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https://www.readbyqxmd.com/read/29165897/lithospermum-erythrorhizon-root-and-its-naphthoquinones-repress-srebp1c-and-activate-pgc1%C3%AE-through-ampk%C3%AE
#1
Rodney A Velliquette, Arun Rajgopal, John Rebhun, Kelly Glynn
OBJECTIVE: To examine specific molecular mechanisms involved in modulating hepatic lipogenesis and mitochondria biogenesis signals by Lithospermum erythrorhizon (gromwell) root extract. METHODS: Stable cell lines with luciferase reporter constructs were generated to examine sterol regulatory element binding protein 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1) α promoter activity and estrogen-related receptor (ERR) α response element activity...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29139179/involvement-of-lemrp-an-atp-binding-cassette-transporter-in-shikonin-transport-and-biosynthesis-in-lithospermum-erythrorhizon
#2
Yu Zhu, Shu-Juan Chu, Yue-Lin Luo, Jiang-Yan Fu, Cheng-Yi Tang, Gui-Hua Lu, Yan-Jun Pang, Xiao-Ming Wang, Rong-Wu Yang, Jin-Liang Qi, Yong-Hua Yang
·Shikonin and its derivatives are important medicinal secondary metabolites accumulating in the roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. ·In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon and further investigated its functions in the transport and biosynthesis of shikonin with the yeast transformation and transgenic hairy root method, respectively...
November 15, 2017: Plant Biology
https://www.readbyqxmd.com/read/29132307/involvement-of-lemdr-an-atp-binding-cassette-protein-gene-in-shikonin-transport-and-biosynthesis-in-lithospermum-erythrorhizon
#3
Yu Zhu, Gui-Hua Lu, Zhuo-Wu Bian, Feng-Yao Wu, Yan-Jun Pang, Xiao-Ming Wang, Rong-Wu Yang, Cheng-Yi Tang, Jin-Liang Qi, Yong-Hua Yang
BACKGROUND: Shikonin is a naphthoquinone secondary metabolite with important medicinal value and is found in Lithospermum erythrorhizon. Considering the limited knowledge on the membrane transport mechanism of shikonin, this study investigated such molecular mechanism. RESULTS: We successfully isolated an ATP-binding cassette protein gene, LeMDR, from L. erythrorhizon. LeMDR is predominantly expressed in L. erythrorhizon roots, where shikonin accumulated. Functional analysis of LeMDR by using the yeast cell expression system revealed that LeMDR is possibly involved in the shikonin efflux transport...
November 13, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29109024/ampk-regulates-immunometabolism-in-sepsis
#4
Jun Huang, Ke Liu, Shan Zhu, Min Xie, Rui Kang, Lizhi Cao, Daolin Tang
Sepsis and septic shock remain challenging for intensive care units worldwide and have limited treatment options; therefore, identification of targetable key players in systemic inflammation and multiple organ failure is urgently needed. Here, we show that AMP-activated protein kinase (AMPK) is a negative regulator of bioenergetic reprogramming in immune cells and suppresses sepsis development in vivo. Mechanistically, AMPK deficiency increases pyruvate kinase isozyme M2 (PKM2)-dependent aerobic glycolysis, which leads to the release of high mobility group box 1 (HMGB1, a late mediator of lethal systemic inflammation) in macrophages and monocytes...
November 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29101810/the-evaluation-of-potent-antitumor-activities-of-shikonin-coumarin-carboxylic-acid-pmmb232-through-hif-1%C3%AE-mediated-apoptosis
#5
Hong-Wei Han, Chao-Sai Zheng, Shu-Juan Chu, Wen-Xue Sun, Lu-Jing Han, Rong-Wu Yang, Jin-Liang Qi, Gui-Hua Lu, Xiao-Ming Wang, Yong-Hua Yang
In current study, a series of shikonin derivatives were synthesized and its anticancer activity was evaluated. As a result, PMMB232 showed the best antiproliferation activity with an IC50 value of 3.25±0.35μM. Further, treatment of HeLa cells with a variety of concentrations of target drug resulted in dose-dependent event marked by apoptosis. What's more, the mitochondrial potential (Δym) analysis was consistent with the apoptosis result. In addition, PARP was involved in the progress of apoptosis revealed by western blotting...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29100031/research-on-major-antitumor-active-components-in-zi-cao-cheng-qi-decoction-based-on-hollow-fiber-cell-fishing-with-high-performance-liquid-chromatography
#6
Miaomiao Li, Shuang Hu, Xuan Chen, Runqin Wang, Xiaohong Bai
Hollow fiber cell fishing (HFCF) based on hepatoma HepG-2 cells, human renal tubular ACHN cells or human cervical carcinoma HeLa cells, coupled with high-performance liquid chromatography (HPLC), was developed and employed to research the major active components in Zi-Cao-Cheng-Qi decoction both in vitro and in vivo. The research showed that the active components, such as hesperidin, magnolol, honokiol, shikonin, emodin and β,β'-dimethylacrylshikonin were screened out by HFCF based on the cancer cells in vitro, furthermore they can be absorbed into blood and reach in the target organ, and some of the active components can be fished by the cells and maintain effective concentrations...
