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The combination of natural products with standard chemotherapeutic agents offers a promising strategy to enhance the efficacy or reduce the side effects of standard chemotherapy. Doxorubicin (DOX), a standard drug for breast cancer, has several disadvantages, including severe side effects and the development of drug resistance. Recently, we reported the potential bioactive markers of Australian propolis extract (AP-1) and their broad spectrum of pharmacological activities. In the present study, we explored the synergistic interactions between AP-1 and DOX in the MCF7 breast adenocarcinoma cells using different synergy quantitation models. Biochemometric and metabolomics-driven analysis was performed to identify the potential anticancer metabolites in AP-1. The molecular mechanisms of synergy were studied by analysing the apoptotic profile via flow cytometry, apoptotic proteome array and measuring the oxidative status of the MCF7 cells treated with the most synergistic combination. Furthermore, label-free quantification proteomics analysis was performed to decipher the underlying synergistic mechanisms. Five prenylated stilbenes were identified as the key metabolites in the most active AP-1 fraction. Strong synergy was observed when AP-1 was combined with DOX in the ratio of 100:0.29 (w/w) as validated by different synergy quantitation models implemented. AP-1 significantly enhanced the inhibitory effect of DOX against MCF7 cell proliferation in a dose-dependent manner with significant inhibition of the reactive oxygen species (p< 0.0001) compared to DOX alone. AP-1 enabled the reversal of DOX-mediated necrosis to programmed cell death, which may be advantageous to decline DOX-related side effects. AP-1 also significantly enhanced the apoptotic effect of DOX after 24 h of treatment with significant upregulation of catalase, HTRA2/Omi, FADD together with DR5 and DR4 TRAIL-mediated apoptosis (p< 0.05), contributing to the antiproliferative activity of AP-1. Significant upregulation of pro-apoptotic p27, PON2 and catalase with downregulated anti-apoptotic XIAP, HSP60 and HIF-1α, and increased antioxidant proteins (catalase and PON2) may be associated with the improved apoptosis and oxidative status of the synergistic combination-treated MCF7 cells compared to the mono treatments. Shotgun proteomics identified 21 significantly dysregulated proteins in the synergistic combination-treated cells versus the mono treatments. These proteins were involved in the TP53/ATM-regulated non-homologous end-joining pathway and double-strand breaks repairs, recruiting the overexpressed BRCA1 and suppressed RIF1 encoded proteins. The overexpression of UPF2 was noticed in the synergistic combination treatment, which could assist in overcoming doxorubicin resistance-associated long non-coding RNA and metastasis of the MCF7 cells. In conclusion, we identified the significant synergy and highlighted the key molecular pathways in the interaction between AP-1 and DOX in the MCF7 cells together with the AP-1 anticancer metabolites. Further in vivo and clinical studies are warranted on this synergistic combination.
Muhammad Alsherbiny; Deep Bhuyan; Ibrahim Radwan; Dennis Chang; Chun-Guang Li. Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells. International Journal of Molecular Sciences 2021, 22, 7840 .
AMA StyleMuhammad Alsherbiny, Deep Bhuyan, Ibrahim Radwan, Dennis Chang, Chun-Guang Li. Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells. International Journal of Molecular Sciences. 2021; 22 (15):7840.
Chicago/Turabian StyleMuhammad Alsherbiny; Deep Bhuyan; Ibrahim Radwan; Dennis Chang; Chun-Guang Li. 2021. "Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells." International Journal of Molecular Sciences 22, no. 15: 7840.
The association between human gut microbiota and cancers has been an evolving field of biomedical research in recent years. The gut microbiota is composed of the microorganisms residing in the gastrointestinal system that interact with the host to regulate behaviours and biochemical processes within the gut. This symbiotic physiological interaction between the gut and the microbiota plays a significant role in the modulation of gut homeostasis, in which perturbations to the microbiota, also known as dysbiosis can lead to the onset of diseases, including cancer. In this review, we analysed the current literature to understand the role of gut microbiota in the five most prevalent cancer types, namely colon (colorectal), lung, breast, prostate, and stomach cancers. Recent studies have observed the immunomodulatory and anti-tumoural effects of gut microbiota in cancers. Furthermore, gut microbial dysbiosis can induce the release of toxic metabolites and exhibit pro-tumoural effects in the host. The gut microbiota was observed to have clinical implications in each cancer type in addition to regulating the efficacy of standard chemotherapy and natural anticancer agents. However, further research is warranted to understand the complex role of gut microbiota in the prevention, diagnosis, treatment, and prognoses of cancer.
Kayla Jaye; Chun Guang Li; Deep Jyoti Bhuyan. The complex interplay of gut microbiota with the five most common cancer types: From carcinogenesis to therapeutics to prognoses. Critical Reviews in Oncology/Hematology 2021, 165, 103429 .
AMA StyleKayla Jaye, Chun Guang Li, Deep Jyoti Bhuyan. The complex interplay of gut microbiota with the five most common cancer types: From carcinogenesis to therapeutics to prognoses. Critical Reviews in Oncology/Hematology. 2021; 165 ():103429.
Chicago/Turabian StyleKayla Jaye; Chun Guang Li; Deep Jyoti Bhuyan. 2021. "The complex interplay of gut microbiota with the five most common cancer types: From carcinogenesis to therapeutics to prognoses." Critical Reviews in Oncology/Hematology 165, no. : 103429.
