.) Hemsl.Methods:The effects of W40 on the cell proliferative of GLC-82 cells were detected by MTT assay and colony formation assay.The migratory abilities of GLC-82 cells were observed by wound healing assay.Cell apoptosis was evaluated by Annexin V-FITC/PI staining analysis.The levels of apoptosis-relative proteins and cell proliferation-related proteins,such as Caspase-3,PARP,Stat3 and ERK,were detected by Western blotting.Results:MTF assay showed that W40 had a significant cytotoxic effect on non-small cell lung cancer GLC-82 cells.Colony formation assays showed that W40 significantly inhibited GLC-82 cells proliferation.The migration of GLC-82 cells was inhibited by W40 in a dose-dependent manner.Flow cytometry showed that the apoptotic rate increased gradually in a concentration-dependent manner.W40 down-regulated Stat3 as decreasing p-Stat3 and downstream proteins of Bcl-2 and Mcl-1.At the same time,W40 up-regulated the expression of pro-apoptotic protein Bax,and increased the cleavaged Caspase-9,Caspase-3 and PARP.W40 also down-regulated BRAF / MAPK / ERK signal pathway as decreasing p-BRAF,p-MEK and p-ERK.Conclusions:W40 induced apoptosis by inhibiting BRAF / MAPK / ERK and Stat3 signaling pathways.

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Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.

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<p><b>OBJECTIVE</b>To study the chemical constituents of the roots of Helicteres angustifolia.</p><p><b>METHOD</b>The compounds were isolated and purified by column chromatographic methods on silica gel, Sephadex LH-20, ODS and preparative HPLC. Their structures were elucidated on the basis of physicochemical properties and spectral data.</p><p><b>RESULTS</b>Fourteen compounds were isolated from this plant. Their structures were identified as methyl helicterate(1),3-acetoxybetulin(2),3beta-acetoxy-27-(p-hydroxyl)benzoyloxylup-20(29)-en-28-oic acid methyl ester(3),3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid(4),3beta-acetoxybetulinic acid(5),pyracrenic acid(6),cucurbitacin D(7),cucurbitacin B(8),isocucurbitacin D(9),3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester (10),beta-sitosterol(11),2alpha,7beta,20alpha-trihydroxy-3beta,21-dimethoxy-5-pregnene(12), hexadecanoic acid(13), and daucosterol(14), respectively.</p><p><b>CONCLUSION</b>Compounds 5,8,9,13, 14 were isolated from this plant for the first time.</p>

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<p><b>OBJECTIVE</b>To study the chemical constituents of Gekko swinhonis.</p><p><b>METHOD</b>The compounds were isolated and purified by several column chromatographic methods with silica gel, ODS, Sephadex LH-20 and preparative HPLC, Their structures were identified by physicochemical properties and spectral data.</p><p><b>RESULT</b>Thirteen compounds were isolated and elucidated as cyclo-(Pro-Leu) (1), cyclo-(Ala-Pro) (2),cyclo-(Gly-Pro) (3),cyclo-(Ala-Val) (4),6-amino-9-beta-D-ribofuranosyl-9H-purine (5), uridine (6), thymidine (7),hypoxanthine-9-beta-D-ribofuranosid (8),L-phenylalanine (9),5alpha-cholest-3,6-dione (10),cholesterol (11), 1-O-hexadecanolenin (12),octadecanoic acid (13),respectively.</p><p><b>CONCLUSION</b>All compounds were isolated from G. swinhonis for the first time.</p>

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<p><b>OBJECTIVE</b>To study the chemical constituents from the root barks of Morus atropurpurea.</p><p><b>METHOD</b>The chemical constituents from the 70% ethanol extract of M. atropurpurea were isolated and purified by column chromatographic methods. Their structures were identified by physico-chemical properties as well as spectral data.</p><p><b>RESULT</b>Fifteen compounds were isolated and identified as sanggenol O(1), kuwanon S(2), moracin C(3), mulberrofuran A(4), mulberrofuran B(5), mulberrofuran C(6), mulberrofuran G(7), mulberroside A(8), mulberroside C(9), 1-deoxynojirimycin(10), 2-O-alpha-D-galactopyranosyl-1-deoxynojirimycin(11), fagomine(12), betulinic acid(13), ursolic acid(14) and beta-sitosterol(15).</p><p><b>CONCLUSION</b>Compounds 1-6 and 8-13 were isolated from M. atropurpurea for the first time.</p>

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Catharanthus roseus (L.) G. Don is a plant of the Catharanthus genus of Apocynaceae which has been reported to have therapeutic effects of detoxication and anticancer. In order to further study the alkaloid constituents of C. roseus, the aerial parts of the plant were extracted with 95% EtOH, and then treated with 2% H2SO4 and NH3H2O to obtain total alkaloids. The total alkaloids were separated and purified by column chromatography over silica gel and prepared by high performance liquid chromatography (HPLC). Their structures were elucidated on the basis of physicochemical properties and spectral data. A new alkaloid together with five known compounds were isolated and identified as vindolinine B (1), lochnericine (2), horhammericine (3), vindorosine (4), vindoline (5), and coronaridine (6). Compound 1 is a new compound and named as vindolinine B.