October 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29071863/-secondary-metabolic-responses-to-treatment-of-2-aminoindan-2-phosphonic-acid-in-cell-lines-from-arnebia-euchroma
#7
Chao-Geng Lv, Sheng Wang, Wan-Zhen Yang, Tan Liu, Lan-Ping Guo
The accumulation of rosmarinic acid, acetylshikonin, deoxyshikonin, β, β'-dimethylacrylshikonin and isovalerylshikonin was investigated in cell suspension cultures of Arnebia euchroma (Royle) Johnst under the influence of 2-aminoindan-2-phosphonic acid (AIP), an inhibitor of phenylalanine ammonia lyase (PAL), and of the effector methyl jasmonate (MeJA). The results showed that methyl jasmonate promoted the accumulation of rosmarinic acid and shikonin derivatives. Conversely, 2-aminoindan-2-phosphonic acid suppressed the formation of rosmarinic acid, which indicated that AIP, indeed, was able to inhibit the phenylpropanoid pathway in A...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29066190/identification-of-new-shikonin-derivatives-as-stat3-inhibitors
#8
Han-Yue Qiu, Jiang-Yan Fu, Min-Kai Yang, Hong-Wei Han, Peng-Fei Wang, Ya-Han Zhang, Hong-Yan Lin, Cheng-Yi Tang, Jin-Liang Qi, Rong-Wu Yang, Xiao-Ming Wang, Hai-Liang Zhu, Yong-Hua Yang
The signal transducer and activator of transcription 3 is a constitutively activated oncogenic protein in various human tumors and represents a valid target for anticancer drug design. In this study, we have achieved a new type of STAT3 inhibitors based on structural modifications on shikonin scaffold, guided by computational modelling. By tests, PMMB-187 exhibited a more outstanding profile than shikonin on a small panel of human breast cancer cells, especially for the MDA-MB-231 cells. For the cellular mechanisms research, PMMB-187 was found to induce cell apoptosis in MDA-MB-231 cells, associated with the reduction of mitochondrial membrane potential, production of ROS and alteration of the levels of apoptosis-related proteins...
October 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29039581/shikonin-induces-apoptosis-and-g0-g1%C3%A2-phase-arrest-of-gallbladder-cancer-cells-via-the-jnk-signaling-pathway
#9
Tianyu Zhai, Zhenyu Hei, Qiang Ma, Haibin Liang, Yi Xu, Yichi Zhang, Longyang Jin, Chao Han, Jiandong Wang
Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with few curative therapeutic stragegies and poor prognosis. In the present study, we detected the effects of shikonin on GBC cells as well as the underlying molecular mechanisms. The results demonstrated that GBC cell proliferation was inhibited by shikonin as determined by MTT and colony formation assays. Flow cytometry results demonstrated that shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC cells...
October 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29032577/pyruvate-kinase-isozymes-m2-and-glutaminase-might-be-promising-molecular-targets-for-the-treatment-of-gastric-cancer
#10
Kishu Kitayama, Masakazu Yashiro, Tamami Morisaki, Yuichiro Miki, Tomohisa Okuno, Haruhito Kinoshita, Tatsunari Fukuoka, Hiroaki Kasashima, Go Masuda, Tsuyoshi Hasegawa, Katsunobu Sakurai, Naoshi Kubo, Kosei HIrakawa, Masaichi Ohira
The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and 4 parent cell lines were used. RT-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozymes M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, Shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo...
