Inhibitory Effect of Sesquiterpenoid M36 from Myrrha on Growth of Human Hepatoma Cells / 中国实验方剂学杂志

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC50） value of M36 for 48 h was 5.03 μmol·L-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Research progress of nitrobenzoyl sesquiterpenoids as marine characteristic natural products / 药学学报

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

A new elemane-type sesquiterpenoid glycoside from Curcuma phaeocaulis / 药学学报

To study the chemical constituents and their biological activities in the rhizomes of Curcuma phaeocaulis, silica gel column chromatography, reverse medium pressure liquid chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were used for isolation and purification and modern spectroscopic methods were used to determine the structure of the isolated compound. Moreover, the effect of the compound on the proliferation of HUVECs was determined by the MTT assay. A new elemane-type sesquiterpenoid glycoside was isolated from the n-butanol soluble fraction of 95% ethanolic extract of the rhizomes of Curcuma phaeocaulis. Its structure was identified as (1Z)-2-hydroxy-curzerenone 2-O-β-D-glucoside. It showed no inhibitory effect on the proliferation of HUVECs.

A new germacrene-type sesquiterpenoid from Elephantopus tomentosus L / 药学学报

Fifteen compounds were isolated from the 95% ethanol extract of the whole plant of Elephantopus tomentosus L. by silica gel column chromatography, Sephadex LH-20 column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, and spectral data (UV, IR, NMR, MS and CD) analysis as tomenlephanlide A (1), molephantinin (2), molephantin (3), 8-O-methacryloylelephanpane (4), apigenin (5), tricin (6), 2-phenyl acetamide (7), 3,4-dihydroxybenzoic acid methyl ester (8), caffeic acid methyl ester (9), caffeic acid ethyl ester (10), (+)-(4S)-(2E)-4-hydroxy-2-nonenoic acid (11), E-4-hydroxyhex-2-enoic acid (12), 1H-indole-3-carboxylic acid (13), 1H-indole-3-carbaldehyde (14) and isohematinic acid (15). Among them, compound 1 is a new germacrene-type sesquiterpenoid, 5-15 were obtained from E. tomentosus L. for the first time. It was the first time the absolute configuration of compound 2 was reported. Compound 1 showed weak cytotoxicity against gastric cancer cells (SGC-7901).

Construction of cell factories for production of valencene in Saccharomyces cerevisiae / 药学学报

Valencene, a kind of sesquiterpenoid with a citrus flavor, is mainly found in Valencia orange and is commonly used in cosmetics and food additives, as well as industrial synthetic nootkatone. In this study, synthetic biology was used to create a Saccharomyces cerevisiae cell factory to produce valencene. Fistly, valencene synthase gene (CnVS) from Callitropsis nootkatensis was inserted into the chromosome of the chassis strain YTT-T5. The resulting strain VAL-01 could produce 1.1 mg·L-1 valencene. Protein fusion technique was used, different valencene synthases were compared and the copy number of key genes was adjusted, yielding valencene to 436.4 mg·L-1. Then, knocking-out the transcription factor ROX1 resulted in valencene improvement by 17.4%. Moreover, the induction system of galactose was regulated, transcription factor PDR3 and INO2 were overexpressed. The engineered strain VAL-10 could produce 2 798.6 mg·L-1 valencene by high cell density fermentation method (nearly 2 500 times higher than VAL-01). This study provides a basis for green production of valencene.

A novel sesquiterpenoid from Curcuma longa L / 药学学报

A new compound was isolated from the 95% ethanolic extract of the rhizomes of Curcuma longa L. using silica gel column chromatography, medium pressure liquid chromatography, and semi-preparative high performance liquid chromatography. The structure and absolute configuration of the compound was elucidated by HR-ESI-MS, NMR, and electronic circular dichroism (ECD) calculations. It is a novel sesquiterpenoid, which is named as isoturmeronol B (1). The carbon skeleton of compound 1 is similar to that of bisabolane-type sesquiterpenoid. The only difference is that the methyl group at C-4 in bisabolene-type sesquiterpenoid is migrated to C-5 in compound 1. Besides, the anti-inflammatory and antioxidant activities of the compound 1 were evaluated. The results showed that 1 has no anti-inflammatory and antioxidant activities.

Sesquiterpenoids and iridoids from Valeriana jatamansi with anti-inflammatory and anti-influenza virus properties / 药学学报

Three sesquiterpenoids and nine iridoids were isolated from the roots and rhizomes of Valeriana jatamansi by various chromatographic methods. Their structures were identified by physicochemical properties, NMR and MS data. Among them, valeriananoid G (1) was a new patchoulol-type sesquiterpenoid, and compound 3 was isolated from the genus Valeriana for the first time. Compounds 3 and 10 exhibited significant inhibitory effects on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, with IC50 values of 19.00 and 3.66 μmol·L-1, respectively. In addition, compounds 4, 6 and 12 showed anti-influenza virus activity with IC50 values of 51.75, 51.40 and 102.08 μmol·L-1, respectively.