NLRP3 inflammasome is a key mediator in ischemic stroke-induced neuroinflammation and subsequent brain injury. Our previous study demonstrated the potent activity of Pien-Tze-Huang (PTH), a well-known Chinese patent formula, in reducing mitochondria-mediated neuronal apoptosis in cerebral ischemia/reperfusion impaired rats. This study aims to elucidate the mechanistic action of PTH related to neuroinflammation in LPS-induced BV2 microglial cells and cerebral ischemia/reperfusion impaired rats. BV2 cells were stimulated with LPS for 12 h and treated with PTH with various concentrations. Modulation by PTH of relevant genes (IL-6, IL-1β, IL-18, TNF-α, COX-2 and iNOS mRNA) and proteins (NLRP3 inflammasome, autophagy and AMPK/mTOR/ULK signaling) was analyzed by real-time PCR and western blot, respectively. Similar analyses were conducted in middle cerebral artery occlusion rat model including neurological deficit, infarct volume, microglial activation, and key genes and proteins in modulating autophagy and NLRP3. Our results showed that PTH significantly inhibited the production of key proinflammatory mediators and protein expressions of NLRP3 and caspase-1 p20 in LPS induced BV2 cells. It also enhanced the autophagy response by modulating the key autophagy proteins via AMPK/mTOR/ULK related pathway. The reduced inflammatory responses and NLRP3 expressions by PTH were partially blocked by the autophagy inhibitor (3-MA) and AMPK blocker (compound C). In rats, PTH significantly reduced infarct size, suppressed microglial activation, and improved neuron deficit. It also promoted autophagy and reduced NLRP3 activity. Our study demonstrated that PTH inhibited NLRP3 inflammasome-mediated neuroinflammation, which was associated with enhanced autophagy via AMPK/mTOR/ULK1 pathway in vitro and in vivo.
Zhenwei Huang; Xian Zhou; Xiaoqin Zhang; Lili Huang; Yibin Sun; Zaixing Cheng; Wen Xu; Chun-Guang Li; Yanfang Zheng; Mingqing Huang. Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway. Biomedicine & Pharmacotherapy 2021, 141, 111814 .
AMA StyleZhenwei Huang, Xian Zhou, Xiaoqin Zhang, Lili Huang, Yibin Sun, Zaixing Cheng, Wen Xu, Chun-Guang Li, Yanfang Zheng, Mingqing Huang. Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway. Biomedicine & Pharmacotherapy. 2021; 141 ():111814.
Chicago/Turabian StyleZhenwei Huang; Xian Zhou; Xiaoqin Zhang; Lili Huang; Yibin Sun; Zaixing Cheng; Wen Xu; Chun-Guang Li; Yanfang Zheng; Mingqing Huang. 2021. "Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway." Biomedicine & Pharmacotherapy 141, no. : 111814.
Whilst the popular use of herbal medicine globally, it poses challenges in managing potential drug-herb interaction. There are two folds of the drug-herb interaction, a beneficial interaction that may improve therapeutic outcome and minimise the toxicity of drug desirably; by contrast, negative interaction may evoke unwanted clinical consequences, especially with drugs of narrow therapeutic index. Scutellaria baicalensis Georgi is one of the most popular medicinal plants used in Asian countries. It has been widely used for treating various diseases and conditions such as cancer, diabetes, inflammation, and oxidative stress. Studies on its extract and bioactive compounds have shown pharmacodynamic and pharmacokinetic interactions with a wide range of pharmaceutical drugs as evidenced by plenty of in vitro, in vivo and clinical studies. Notably, S. baicalensis and its bioactives including baicalein, baicalin and wogonin exhibited synergistic interactions with many pharmaceutical drugs to enhance their efficacy, reduce toxicity or overcome drug resistance to combat complex diseases such as cancer, diabetes and infectious diseases. On the other hand, S. baicalensis and its bioactives also affected the pharmacokinetic profile of many drugs in absorption, distribution, metabolism and elimination via the regulatory actions of the efflux pumps and cytochrome P450 enzymes. This review provides comprehensive references of the observed pharmacodynamic and pharmacokinetic drug interactions of Scutellaria baicalensis and its bioactives. We have elucidated the interaction with detailed mechanistic actions, identified the knowledge gaps for future research and potential clinical implications. Such knowledge is important for the practice of both conventional and complementary medicines, and it is essential to ensure the safe use of related herbal medicines. The review may be of great interest to practitioners, consumers, clinicians who require comprehensive information on the possible drug interactions with S. baicalensis and its bioactives.
Xian Zhou; Ling Fu; Pengli Wang; Lan Yang; Xiaoshu Zhu; Chun Guang Li. Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications. Biomedicine & Pharmacotherapy 2021, 138, 111445 .
AMA StyleXian Zhou, Ling Fu, Pengli Wang, Lan Yang, Xiaoshu Zhu, Chun Guang Li. Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications. Biomedicine & Pharmacotherapy. 2021; 138 ():111445.
Chicago/Turabian StyleXian Zhou; Ling Fu; Pengli Wang; Lan Yang; Xiaoshu Zhu; Chun Guang Li. 2021. "Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications." Biomedicine & Pharmacotherapy 138, no. : 111445.
The broad-spectrum pharmacological activity of Australian propolis and identification of key markers of propolis samples from Australia, Brazil and China.
Deep Jyoti Bhuyan; Muhammad A. Alsherbiny; Mitchell Nolan Low; Xian Zhou; Kirandeep Kaur; George Li; Chun Guang Li. Broad-spectrum pharmacological activity of Australian propolis and metabolomic-driven identification of marker metabolites of propolis samples from three continents. Food & Function 2021, 1 .
AMA StyleDeep Jyoti Bhuyan, Muhammad A. Alsherbiny, Mitchell Nolan Low, Xian Zhou, Kirandeep Kaur, George Li, Chun Guang Li. Broad-spectrum pharmacological activity of Australian propolis and metabolomic-driven identification of marker metabolites of propolis samples from three continents. Food & Function. 2021; ():1.
Chicago/Turabian StyleDeep Jyoti Bhuyan; Muhammad A. Alsherbiny; Mitchell Nolan Low; Xian Zhou; Kirandeep Kaur; George Li; Chun Guang Li. 2021. "Broad-spectrum pharmacological activity of Australian propolis and metabolomic-driven identification of marker metabolites of propolis samples from three continents." Food & Function , no. : 1.
