Chemical constituents of diterpenoids from Boswellia carterii / 中国中药杂志

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.

Advances on the microbial synthesis of plant-derived diterpenoids / 生物工程学报

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.

New di-spirocyclic labdane diterpenoids from the aerial parts of Leonurus japonicus / 中国天然药物

Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.

Five new terpenoids from Viburnum odoratissimum var. sessiliflorum / 中国天然药物

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC50 value of 55.64 μmol·L-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC50 values of 13.8 and 12.3 μmol·L-1, respectively.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

Progress in antitumor activity of diterpenoid alkaloids in plants of Aconitum / 中国中药杂志

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.

Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro / 中国中药杂志

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.

Efecto citotóxico de diterpenos derivados del ácido ent-kaureno aislados de Coespeletia moritziana (Sch. Bip. ex Wedd.) Cuatrec / Cytotoxic effect of ent-kaurene acid-derived diterpenes isolated from Coespeletia moritziana (Sch. Bip. Ex Wedd.) Cuatrec

The objective of the work was to study the cytotoxic effect of ent-kaurene acid derivatives obtained from Coespeletia moritziana (Sch. Bip. Ex Wedd.) Cuatrec., After analysis by GC/MS, IR and NMR. Isolating: kaurenic acid (I), grandifloric acid (II), 15-α-hydroxy kaurenic acid (III), 15 α-acetoxy-kaur 16-en-19-oic acid (IV), Kaurenol (V); and by hemisynthesis: 15,16-epoxy-17-acetoxy-kauran 19-oic acid (VI), 15-oxo-ent-kaur-16-en-19-oic acid (VIII), ester 2,3,4,6 -15-oxo-kaur-16-en-19-oic acid acetyl α-D-pyranosyl tetra-tetra (VII). Cytotoxicity was tested in human cancer cell lines: uterus (HeLa), lung (A-549), breast (MCF-7), African green monkey kidney non-tumor line (Vero) and human peripheral blood mononuclear cells (CMPS). Compound (I) was active against HeLa, A-549 and Vero. Compounds (II and VIII) showed moderate and good (IC50 ≤ 9 µM) cytotoxicity, respectively, against the five cell lines. Compound (V) showed moderate activity against A-549 and compound (VII), slight cytotoxicity against HeLa and A-549. Results that show the cytotoxic specificity of the isolated kaurenes and derivatives of Coespeletia moritzianaand their therapeutic potential.

El objetivo del trabajo fue estudiar el efecto citotóxico de derivados del ácido ent-kaureno obtenidos de Coespeletia moritziana (Sch. Bip. ex Wedd.) Cuatrec., previo análisis mediante GC/MS, IR y RMN. Aislandose: ácido kaurénico(I), ácido grandiflorénico (II), ácido 15-α-hidroxi kaurénico(III), ácido 15 α-acetoxi-kaur 16-en-19-oico (IV), Kaurenol (V); y por hemisíntesis: ácido 15,16-epoxi-17-acetoxi-kauran 19-oico (VI), ácido15-oxo-ent-kaur-16-en-19-oico (VIII), éster 2,3,4,6-tetra acetil α-D-piranosilo del ácido 15-oxo-kaur-16-en-19-oico (VII). La citotóxicidad fue ensayada en líneas celulares cancerosas humanas: útero (HeLa), pulmón(A-549), mama (MCF-7), línea no tumoral de riñón de mono verde africano (Vero) y células mononucleares humanas de sangre periférica (CMPS). El compuesto (I) resultó activo frente a HeLa, A-549 y Vero. Los compuestos (II y VIII), mostraron moderada y buena (IC50≤9µM) citotoxicidad respectivamente, frente a las cinco líneas celulares. El compuesto (V) presentó moderada actividad frente a A-549 y el (VII), leve citotoxicidad frente a HeLa y A-549. Resultados que evidencian la especificidad citotóxica de los kaurenos aislados y derivados de Coespeletia moritzianay su potencial terapéutico.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Diterpenoids from Rabdosia flexicaulis / 中国中药杂志

The genus Rabdosia is famous for the abundance of diverse and novel ent-kaurane diterpenoids. However, only a few ent-kauranoids have been discovered from R. flexicaulis since the investigation on its chemical constituents is not systematic. To find novel bioactive diterpenoids, the ethyl acetate extract of the above ground part of R. flexicaulis in Daofu County, Sichuan Province was obtained by column chromatography. One new compound and five known ones were identified as flexicaulin E(1), forrestin B(2), inf-lexarabdonin D(3), 7α-hydroxydehydroabietic acid(4), 15-hydroxydehydroabietic acid(5), and pomiferin F(6) by spectral techniques. Compounds 1-3 were the ent-kaurane diterpenoids isolated from this species for the first time. Compounds 4-6, aromatic abie-tanoids, were isolated from the genus Rabdosia for the first time.