October 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28972001/the-metabolic-and-proliferative-state-of-vascular-adventitial-fibroblasts-in-pulmonary-hypertension-is-regulated-through-a-mir-124-ptbp1-pkm-axis
#11
Hui Zhang, Daren Wang, Min Li, Lydie Plecitá-Hlavatá, Angelo D'Alessandro, Jan Tauber, Suzette Riddle, Sushil Kumar, Amanda R Flockton, B Alexandre McKeon, Maria G Frid, Julie A Reisz, Paola Caruso, Karim C El Kasmi, Petr Ježek, Nicholas W Morrell, Cheng-Jun Hu, Kurt R Stenmark
Background -An emerging "metabolic theory" of pulmonary hypertension (PH) suggests that cellular and mitochondrial metabolic dysfunction underlies the pathology of this disease. We and others have previously demonstrated the existence of hyper-proliferative, apoptosis-resistant, pro-inflammatory adventitial fibroblasts from human and bovine hypertensive pulmonary arterial walls (PH-Fibs) exhibit constitutive reprogramming of glycolytic and mitochondrial metabolism, accompanied by an increased ratio of glucose catabolism through glycolysis versus the TCA cycle...
September 26, 2017: Circulation
https://www.readbyqxmd.com/read/28943938/shikonin-enhances-adriamycin-antitumor-effects-by-inhibiting-efflux-pumps-in-a549-cells
#12
Xuchun Liu, Gengyun Sun
Shikonin (SHK) is a natural naphthoquinone pigment isolated from Lithospermum erythrorhizon, that has been reported to suppress the growth of a number of cancer cell types. Adriamycin (AD) is typically used as an effective anticancer agent; however, it has the propensity to induce drug resistance. The aim of the present study was to investigate the effects of SHK alone and in combination with AD on lung adenocarcinoma cells and the underlying molecular mechanisms of their effects. Colony formation, MTT and propidium iodide staining assays demonstrated that the co-treatment of A549 cells with SHK and AD significantly decreased cell viability and potently induced apoptosis...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28941798/assessment-of-the-inhibition-risk-of-shikonin-on-cytochrome-p450-via-cocktail-inhibition-assay
#13
Shuowen Tang, Ang Chen, Xiaojing Zhou, Li Zeng, Mingyao Liu, Xin Wang
Shikonin is a naphthoquinone pigment extracted from roots of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), and possesses various pharmaceutical activities, such as anti-inflammation and anti-cancer effects. In addition, shikonin as a natural red colorant for food garnishment and cosmetics ingredient is widely used in the world. However, the inhibition risk of shikonin on cytochrome P450 (CYP) remains unclear. The aim of this study was to investigate the potential inhibition of shikonin against CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver microsomes through cocktail approach in vitro...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28934735/effect-of-shikonin-on-spinal-cord-injury-in-rats-via-regulation-of-hmgb1-tlr4-nf-kb-signaling-pathway
#14
Yihui Bi, Yapeng Zhu, Mingkai Zhang, Keke Zhang, Xingyi Hua, Zheng Fang, Jian Zhou, Wenjie Dai, Yixing Cui, Jun Li, Tao You
BACKGROUND/AIMS: Shikonin, a compound extracted from Zicao, has been demonstrated to hold anti-bacterial, anti-inflammatory, and anti-tumor activities in various diseases and it has been shown to protect human organs from injuries. However, the effect of shikonin on the recovery of spinal cord injury (SCI) remains unknown. This study was designed to estimate the potential therapeutic effect and underlying mechanism of shikonin on SCI in vivo. METHODS: In the study, we used HE staining, ELISA assay, transfection assay, TUNEL assay, real time PCR and Western blot to detect the effects of shikonin on spinal cord injury in rats...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934417/production-of-3-geranyl-4-hydroxybenzoate-acid-in-yeast-an-important-intermediate-of-shikonin-biosynthesis-pathway
#15
Sheng Wang, Ruishan Wang, Tan Liu, Zhilai Zhan, Liping Kang, Yanan Wang, Chaogeng Lv, Daniele Werck-Reichhart, Lanping Guo, Luqi Huang
Shikonin and its derivatives are the main active components in the medicinal plant Arnebia euchroma and possess extensive pharmaceutical properties. In this study, we developed an optimized yeast system to obtain high-level production of 3-geranyl-4-hydroxybenzoate acid (GBA), an important intermediate involved in shikonin biosynthesis pathway. For host selection, recombinant expression of p-hydroxybenzoate:geranyltransferase (PGT) derived from A. euchroma was performed in Saccharomyces cerevisiae WAT11U strain and high yield monoterpene strain...
