Effect of Syzygium cumini on Oxidative Stress Induced Cardiac Cellular Anomalies.

INTRODUCTION: Doxorubicin (Dox), an antineoplastic agent is used as a primary anticancerous drug against various types of cancers. However, its associated toxicity to the cardiovascular system is major. Literature has recorded the cases of mortality due to poor validation and lack of prediagnosis of Dox-induced cardiotoxicity. Therapeutic interventions using natural products having cardioprotective properties with low toxic outcomes hold therapeutic potential for future cardio-oncological therapies. Syzygium cumini (Black berry), a traditional Indian herbal plant, has been researched and found to exert cardioprotective, anti-inflammatory, and antioxidant activities, which have been credited due to the presence of polyphenols, flavonoids, and tannins. METHODS: In the current research, we investigated the cardioprotective potential of Syzygium cumini against Doxorubicin-induced cardiotoxicity (DIC) in H9C2 cardiomyocytes. Methanolic seed extract preparation of Syzygium cumini was performed using the Soxhlet apparatus. Cell viability and cell death assays were performed to determine the cardiotoxic doses of Doxorubicin. Furthermore, the cardioprotective potential of Syzygium cumini extract against DIC was studied. Morphological and nuclear alterations in H9C2 cells were studied by microscopic assays using Giemsa, Haematoxylin-Eosin stain, and PI. The intracellular stress level and ROS production were studied using DCFH-DA followed by mitochondrial integrity analysis using fluorescent microscopic methods. RESULTS: In the results, we investigated that Dox exerted a dose and time-dependent cardiotoxicity on H9C2 cardiomyocytes. Moreover, we observed that morphological and nuclear alterations caused by doxorubicin in dose-dependent manner were prevented by supplementing with Syzygium cumini polyphenols and it attenuated the oxidative stress in H9C2 cardiomyocytes effectively. CONCLUSION: Conclusively, Syzygium cumini possesses cardioprotective potential in H9C2 cardiomyocytes in dox-induced cardiotoxicity.

Protective Effect of Quercetin and p-Coumaric Acid (p-CA) Against Cardiotoxicity: An In Silico Study.

BACKGROUND: Hydroxychloroquine (HCQ) is a common antimalarial drug that has been used effectively in the treatment of various rheumatic and auto-immunity diseases. The major side effects and drawbacks associated with HCQ are cardiotoxicity, retinopathy, gastrointestinal upset, and neuromyopathy however, cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by HCQ. The present work is focused on receptor and signaling molecules associated with pathways attributing to drug-induced cardiotoxicity. We analyzed the therapeutic efficacy of selected natural products in HCQ-induced cardiotoxicity through insilico. We selected Syzygium cumini polyphenols, quercetin, and p-coumaric acid. The motivation behind selecting quercetin, and p-coumaric acid is their wide applicability as an antioxidative, anti-inflammatory, antiapoptotic, and cardioprotective. METHODS: For predicting quercetin, p-coumaric acid, and HCQ toxicity and physicochemical properties, in silico studies were performed using ProTox II and Swiss ADME. We further performed molecular docking using Autodock Vina and Discovery Studio visualizer to find the affinity of selected polyphenols against signaling molecules and receptors. Then we performed network pharmacological studies of selected signaling molecules. RESULTS: We analyzed that the computational method indicated quercetin (Δ G -9.3 kcal/mol) has greater binding affinity than p-Coumaric acid for prevention and restoration of the disease while hydroxychloroquine was taken as a control. CONCLUSION: It can be concluded that Syzygium cumini, polyphenols may aid in the future therapeutic potential against HCQ-induced cardiotoxicity.

A Patent Review on Cardiotoxicity of Anticancerous Drugs.

Chemotherapy-induced cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by medications used in various cancers. Dysregulated cardiomyocyte homeostasis is a critical phenomenon of drug-induced cardiotoxicity, which hinders the cardiac tissue's natural physiological function. Drug-induced cardiotoxicity is responsible for various heart disorders such as myocardial infarction, myocardial hypertrophy, and arrhythmia, among others. Chronic cardiac stress due to drug toxicity restricts the usage of cancer medications. Anticancer medications can cause a variety of adverse effects, especially cardiovascular toxicity. This review is focused on anticancerous drugs anthracyclines, trastuzumab, nonsteroidal anti-inflammatory medications (NSAIDs), and immune checkpoint inhibitors (ICI) and associated pathways attributed to the drug-induced cardiotoxicity. Several factors responsible for enhanced cardiotoxicity are age, gender specificity, diseased conditions, and therapy are also discussed. The review also highlighted the patents assigned for different methodologies involved in the assessment and reducing cardiotoxicity. Recent advancements where the usage of trastuzumab and bevacizumab have caused cardiac dysfunction and their effects alone or in combination on cardiac cells are explained. Extensive research on patents associated with protection against cardiotoxicity has shown that chemicals like bis(dioxopiperazine)s and manganese compounds were cardioprotective when combined with other selected anticancerous drugs. Numerous patents are associated with drug-induced toxicity, prevention, and diagnosis, that may aid in understanding the current issues and developing novel therapies with safer cardiovascular outcomes. Also, the advancements in technology and research going on are yet to be explored to overcome the present issue of cardiotoxicity with the development of new drug formulations.

Role of gut microbiota in tumorigenesis and antitumoral therapies: an updated review.

Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.

Human Gut Microbiome: A New Frontier in Cancer Diagnostics & Therapeutics.

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body. The dynamic gut microbiota of our body houses an astonishing number of microorganisms, mainly bacteria. The balance of the gut microbiota is essential for good health as imbalances may result in dysbiosis leading to various diseases such as cancer. The gut microbiota can be manipulated by using prebiotics, probiotics, synbiotics, postbiotics, and antibiotics for better therapeutic outcomes, as well as to improve the quality of life of patients undergoing conventional cancer treatment. Administration of bacteria as a probiotic agent accompanied with prebiotics obtained from a wide variety of herbs has been used effectively to enhance the treatment of various cancers. Although the theoretical basis of Gut therapy can be ascertained, further clinical trials will be essential to determine the scope and limitations fully. The present review provides a glimpse of conventional and novel cancer therapeutics and their drawbacks, along with the role of the gut microbiome and its modulation to design new pharmaceutics against cancer.