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PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396 -
Antioxidants (Basel, Switzerland) Mar 2024Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis,... (Review)
Review
Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis, necroptosis, and autophagy. It is characterized by the accumulation of intracellular iron, overproduction of reactive oxygen species, depletion of glutathione, and extensive lipid peroxidation of lipids in the cell membrane. It was discovered that ferroptosis is interconnected with many diseases, such as neurodegenerative diseases, ischemia/reperfusion injury, cancer, and chronic kidney disease. Polyphenols, plant secondary metabolites known for many bioactivities, are being extensively researched in the context of their influence on ferroptosis which resulted in a great number of publications showing the need for a systematic review. In this review, an extensive literature search was performed. Databases (Scopus, Web of Science, PubMed, ScienceDirect, Springer) were searched in the time span from 2017 to November 2023, using the keyword "ferroptosis" alone and in combination with "flavonoid", "phenolic acid", "stilbene", "coumarin", "anthraquinone", and "chalcone"; after the selection of studies, we had 311 papers and 143 phenolic compounds. In total, 53 compounds showed the ability to induce ferroptosis, and 110 compounds were able to inhibit ferroptosis, and out of those compounds, 20 showed both abilities depending on the model system. The most researched compounds are shikonin, curcumin, quercetin, resveratrol, and baicalin. The most common modes of action are in the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axis and the modulation of iron metabolism.
PubMed: 38539867
DOI: 10.3390/antiox13030334 -
BMC Cancer Sep 2023Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main...
BACKGROUND
Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart.
METHODS
A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed.
RESULTS
Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor.
CONCLUSIONS
Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.
Topics: Humans; Adolescent; Child; Cardiotoxicity; Mitoxantrone; Neoplasms; Heart; Anthracyclines; Polyketides
PubMed: 37710224
DOI: 10.1186/s12885-023-11353-9 -
Journal of Orthopaedic Surgery and... Apr 2023Knee osteoarthritis (KOA) is a common musculoskeletal condition affecting millions of people worldwide and posing a significant challenge to clinicians and researchers.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Knee osteoarthritis (KOA) is a common musculoskeletal condition affecting millions of people worldwide and posing a significant challenge to clinicians and researchers. Emerging evidence suggests that the multifaceted symptomatology of KOA may be alleviated by diacerein. With this in mind, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of diacerein in patients with KOA.
METHODS
We systematically searched Embase, PubMed, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), Wanfang Database (WanFang), China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) from their inception to August 2022 for randomized controlled trials (RCTs) of diacerein intervention on patients with KOA. Two reviewers independently performed the selection of eligible studies and the extraction of relevant data. The meta-analysis was performed using RevMan 5.4 and R 4.1.3 software tools. Depending on the type of outcome indicator selected, summary measures were expressed as mean differences (MD), standardized mean differences (SMD), or odds ratio (OR) with 95% confidence intervals (CI).
RESULTS
Twelve RCTs with 1732 patients were included. The results revealed that diacerein had comparable efficacy to non-steroidal anti-inflammatory drugs (NSAIDs) in reducing pain indicators such as Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = 0.09, 95% CI [-0.10, 0.28], P = 0.34) and visual analogue scale (VAS) (SMD = -0.19, 95% CI [-0.65, 0.27], P = 0.42). However, diacerein outperformed NSAIDs in terms of global efficacy assessment by both patients and investigators (patients: 1.97, 95% CI [1.18, 3.29], P = 0.01; investigator: 2.18, 95% CI [0.99, 4.81], P = 0.05) at the end of treatment and sustained effectiveness in reducing WOMAC score and VAS score at four weeks after treatment. Moreover, there was no significant difference in adverse events incidence between the diacerein and NSAID groups. However, the GRADE evaluation indicated that the majority of the evidence quality was low.
CONCLUSIONS
The results of this study suggest that diacerein could potentially be considered as a pharmacological agent with significant efficacy for the treatment of patients suffering from KOA, offering a potential alternative treatment strategy for those patients contraindicated to NSAIDs. However, further high-quality studies with longer follow-up are needed to make more informed decisions about its efficacy in the treatment of KOA.