Neuroinflammation is believed to play a primary role in the pathogenesis of most neurodegenerative diseases including Alzheimer’s disease, Parkinson’s and schizophrenia. Currently, suitable in vitro neuroinflammation models for studying cellular interactions and inflammatory mechanisms at the neurovascular unit are still scarce. In this study, we established an experimentally flexible tri‐culture neuroinflammation model combining murine microglial cells (N11), neurons (N2A) and brain microvascular endothelial MVEC(B3) cells (MVEC) in a transwell co‐culture system stimulated with lipopolysaccharides (LPS). Neuroinflammation was induced in this tri‐culture model as manifested by activated N11 cells via toll‐like receptor 4, resulting in increased release of proinflammatory mediators (nitric oxide, interleukin‐6, and tumor necrosis factor‐α) through the activation of nuclear factor‐κB signaling pathways. The released inflammatory cytokines from N11 in turn, damaged the tight junction in MVEC cells, increased permeability of endothelial barrier, and induced Tau phosphorylation and upregulated caspase‐3 expression in N2A cells, leading to neuroinflammation injury. In summary, this tri‐culture inflammation model mimics the microenvironment, the cellular crosstalk and the molecular events that take place during neuroinflammation. It provides a robust in vitro model for studying neuroinflammation mechanisms and screening for potential therapeutic compounds or drugs candidates to treat various neurodegenerative diseases.
Yan‐Fang Zheng; Xian Zhou; Dennis Chang; Deep Jyoti Bhuyan; Jie Ping Zhang; Wen‐Zhen Yu; Xia‐Sen Jiang; Sai Wang Seto; Seung Yeon Yeon; Jia Li; Chun Guang Li. A novel tri‐culture model for neuroinflammation. Journal of Neurochemistry 2020, 156, 249 -261.
AMA StyleYan‐Fang Zheng, Xian Zhou, Dennis Chang, Deep Jyoti Bhuyan, Jie Ping Zhang, Wen‐Zhen Yu, Xia‐Sen Jiang, Sai Wang Seto, Seung Yeon Yeon, Jia Li, Chun Guang Li. A novel tri‐culture model for neuroinflammation. Journal of Neurochemistry. 2020; 156 (2):249-261.
Chicago/Turabian StyleYan‐Fang Zheng; Xian Zhou; Dennis Chang; Deep Jyoti Bhuyan; Jie Ping Zhang; Wen‐Zhen Yu; Xia‐Sen Jiang; Sai Wang Seto; Seung Yeon Yeon; Jia Li; Chun Guang Li. 2020. "A novel tri‐culture model for neuroinflammation." Journal of Neurochemistry 156, no. 2: 249-261.
Special Chinese propolis sourced from the Changbai Mountains (CBMP) in Northeast China is rich in specific flavonoids and phenolic acids and its bioactivity has not been reported. This study aimed to investigate the antiproliferative effect of CBMP on cancer cells and its molecular mechanisms. Different cancer cell lines were treated with the ethanol extracts of CBMP for 24 hours before the cell viability and mechanism measurements. The results showed CBMP had weak activities against human pancreatic cancer cell PANC1, human lung cancer cell A549, human colon cancer cell HCT116, human liver cancer cell HepG2, human bladder cancer cell T24, and human breast cancer cell MDA-MB-231, but it significantly inhibited the growth of human gastric cancer SGC-7901 cells, caused cell apoptosis and cell cycle arrest in S phase, with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (MMP). The results indicate that Chinese propolis sourced from the Changbai Mountains selectively inhibits the proliferation of human gastric cancer SGC-7901 cells by inducing both death receptor-induced apoptosis and mitochondria-mediated apoptosis, and cell cycle arrest in S phase. These activities and mechanisms help understand the anticancer action of propolis and its active compounds.
Xia-Sen Jiang; Hong-Qing Xie; Chun-Guang Li; Meng-Meng You; Yu-Fei Zheng; George Q. Li; Xiang Chen; Cui-Ping Zhang; Fu-Liang Hu. Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest. Evidence-Based Complementary and Alternative Medicine 2020, 2020, 1 -11.
AMA StyleXia-Sen Jiang, Hong-Qing Xie, Chun-Guang Li, Meng-Meng You, Yu-Fei Zheng, George Q. Li, Xiang Chen, Cui-Ping Zhang, Fu-Liang Hu. Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest. Evidence-Based Complementary and Alternative Medicine. 2020; 2020 ():1-11.
Chicago/Turabian StyleXia-Sen Jiang; Hong-Qing Xie; Chun-Guang Li; Meng-Meng You; Yu-Fei Zheng; George Q. Li; Xiang Chen; Cui-Ping Zhang; Fu-Liang Hu. 2020. "Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest." Evidence-Based Complementary and Alternative Medicine 2020, no. : 1-11.
49 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic acid (TPC) and antioxidant activity. High-performance liquid chromatography (HPLC) analysis identified 15 common components, including key marker compounds pinocembrin, 3-O-acetylpinobanksin, galangin, chrysin, benzyl p-coumarate, pinobanksin and caffeic acid phenethyl ester (CAPE). Cluster analysis (CA) and correlation coefficients (CC) analysis showed that these propolis could be divided into three distinct groups. Principal component analysis (PCA) and multiple linear regression analysis (MLRA) revealed that the contents of isoferulic acid, caffeic acid, CAPE, 3,4-dimethoxycinnamic acid, chrysin and apigenin are closely related to the antioxidant properties of propolis. In addition, eight peak areas decreased after reacting with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals, indicating that these compounds have antioxidant activity. The results indicate that the grouping and spectrum–effect relationship of Chinese propolis are related to their chemical compositions, and several compounds may serve as a better marker for the antioxidant activity of Chinese propolis than TFC and TPC. The findings may help to develop better methods to evaluate the quality of propolis from different geographic origins.
Xiasen Jiang; Linchen Tao; Chunguang Li; Mengmeng You; George Q. Li; Cuiping Zhang; Fuliang Hu. Grouping, Spectrum–Effect Relationship and Antioxidant Compounds of Chinese Propolis from Different Regions Using Multivariate Analyses and Off-Line Anti-DPPH Assay. Molecules 2020, 25, 3243 .
AMA StyleXiasen Jiang, Linchen Tao, Chunguang Li, Mengmeng You, George Q. Li, Cuiping Zhang, Fuliang Hu. Grouping, Spectrum–Effect Relationship and Antioxidant Compounds of Chinese Propolis from Different Regions Using Multivariate Analyses and Off-Line Anti-DPPH Assay. Molecules. 2020; 25 (14):3243.