Research progress on chemical constituents and biological activities of Sarcandra glabra / 中国中药杂志

Sarcandra glabra, a medicinal plant in family Chloranthaceae, has been taken as an important raw material for multiple Chinese patent drugs due to its diverse indications. Considering the diversified chemical constituents and rich biological activities of S. glabra, numerous phytochemical and pharmacodynamic investigations were conducted to explore the material basis for its medicinal use. It has been found that its main chemical constituents were sesquiterpenoids, sesquiterpenoid polymers, phenolic acids, coumarins, and flavonoids. As revealed by pharmacological research, it possesses multiple biological activities like anti-inflammation, anti-bacteria, anti-tumor, anti-oxidation, and neuroprotection. Some unreported novel structures, including polymers of lindenane sesquiterpenes and monoterpenes, sesquiterpene trimers, and adducts of flavonoids and monoterpenes, have been identified from S. glabra in recent years. Moreover, biological studies relating to its anti-tumor, anti-inflammatory, and anti-oxidant activities have been deepened. This paper reviewed the chemical constituents and bioactivities of S. glabra explored over the past ten years, so as to provide a scientific basis for further development and utilization of this plant.

New eudesmane sesquiterpenoids from Atractylodis Macrocephalae Rhizoma and their inhibitory activities against SREBPs / 中国中药杂志

Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).

Polyhydroxylated eudesmane sesquiterpenoids and sesquiterpenoid glucoside from the flower buds of Tussilago farfara / 中国天然药物

Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.

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.

Three new carabrane sesquiterpenoid derivatives from the whole plant of Carpesium abrotanoides L / 中国天然药物

Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C

Lindera aggregata (Sims) Kosterm: review on phytochemistry and biological activities / Lindera agreggata (Sims) Kosterm: revisión de su fitoquímica y actividades biológicas

The genus Lindera consists of approximately 100 species that are widely distributed in tropical and subtropical areas throughout the world. Most Lindera plants, particularly Lindera aggregata is a well-known traditional Chinese medicine that has important medicinal value and health benefits. Contemporary chemical and pharmacological studies have shown that L. aggregata are a source of structurally diverse molecules having pharmacological potential. In an effort to promote research on L. aggregata and develop therapeutic and pharmacological products, this review describes the structural diversity of its components and pharmacological and biological significance of L. aggregata. This review is based on a literature analysis of scientific journals from electronic sources, such as Science Direct, PubMed, Google Scholar, Scopus and Web of Science. Thus, with the growing interest in traditional medicine and botanical drugs worldwide, L. aggregata will increasingly capture chemists' and pharmacologists' attention because they produce diverse and structurally novel compounds having pharmacological significance.

El género Lindera consta de aproximadamente 100 especies que están ampliamente distribuidas en áreas tropicales y subtropicales en todo el mundo. La mayoría de las plantas de Lindera, particularmente Lindera aggregata, es parte conocida de la medicina tradicional china con un importante valor medicinal y beneficios para la salud. Estudios químicos y farmacológicos contemporáneos han demostrado que L. aggregata es una fuente de moléculas estructuralmente diversas que con potencial farmacológico. En un esfuerzo por promover la investigación sobre L. aggregata y desarrollar productos terapéuticos y farmacológicos, esta revisión describe la diversidad estructural de sus componentes y la importancia farmacológica y biológica de L. aggregata. Esta revisión se basa en un análisis de literatura de revistas científicas de fuentes electrónicas, como Science Direct, PubMed, Google Scholar, Scopus y Web of Science. Por lo tanto, con el creciente interés en la medicina tradicional y las drogas botánicas en todo el mundo, L. aggregata captará cada vez más la atención de los químicos y farmacólogos debido a que producen compuestos diversos y estructuralmente novedosos que tienen importancia farmacológica.

A new cadinane-type sesquiterpenoid from Eupatorium adenophorum Spreng / 药学学报

Four cadinane-type sesquiterpenes were obtained from the petroleum ether of 95% ethanol extract of Eupatorium adenophorum Spreng by using an HP-20 macroporous resin column, silica gel, and semi-preparative HPLC. Their structures were determined by physical, chemical and spectroscopic methods and identified as eupatorinol (1), (+)-(5R,7S,9R,10S)-2-oxocadinan-3,6(11)-dien-12,7-olide (2), (1S,4R)-7-hydroxycalamenen-3-one(3) and (-)-(5R,6R,7S,9R,10S)-cadinan-3-ene-6,7-diol (4). Among them, compound 1 is a new cadinane-type sesquiterpene, and compound 3 was isolated from this genus for the first time. In bioassay, none of these compounds displayed obvious cytotoxicity.

