[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Incaspitolide A isolated from Carpesium cernuum L. inhibits the growth of prostate cancer cells and induces apoptosis via regulation of the PI3K/Akt/xIAP pathway.

Carpesium cernuum L. is a traditional medicine primarily used in Southwestern China, and it has been shown to exhibit a range of biological properties, including anti-inflammatory and antitumor activities. Incaspitolide A (IA) is a sesquiterpene isolated from C. cernuum L. The aim of the present study was to investigate the antiproliferative effects of IA on PC-3 prostate cancer cells and determine the underlying mechanism. Results from a Cell Counting Kit-8 assay demonstrated that IA significantly reduced the numbers of viable PC-3 cells in a time and dose-dependent manner. Phase-contrast microscopy revealed that the number and morphology of cells were markedly altered. Hoechst and EdU staining assays showed that IA reduced the proliferation of PC-3 cells. Flow cytometry analysis revealed that IA arrested cell cycle progression at the S phase and promoted cell apoptosis in a dose-dependent manner. Western blot analysis demonstrated that treatment with IA resulted in downregulation of phosphorylated (p-) PI3K, p-Akt, X-linked inhibitor of apoptosis (xIAP), CKD2, cyclin A2 and pro-Caspase-3 protein expression, and upregulation of cleaved poly(ADP-ribose) polymerase and P53 expression. The present results suggested that IA inhibited the growth of PC-3 cells and induced apoptosis. The underlying mechanism appeared to involve the inhibition of the PI3K/Akt/xIAP pathway. The present study indicated that IA may serve as a therapeutic for the management of prostate cancer and provided a theoretical basis for the pathogenesis of prostate cancer.

Phytochemical Profile and Anti-Inflammatory Activity of the Fraction from Artemisia lavandulaefolia.

Artemisia lavandulaefolia, a traditional herbal medicine, has been utilized as anti-inflammatory and analgesia agent in clinic. Bioassay-guided fractionation resulted in a fraction (ALDF) with anti-inflammatory effect obtained from A. lavandulaefolia. Its main constituents were analyzed and identified by UPLC-ESI-Q-TOF-MS technology. ALDF showed the strong inhibitory activity on the nitrogen oxide (NO) production in LPS-induced RAW 264.7 macrophages with an IC50 value of 1.64±0.41 µg/mL. Further results displayed that ALDF also significantly suppressed the secretion of key pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2 ) and interleukin-1ß (IL-1ß), and the increase of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression induced by LPS stimulation. Mechanism study indicated that ALDF was able to block NF-κB signaling pathway through inhibiting IκB and p65 phosphorylation, as well as NF-κB p65 nuclear translocation. Furthermore, in vivo results in mice revealed that treatments with ALDF evoked significant inhibition on ear edema induced by xylene and on the writhing responses induced by acetic acid. These results suggest that ALDF holds great potential in the prevention and treatment of inflammatory disorders.

Nitric Oxide Production Inhibitory Eudesmane-Type Sesquiterpenoids from Artemisia argyi.

Six new eudesmane-type sesquiterpene derivatives, artemargyinins A-F were isolated from the leaves of Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. Artemargyinins A-F feature a lactone ring-opening eudesmane-type sesquiterpene with an isoprenoid group at C(8). All compounds were tested for their inhibitory effects on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 macrophages. Artemargyinins A-F showed more potent NO production inhibitory activity with IC50 values ranging from 7.66±0.53 to 61.19±2.54 µM than the positive control quercetin (IC50 =74.34±1.39 µM). Among them, artemargyinins C and D exhibited strong inhibitory activity with IC50 values of 8.08±0.21 and 7.66±0.53 µM, respectively.

Triterpenoids with α-glucosidase inhibitory activity from Artemisia argyi.

Two new nordammarane-type triterpenoids, 3ß-acetoxy-20-oxo-21-nordammaran-23-carboxylic acid methyl ester (1) and 3ß-acetoxy-17ß-dammaranic acid (2), along with two known cycloartane-type triterpenoids (3-4), were isolated from the petroleum ether-soluble extract of Artemisia argyi. Their structures were elucidated based on 1D and 2D NMR spectroscopic data analysis. All compounds were evaluated for their α-glucosidase inhibitory activity in vitro. Compounds 1-4 exhibited significant inhibitory effects on α-glucosidase with IC50 values ranging from 38.34 ± 0.23 to 105.54 ± 0.33 µM.

Sesquiterpenoids from Artemisia argyi and their COXs inhibitory activities.