Chicago/Turabian StyleXiasen Jiang; Linchen Tao; Chunguang Li; Mengmeng You; George Q. Li; Cuiping Zhang; Fuliang Hu. 2020. "Grouping, Spectrum–Effect Relationship and Antioxidant Compounds of Chinese Propolis from Different Regions Using Multivariate Analyses and Off-Line Anti-DPPH Assay." Molecules 25, no. 14: 3243.
Persea americana, commonly known as avocado, has recently gained substantial popularity and is often marketed as a “superfood” because of its unique nutritional composition, antioxidant content, and biochemical profile. However, the term “superfood” can be vague and misleading, as it is often associated with unrealistic health claims. This review draws a comprehensive summary and assessment of research performed in the last few decades to understand the nutritional and therapeutic properties of avocado and its bioactive compounds. In particular, studies reporting the major metabolites of avocado, their antioxidant as well as bioavailability and pharmacokinetic properties, are summarized and assessed. Furthermore, the potential of avocado in novel drug discovery for the prevention and treatment of cancer, microbial, inflammatory, diabetes, and cardiovascular diseases is highlighted. This review also proposes several interesting future directions for avocado research.
Deep Jyoti Bhuyan; Muhammad A. Alsherbiny; Saumya Perera; Mitchell Low; Amrita Basu; Okram Abemsana Devi; Mridula Saikia Barooah; Chun Guang Li; Konstantinos Papoutsis; Low; Basu; Devi; Li. The Odyssey of Bioactive Compounds in Avocado (Persea americana) and their Health Benefits. Antioxidants 2019, 8, 426 .
AMA StyleDeep Jyoti Bhuyan, Muhammad A. Alsherbiny, Saumya Perera, Mitchell Low, Amrita Basu, Okram Abemsana Devi, Mridula Saikia Barooah, Chun Guang Li, Konstantinos Papoutsis, Low, Basu, Devi, Li. The Odyssey of Bioactive Compounds in Avocado (Persea americana) and their Health Benefits. Antioxidants. 2019; 8 (10):426.
Chicago/Turabian StyleDeep Jyoti Bhuyan; Muhammad A. Alsherbiny; Saumya Perera; Mitchell Low; Amrita Basu; Okram Abemsana Devi; Mridula Saikia Barooah; Chun Guang Li; Konstantinos Papoutsis; Low; Basu; Devi; Li. 2019. "The Odyssey of Bioactive Compounds in Avocado (Persea americana) and their Health Benefits." Antioxidants 8, no. 10: 426.
Traditional Chinese medicine (TCM) is not only used prevalently in Asian countries but has also gained a stable market globally. As a principal form of TCM, Chinese herbal medicine (CHM) is comprised of treatments using multiple Chinese herbs which have complex chemical profiles. Due to a lack of understanding of its modality and a lack of standardization, there are significant challenges associated with regulating CHM’s safety for practice and understanding its mechanisms of efficacy. Currently, there are many issues that need to be overcome in regard to the safety and efficacy of CHM for the further development of evidence-based practices. There is a need to better understand the mechanisms behind the efficacy of CHM, and develop proper quality standards and regulations to ensure a similar safety standard as Western drugs. This paper outlines the status of CHM in terms of its safety and efficacy and attempts to provide approaches to address these issues.
Xian Zhou; Chun-Guang Li; Dennis Chang; Alan Bensoussan. Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine. Medicines 2019, 6, 14 .
AMA StyleXian Zhou, Chun-Guang Li, Dennis Chang, Alan Bensoussan. Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine. Medicines. 2019; 6 (1):14.
Chicago/Turabian StyleXian Zhou; Chun-Guang Li; Dennis Chang; Alan Bensoussan. 2019. "Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine." Medicines 6, no. 1: 14.
The endocannabinoids system (ECS) has garnered considerable interest as a potential therapeutic target in various carcinomas and cancer-related conditions alongside neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy-induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed light on the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug–drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breast cancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases). Caution should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
Muhammad A. Alsherbiny; Chun Guang Li. Medicinal Cannabis—Potential Drug Interactions. Medicines 2018, 6, 3 .
AMA StyleMuhammad A. Alsherbiny, Chun Guang Li. Medicinal Cannabis—Potential Drug Interactions. Medicines. 2018; 6 (1):3.
Chicago/Turabian StyleMuhammad A. Alsherbiny; Chun Guang Li. 2018. "Medicinal Cannabis—Potential Drug Interactions." Medicines 6, no. 1: 3.
Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
Muhammad A. Alsherbiny; Chun G. Li. Medicinal Cannabis - Potential Drug Interactions. 2018, 1 .
AMA StyleMuhammad A. Alsherbiny, Chun G. Li. Medicinal Cannabis - Potential Drug Interactions. . 2018; ():1.
Chicago/Turabian StyleMuhammad A. Alsherbiny; Chun G. Li. 2018. "Medicinal Cannabis - Potential Drug Interactions." , no. : 1.
Fatal unintentional poisoning is widespread upon human exposure to toxic agents such as pesticides, heavy metals, environmental pollutants, bacterial and fungal toxins or even some medications and cosmetic products. In this regards, the application of the natural dietary agents as antidotes has engrossed a substantial attention. One of the ancient known traditional medicines and spices with an arsenal of metabolites of several reported health benefits is ginger. This extended literature review serves to demonstrate the protective effects and mechanisms of ginger and its phytochemicals against natural, chemical and radiation-induced toxicities. Collected data obtained from the in-vivo and in-vitro experimental studies in this overview detail the designation of the protective effects to ginger's antioxidant, anti-inflammatory, and anti-apoptotic properties. Ginger's armoury of phytochemicals exerted its protective function via different mechanisms and cell signalling pathways, including Nrf2/ARE, MAPK, NF-ƙB, Wnt/β-catenin, TGF-β1/Smad3, and ERK/CREB. The outcomes of this review could encourage further clinical trials of ginger applications in radiotherapy and chemotherapy regime for cancer treatments or its implementation to counteract the chemical toxicity induced by industrial pollutants, alcohol, smoking or administered drugs.
