Article
Biochemistry & Molecular Biology
Ean-Jeong Seo, Daycem Khelifi, Shaimaa Fayez, Doris Feineis, Gerhard Bringmann, Thomas Efferth, Mona Dawood
Summary: Geldanamycin is a benzoquinone-derived ansamycin that inhibits tyrosine kinases and heat shock protein 90 (HSP90). Among its derivatives, 17-desmethoxy-17-N,N-dimethylamino-geldanamycin (17-DMAG) has the highest binding affinity and lowest inhibition constant to HSP90. Both geldanamycin and 17-DMAG show cytotoxic activity against different tumor cell lines, with resistance observed in multidrug-resistant cells and sensitivity in certain tumor cells. Bioinformatic analysis suggests the involvement of the NF-KB pathway in their mechanism of action, which was confirmed by NF-KB reporter assays.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Review
Oncology
Thomas Efferth, Franz Oesch
Summary: Drug repurposing is the concept of using old drugs for new treatments, and plant alkaloids have potential for repositioning in cancer therapy. They can affect cancer cell growth through various mechanisms, including inhibiting tumor growth, inducing apoptosis, and inhibiting angiogenesis. However, some plant alkaloids also exhibit toxicities that need to be carefully considered.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xin Hu, Kui Zhang, Guangzhao Pan, Yinggang Wang, Yue Shen, Cheng Peng, Longfei Deng, Hongjuan Cui
Summary: This study investigated the anti-melanoma effects of Cortex Mori (CM), a traditional Chinese medicine, using network pharmacology and bioinformatic analyses, as well as in vitro and in vivo experiments. The results showed that CM has anti-melanoma activity and contains bioactive compounds that target melanoma. The study also revealed the potential mechanisms of CM in inhibiting melanoma, suggesting that CM could be a promising natural product for the treatment of melanoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Aveen N. Adham, Sara Abdelfatah, Alaadin Naqishbandi, Yoshikazu Sugimoto, Edmond Fleischer, Thomas Efferth
Summary: This study reveals that Nobiletin has broad-spectrum activity and multiple modes of action as a potential candidate for cancer therapy. Through bioinformatic and transcriptomic techniques, it is found that Nobiletin exerts cytotoxic effects on tumor cells and binds to the transcription factor SOX5. Nobiletin also shows synergistic effects when combined with other drugs.
Review
Pharmacology & Pharmacy
Gul-e-Saba Chaudhry, Abdah Md Akim, Yeong Yik Sung, Tengku Muhammad Tengku Sifzizul
Summary: Cancer is a complex and challenging disease, but the screening of plant and marine extracts may lead to the discovery of more effective anti-cancer compounds. Inducing apoptosis, a deeper mechanism of cell death, is essential for successful chemotherapy. Several plant and marine-derived anti-cancer compounds have been approved for clinical trials. Therefore, the development of new natural anti-cancer drugs is crucial.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Feng Jin, Xiaochen Ni, Shilong Yu, Xiaomin Jiang, Jun Zhou, Defang Mao, Yanqing Liu, Feng Wu
Summary: Triptonodiol, a potential antitumor drug candidate, may regulate cell processes such as proliferation, drug resistance, metastasis, and anti-apoptosis by targeting GSK3B, PKC, PAK, etc. This study provides new insights into the development and therapeutic application of Triptonodiol, and identifies it as a potential GSK inhibitor.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Licia T. S. Pina, Mairim R. Serafini, Marlange A. Oliveira, Laeza A. Sampaio, Juliana O. Guimaraes, Adriana G. Guimaraes
Summary: This study reviews the pharmacological activities of carvone in experimental models in vitro and in vivo, and finds that it has multiple pharmacological activities, such as antimicrobial, antispasmodic, anti-inflammatory, antioxidant, analgesic, and anticonvulsant effects. However, most studies have a risk of bias, highlighting the need for further research on the mechanisms of action and safety of carvone.
Article
Chemistry, Medicinal
Bing Liu, Hao Lian
Summary: Sappan extract can induce apoptosis of HepG2 cells in a dose-dependent manner and down regulate the phosphorylation level of Akt protein thr308 in a dose-dependent manner. This study provides new ideas for Sappan's anticancer research through the strategy of system pharmacology.