Topics: Humans; Osteoarthritis, Knee; Pain; Anti-Inflammatory Agents, Non-Steroidal; Anthraquinones
PubMed: 37072810
DOI: 10.1186/s13018-023-03786-6 -
Biomedicine & Pharmacotherapy =... May 2023The morbidity and mortality of cardiovascular diseases (CVDs) are increasing in recent years, and atherosclerosis (AS), a major CVD, becomes a disorder that afflicts... (Review)
Review
The morbidity and mortality of cardiovascular diseases (CVDs) are increasing in recent years, and atherosclerosis (AS), a major CVD, becomes a disorder that afflicts human beings severely, especially the elders. AS is recognized as the primary cause and pathological basis of some other CVDs. The active constituents of Chinese herbal medicines have garnered increasing interest in recent researches owing to their influence on AS and other CVDs. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a naturally occurring anthraquinone derivative found in some Chinese herbal medicines such as Rhei radix et rhizome, Polygoni cuspidati rhizoma et radix and Polygoni multiflori root. In this paper, we first review the latest researches about emodin's pharmacology, metabolism and toxicity. Meanwhile, it has been shown to be effective in treating CVDs caused by AS in dozens of previous studies. Therefore, we systematically reviewed the mechanisms by which emodin treats AS. In summary, these mechanisms include anti-inflammatory activity, lipid metabolism regulation, anti-oxidative stress, anti-apoptosis and vascular protection. The mechanisms of emodin in other CVDs are also discussed, such as vasodilation, inhibition of myocardial fibrosis, inhibition of cardiac valve calcification and antiviral properties. We have further summarized the potential clinical applications of emodin. Through this review, we hope to provide guidance for clinical and preclinical drug development.
Topics: Humans; Aged; Emodin; Drugs, Chinese Herbal; Cardiovascular Diseases; Plant Extracts; Atherosclerosis; Phytochemicals
PubMed: 36933375
DOI: 10.1016/j.biopha.2023.114539 -
Medicine Nov 2022Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein.
OBJECTIVES
To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs).
METHODS
On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed.
RESULTS
Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]).
CONCLUSION
Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.
Topics: Humans; Aged; Osteoarthritis, Knee; Anthraquinones; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Diarrhea; Randomized Controlled Trials as Topic
PubMed: 36401382
DOI: 10.1097/MD.0000000000031700 -
Frontiers in Pharmacology 2022Under normal circumstances, wound healing can be summarized as three processes. These include inflammation, proliferation, and remodeling. The vast majority of wounds...
Under normal circumstances, wound healing can be summarized as three processes. These include inflammation, proliferation, and remodeling. The vast majority of wounds heal rapidly; however, a large percentage of nonhealing wounds have still not been studied significantly. The factors affecting wound nonhealing are complex and diverse, and identifying an effective solution from nature becomes a key goal of research. This study aimed to highlight and review the mechanisms and targets of natural products (NPs) for treating nonhealing wounds. The results of relevant studies have shown that the effects of NPs are associated with PI3K-AKT, P38MAPK, fibroblast growth factor, MAPK, and ERK signaling pathways and involve tumor growth factor (TNF), vascular endothelial growth factor, TNF-α, interleukin-1β, and expression of other cytokines and proteins. The 25 NPs that contribute to wound healing were systematically summarized by an inductive collation of the six major classes of compounds, including saponins, polyphenols, flavonoids, anthraquinones, polysaccharides, and others, which will further direct the attention to the active components of NPs and provide research ideas for further development of new products for wound healing.
PubMed: 35935866
DOI: 10.3389/fphar.2022.900439 -
Frontiers in Pharmacology 2022Polygoni Cuspidati Rhizoma et Radix, the dry roots and stems of Houtt (called Huzhang, HZ in Chinese), is a traditional and popular chinese medicinal herb for thousands...
Polygoni Cuspidati Rhizoma et Radix, the dry roots and stems of Houtt (called Huzhang, HZ in Chinese), is a traditional and popular chinese medicinal herb for thousands of years. As a widely used ethnomedicine in Asia including China, Japan, and Korea, HZ can invigorate the blood, cool heat, and resolve toxicity, which is commonly used in the treatment of favus, jaundice, scald, and constipation. However, HZ is now considered an invasive plant in the United States and many European countries. Therefore, in order to take advantage of HZ and solve the problem of biological invasion, scholars around the world have carried out abundant research studies on HZ. Until now, about 110 compounds have been isolated and identified from HZ, in which anthraquinones, stilbenes, and flavonoids would be the main bioactive ingredients for its pharmacological properties, such as microcirculation improvement, myocardial protective effects, endocrine regulation, anti-atherosclerotic activity, anti-oxidant activity, anti-tumor activity, anti-viral activity, and treatment of skin inflammation, burns, and scalds. HZ has a variety of active ingredients and broad pharmacological activities. It is widely used in health products, cosmetics, and even animal husbandry feed and has no obvious toxicity. Efforts should be made to develop more products such as effective drugs, health care products, cosmetics, and agricultural and animal husbandry products to benefit mankind.
PubMed: 35770098
DOI: 10.3389/fphar.2022.863707 -
RSC Advances Nov 2021Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of... (Review)
Review
Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.
PubMed: 35492773
DOI: 10.1039/d1ra05686g -
Phytotherapy Research : PTR Mar 2022This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase,... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.
Topics: Anthraquinones; Colorectal Neoplasms; Constipation; Humans; Laxatives
PubMed: 35040201
DOI: 10.1002/ptr.7373