Muhammad A. Alsherbiny; Wessam H. Abd-Elsalam; Shymaa A. El Badawy; Ehab Taher; Mohamed Fares; Allan Torres; Dennis Chang; Chun Guang Li. Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review. Food and Chemical Toxicology 2018, 123, 72 -97.
AMA StyleMuhammad A. Alsherbiny, Wessam H. Abd-Elsalam, Shymaa A. El Badawy, Ehab Taher, Mohamed Fares, Allan Torres, Dennis Chang, Chun Guang Li. Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review. Food and Chemical Toxicology. 2018; 123 ():72-97.
Chicago/Turabian StyleMuhammad A. Alsherbiny; Wessam H. Abd-Elsalam; Shymaa A. El Badawy; Ehab Taher; Mohamed Fares; Allan Torres; Dennis Chang; Chun Guang Li. 2018. "Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review." Food and Chemical Toxicology 123, no. : 72-97.
Background: This study investigated the combination effects of the Danshen and Sanqi herb pair on angiogenesis in vitro. Methods: Nine combination ratios of Danshen-Sanqi extracts (DS-SQ) were screened for their angiogenic effects in the human vascular endothelial EAhy 926 cell line via cell proliferation, cell migration and tube formation activities against the damage to the cells exerted by DL-homocysteine (Hcy) and adenosine (Ado). The type of interaction (synergistic, antagonistic, additive) between Danshen and Sanqi was analyzed using combination index (CI) and isobologram models. The angiogenic activities of key bioactive compounds from Danshen and Sanqi were tested in the same models. Results: DS-SQ ratios of 2:8 and 3:7 (50–300 µg/mL) potentiated angiogenic synergistic effects (CI < 1) in all three assays. The observed wound healing effects of DS-SQ 2:8 was significantly attenuated by phosphatidylinositol-3 kinases (PI3K), mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinases (ERK) inhibitors which inferred the potential mechanistic pathways. Out of all the tested compounds, Notoginsenoside R1 from Sanqi exhibited the most potent bioactivity in cell proliferation assay. Conclusions: This study provides scientific evidence to support the traditional use of the Danshen-Sanqi combination for vascular disease, in particular through their synergistic interactions on previously unexamined angiogenic pathways.
Xian Zhou; Valentina Razmovski-Naumovski; Antony Kam; Dennis Chang; Chunguang Li; Alan Bensoussan; Kelvin Chan. Synergistic Effects of Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Angiogenesis Behavior in EAhy 926 Cells. Medicines 2017, 4, 85 .
AMA StyleXian Zhou, Valentina Razmovski-Naumovski, Antony Kam, Dennis Chang, Chunguang Li, Alan Bensoussan, Kelvin Chan. Synergistic Effects of Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Angiogenesis Behavior in EAhy 926 Cells. Medicines. 2017; 4 (4):85.
Chicago/Turabian StyleXian Zhou; Valentina Razmovski-Naumovski; Antony Kam; Dennis Chang; Chunguang Li; Alan Bensoussan; Kelvin Chan. 2017. "Synergistic Effects of Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Angiogenesis Behavior in EAhy 926 Cells." Medicines 4, no. 4: 85.
The last few decades have seen the rise of alternative medical approaches including the use of herbal supplements, natural products, and traditional medicines, which are collectively known as 'Complementary medicines'. However, there are increasing concerns on the safety and health benefits of these medicines. One of the main hazards with the use of complementary medicines is the presence of heavy metal(loid)s such as arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg). This review deals with the characteristics of complementary medicines in terms of heavy metal(loid)s sources, distribution, bioavailability, toxicity, and human risk assessment. The heavy metal(loid)s in these medicines are derived from uptake by medicinal plants, cross-contamination during processing, and therapeutic input of metal(loid)s. This paper discusses the distribution of heavy metal(loid)s in these medicines, in terms of their nature, concentration, and speciation. The importance of determining bioavailability towards human health risk assessment was emphasized by the need to estimate daily intake of heavy metal(loid)s in complementary medicines. The review ends with selected case studies of heavy metal(loid) toxicity from complementary medicines with specific reference to As, Cd, Pb, and Hg. The future research opportunities mentioned in the conclusion of review will help researchers to explore new avenues, methodologies, and approaches to the issue of heavy metal(loid)s in complementary medicines, thereby generating new regulations and proposing fresh approach towards safe use of these medicines.
Shiv Bolan; Anitha Kunhikrishnan; Balaji Seshadri; Girish Choppala; Ravi Naidu; Nanthi S. Bolan; Yong Sik Ok; Ming Zhang; Chun Guang Li; Feng Li; Barry Noller; Mary Beth Kirkham. Sources, distribution, bioavailability, toxicity, and risk assessment of heavy metal(loid)s in complementary medicines. Environment International 2017, 108, 103 -118.
AMA StyleShiv Bolan, Anitha Kunhikrishnan, Balaji Seshadri, Girish Choppala, Ravi Naidu, Nanthi S. Bolan, Yong Sik Ok, Ming Zhang, Chun Guang Li, Feng Li, Barry Noller, Mary Beth Kirkham. Sources, distribution, bioavailability, toxicity, and risk assessment of heavy metal(loid)s in complementary medicines. Environment International. 2017; 108 ():103-118.
Chicago/Turabian StyleShiv Bolan; Anitha Kunhikrishnan; Balaji Seshadri; Girish Choppala; Ravi Naidu; Nanthi S. Bolan; Yong Sik Ok; Ming Zhang; Chun Guang Li; Feng Li; Barry Noller; Mary Beth Kirkham. 2017. "Sources, distribution, bioavailability, toxicity, and risk assessment of heavy metal(loid)s in complementary medicines." Environment International 108, no. : 103-118.