NATURAL PRODUCT COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Haoxian Wang, Gang Zhou, Mingyan Zhuang, Wei Wang, Xianyun Fu
Summary: This study used network pharmacology and molecular docking technology to predict the key targets and mechanisms of Guizhi Fuling Wan in the treatment of endometriosis. The results showed that Guizhi Fuling Wan has a therapeutic effect on endometriosis through a multi-target mechanism, providing a foundation for further experimental research.
Article
Biochemistry & Molecular Biology
Bhaskarjyoti Gogoi, Dhrubajyoti Gogoi, Neelutpal Gogoi, Saurov Mahanta, Alak K. Buragohain
Summary: This study utilized an integrated multidisciplinary concept of Network Pharmacology to evaluate the efficacy of potent anti-diabetic compound from traditionally used anti-diabetic plants of north east India and conducted DFT analysis. Ultimately, auraptene was identified as a candidate for the management of Type 2 diabetes mellitus.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Pharmacology & Pharmacy
Pandiyan Muthuramalingam, Sakthivel Akassh, Saravanan Bhavanisha Rithiga, Senthilkumar Prithika, Ravikumar Gunasekaran, Hyunsuk Shin, Reetesh Kumar, Venkidasamy Baskar, Jinwook Kim
Summary: This pilot study used various methods including network pharmacology, cheminformatics, integrative omics, molecular docking, and in vitro anti-cancer analysis to uncover the multi-targeted treatment mechanisms of novel plant bioactives in treating lung cancer. The study found that bioactive molecules from medicinal plants can efficiently target 390 human and lung cancer associated genes, and identified 7 bioactive molecules significantly targeting 8 lung cancer genes. In addition, unique genes between lung cancer and normal lung tissues were discovered and validated, and lupeol and p-coumaric acid exhibited high binding affinities with MIF, CCNB1, and FABP4.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Huaquan Guan, Wenbin Luo, Beihua Bao, Yudan Cao, Fangfang Cheng, Sheng Yu, Qiaoling Fan, Li Zhang, Qinan Wu, Mingqiu Shan
Summary: Rosmarinic acid is a widely occurring polyphenolic acid in herbal plants with various biological activities, such as anti-inflammation, anti-oxidation, and anti-diabetes. Its natural derivatives have also been extensively studied. Despite the advancements in research, there are still unresolved issues regarding its toxicity and bioavailability.
Article
Plant Sciences
Miao Zeng, Yue Zhang, Xiaolu Zhang, Wenlan Zhang, Qun Yu, Wenyun Zeng, Dongming Ma, Jiali Gan, Zhen Yang, Xijuan Jiang
Summary: This study confirmed that YQSSF can promote the proliferation of bone marrow cells and inhibit cell apoptosis, thus alleviating chemotherapy-induced myelosuppression.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mohammad Reza Kalhori, Masoud Soleimani, Ehsan Arefian, Ali Mohammad Alizadeh, Kamran Mansouri, Javier Echeverria
Summary: miR-1290 is dysregulated in many cancers and plays a crucial role in their development, making it a potential diagnostic and therapeutic target. This systematic review study also discussed how miR-1290 alters the expression of genes related to cancer development and resistance to chemo-radiation, as well as the regulatory effect of natural products on miR-1290 expression and its interaction with lncRNAs.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Plant Sciences
Pei-wen Yang, Pan-ling Xu, Chien-shan Cheng, Ju-ying Jiao, Yuan Wu, Shu Dong, Jing Xie, Xiao-yan Zhu
Summary: This study explores the therapeutic mechanism of the Qingyihuaji decoction (QYHJ) in the treatment of pancreatic adenocarcinoma (PAAD) using network pharmacology. The results show that QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eman H. Reda, Nesrine M. Hegazi, Mona Marzouk, Zienab T. Abdel Shakour, Ali M. El-Halawany, El-Sayeda A. El-Kashoury, Tarik A. Mohamed, Mahmoud A. A. Ibrahim, Khaled A. Shams, Nahla S. Abdel-Azim, Christopher J. Kampf, Thomas Efferth, Paul. W. Pare, Mohamed-Elamir F. Hegazy
Summary: LC-MS/MS analysis was used to investigate the metabolome of Centaurea lipii and identified cinnamic acids, sesquiterpene lactones, flavonoids, and lignans as the major chemical classes. Bioassay-guided fractionation confirmed that sesquiterpene lactones were responsible for the cytotoxic activity.