Four new sesquiterpene lactones, named artemargyinolides A-D (1-4), and seven known sesquiterpenoids (5-11) were isolated from Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. The absolute configuration of 1 was assigned by X-ray crystallographic analysis. Compound 1 is an unprecedented sesquiterpene dimer-monoterpene lactone. The cyclooxygenases (COX-1 and COX-2) inhibitory activities of all isolated compounds were evaluated. Compounds 1, 2, 4, and 6-11 showed inhibitory activity against COX-2 with IC50 values ranging from 35.78 ±â€¯0.39 to 256.07 ±â€¯0.38 µM. However, compounds 7, 9, and 10 exhibited weak inhibitory activity against COX-1 with IC50 values of 465.70 ±â€¯1.53, 281.43 ±â€¯3.56, and 490.45 ±â€¯6.07 µM, respectively. Other compounds are inactive against COX-1. Therefore, compounds 1, 2, 4, 6, 8, and 11 displayed selective COX-2 inhibitory activity.

A chloroplast-inspired nanoplatform for targeting cancer and synergistic photodynamic/photothermal therapy.

Specific targeting capabilities and effective phototherapeutic functions are the key demands for precise cancer phototherapeutic agents. Herein, a bioinspired nanoplatform composed of Cu(ii)-chlorophyll-hyaluronic acid nanoparticles (Cu(ii)Chl-HA NPs) was developed for targeting cancer and synergistic photodynamic/photothermal therapy. Inspired by the photonic biosystem of the chloroplast, Cu(ii) chlorophyll was used as a photosensitive substituent to covalently connect with a hydrophilic HA tail rather than a natural phytol tail, and this conjugate further assembled into a nanoparticle-like morphology under non-covalent interaction. Time-dependent density functional theory calculations reveal that the Cu(ii) chlorophyll has a much smaller energy gap between an excited singlet and excited triplet, and theoretically leads to rapid electron intersystem crossing that would benefit the PDT effect. In addition, a series of experiments have proven that, under 650 nm laser irradiation, the nanoplatform of Cu(ii)Chl-HA can produce a high amount of singlet oxygen and exhibit an outstanding photothermal conversion capability. More interestingly, owing to the specific interactions between the HA component and the CD44 receptor on the cell membrane, the HA tails impart Cu(ii)Chl-HA NPs an excellent receptor-mediated targeting performance toward CD44-overexpressing cancer cells. Based on these features, the nanoplatform of Cu(ii)Chl-HA NPs presents active targeting and outstanding dual modality synergistic PDT/PTT performance of cancer both in vitro and in vivo. Thus, this work opens up a new strategy to fabricate a bioinspired multifunctional cancer phototherapy nanoplatform.

[Verification of the theory of "Lieque (LU 7) for the disorders of the head and neck" based on infrared thermography].

OBJECTIVE: To verify that whether or not through the effects of the externally and internally related meridians in treatment, Lieque (LU 7) is adopted specially for the disorders of the head and neck. METHODS: A total of 36 healthy volunteers were collected from the students of Gansu University of CM and were divided into a Lieque group and a Jingqu group according to the random number table, 18 cases in each one. In the Lieque group, Lieque (LU 7) on the unilateral side was punctured in the subjects. In the Jingqu group, Jingqu (LU 8) was taken as the control because it was located close to Lieque (LU 7) and on the same meridian. Before and after acupuncture in the two groups, separately, the infrared thermography was adopted to determine the temperature changes at the acupoints of the lung meridian of hand-taiyin, i.e. Jingqu (LU 8), Lieque (LU 7), Kongzui (LU 6), Chize (LU 5) and Tianfu (LU 3) as well as the acupoints of the large intestine meridian of hand-yangming, i.e., Wenliu (LI 7), Shousanli (LI 10), Quchi (LI 11), Shouwuli (LI 13) and Binao (LI 14). RESULTS: After acupuncture stimulation at Lieque (LU 7), the temperature at the acupoints of the lung meridian of hand-taiyin, i.e. Jingqu (LU 8), Lieque (LU 7), Kongzui (LU 6), Chize (LU 5) and Tianfu (LU 3) and the acupoints of the large intestine meridian of hand-yangming, i.e. Wenliu (LI 7), Shousanli (LI 10), Quchi (LI 11), Shouwuli (LI 13) and Binao (LI 14) was all higher obviously as compared with the temperature before acupuncture stimulation (all P<0.05). After acupuncture stimulation at Jingqu (LU 8), the temperature at the acupoints of the lung meridian of hand-taiyin was all increased obviously as compared with the temperature before acupuncture stimulation (all P<0.05), but there was no significant difference in the temperature at the large intestine meridian of hand-yangming (all P>0.05). CONCLUSION: For the disorders of the head and neck, acupuncture at Lieque (LU 7) achieves the stimulation and communication of both the lung meridian and the large intestine meridians, so that it is applicable for the disorders of the externally and internally related meridians.