There is a recognized challenge in analyzing traditional Chinese medicine formulas because of their complex chemical compositions. The application of modern analytical techniques such as high-performance liquid chromatography coupled with a tandem mass spectrometry has improved the characterization of various compounds from traditional Chinese medicine formulas significantly. This study aims to conduct a bibliometric analysis to recognize the overall trend of high-performance liquid chromatography coupled with tandem mass spectrometry approaches in the analysis of traditional Chinese medicine formulas, its significance and possible underlying interactions between individual herbs in these formulas. Electronic databases were searched systematically, and the identified studies were collected and analyzed using Microsoft Access 2010, Graph Pad 5.0 software and Ucinet software package. 338 publications between 1997 and 2015 were identified, and analyzed in terms of annual growth and accumulated publications, top journals, forms of traditional Chinese medicine preparations and highly studied formulas and single herbs, as well as social network analysis of single herbs. There is a significant increase trend in using high-performance liquid chromatography coupled with tandem mass spectrometry related techniques in analysis of commonly used forms of traditional Chinese medicine formulas in the last 3 years. Stringent quality control is of great significance for the modernization and globalization of traditional Chinese medicine, and this bibliometric analysis provided the first and comprehensive summary within this field.
Xi-Ran He; Chun Guang Li; Xiao-Shu Zhu; Yuan-Qing Li; Mariam Jarouche; Alan Bensoussan; Ping-Ping Li. High-performance liquid chromatography coupled with tandem mass spectrometry technology in the analysis of Chinese Medicine Formulas: A bibliometric analysis (1997-2015). Journal of Separation Science 2016, 40, 81 -92.
AMA StyleXi-Ran He, Chun Guang Li, Xiao-Shu Zhu, Yuan-Qing Li, Mariam Jarouche, Alan Bensoussan, Ping-Ping Li. High-performance liquid chromatography coupled with tandem mass spectrometry technology in the analysis of Chinese Medicine Formulas: A bibliometric analysis (1997-2015). Journal of Separation Science. 2016; 40 (1):81-92.
Chicago/Turabian StyleXi-Ran He; Chun Guang Li; Xiao-Shu Zhu; Yuan-Qing Li; Mariam Jarouche; Alan Bensoussan; Ping-Ping Li. 2016. "High-performance liquid chromatography coupled with tandem mass spectrometry technology in the analysis of Chinese Medicine Formulas: A bibliometric analysis (1997-2015)." Journal of Separation Science 40, no. 1: 81-92.
Aims. This study aims to investigate the possible synergistic interactions of the Danshen-Sanqi combination on vascular disease via their anti-inflammatory activities.Methods. Nine combination ratios of Danshen-Sanqi extracts were screened in the RAW264.7 cell line and their anti-inflammatory effects were examined in lipopolysaccharide- (LPS-) induced nitric oxide (NO), tumor necrosis factor (TNF), and monocyte chemoattractant protein-1 (MCP-1) generation pathways. The interaction between Danshen and Sanqi on each target was analysed using combination index (CI) and isobologram models. Additionally, the anti-inflammatory activities of key bioactive compounds from Danshen and Sanqi were tested using the same models. The compounds from each herb that exerted the most potent activity were combined to evaluate their possible synergistic/antagonistic interactions.Results. Danshen-Sanqi 8 : 2 was found to be the optimal ratio and exerted a synergistic effect in inhibiting NO, TNF, and MCP-1 when the concentrations were higher than 1.24, 1.89, and 2.17 mg/mL, respectively. Although dihydrotanshinone I (DT) and ginsenoside Rd (Rd) from Danshen and Sanqi, respectively, exhibited the greatest individual bioactivity in the assays, antagonistic effects were observed for the DT-Rd combination 7 : 3.Conclusion. This study provided scientific evidence to support the traditional use of the Danshen-Sanqi combination for vascular disease through their synergistic interactions on anti-inflammatory pathways.
Xian Zhou; Valentina Razmovski-Naumovski; Dennis Chang; Chunguang Li; Antony Kam; Mitchell Low; Alan Bensoussan; Kelvin Chan. Synergistic Effects of Danshen (Salvia Miltiorrhiza Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells. BioMed Research International 2016, 2016, 1 -12.
AMA StyleXian Zhou, Valentina Razmovski-Naumovski, Dennis Chang, Chunguang Li, Antony Kam, Mitchell Low, Alan Bensoussan, Kelvin Chan. Synergistic Effects of Danshen (Salvia Miltiorrhiza Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells. BioMed Research International. 2016; 2016 ():1-12.
Chicago/Turabian StyleXian Zhou; Valentina Razmovski-Naumovski; Dennis Chang; Chunguang Li; Antony Kam; Mitchell Low; Alan Bensoussan; Kelvin Chan. 2016. "Synergistic Effects of Danshen (Salvia Miltiorrhiza Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells." BioMed Research International 2016, no. : 1-12.
Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza Bge. Tanshinone IIA and cryptotanshinone are the major components in total tanshinones. However, the bioavailability of both compounds is low due to poor water solubility. To enhance the solubility and dissolution rate of tanshinone IIA, cryptotanshinone and total tanshinones, three common used hydrophilic carriers including PEG 6000, poloxamer 188 and PVP K30 were used to prepare the solid dispersions at different ratios, respectively. The solid dispersions were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The results of powder X-ray diffraction confirmed the microcrystal state of total tanshinones in solid dispersions and no chemical interaction between total tanshinones and carriers was observed in FTIR spectra. The solubility and dissolution rate of tanshinone IIA and cryptotanshinone were significantly increased in all solid dispersions. Regarding tanshinone IIA, the solubility and dissolution rate of in solid dispersions prepared with poloxamer 188 were significantly higher than that with PEG 6000 and PVP K30. The higher solubility and dissolution rate of cryptotanshinone were obtained in solid dispersion of PVP K30 than that of PEG 6000 solid dispersions but no significant difference from poloxamer 188 solid dispersions. The results indicate that the superior carrier for preparation of tanshinone IIA and total tanshinones solid dispersions is poloxamer 188, and that for cryptotanshinone is PVP K30.
Xifeng Zhai; Chun Guang Li; George Binh Lenon; Charlie C.L. Xue; Weize Li. Preparation and characterisation of solid dispersions of tanshinone IIA, cryptotanshinone and total tanshinones. Asian Journal of Pharmaceutical Sciences 2016, 12, 85 -97.