Triptolide inhibits inflammatory response and migration of fibroblast like synovial cells in rheumatoid arthritis through the circRNA 0003353/JAK2/STAT3 signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of triptolide (TPL) on inflammatory response and migration of fibroblast like synovial cells (FLS) in rheumatoid arthritis (RA-FLS) and the mechanism of circular noncoding RNA (circRNA) 0003353 for mediating this effect.@*METHODS@#We collected peripheral blood mononuclear cells (PBMCs) and serum samples from 50 hospitalized RA patients and 30 healthy individuals for detecting the expression of circRNA 0003353, immune and inflammatory indexes (ESR, CRP, RF, anti-CCP, IgA, IgG, IgM, C3, and C4) and DAS28 score. Cultured RA-FLS was treated with 10 ng/mL TPL and transfected with a circRNA 0003353 overexpression plasmid, and cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the changes in the viability and migration of the cells. Enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokines IL-4, IL-6, and IL-17, and real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the expression of circRNA 003353; Western blotting was used to detect the expressions of p-JAK2, pSTAT3, JAK2 and STAT3 proteins in the treated cells.@*RESULTS@#The expression of circRNA 0003353 was significantly increased in PBMCs from RA patients and showed a good performance in assisting the diagnosis of RA (AUC=90.5%, P < 0.001, 95% CI: 0.83-0.98). CircRNA 0003353 expression was positively correlated with ESR, RF and DAS28 (P < 0.05). Treatment with TPL significantly decreased the expression of circRNA 0003353, suppressed the viability and migration ability, decreased the expressions of IL-6 and IL-17, and increased the expression IL-4 in cultured RA-FLS in a time-dependent manner (P < 0.01). TNF-α stimulation of RA-FLS significantly increased the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, which were obviously lowered by TPL treatment (P < 0.01). TPL-treated RA-FLS overexpressing circRNA 0003353 showed significantly increased cell viability and migration ability with decreased IL-4 expression and increased IL-6 and IL-17 expressions and ratios of p-JAK2/ JAK2 and p-STAT3/STAT3 (P < 0.01).@*CONCLUSION@#The expression of circRNA 0003353 is increased in PBMCs in RA patients and in RA-FLS. TPL treatment can regulate JAK2/STAT3 signal pathway and inhibit the inflammatory response and migration of RA-FLS through circRNA 0003353.

Actividad antibacteriana del extracto etanólico de Plantago major frente a Streptococcus mutans / Antibacterial activity of Plantago major ethanolic extract against Streptococcus mutans

Introducción: Las propiedades antibacterianas de Plantago major frente a microorganismos orales no se ha estudiado ampliamente. Objetivo: Identificar los metabolitos secundarios presentes en el extracto etanólico de Plantago major y determinar su actividad antibacteriana frente a Streptococcus mutans. Métodos: Se prepararon concentraciones del 25 por ciento, 50 por ciento, 75 por ciento y 100 por ciento de extracto etanólico (EE) de Plantago major. Se cargaron seis discos de papel con 10 µL, 15 µL, 20 µL y 25 µL de cada concentración, haciendo un total de 96 discos. Los discos fueron colocados en placas Petri con agar cerebro-corazón inoculadas con Streptococcus mutans, se empleó clorhexidina al 0,12 por ciento como control positivo. Se calcularon seis repeticiones para cada concentración. Las placas fueron incubadas a 37 °C por 48 horas. La medición de los halos de inhibición se realizó con un compás digital. El análisis estadístico se realizó mediante la prueba ANOVA de un factor seguido por la prueba post hoc de Tukey. Resultados: El análisis químico del extracto etanólico de Plantago major identificó la presencia de terpenos, diterpenos, saponinas, terpenoidales y aceites esenciales. Las concentraciones del 25 por ciento y 50 por ciento no mostraron efecto antibacteriano, los volúmenes mayores de 20 µL de la concentración del 75 por ciento y todas los del 100 por ciento fueron efectivos para inhibir el crecimiento de Streptococcus mutans con halos de inhibición de 8,36 mm a 14,64 mm. La clorhexidina al 0,12 por ciento inhibió el crecimiento de Streptococcus mutans con halos de inhibición de 17,77 mm en promedio, presentando diferencias significativas con todas las concentraciones del extracto etanólico de Plantago major (P < 0,05). Conclusiones: El extracto etanólico de Plantago major presentó derivados de los terpenos y saponinas, y mostró actividad antibacteriana frente a Streptococcus mutans en volúmenes y concentraciones mayores a 20 µL/75 por ciento(AU)

