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https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#1
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311595/shikonin-protects-pc12-cells-against-%C3%AE-amyloid-peptide-induced-cell-injury-through-antioxidant-and-antiapoptotic-activities
#2
Yuna Tong, Lan Bai, Rong Gong, Junlan Chuan, Xingmei Duan, Yuxuan Zhu
Excessive accumulation of β-amyloid (Aβ) is thought to be a major causative factor in the pathogenesis of Alzheimer's disease (AD). Pretreating Aβ-induced neurotoxicity is a potential therapeutic approach to ameliorate the progression and development of AD. The present study aimed to investigate the neuroprotective effect of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on Aβ1-42-treated neurotoxicity in PC12 cells. Pretreating cells with shikonin strongly improved cell viability, decreased the malondialdehyde and reactive oxygen species (ROS) content, and stabilized the mitochondrial membrane potential in Aβ1-42-induced PC12 cells...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29304496/the-protective-effect-of-shikonin-on-renal-tubular-epithelial-cell-injury-induced-by-high-glucose
#3
Yuna Tong, Junlan Chuan, Lan Bai, Jianyou Shi, Lei Zhong, Xingmei Duan, Yuxuan Zhu
Hyperglycemia-induced oxidative stress is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). Treating high-glucose (HG)-induced proximal tubule injury has become a patential therapeutic option to attenuate the onset and progression of DN. The present study aimed to investigate the renoprotective effect of shikonin, the chief active compound extracted from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on HG-induced cytotoxicity in NRK-52E cells. Treating cells with HG significantly reduce cell viability while also significantly increasing content of reactive oxygen species (ROS)...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29290767/efficacy-of-shikonin-against-esophageal-cancer-cells-and-its-possible-mechanisms-in-vitro-and-in-vivo
#4
Jian-Cai Tang, Jia Zhao, Feng Long, Jian-Ye Chen, Bo Mu, Zhen Jiang, Yonggan Ren, Jian Yang
Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. CCK-8 was used to examine the esophageal cancer cell viability. Apoptosis and cell cycle were analyzed by flow cytometry...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29290031/specialized-plant-metabolism-characteristics-and-impact-on-target-molecule-biotechnological-production
#5
REVIEW
Hélio Nitta Matsuura, Sonia Malik, Fernanda de Costa, Morteza Yousefzadi, Mohammad Hossein Mirjalili, Randolph Arroo, Avninder S Bhambra, Miroslav Strnad, Mercedes Bonfill, Arthur Germano Fett-Neto
Plant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules...
December 30, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/29243243/shikonin-inhibits-myeloid-differentiation-protein-2-to-prevent-lipopolysaccharide-induced-acute-lung-injury
#6
Yali Zhang, Tingting Xu, Zheer Pan, Xiangting Ge, Chuchu Sun, Chun Lu, Hongjin Chen, Zhongxiang Xiao, Bing Zhang, Yuanrong Dai, Guang Liang
BACKGROUND AND PURPOSE: Acute lung injury (ALI) is a challenging clinical syndrome which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating lipopolysaccharide (LPS)-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin (SHI), a natural naphthoquinone, prevents LPS-inflammation...
December 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29225125/interdependence-of-glo-i-and-pkm2-in-the-metabolic-shift-to-escape-apoptosis-in-glo-i-dependent-cancer-cells
#7
Nami Shimada, Ryoko Takasawa, Sei-Ichi Tanuma
Many cancer cells undergo metabolic reprogramming known as the Warburg effect, which is characterized by a greater dependence on glycolysis for ATP generation, even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis and which is known to be highly expressed in many cancer cells. Thus, specific inhibitors of GLO I are expected to be effective anticancer drugs. We previously discovered a novel GLO I inhibitor named TLSC702...
December 8, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29223049/determination-of-blood-concentrations-of-main-active-compounds-in-zi-cao-cheng-qi-decoction-and-their-total-plasma-protein-binding-rates-based-on-hollow-fiber-liquid-phase-microextraction-coupled-with-high-performance-liquid-chromatography
#8
Miaomiao Li, Xuan Chen, Shuang Hu, Runqin Wang, Xiaoli Peng, Xiaohong Bai
Oil-in-salt hollow fiber liquid phase microextraction coupled with high performance liquid chromatography ultraviolet detection (HPLC-UV) was developed for determination of the blood concentrations of the main active compounds, hesperidin, honokiol, shikonin, magnolol, emodin and β,β'-dimethylacrylshikonin, after oral administration of Zi-Cao-Cheng-Qi decoction (ZCCQD) and their total plasma protein binding rates. In the procedure, a hollow fiber segment was immersed in organic solvent to fill the solvent in the fiber lumen and wall pore, and then the fiber was immersed into sodium chloride solution to cover a thin salt membrane on the fiber wall pore filling organic solvent...