AMA StyleXifeng Zhai, Chun Guang Li, George Binh Lenon, Charlie C.L. Xue, Weize Li. Preparation and characterisation of solid dispersions of tanshinone IIA, cryptotanshinone and total tanshinones. Asian Journal of Pharmaceutical Sciences. 2016; 12 (1):85-97.
Chicago/Turabian StyleXifeng Zhai; Chun Guang Li; George Binh Lenon; Charlie C.L. Xue; Weize Li. 2016. "Preparation and characterisation of solid dispersions of tanshinone IIA, cryptotanshinone and total tanshinones." Asian Journal of Pharmaceutical Sciences 12, no. 1: 85-97.
Euonymus alatus (E. alatus)is a medicinal plant used in some Asian countries for treating various conditions including cancer, hyperglycemia, and diabetic complications. This review outlines the phytochemistry and bioactivities ofE. alatusrelated to antidiabetic actions. More than 100 chemical constituents have been isolated and identified fromE. alatus, including flavonoids, terpenoids, steroids, lignans, cardenolides, phenolic acids, and alkaloids. Studiesin vitroandin vivohave demonstrated the hypoglycemic activity ofE. alatusextracts and its certain constituents. The hypoglycemic activity ofE. alatusmay be related to regulation of insulin signaling and insulin sensitivity, involving PPARγand aldose reductase pathways. Further studies onE. alatusand its bioactive compounds may help to develop new agents for treating diabetes and diabetic complications.
Xifeng Zhai; George Binh Lenon; Charlie C. L. Xue; Chun-Guang Li. Euonymus alatus: A Review on Its Phytochemistry and Antidiabetic Activity. Evidence-Based Complementary and Alternative Medicine 2016, 2016, 1 -12.
AMA StyleXifeng Zhai, George Binh Lenon, Charlie C. L. Xue, Chun-Guang Li. Euonymus alatus: A Review on Its Phytochemistry and Antidiabetic Activity. Evidence-Based Complementary and Alternative Medicine. 2016; 2016 ():1-12.
Chicago/Turabian StyleXifeng Zhai; George Binh Lenon; Charlie C. L. Xue; Chun-Guang Li. 2016. "Euonymus alatus: A Review on Its Phytochemistry and Antidiabetic Activity." Evidence-Based Complementary and Alternative Medicine 2016, no. : 1-12.
Tanshinones are lipophilic compounds derived from Salvia miltiorrhiza (Danshen) that has been widely used to treat coronary heart diseases in China. The cardioprotective actions of tanshinones have been extensively studied in various models of myocardial infarction, cardiac ischemia reperfusion injury, cardiac hypertrophy, atherosclerosis, hypoxia, and cardiomyopathy. This review outlines the recent development in understanding the molecular mechanisms and signaling pathways involved in the cardioprotective actions of tanshinones, in particular on mitochondrial apoptosis, calcium, nitric oxide, ROS, TNF-α, PKC, PI3K/Akt, IKK/NF-κB, and TGF-β1/Smad mechanisms, which highlights the potential of these compounds as therapeutic agents for treating cardiovascular diseases.1. IntroductionDanshen, also called red sage root, is dried roots of Salvia miltiorrhiza that is cultivated widely in many Asian countries including China, Korea, and Japan. Danshen and Danshen related products have long been used as traditional Chinese medicine to treat cardiovascular dysfunctions such as angina pectoris, stroke, and hypertension [1–4]. For example, a recent systematic review indicates that Danshen dripping pill is more effective than isosorbide dinitrate in treating angina pectoris [5]. Although with its long history of medicinal use, the mechanism of actions of Danshen has only been intensively investigated in recent years, with the progress in elucidating its phytochemistry and active compounds. The identified chemical constituents of Danshen can be classified into lipophilic and hydrophilic components. The main lipophilic constituents are tanshinones which are diterpene quinones. There are more than 40 tanshinones that have been isolated [6]. The main tanshinones include tanshinone I (TI), tanshinone IIA (TIIA), tanshinone IIB (TIIB), tanshinone VI (TVI), cryptotanshinone (CT), and dihydrotanshinone (DHT) as illustrated in Figure 1.Figure 1: Chemical structures of major tanshinones.Tanshinones have been demonstrated with various pharmacological activities including antioxidant, anti-inflammatory, antibacterial, antineoplastic, immunomodulatory, cardioprotective, and neuroprotective actions and have been used in treating various conditions, including cardiovascular diseases, cancer, and diabetes [7–14]. One of the promising therapeutic actions of tanshinones is their cardioprotective actions [15]. For example, TIIA has been shown to dilate coronary vessels [16] and regulate vascular endothelial functions [17] and inhibit myocardial infarction [18], ischemia reperfusion (I/R) injury [19, 20], and cardiomyopathy [21]. It also reduced atherosclerosis [22]. CT has also been shown to reduce atherosclerosis and I/R induced cardiac injuries [23, 24], potentially via vasodilatation [25] and anti-inflammatory actions [26]. Similarly, TVI has been shown with antihypertrophy activity in cardiomyocytes [27], and DHT has been reported with vasorelaxation and antiplatelet actions [28, 29]. Tables 1 and 2 summarize cardioprotective actions of major tanshinones in vitro and in vivo. This short review outlines the recent development in understanding the molecular mechanisms of cardioprotective actions of tanshinones, with a focus on their regulation of various signaling pathways.Table 1: Pharmacological actions of tanshinones in vitro.Table 2: Pharmacological actions of tanshinones in vivo. 2. Effects of Tanshinones on AtherosclerosisAtherosclerosis is a vascular endothelial dysfunction caused by inflammation promoted by low-density lipoproteins (LDL) [30]. Various atherogenic stimuli, including diabetes and oxidative stress, can induce endothelial dysfunction, leading to atherosclerosis [31]. Current approaches for reducing atherosclerosis have been focused on anti-inflammatory, antioxidant, and vasodilator mechanisms [32]. Studies have demonstrated the antiatherosclerosis actions of various tanshinones and their associations with various signaling pathways. For example, a tanshinone mixture was shown to inhibit proliferation of vascular smooth muscle cells (VSMCs) in vitro, which is associated with reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, cyclin D1, and enhancing (cyclin-dependent kinase inhibitor 1) expressions [33]. This is supported by the finding of inhibition of intimal hyperplasia by tanshinone in the ligated mouse carotid artery in vivo [34]. Treatment with total tanshinone reduced the development of intimal thickening of injured vessels and proliferating cell nuclear antigen- (PCNA-) positive vascular smooth muscle cells in mice, indicating that tanshinone may potentially inhibit VSMCs proliferation from arterial injury and reduce occurrence of atherosclerosis [34].TIIA has been shown to increase nitric oxide (NO) generation and inhibiting platelet aggregation/leukocyte adhesion in vitro [73]. It also attenuated H2O2 induced endothelial dysfunction by enhancing superoxide dismutase (SOD) activity [38] and reducing caspase 3 activity in human umbilical vein endothelial cell (HUVECs) [39]. The antiatherosclerosis action of TIIA was associated with its anti-inflammatory activities by inhibition of cluster of differentiation 40 (CD40) and p53 protein expression [38, 39], and inhibition of tumor necrosis factor-α (TNF-α) induced expressions of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and fractalkine, possibly through inhibition of IKK/NF-κB signaling pathway [37, 74]. TIIA was found to reduce oxidized LDL protein production and superoxide production by enhancing Cu/Zn SOD in rat [70] and also decreased cholesterol content and oxLDL level in apolipoprotein E deficient (ApoE−/−) mice [22]. It also inhibited the expression of inflammatory regulator CD40 and matrix metalloproteinase-2 (MMP-2) in high fat diet induced atherosclerosis in rabbits [71]. A recent study in ovariectomized ApoE−/− mice found that TIIA had a phytoestrogen-like activity reducing aortic lipid deposition and serum levels of malonyl dialdehyde (MDA), nuclear factor-kappa B (NF-κB), and lipids, involving inhibiting p-ERK 1/2 [75]. Further study is required to elucidate the role of NO synthesis and redox signaling (specifically on regulation of mitochondrial anti/prooxidative stress) in the actions of TIIA.Similarly, CT was found to attenuate TNF-α induced endothelial dysfunction in HUVECs by reducing endothelin-1 accumulation, enhancing eNOS/NO, and inhibiting of NF-κB pathways [26]. In human aortic smooth muscle cells (HASMCs), CT inhibited TNF-α induced activation of NF-κB and activator protein 1 (AP1, a transcriptional factor that regulates genes of cytokines and growth factors), as well as activation of matrix metalloproteinases-9 (MMP-9), which plays an important role in migration and proliferation of vascular smooth cells and into the intima [23]. On the other hand, CT was found to reduce calcium flux and calcium induced contraction in rat coronary artery [25] and inhibit thromboxane A2 analogue U46619-induced constriction of the porcine coronary artery [76].Another tanshinone, DHT, was shown with a vasodilator activity by reducing CaCl2 elicited contraction in rat coronary artery [28]. The calcium regulation effect of DHT was also demonstrated in its inhibition of collagen-induced rabbit platelet aggregation, which involves intracellular calcium mobilization, arachidonic acid liberation, and thromboxane B2 generation mechanisms [29].3. Effects of Tanshinones on Myocardial InfarctionMyocardial infarction (MI) is caused by disruption of blood supply to the heart and often accompanied by ventricular remodeling and cardiac hypertrophy, which can lead to cardiac cell death [77]. Cardiomyocytes apoptosis is an important mechanism in MI [78], and it is closely associated with cellular inflammatory reaction, intracellular calcium homeostasis, and NO and oxidative stress [79].There is evidence that tanshinones reduced cardiac infarct size and improved cardiac function in MI via inhibiting intracellular calcium, cell adhesion molecules, apoptotic protein, and inflammation protein expressions. An in vivo study demonstrated that acute myocardial infarction induced by occlusion of rat coronary vessel was decreased by posttreatment of a tanshinone extract [57]. This improvement was partially mediated by modulation of expression of genes which regulate intracellular calcium, cell adhesion molecules, and alternative complementary pathways (i.e., neuronal pentraxin 1, intercellular adhesion molecule 1, and C3 convertase) [46, 57]. The anti-inflammatory and antiapoptotic properties of tanshinones may play an important role in their anti-MI actions [18, 46]. TIIA was shown to inhibit TNF-α induced monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β1 (TGF-β1) expression in cardiac fibroblasts in vitro [18]. It reduced TNF-α, NF-κB, MCP-1, and TGF-β1 expressions [18] and improved cardiac dysfunction with inhibition of expressions of p-38, serum response factor (SRF: a transcription factor that has a role in modulating muscle proliferation and cell migration and apoptosis), and myocyte enhancer factor 2 (MEF2: a transcription factor that regulates tissue remodeling in cardiac muscle) [46].4. Effects of Tanshinones on Ischemia Reperfusion InjuriesMyocardial ischemia reperfusion (I/R) injury is caused by insufficient oxygen supply to the cardiac tissue which can occur in various conditions, such as thrombosis, coronary atherosclerotic plaques, and diabetes complications [80]. Sudden oxygen supply during reperfusion after prolonged ischemia can lead to impairment of myocardial cells via reactive oxygen species (ROS) dependent mechanisms [81]. The myocardial I/R injury can be affected by a number of cellular factors/regulators including calcium, pH, ROS, and in particular mitochondrial function. For example, mitochondrial membrane transition pore (MPTP) opening has been a research f
Hyou-Ju Jin; Chun-Guang Li. Molecular Mechanisms of Cardioprotective Actions of Tanshinones. Journal of Chemistry 2016, 2016, 1 -14.
AMA StyleHyou-Ju Jin, Chun-Guang Li. Molecular Mechanisms of Cardioprotective Actions of Tanshinones. Journal of Chemistry. 2016; 2016 ():1-14.
Chicago/Turabian StyleHyou-Ju Jin; Chun-Guang Li. 2016. "Molecular Mechanisms of Cardioprotective Actions of Tanshinones." Journal of Chemistry 2016, no. : 1-14.