[Research progress on anti-inflammatory mechanism of natural sesquiterpenoids].

Sesquiterpenoid is a kind of compound widely distributed in nature, which has a wide range of biological activities, such as anti-inflammatory, anti-tumor and immunomodulatory activities. This paper would review the anti-inflammatory mechanism of sesquiterpenoid. The mechanism is mainly by inhibiting the activation of nuclear factor (NF-κB), mitogen-activated protein kinase (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways and down-regulating the inflammatory gene expression including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-1(IL-1), IL-6, IL-8 and other inflammatory factors. Thereby, the production and release of inflammatory cytokines are reduced to exert anti-inflammatory effect. This review is intended to provide reference for related research.

Blue light emitting diodes irradiation causes cell death in colorectal cancer by inducing ROS production and DNA damage.

The light emitting diodes (LEDs) irradiation has been demonstrated to be potential therapeutic strategies for several diseases. However, the blue LED effects remain largely unknown in colorectal cancer (CRC), which is a major cause of morbidity and mortality throughout the world. In this study, we determined the effects of blue LED irradiation, the maximal light emission at 470 nm in wavelength, in human CRC cell lines SW620 and HT29. The cells were irradiated with blue LED light for 0 J/cm2, 72 J/cm2, 144 J/cm2, 216 J/cm2 and 288 J/cm2 respectively. We found that irradiation with blue LED light induced a marked decrease of live cells and an increase of dead cells. Additionally, lower cell proliferation and a remarkably increase of cell apoptosis were observed in blue LED-irradiated cells as compared with non-irradiated control group. The cell migration was significantly inhibited by blue LED irradiation 24, 48 and 72 h later compared with non-treated group. Blue LED-treated CRC cells further displayed a remarkably inhibition of EMT process in CRC cells. Finally, we found the accumulation of ROS production and DNA damage were induced by blue LED irradiation. These results indicated that blue LED irradiation inhibits CRC cell proliferation, migration and EMT process as well as induces cell apoptosis, which may result from increased ROS accumulation and induction of DNA damage.

By Targeting Atg7 MicroRNA-143 Mediates Oxidative Stress-Induced Autophagy of c-Kit+ Mouse Cardiac Progenitor Cells.

Therapeutic efficiency of cardiac progenitor cells (CPCs) transplantation is limited by its low survival and retention in infarcted myocardium. Autophagy plays a critical role in regulating cell death and apoptosis, but the role of microRNAs (miRNAs) in oxidative stress-induced autophagy of CPCs remains unclear. This study aimed to explore if miRNAs mediate autophagy of c-kit+ CPCs. We found that the silencing of miR-143 promoted the autophagy of c-kit+ CPCs in response to H2O2, and the protective effect of miR-143 inhibitor was abrogated by autophagy inhibitor 3-methyladenine (3-MA). Furthermore, autophagy-related gene 7 (Atg7) was identified as the target gene of miR-143 by dual luciferase reporter assays. In vivo, after transfection with miR-143 inhibitor, c-kit+ CPCs from green fluorescent protein transgenic mice were more observed in infarcted mouse hearts. Moreover, transplantation of c-kit+ CPCs with miR-143 inhibitor improved cardiac function after myocardial infarction. Take together, our study demonstrated that miR-143 mediates oxidative stress-induced autophagy to enhance the survival of c-kit+ CPCs by targeting Atg7, which will provide a complementary approach for improving CPC-based heart repair.

Phthalide dimers from Angelica sinensis and their COX-2 inhibition activity.

Four new dimeric phthalides, angesinenolides C-F (1-4), along with three known ones, were isolated from the roots of Angelica sinensis. Their structures were determined by means of HRMS and NMR experiments. The structures of compounds 1 and 3 were confirmed using X-ray crystallographic data. All isolated compounds were tested for activities on the inhibition of COX-2 enzyme in vitro. Compounds 1-6 exhibited inhibitory activity against COX-2 with IC50 values ranging from 29.32 ±â€¯0.07 to 137.91 ±â€¯0.24 µM.

Sesquiterpene Lactones with COX-2 Inhibition Activity from Artemisia lavandulaefolia.

Two new sesquiterpene lactones, artelavanolides A (1) and B (2), and four known sesquiterpene lactones (3 - 6) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D-NMR and HR-ESI-MS). The absolute configuration of 1 was determined by the analysis of single-crystal X-ray diffraction data. Artelavanolide A (1) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)-C(1) that is probably formed through a rearrangement of the guaiane-type sesquiterpenoids. Artelavanolide B (2) is a new highly unsaturated guaianolide. Compounds 1 - 6 were tested for activities on the inhibition of COX-2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX-2 with IC50 values ranging from 43.29 to 287.07 µm compared with the positive control, celecoxib (IC50 = 18.10 µm). Among them, 3 showed the best COX-2 inhibitory activity with an IC50 value of 43.29 µm.