Chemical Constituents from the Aerial Parts of Korean Medicinal Herba Artemisiae sacrorum / 中国药学杂志

OBJECTIVE: To isolate and purify the reference compounds and improve the quality standard of Korean medicinal Herba Artemisiae sacrorum. METHODS: The chemical constituents were isolated from the aerial parts of Korean medicinal herb Artemisia sacrorum by silica gel, ODS column chromatography and preparative HPLC, and the structures were identified by NMR and MS. RESULTS: Fourteen known compounds were isolated and identified as follows:1α-acetoxyeudesm-4-en-6β,11βH-12,6-olide(1),(11S)-3-oxoeudesma-1,4(15)-dieno-12,6α-lactone(2), 1-epi-dehydroisoerivanin(3), 11-epi-taurin(4), chrysanthemolide(5), 1α-acetyl-gallicadiol(6), erivanin(7), 1α, 4α-dihydroxyeudesm-2-en-5α, 6β, 11βH-12, 6-olide(8), vulgarin(9),(+)-dehydrovomifoliol(10), isoevodionol(11),(+)-epi-pinoresinol(12), lariciresinol-4'-O-β-D-glucopyranoside(13), and lariciresinol-4-O-β-D-glucopyranoside(14). CONCLUSION: All compounds are obtained from this plant for the first time. These compounds can be used as reference substances for the quality control of this ethnic medicine.

Study on sesquiterpenoids from Aquilaria sinensis / 中草药

Objective: To investigate the sesquiterpenoid constituents from Aquilaria sinensis. Methods: The chemical constituents were isolated and purified by various separation techniques such as silica gel, ODS, Sephadex LH-20, and preparative high- performance liquid chromatography, and their structures were determined according to their physicochemical properties, MS, 1D, and 2D NMR. The antibacterial activity of the obtained compounds against methicillin-resistant Staphylococcus aureus was tested by 96-well plate microdilution method. Results: Seven sesquiterpenoids were obtained from 95% ethanol aqueous extract of Aquilaria sinensis and their structures were identified as (+)-4a,5-dimethyl-3-(prop-1-en-2yl)-octahydronaphthalene-2β,8a-diol (1), baimuxinic acid (2), baimuxinol (3), vetaspira-2(11),6-dien-14-al (4), baimuxinal (5), (-)-10-epi-γ-eudesmol (6), and 9β-hydroxyl-α-agarofuran (7). The minimum inhibitory concentration (MIC) of compound 1 against methicillin-resistant Staphylococcus aureus was 210 μmol/L. Conclusion: Compound 1 is a new compound named as 2β,8aα-dihydroxy-11-en-eremophilane, which has a good inhibitory effect against methicillin-resistant Staphylococcus aureus.

Minor Sesquiterpenoid and Steroid Constitutes from Azadirachta indica A. Juss and Their Cytotoxic Activity

Background Neem (Azadirachta indica A. Juss) is a plant belonging to the meliaceae family. It was used widely asherbal medicine in ancient India and Burma. It possesses a variety of chemical constitutes. Recent studies showedthat some of major constitutes have remarkable anticancer activities. However, the minor constitutes in neem arestill studied insufficiently.Aim The aim of the study is to identify the minor constitutes in neem, and investigate their cytotoxic activity.Material & methods The dry seeds of neem were extracted with 95% ethanol. The ethyl acetate fraction of theextract was systematically separated by silica gel, Sephadex LH-20, High Performance Liquid Chromatography(HPLC) and other chromatographic techniques. The structures of the resulting isolates were elucidated byspectroscopic methods, such as mass spectrum (MS), nuclear magnetic resonance spectrum (NMR), etc.Results A sesquiterpenoid, 11,13-dihydroqinghaosu V (1), together with two known steroids, (24R)-ergosta5,7,22E-trien-3β-ol (2) and 5α,8α-epidioxiergosta-6,22-dien-3β-ol (3), was isolated from the dry seeds of neem. 1is a compound which is isolated from nature for the first time. In vitro cytotoxic bioassays showed that compound1 selectively inhibited the growth of Hela cell lines, with an IC50 value of 37.26 ±6.02 µM.Conclusion The study indicated that besides some major constituents of neem possessing anticancer activity, itsminor metabolites may also inhibit growth of cancer cells

Identification of Chemical Components of Yangzheng Xiaoji Capsule by GC-MS and UPLC-Q-TOF-MS / 中国药学杂志