Article
Biochemistry & Molecular Biology
Ejlal A. Omer, Sara Abdelfatah, Max Riedl, Christian Meesters, Andreas Hildebrandt, Thomas Efferth
Summary: During the past three decades, humans have faced different coronavirus outbreaks, including the recent COVID-19 pandemic. In this study, researchers targeted a protein called nsp16, which is present in multiple coronavirus strains, to develop inhibitors. Using computational methods, they identified nine compounds with strong binding to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Further experiments confirmed the effectiveness of these compounds and their potential as therapeutic agents. Overall, three novel inhibitors were discovered, showing broad-spectrum activity against multiple coronavirus strains.
Article
Pharmacology & Pharmacy
Nadire Oezenver, Thomas Efferth
Summary: Oxidative stress is crucial in carcinogenesis and treatment response, and antioxidant genes play important roles in chemotherapy and radiotherapy resistance. This study investigated the role of 205 antioxidant genes in 21 different tumor types and identified 84 genes whose expression was significantly correlated with overall survival. Renal clear cell carcinoma, renal papillary cell carcinoma, and hepatocellular carcinoma were the tumor types most frequently associated with antioxidant gene expression and worse overall survival. Additionally, 17 genes were found to be overexpressed in tumors and may serve as druggable targets.
Article
Oncology
Eva-Maria Hartinger, Anne Mahringer, Soumitra Kumar Choudhuri, Gert Fricker, Thomas Efferth
Summary: Copper N-(2hydroxy acetophenone) glycinate (CuNG) has shown anticancer activity and modulates drug resistance. This study investigated the modulatory effects of CuNG on four ABC transporters (MRP1, MRP1, BCRP, and P-glycoprotein). Results showed that CuNG increased sensitivity to doxorubicin and efflux activity in cells over-expressing MRP1 and hBCRP, but increased resistance and decreased efflux activity in Caco-2 cells.
ANTICANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Jun Li, Nasir Tajuddeen, Doris Feineis, Virima Mudogo, Marcel Kaiser, Ean-Jeong Seo, Thomas Efferth, Gerhard Bringmann
Summary: A new dimeric naphthylisoquinoline alkaloid, jozibrevine D (4e), was isolated from the liana Ancistrocladus ileboensis in Central Africa. It has potent antiprotozoal activity against P. falciparum and exhibits good cytotoxic activities against acute lymphoblastic leukemia cells and their multidrug-resistant subline. The absolute stereostructure of the new compound was determined using various methods including NMR, oxidative degradation, and electronic circular dichroism (ECD) spectroscopy.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Cell Biology
Min Zhou, Joelle C. Boulos, Sabine M. Klauck, Thomas Efferth
Summary: This study investigates the cytotoxicity and molecular mode of action of the synthetic cardenolide ZINC253504760 on multidrug-resistant cancer cells. The results show that ZINC253504760 induces cell death and inhibits cell proliferation through the induction of parthanatos and inhibition of MEK phosphorylation.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luay. J. J. Rashan, Nadire Oezenver, Joelle. C. C. Boulos, Mona Dawood, Wynand. P. P. Roos, Katrin Franke, Ioannis Papasotiriou, Ludger. A. A. Wessjohann, Heinz-Herbert Fiebig, Thomas Efferth
Summary: A study found that a cold-water leaf extract called Breastin from Nerium oleander L. has potential as an anticancer agent, inhibiting the growth of multiple cancer cell lines and bypassing some traditional drug resistance mechanisms. The study also showed that protein expression profiles can be used to predict the sensitivity of tumor cells to Breastin constituents.