November 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28933271/targeting-cell-necroptosis-and-apoptosis-induced-by-shikonin-via-receptor-interacting-protein-kinases-in-estrogen-receptor-positive-breast-cancer-cell-line-mcf-7
#16
Zahra Shahsavari, Fatemeh Karami-Tehrani, Siamak Salami
Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer. Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7. In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells...
September 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28922731/shikonin-suppresses-pulmonary-fibroblasts-proliferation-and-activation-by-regulating-akt-and-p38-mapk-signaling-pathways
#17
Yunjuan Nie, Yaoyao Yang, Jian Zhang, Guowei Cai, Yanhua Chang, Gaoshang Chai, Chongyong Guo
Fibroblast is believed to be the primary effector in idiopathic pulmonary fibrosis (IPF), a progressive lung disorder characterized by aberrant tissue remodeling and the formation of fibroblastic foci. Due to the complicated etiology and mechanism, there are few effective drugs for this fatal disease. Shikonin (SHI), which is the major ingredient isolated from the plant Lithospermum Erythrorhizon, has long been used as traditional medicine for many diseases including inflammation and cancer. The roles of SHI in attenuating skin scar and renal fibrosis by reducing TGFβ1-stimulated fibroblast activation are also reported...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28863897/lactoferrin-functionalized-peg-plga-nanoparticles-of-shikonin-for-brain-targeting-therapy-of-glioma
#18
Hanmei Li, Yuna Tong, Lan Bai, Lei Ye, Lei Zhong, Xingmei Duan, Yuxuan Zhu
Shikonin (SHK) is a highly liposoluble naphthoquinone pigment has recently been investigated as a potential antiglioma agent. However, shikonin shows several limitations like poor aqueous solubility, short half-life and non-selective biodistribution. Herein, we have developed a nanoparticles (NPs) prepared from PEG-PLGA using an emulsion solvent evaporation method. Nanoparticle surfaces were modified by coating with lactoferrin (Lf) to improve the crossing of the blood brain barrier and targeting of glioma cells via receptor-mediated path-ways...
August 31, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28842339/gangjihwan-a-polyherbal-composition-inhibits-fat-accumulation-through-the-modulation-of-lipogenic-transcription-factors-srebp1c-ppar%C3%AE-and-c-ebp%C3%AE
#19
Jaewoong Jang, Yoonju Jung, Seyeon Chae, Soo Hyun Cho, Michung Yoon, Heejung Yang, Soon Shik Shin, Yoosik Yoon
ETHNOPHARMACOLOGICAL RELEVANCE: Gangjihwan (DF) which is composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum has been used for the treatment of obesity in traditional medical clinics in Korea. AIM OF THE STUDY: This study was conducted to standardize DF and elucidate its mechanism of action for inhibiting fat accumulation in adipocytes and adipose tissues. MATERIALS AND METHODS: The herbal ingredients of DF were extracted in water, 30% ethanol or 70% ethanol and freeze-dried followed by HPLC analyses...
August 24, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28840695/-simultaneous-determination-of-eight-hydroxyl-naphthoquinones-in-different-parts-of-arnebiae-euchroma-by-hplc
#20
Ke Zan, Huang-Ya Zheng, Jie Liu, Li-Nong Guo, Jian Zheng, Shuang-Cheng Ma
This present study is to develop an HPLC method for simultaneous determination of eight hydroxyl naphthoquinones, shikonin, β-hydroxy-isovalerylshikonin, acetylshikonin, β-acetoxy-isovalerylshikonin, deoxyshikonin, isobutyrylshikonin, β,β'-dimethylacrylshikonin and isovalerylshikonin. The eight constituents were measured on a Waters Xbridge C18 column (4.6 mm×250 mm,5 μm) with isocratic elution of acetonitrile-0.05% formic acid solution (70∶30) at a flow rate of 1.0 mL•min⁻¹. The detection wavelength was 275 nm and the column temperature was 30 ℃...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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