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Biological Activity of Natural Compounds in Combination with Drugs

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 14735

Special Issue Editors


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Guest Editor
Associate Professor, University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, A. Kovačića 1, 10000 Zagreb, Croatia
Interests: natural and derivatives products; medicinal chemistry; ADME-Tox; functional foods; drug design; additive, synergistic and antagonistic effects of drugs

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Guest Editor
Senior Research Associate, Ruđer Bošković Institute, Division of Molecular Biology, Bijenička cesta 54, 10000 Zagreb, Croatia
Interests: toxicology; pharmacology; basic oncology; tumour drug resistance; epithelial–mesenchymal transition; cell signalling; tumour therapy; molecular mechanisms of drug resistance
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Senior Research Associate, Ruđer Bošković Institute, Division of Molecular Biology, Bijenička cesta 54, 10000 Zagreb, Croatia
Interests: physiology; cell biology; Tff proteins in inflammation; metabolism and neurodegeneration; animal models; tumour therapy

Special Issue Information

Dear Colleagues,

The uncontrolled growth of abnormal cells in a body forms cancer, which second only to cardiovascular diseases as a major cause of death all over the world. One of the therapies used in the treatment of different types of cancer is chemotherapy. Despite the mostly successful use of one or more anti-cancer drugs during a first treatment cycle, side effects and the development of tumour drug resistance are major obstacles to therapy success. One of the approaches to solving these problems is the discovery of more effective therapeutic agents, either newly synthesised compounds or compounds isolated from terrestrial and marine organisms and microorganisms. Many natural compounds have been reported to have a variety of interesting and significant biological activities, such as antioxidant, anti-inflammatory, antitumour, antibacterial, antiviral, antifungal, antiparasitic, analgesic, antidiabetic, anti-atherogenic, antiproliferative as well as cardio- and neuroprotective activities. In addition, natural compounds can interact additively, synergistically or antagonistically with each other, with food components as well as with drugs. Combinations of natural compounds and drugs can increase the efficacy of the therapy and therefore reduce the prescribed dosage while also reducing its side effects.

This Special Issue of Molecules is dedicated to original research and review articles that cover the latest findings about extracts and/or molecules from natural sources, their chemical characterization and their biological activity. Studies on additive, synergistic or antagonistic effects of natural compounds with each other or in combination with drugs must be included. Although these effects are mostly determined by using in vitro, in vivo and ex vivo experimental models, studies conducted using computer methods are also welcome.

Dr. Monika Barbarić
Dr. Anamaria Brozovic
Dr. Mirela Baus Lončar
Guest Editors

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Keywords

  • natural compounds
  • extraction
  • chemical characterization
  • biological activity
  • additive, synergistic and antagonistic effects
  • in silico study

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Published Papers (4 papers)

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Research

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16 pages, 4644 KiB  
Article
Artemisia santolinifolia-Mediated Chemosensitization via Activation of Distinct Cell Death Modes and Suppression of STAT3/Survivin-Signaling Pathways in NSCLC
by Uyanga Batbold and Jun-Jen Liu
Molecules 2021, 26(23), 7200; https://doi.org/10.3390/molecules26237200 - 27 Nov 2021
Cited by 6 | Viewed by 2455
Abstract
Conventional chemotherapy remains an integral part of lung cancer therapy, regardless of its toxicity and drug resistance. Consequently, the discovery of an alternative to conventional chemotherapy is critical. Artemisia santolinifolia ethanol extract (AS) was assessed for its chemosensitizer ability when combined with the [...] Read more.
Conventional chemotherapy remains an integral part of lung cancer therapy, regardless of its toxicity and drug resistance. Consequently, the discovery of an alternative to conventional chemotherapy is critical. Artemisia santolinifolia ethanol extract (AS) was assessed for its chemosensitizer ability when combined with the conventional anticancer drug, docetaxel (DTX), against non-small cell lung cancer (NSCLC). SRB assay was used to determine cell viability for A549 and H23 cell lines. The potential for this combination was examined by the combination index (CI). Further cell death, analyses with Annexin V/7AAD double staining, and corresponding protein expressions were analyzed. Surprisingly, AS synergistically enhanced the cytotoxic effect of DTX by inducing apoptosis in H23 cells through the caspase-dependent pathway, whereas selectively increased necrotic cell population in A549 cells, following the decline in GPX4 level and reactive oxygen species (ROS) activation with the highest rate in the combination treatment group. Furthermore, our results highlight the chemosensitization ability of AS when combined with DTX. It was closely associated with synergistic inhibition of oncogenesis signaling molecule STAT3 in both cell lines and concurrently downregulating prosurvival protein Survivin. Conclusively, AS could enhance DTX-induced cancer cells apoptosis by abrogating substantial prosurvival proteins’ expressions and triggering two distinct cell death pathways. Our data also highlight that AS might serve as an adjunctive therapeutic option along with a conventional chemotherapeutic agent in the management of NSCLC patients. Full article
(This article belongs to the Special Issue Biological Activity of Natural Compounds in Combination with Drugs)
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14 pages, 1858 KiB  
Article
Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice
by Aishah E. Albalawi, Norah A. Althobaiti, Salma Saleh Alrdahe, Reem Hasaballah Alhasani, Fatima S. Alaryani and Mona Nasser BinMowyna
Molecules 2021, 26(22), 7021; https://doi.org/10.3390/molecules26227021 - 20 Nov 2021
Cited by 23 | Viewed by 2981
Abstract
Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of [...] Read more.
Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results. Full article
(This article belongs to the Special Issue Biological Activity of Natural Compounds in Combination with Drugs)
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17 pages, 3235 KiB  
Article
Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation
by Anna Woziwodzka, Marta Krychowiak-Maśnicka, Grzegorz Gołuński, Anna Felberg, Agnieszka Borowik, Dariusz Wyrzykowski and Jacek Piosik
Molecules 2021, 26(12), 3628; https://doi.org/10.3390/molecules26123628 - 14 Jun 2021
Cited by 4 | Viewed by 3682
Abstract
Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and [...] Read more.
Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M−1 and enthalpy change values up to −4 kJ·M−1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance. Full article
(This article belongs to the Special Issue Biological Activity of Natural Compounds in Combination with Drugs)
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Review

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42 pages, 1940 KiB  
Review
Combination Chemotherapy with Selected Polyphenols in Preclinical and Clinical Studies—An Update Overview
by Cvijeta Jakobušić Brala, Ana Karković Marković, Azra Kugić, Jelena Torić and Monika Barbarić
Molecules 2023, 28(9), 3746; https://doi.org/10.3390/molecules28093746 - 26 Apr 2023
Cited by 13 | Viewed by 4256
Abstract
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. [...] Read more.
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required. Full article
(This article belongs to the Special Issue Biological Activity of Natural Compounds in Combination with Drugs)
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