Article
Pharmacology & Pharmacy
Yuan-Qing Qu, Lin-Lin Song, Su-Wei Xu, Margaret Sum Yee Yu, Onat Kadioglu, Francesco Michelangeli, Betty Yuen Kwan Law, Thomas Efferth, Christopher Wai- Kei Lam, Vincent Kam Wai Wong
Summary: In this study, pomiferin, a natural product from Osage Orange, was found to activate autophagy and inhibit drug efflux to overcome innate and acquired drug resistance in cancer cells. It also exhibited tumor suppression and anti-metastatic effects in animal models. Pomiferin could serve as a novel effective agent for circumventing drug resistance in clinical applications.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Plant Sciences
Yue Jia, Juzhao Liu, Qin Yang, Wanjiang Zhang, Thomas Efferth, Siguo Liu, Xin Hua
Summary: A natural compound called cajanin stilbene acid (CSA) has been found to effectively restore the sensitivity of polymyxin B to MCR-1 positive Escherichia coli (E. coli). CSA can bind to the key amino acids of the MCR-1 protein, inhibiting its enzymatic activity and thus restoring the sensitivity of polymyxin B.
Article
Plant Sciences
Zhiwei Xu, Xiaojie Zhou, Xiao Hong, Sichen Wang, Jiale Wei, Junhao Huang, Liting Ji, Yuanxiao Yang, Thomas Efferth, Chunlan Hong, Changyu Li
Summary: In this study, it was found that Shi chang pu (SCP-oil) can improve cognitive impairment, reduce pathological damage, and inhibit neuroinflammation in AD mice. This neuroprotective effect is achieved through the inhibition of the NF-kappa B signaling pathway and reduced activation of the NLRP3 inflammasome.
Review
Biology
Janani Manochkumar, Aswani Kumar Cherukuri, Raju Suresh Kumar, Abdulrahman I. Almansour, Siva Ramamoorthy, Thomas Efferth
Summary: This review provides a comprehensive overview of the -omics and multi-omics approaches used for characterizing marine metabolites, along with the need for data integration and machine learning algorithms. It also discusses the challenges and recommendations for conducting multi-omics studies.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Min Zhou, Joelle C. Boulos, Ejlal A. Omer, Hadi Amiri Rudbari, Tanja Schirmeister, Nicola Micale, Thomas Efferth
Summary: The study selected two palladium (II) complexes with double chlorine or double iodine substitution, which showed the best cytotoxicity against drug-sensitive leukemia cells. Surprisingly, these complexes induced a novel mode of cell death called parthanatos. This study suggests that these complexes may be potential drug candidates to overcome tumor resistance to apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Min Zhou, Joelle C. Boulos, Ejlal A. Omer, Sabine M. Klauck, Thomas Efferth
Summary: The aim of this study was to investigate the molecular modes of action of a 1,2,4-oxadiazole derivative (ZINC15675948) as a c-MYC inhibitor. It was found that ZINC15675948 strongly bound to c-MYC and downregulated its expression. In both leukemia and breast cancer cells, ZINC15675948 affected signaling pathways downstream of c-MYC through inducing DNA damage, cell cycle arrest, and apoptosis.
Article
Biochemistry & Molecular Biology
Matteo Rosellini, Alicia Schulze, Ejlal A. Omer, Nadeen T. Ali, Federico Marini, Jan-Heiner Kuepper, Thomas Efferth
Summary: In recent years, plastic and microplastic in the oceans have caused problems to marine flora and fauna, and have also been found in human blood and milk, suggesting their ability to enter the human body. This study examined the interactions between plastic-related compounds and the cytochrome CYP2C19, and identified candidates that can interact with this protein. These compounds exhibited cytotoxic activity and affected various metabolic pathways, suggesting a potential for liver damage.
Review
Plant Sciences
Ressin Varghese, Thomas Efferth, Siva Ramamoorthy
Summary: Lung cancer, a leading malignancy worldwide, has been mitigated through the use of phytopigments such as carotenoids. While in vitro and animal studies have shown promising results, clinical trials have yielded contradictory outcomes, highlighting the need for further verification.