Study towards improving artemisinin-based combination therapies.

Covering: Up to 2020 Artemisinin has made a significant contribution towards global malaria control since its initial discovery. Countless lives have been saved by this unique and miraculous molecule. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria infection and have since remained as the mainstays of the antimalarial treatment. Even so, substantial efforts to pursue better curative effects for the treatment of malaria have never ceased, particularly with regards to the circumstances surrounding the appearance of delayed clearance of malaria parasites by 3 day ACT treatments in South-East Asian countries. Strategies to further optimize artemisinin-based therapies, including synthesizing better artemisinin derivatives, developing advanced drug delivery systems, and diversifying artemisinin partner drugs, have been proposed over the past few years. Here, we provide an updated account of the continuous efforts in improving ACTs for better efficacy in curing malarial infection.

Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture).

Malaria has long been a devastating and life-threatening global epidemic disease in human history. Artemisinin, the active substance against malaria, was first isolated and tested in the 1970s in China. The important role played by traditional Chinese medicine in the discovery of artemisinin is described by Y. Tu in her Nobel Lecture.

High Photoreactivity on a Reconstructed Anatase TiO2(001) Surface Predicted by Ab Initio Nonadiabatic Molecular Dynamics.

Anatase TiO2(001) surface with (4 × 1) reconstruction is proposed to be a highly active catalytic surface. In this work, using time-domain ab initio nonadiabatic molecular dynamics, we reveal that the ridge structure formed by anatase(001) surface reconstruction is the photoreactive site for hole migration and trapping. Moreover, the ridge structure is destroyed by low-coverage CH3OH adsorption, leading to the suppression of its high photoreactivity. However, when the CH3OH coverage is increased and intermolecular hydrogen bonds (H-bonds) form, the ridge structure and its high photoreactivity are restored. Furthermore, the hole trapping dynamics is strongly coherent with intermolecular proton transfer in structures with intermolecular H-bonds. Our study proves that anatase TiO2(001)-(4 × 1) is a highly photoreactive surface where the ridge is the photoreactive site for hole trapping, which is coherent with the proton transfer process.

The birth of artemisinin.

As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were with far-reaching implications. Herein, we will give a brief description of various aspects of the development of artemisinin and discuss the position and perspectives of artemisinin-based drugs.

[Studies on chemical constituents of rhizome of Matteuccia struthiopteris].

OBJECTIVE: To study the chemical constituents of the rhizome of Matteuccia struthiopteris. METHOD: The constituents were separated and purified by column chromatography with silica gel and Sephadex LH-20. Their structures were identified on the basis of physical and spectral data. RESULT: Six compounds were isolated and identified as demethoxymatteucinol (1), matteucinol (2), pinosylvin (3), matteuorien (4), pinosylvin 3-O-beta-D-glucopyranoside (5), matteuorienate A (6). CONCLUSION: All Compounds were isolated from this plant for the first time.

[Determination of artemisinin, arteannuin B and artemisinic acid in Herba Artemisiae Annuae by HPLC-UV-ELSD].

To establish an HPLC-UV-ELSD method for the determination of the content of artemisinin, arteannuin B and artemisinic acid in Herba Artemisiae Annuae. The analytical column was Nucleodur RP-C18 (250 mm x 4.6 mm, 5 microm ID). The mobile phase was acetonirile-0.1% acetic acid (50: 50) and the flow rate was 1.0 mL x min(-1) with a UV detector for artemisinin, the detection wavelength at 209 nm, and the evaporative light-scattering detector (ELSD) for arteannuin B and artemisinic acid, the drift tube temperature: 50 degrees C, the nitrogen flow rate 30 psi and the gain was 50. The resolution of artemisinin, arteannuin B and artemisinic acid was good. The linear calibration curves were obtained over the range of 0.52 - 2.6 microg for artemisinin (r = 0.999 4, n = 5), 0.022 - 4.4 microg for artemisinin B (r = 0.999 9, n = 5) and 0.203 - 8.12 microg for artemisinic acid (r = 0.999 8, n = 5), separately. The mean recoveries of the three compounds were 99.45%, 102.37% and 101.10% with RSD of 2.3%, 1.7% and 0.79%, respectively. This method is simple, rapid, accurate and suitable for the determination of the content of the three compounds in the herbs.

Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation.

The aim of this study was to investigate the mechanisms of action of Dihydroarteannuin (DHA), a semi-synthesized agent from the starting material artemisinin extracted from the Chinese Traditional Herbs Artemisia annua, on ameliorating the symptoms of lupus on BXSB mice. The concentration of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice was determined by the ELISA method. NF-kappaB protein expression and translocation were assayed by the EMSA method and laser confocal scanning microscopy method, respectively. IkappaB-alpha and NF-kappaB p65 protein expression were determined by the Western blot method. Renal tissue of the BXSB mice was prepared for assaying inhibitory activity of DHA on NF-kappaB, p65 and IkappaB-alpha protein expression in vivo. The peritoneal macrophages were prepared for analysis inhibitory effects of DHA on translocation of NF-kappaB into nuclear in vitro. We found that DHA strongly reduced the production of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice in vitro or in vivo. The results demonstrated that DHA decreased the expression of NF-kappaB subunit p65 protein and the activation of NF-kappaB in the renal tissue of BXSB mice in vivo. DHA effectively inhibited the nuclear translocation of NF-kappaB in peritoneal macrophages of BXSB mice in vitro. Furthermore, it was demonstrated that the degradation of IkappaB-alpha protein was significantly inhibited by DHA. These observations suggested that the inhibitory effects of DHA on TNF-alpha production may result from the block in the NF-kappaB signaling pathway upstream of IkappaB degradation.