Introduction: The antibacterial properties of Plantago major against oral microorganisms have not been widely studied. Objective: Identify the secondary metabolites present in an ethanolic extract of Plantago major and determine their antibacterial activity against Streptococcus mutans. Methods: The Plantago major ethanolic extract (EE) was prepared at concentrations of 25 percent, 50 percent, 75 percent and 100 percent. Six paper discs were loaded with 10 µl, 15 µl, 20 µl and 25 µl of each concentration, for a total 96 discs, which were then placed on Petri plates with brain heart agar inoculated with Streptococcus mutans. The positive control was 0.12 percent chlorhexidine. Six replicates were estimated for each concentration. The plates were incubated at 37ºC for 48 hours. Inhibition haloes were measured with a digital caliper. Statistical analysis was based on one-factor ANOVA testing followed by Tukey's post hoc test. Results: Chemical analysis of the Plantago major ethanolic extract identified the presence of terpenes, diterpenes, saponins, terpenoids and essential oils. The 25 percent and 50 percent concentrations did not display an antibacterial effect, whereas volumes above 20 µl of the 75 percent concentration and all 100 percent volumes were effective to inhibit Streptococcus mutans growth with inhibition haloes of 8.36 mm to 14.64 mm. 0.12 percent chlorhexidine inhibited Streptococcus mutans with inhibition haloes of 17.77 mm on average, presenting significant differences with all the concentrations of the Plantago major ethanolic extract (p < 0.05). Conclusions: The Plantago major ethanolic extract was found to contain terpene and saponin derivatives, and displayed antibacterial activity against Streptococcus mutans at volumes and concentrations above 20 µl / 75 percent(AU)

3, 4-seco-Isopimarane and 3, 4-seco-pimarane diterpenoids from Callicarpa nudiflora / 中国天然药物

A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.

Diterpenoid alkaloids from roots of Aconitum kongboense / 中国中药杂志

The chemical constituents from the roots of Aconitum kongboense were studied. Twenty-five diterpenoid alkaloids were isolated from the 95% methanol extract of the roots of A. kongboense by silica gel, reverse-phase silica gel and basic alumina column chromatography. They included a new aconitine-type diterpenoid alkaloid, named as kongboensenine(1), and twenty-four known ones(2-25), i.e., acotarine F(2), acotarine G(3), 14-acetyltalatisamine(4), talatisamine(5), indaconitine(6), yunaconitine(7), chasmanine(8), 6-epi-foresticine(9), homochasmanine(10), 8-deacetyl-yunaconitine(11), chasmaconitine(12), ajaconine(13), franchetine(14), ezochasmanine(15), crassicautine(16), 14-O-deacylcrassicausine(17), genicunine A(18), falconeridine(19), sachaconitine(20), liljestrandisine(21), 8-methyl-14-acetyltalatisamine(22), kongboendine(23), 14-benzoylchasmanine(24) and pseudaconine(25). Their structures were elucidated by common spectroscopic methods including high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and nuclear magnetic resonance(NMR) techniques. Compounds 2-4, 10, 13, 15-19 and 21-22 were isolated from this plant for the first time. Experimental results showed that all compounds did not have a significant inhibitory activity against acetylcholinesterase(AChE).

Research progress on chemical constituents from Chloranthus plants and their biological activities / 中国中药杂志

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.

A new labdane-type diterpenoids from Callicarpa nudiflora / 中国中药杂志

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-β-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.

Mechanisms and application of triptolide against breast cancer / 中国中药杂志

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.

Effect of isopentenyl pyrophosphate translocation on the biosynthesis of triptolide / 生物工程学报

Triptolide has wide clinical applications due to its anti-inflammatory, anti-tumor and immunosuppressive activities. In this study, we investigated the effect of blocking isopentenyl pyrophosphate (IPP) translocation on the biosynthesis of triptolide by exogenously adding D,L-glyceraldehyde (DLG) to the suspension cells of Ttripterygium wilfordii at different stages (7 d, 14 d). Subsequently, the cell viability, biomass accumulation, triptolide contents, as well as the profiles of the key enzyme genes involved in the upstream pathway of triptolide biosynthesis, were analyzed. The results showed that IPP translocation is involved in the biosynthesis of triptolide. IPP is mainly translocated from the plastid (containing the MEP pathway) to the cytoplasm (containing the MVA pathway) in the early stage of the culture, but reversed in the late stage. Blocking the translocation of IPP affected the expression of key enzyme genes involved in the upstream pathway of triptolide, which in turn affected the accumulation of triptolide. Understanding the characteristics and mechanism of IPP translocation provides a theoretical basis for further promoting triptolide biosynthesis through synthetic biology.

A new cembranoid diterpene from Olibanum / 中国中药杂志

Five compounds were isolated from the alcohol extract of Olibanum by MCI, silica gel, ODS, and Sephadex LH-20 column chromatographies and preparative high-performance liquid chromatography(HPLC). On the basis of spectral data and literature data, the compounds were identified as:(1S,3R,4S,7R,11S,12R)-1:12,4:7-diepoxisonane-8(19)-ene-3,11-diol(1), boscartin A(2),(+)-resinolin(3),(+)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(4), and acerogenin A(5). Compound 1 is a new compound, and compounds 3-5 were isolated from Olibanum for the first time. The structure of compound 1 was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 were tested for PC12 neurotoxicity, and the results showed that they were both safe compounds.

Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration / 中国中药杂志

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.