December 2, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29207664/shikonin-protects-against-d-galactosamine-and-lipopolysaccharide-induced-acute-hepatic-injury-by-inhibiting-tlr4-signaling-pathway
#9
Meng-Xiang Lin, Yong-Xiang Yi, Pei-Pei Fang, Shan-Shan Huang, Chen-Wei Pan, Ling-Xiang Jin, Tong Zhang, Guang-Yao Zhou
Shikonin, a naphthoquinone isolated from the root of medical herb Lithospermum erythrorhizon, has been reported to have anti-inflammatory effect. However, there is no related research for the treatment of shikonin on hepaic injury. The purpose of this study was to investigate the effects of shikonin on D-Galactosamine and Lipopolysaccharide-induced hepatic injury in mice. Male BALB/c mice were pretreated with shikonin 1 h before LPS/D-GalN treatment. The pathological changes of hepatic injury were detected by H&E staining...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29193775/application-of-ionic-liquid-magnetized-stirring-bar-liquid-phase-microextraction-coupled-with-hplc-for-the-determination-of-naphthoquinones-in-zicao
#10
Lianyue Guan, Qiang Luo, Jiayuan Shi, Wei Yu
In this paper, a green, rapid and simple method, ionic liquid-magnetized stirring bar liquid-phase microextraction was developed for the determination of naphthoquinones, including shikonin and β,β'-dimethylacrylshikonin, in Zicao. This method permits active magnetic stirring, extraction and pre-enrichment in a single device simultaneously, so the extract is conveniently collected. The analytes were extracted from the sample to ionic liquid-magnetized stirring bar, then the analyte-adsorbed magnetized stirring bar can be readily isolated from the sample solution by a magnet...
November 28, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/29185365/synthesis-and-antitumor-activity-of-novel-2-3-didithiocarbamate-substituted-naphthoquinones-as-inhibitors-of-pyruvate-kinase-m2-isoform
#11
Xianling Ning, Hailong Qi, Ridong Li, Yan Jin, Michael A McNutt, Yuxin Yin
The M2 isoform of pyruvate kinase (PKM2) is a potential antitumor therapeutic target. In this study, we designed and synthesised a series of 2, 3-didithiocarbamate substituted naphthoquinones as PKM2 inhibitors based on the lead compound 3k that we previously reported. Among them, compound 3f (IC50 = 1.05 ± 0.17 µM) and 3h (IC50 = 0.96 ± 0.18 µM) exhibited potent inhibition of PKM2, and their inhibitory activities are superior to compound 3k (IC50 = 2.95 ± 0.53 µM) and the known PKM2 inhibitor shikonin (IC50 = 8...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29179465/shikonin-reduces-tamoxifen-resistance-through-long-non-coding-rna-uc-57
#12
Chen-Han Zhang, Jue Wang, Lin-Xin Zhang, Yi-Han Lu, Tian-Hao Ji, Lu Xu, Li-Jun Ling
Tamoxifen resistance is a serious problem in the endocrine therapy of breast cancer. Long non-coding RNAs play important roles in tumor development. In this study, we revealed the involvement of lncRNA uc.57 and its downstream gene BCL11A in TAM resistance. Tamoxifen-resistant MCF-7R cells showed lower expression of uc.57 and higher expression of BCL11A mRNA and protein than the parental MCF-7 cells. Moreover, levels of uc.57 mRNA were lower and BCL11A mRNA were higher in breast cancer tissues than in precancerous breast tissues...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29174813/synthesis-and-biological-evaluation-of-sulfur-containing-shikonin-oxime-derivatives-as-potential-antineoplastic-agents
#13
Guang Huang, Hui-Ran Zhao, Qing-Qing Meng, Qi-Jing Zhang, Jin-Yun Dong, Bao-Quan Zhu, Shao-Shun Li
As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells...
November 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#14
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
https://www.readbyqxmd.com/read/29165897/lithospermum-erythrorhizon-root-and-its-naphthoquinones-repress-srebp1c-and-activate-pgc1%C3%AE-through-ampk%C3%AE
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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