[Studies on the chemical constituents from stem of Chirita longgangensis var. Hongyao].

OBJECTIVE: To isolate and elucidate the constituents from stem of Chirita longgangensis var. hongyao. METHOD: The constituents were extracted with methanol and isolated by chromatography on silica gel, Sephadex LH-20 and ODS. The structures were determined by NMR and MS spectral analysis. RESULT: Seven compounds were identified as 2-hydroxy-7-methyl-9, 10-anthraquinone (1), 2-methyl-9, 10-anthraquinone (tectoquinone) (2), ursolic acid (3), vanillic acid (4), beta-sitosteryl-D-glucoside-6'-palmitate (5), beta-sitosterol (6), daucosterol (7), respectively. CONCLUSION: Compounds 1, 2, 3 and 5 were isolated for the first time from the family Gesneriaceae, compounds 4 and 6 were isolated for the first time from the genus Chirita, and compound 7 was isolated for the frist time from Chirita longgangensis var.

[Chemical constituents of the rhizome of Matteuccia struthiopteris].

AIM: To study the chemical constituents of the rhizome of Matteuccia struthiopteris (L.) The constituents were separated and purified by column chromatography with normal Todaro. METHODS: phase silica gel and Sephadex LH-20. Their structures were identified on the basis of physical and spectral data (MS, NMR, HMBC and HMQC). RESULTS: Four compounds were isolated and identified as 1-O-beta-D-gl ucopyranosyl-(2S,3R,4E, 8Z) -2-N-(2'-hydroxydocosanoyl) eicosasphinga-4,8-dienine (1), 1-O-beta-D-galactosyl-(6-->1)-alpha-D-galactosyl-2,3-O-dihexadecanoyl-glycerol (2), succinic acid (3), D-mannitol (4). CONCLUSION: Compounds 1 and 2 are new compounds. Compounds 3 and 4 were isolated from this plant for the first time.

[Phenylethanoid glycosides from stem of Chirita longgangensis var. hongyao].

OBJECTIVE: To isolate and elucidate the constituents from stem of Chirita longgangensis var. hongyao. METHOD: The constituents were extracted with methanol and isolated by chromatography on silica gel, Sephadex LH-20 and ODS. The structures were determined by NMR and MS spectral analysis. RESULT: Five phenylethanoid glycosides were identified as 3, 4-dihydroxyphenyl alcohol-beta-D-glucopyranoside (1), 3, 4-dihydroxyphenyl alcohol-6-O-caffeoyl--D-glucopyranoside (calceolarioside B) (2), 3, 4-dihydroxyphenyl alcohol-beta-D-glucopyranosyl-(1 --> 3)-6-O-caffeoyl-beta-D-glucopyranoside (plantainoside D) (3), 3, 4-dihydroxyphenyl alcohol-beta-D-glucopyranosyl-(1 --> 3)-4-O-caffeoyl-beta-D-glucopyranoside (plantamajoside) (4), 3, 4-dihydroxyphenyl alcohol-beta-D-glucopyranosyl-(1 --> 3)-6-O-feruloyl-beta-D-glucopyranoside (scroside E) (5), respectively. CONCLUSION: Compounds 3 and 5 were isolated for the first time from the family Gesneriaceae, and compounds 1, 2 and 4 were isolated for the first time from the genus Chirita.

[Effect of dihydro-qinghaosu on auto-antibody production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB mice].

OBJECTIVE: To investigate the effect of dihydro-qinghaosu (DQHS) on auto-antibody production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB mice and the possible mechanism of DQHS in treating systemic lupus erythematosus (SLE). METHODS: Anti ds-DNA antibody and TNF alpha in serum of the BXSB mice were detected by enzyme linked immunosorbent assay (ELISA). Renal tissue was stained by HE and Masson. RESULTS: In the height and moderate dose DQHS groups, as compared with the model group, levels of anti-ds-DNA antibody and serum TNF alpha were significantly lower (P < 0.05); and renal pathological change was milder. CONCLUSION: DQHS could inhibit the production of anti-ds-DNA antibody and secretion of TNF alpha and improve the pathologic lesion of lupus nephritis in BXSB mice.

[Studies on chemical constituents in rhizome of Matteuccia struthiopteris].

OBJECTIVE: To study the chemical constituents in rhizome of Matteuccia struthiopteris. METHOD: The compounds were isolated by normal phase silica gel chromatography. The structures were identified by physical and spectral data. RESULT: Six compounds were isolated and identified as woodwardic acid (1), ergost-6,22-diene-3beta,5alpha,8alpha-triol (2), apigenin (3), riboflavin (4), 4-O-beta-D-glucopyranosyl-p-coumaric acid (5), 4-O-beta-D-glucopyranosylcaffeic acid (6). CONCLUSION: All the compounds were obtained from this plant for the first time.