OBJECTIVE: To study the chemical components of Yangzheng Xiaoji capsule. METHODS: The liposoluble constituents and water-soluble constituents of Yangzheng Xiaoji capsule were analyzed by GC-MS and UPLC-Q-TOF-MS. The GC-MS conditions were as follows, PH-5 capillary column(0.25 mm×30 m,0.25 μm) for column chromatography, temperature-programmed and EI were used, the scanning range of quality was m/z 40-650; the UPLC-Q-TOF-MS conditions were as follows, ACQUITY UPLC HSS T3(2.1 mm×100 mm,1.8 μm) with mobile phase of 15 mmol·L-1ammonium formate solution and acetonitrile under gradient elution, with the ESI source. The scanning range was m/z 50-1 500. RESULTS: Twenty liposoluble constituents were identified by GC-MS, including volatile oils,sesquiterpenoids, phenols and lipids, et al. These components were mainly derived from Rhizoma Curcumae, Cynanchum Paniculatum and Tuckahoe. And 38 water-soluble constituents were identified by UPLC-Q-TOF-MS, including triterpenes, triterpenoid saponins, flavonoids, iridoid glycoside and phenolic acid, mainly derived from Panax ginseng, Astragalus membranaceus and Ligustrum lucidumait. CONCLUSION: This study provides a fast and effective method to understand the chemical components of Yangzheng Xiaoji capsule comprehensively, and makes a qualitative analysis and theoretical support for pharmacodynamic substance foundation, quality control and pharmacological mechanism study.

Anti-inflammatory Effect of Chinese Agarwood Essential Oil Via Inhibiting p-STAT3 and IL-1β/IL-6 / 中国药学杂志

OBJECTIVE: Eaglewood is a commonly used precious herbal medicine. Due to the multiple drug effects and shortage of medicinal resources, it is currently a hot research topic. Chinese agarwood essential oil (CEEO) is the main active ingredient of eaglewood. To investigate the anti-inflammatory effect and mechanism of CEEO. METHODS: The anti-inflammatory effect of CEEO was evaluated on xylene-induced ear edema in mice and carrageenan-induced paw swelling in rats. The production and transcription levels of pro-inflammatory cytokines IL-1β and IL-6 were detected by ELISA or quantitative RT-PCR in LPS-activated RAW264.7 macrophages. The protein levels of p-transducer and activator of transcription 3 (STAT3) and p-IκBα/p-NF-κBp65 were detected by Western blot analysis. The chemical profiles of CEEO were identified by GC-MS. RESULTS: Intragastric administration with CEEO (60-960 mg•kg-1 in mice and 680 mg•kg-1 in rats) produced significant anti-inflammatory effect in vivo, the highest inhibition percentages were 73% and 51%, respectively (P<0.001). After treatment with CEEO (10, 5, and 2.5 μg•mL-1), ELISA and RT-PCR analysis showed that the production and mRNA level of IL-1β and IL-6 were attenuated by 68% and 39%, 64% and 52% (P<0.001), respectively, at the highest concentration. Western blot analysis showed that CEEO (680 mg•kg-1, ig) significantly restrained the phosphorylation of STAT3 by 21% (P<0.05). Totally 117 compounds were identified in CEEO by GC-MS analysis and the chemical analysis revealed that sesquiterpenoids were the major compounds (68.83%). CONCLUSION: This study shows for the first time that intragastric administration of CEEO has significant anti-inflammatory effect, which may be due to the suppression of pro-inflammatory cytokines IL-1β and IL-6 by reducing the overexpression of p-STAT3, thereby inhibiting the occurrence and development of inflammation. The anti-inflammatory effect of CEEO may be related to the primary component sesquiterpenoids.

Research progress on constituents of alkaloids in plants from Dendrobium Sw / 中草药

Alkaloids were regarded as important biological activity constituent in medicinal Dendrobium Sw., being characteristic pharmacodynamic components in plants from Dendrobium Sw. A total of 52 constituents of alkaloids were found in plants of Dendrobium Sw. They could be divided into five types, according to different structures. They were sesquiterpenoid alkaloids, octahydroindolizine alkaloids, amides alkaloids, pyrrolidine alkaloids, and imidazole alkaloids etc. Sesquiterpenoid alkaloids could be divided into dendrobine type, dendroxine type, nobiline type, etc. Over 19 Dendrobium species contain alkaloids, and the main species included D. nobile, D. chrysanthum, D. crepidatum, D. findleyanum, D. signatum, D. friedericksianum, etc. This paper reviews the structural classification of alkaloids in Dendrobium, and the species which containing alkaloids and the influencing factors of alkaloids in Dendrobium Sw., in order to provide reference for the in-depth study and the development of alkaloids in plants from Dendrobium Sw.