Two new flavonoids from Artemisia argyi with their anticoagulation activities.

A new flavone glycoside, eupatilin 7-O-ß-d-glucopyranoside (1) and a new flavone, 5,6,2',4'-tetrahydroxy-7,5'-dimethoxyflavone (2), were isolated from Artemisia argyi. Their structures were unambiguously elucidated by extensive spectroscopic analysis. Both flavonoids were evaluated for in vitro anticoagulation activities. Compound 1 significantly extended thrombin time. Compound 2 had obvious effect in increasing prothrombin time.

Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS.

BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS) is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. METHODS: BMSCs were exposed to ferric ammonium citrate (FAC) with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, ß-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS) level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. RESULTS: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 µg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. CONCLUSION: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

Phthalide Derivatives with Anticoagulation Activities from Angelica sinensis.

Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C-6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB.

[Hair roots induction and culture of Withania somnifera and its withanolide A synthesis].

Withanolide A is a biologically active secondary metabolite occuring in roots and leaves of Withania somnifera. In the present study, adventitious roots from leaf explants of W. somnifera were induced for the production of withanolide-A by Agrobacterium tumefaciens strain C58C1 to obtain hair roots. Hair roots induction rate reached 30%. The withanolide A was determined by HPLC in different hair roots lines and different parts of W. somnifera. The average content of withanolide A in all hair roots lines were 1.96 times as high as that in wild-plant, the concentration of withanolide A in hair roots (1.783 mg x g(-1) dry weight) were 1.51 times as high as the roots of wild W. somnifera (1.180 mg x g(-1) dry weight), respectively. It is possible to obtain withanolide A from hair roots culture of W. somnifera.

[Plant regeneration and clonal propagation system of Datura metel].

OBJECTIVE: To study the condition of plant regeneration and clonal propagation system of Datura metel. METHODS: Stems and leaves of Datura metel were used as explants, effects of different hormones for callus induction and plant regeneration of leaves and clonal propagation system of stems were studied and optimized. RESULTS: The optimal way to obtain sterile explant for leaves were sterilized in 75% ethyl alcohol for 6 s then 0.1% HgCl2 for 6 min; Stems were sterilized in 75% ethyl alcohol for 8 s then 0.1% HgCl2 for 7 min. The optimal medium for callus of leaves was MS + 1.0 mg/L 6-BA + 0.1 mg/L NAA; The optimal medium for callus induction of clustered buds was MS + 2.0 mg/L 6-BA + 0.2 mg/L NAA; The optimal medium for clonal propagation system of stems was MS + 3.0 mg/L 6-BA + 0.05 mg/L NAA. The best medium for rooting induction was MS + 0.5 mg/L IBA. Transplant survival rate of plantlet was greater than 90% in humus soil-pearlite (5:1). CONCLUSION: The condition of plant regeneration and clonal propagation system of Datura metel is established.

Massage interventions and treatment-related side effects of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Massage as a complementary and alternative therapy has been associated with enhancing health and coping with treatment-related side effects in patients with breast cancer worldwide. This systematic review examined whether massage interventions provide any measurable benefit in breast cancer-related symptoms. METHODS: Randomized controlled trials (RCTs) were searched for in PubMed, EMBASE.com and the Cochrane Library through June 2013. We evaluated the quality of the studies included by the Cochrane Handbook 5.2 standards and analyzed the data using the Cochrane Collaboration's RevMan 5.2 software. RESULTS: Eighteen RCTs with a total of 950 participants were included. Compared with the control group, our meta-analysis showed that patients receiving regular use of massage had significantly greater reductions in anger and fatigue symptoms. However, there were no significant differences in depression, anxiety, pain, upper limb lymphedema, cortisol and health-related quality of life. CONCLUSIONS: The current evidence demonstrates that there was mild evidence that massage may be a useful intervention in alleviating negative emotions and fatigue in patients with breast cancer. More trials with longer follow-up are needed to determine the exact long-term efficacy of this class of complementary and alternative medicine on breast cancer-related symptoms and quality of life.

Geranyl flavonoids from Robinia pseudoacacia.

A new geranyl flavonol, robipseudin A (1), and a known geranyl flavone, kuwanon S (2), were isolated from the leaves of Robinia pseudoacacia. The structure of the new compound was determined by spectroscopic methods. Compounds 1 and 2 showed moderate antioxidant activities in the DPPH radical scavenging assay.