A Systematic Review of Nonclinical Studies on the Effect of Curcumin in Chemotherapy- induced Cardiotoxicity.

BACKGROUND: Various anticancer drugs are effective therapeutic agents for cancer treatment; however, they cause severe toxicity in body organs. Cardiotoxicity is one of the most critical side effects of these drugs. Based on various findings, turmeric extract has positive effects on cardiac cells. OBJECTIVE: This study aims to evaluate how curcumin, as the main component of turmeric, may affect chemotherapy- induced cardiotoxicity. METHODS: A database search was performed up to April 2021 using "curcumin OR turmeric OR Curcuma longa" and "chemotherapy-induced cardiac disease", including their equivalents and similar terms. After screening the total articles obtained from the electronic databases, 25 relevant articles were included in this systematic review. RESULTS: The studies demonstrate lower body weight and increased mortality rates due to doxorubicin administration. Besides, cancer therapeutic agents induced various morphological and biochemical abnormalities compared to the non-treated groups. Based on most of the obtained results, curcumin at nontoxic doses can protect the cardiac cells mainly through modulating antioxidant capacity, regulation of cell death, and antiinflammatory effects. Nevertheless, according to a minority of findings, curcumin increases the susceptibility of the rat cardiomyoblast cell line (H9C2) to apoptosis triggered by doxorubicin. CONCLUSION: According to most nonclinical studies, curcumin could potentially have cardioprotective effects against chemotherapy-induced cardiotoxicity. However, based on limited, contradictory findings demonstrating the function of curcumin in potentiating doxorubicin-induced cardiotoxicity, well-designed studies are needed to evaluate the safety and effectiveness of treatment with new formulations of this compound during cancer therapy.

In silico Study Phytosterol Cymbopogon citratus and Curcuma longa as Inhibitor Agent 3C-Like Protease SARS-CoV-2.

<b>Background and Objective:</b> Lemongrass (<i>Cymbopogon citratus</i>) and turmeric (<i>Curcuma longa</i>) are widely used by the community for traditional medicinal spices and cooking spices. In the era of the COVID-19 pandemic, people use lemongrass and turmeric to increase immunity and protect the body from infection with the SARS-CoV-2 virus. However, the antiviral mechanisms have not been studied much. This study aims to predict the bioactivity of the phytosterol compounds of lemongrass and turmeric for COVID-19 therapy through inhibition of 3C-like protease (3CLPro) <i>in silico</i>. <b>Materials and Methods:</b> The 3CLPro protein 3D structure was downloaded from the PDB database with the access code 2ZU2 and the phytosterol compounds of lemongrass and turmeric were taken from PubChem. A total of 59 total phytosterol compounds from turmeric and lemongrass were screened for their bioactivity as an antiviral by using online PASS. Compounds with a high activating potential (Pa) were interacted with 3CLPro protein with the PyRx program and analyzed by Discovery Studio version 19.0 and LigPlus. <b>Results:</b> A total of 22 total phytosterol compounds were identified as potential antiviral agents. Based on the Pa value, 15 phytosterol compounds have the potential to act as inhibitor agents for 3CLPro SARS-CoV-2. The phytosterol compounds of lemongrass and turmeric bind to the 3CLPro protein in the N-finger domain region and the A and B domain inhibitors connect residues of the 3CLPro protein. The phytosterols of lemongrass and turmeric show a low binding affinity with 3CLPro SARS-CoV-2, indicating a strong interaction between ligand and protein. The inhibition of phytosterols against 3CLPro protein can be used as a basis for determining candidates for COVID-19 therapeutic agents. <b>Conclusion:</b> The phytosterol compounds contained in lemongrass and turmeric have the potential to act as 3CLPro inhibitors. Further studies both <i>in vitro</i> and <i>in vivo</i> need to be done to prove the inhibitory potential of phytosterol compounds.

Ayurveda and COVID-19: Where psychoneuroimmunology and the meaning response meet.

The COVID-19 pandemic has led to high levels of psychological distress in the general public, including symptoms of anxiety and depression. Such distress is associated with alterations in immune function, including an elevated risk of viral respiratory tract infections. In this light, the possible effects of Ayurveda, a traditional system of medicine promoted by the Indian government as an "immune booster", are examined from the point of view of psychoneuroimmune mechanisms as well as the "meaning response" described by Moerman. It was found that many of the measures advocated in their guidelines could positively influence immunity either by direct effects on symptoms of depression or anxiety, or through their symbolic significance. Therefore, it is possible that such traditional practices could be beneficial both in terms of psychological quality of life, and in terms of moderating the risk of infection.

Preparation and characterization of immobilized 5-HT1A receptor stationary phase for high throughput screening of the receptor-binding ligands from complex systems like Curcuma wenyujin Y. H. Chen et C. Ling extract.

The incidence of depression has increased significantly during the COVID-19 pandemic. This disease is closely associated with serotonin 1A (5-HT1A) receptor and often treated by complex prescription containing Curcuma wenyujin Y. H. Chen et C. Ling. Therefore, we hypothesized that this herb contains bioactive compounds specially binding to the receptor. However, the rapid discovery of new ligands of 5-HT1A receptor is still challenging due to the lack of efficient screening methods. To address this problem, we developed and characterized a novel approach for the rapid screening of ligands by using immobilized 5-HT1A receptor as the chromatographic stationary phase. Briefly, haloalkane dehalogenase was fused at the C-terminal of 5-HT1A receptor, and the modified 5-HT1A receptor was immobilized on amino-microspheres by the reaction between haloalkane dehalogenase and 6-chlorohexanoic acid linker. Scanning electron microscope and X-ray photo-electron were used to characterize the morphology and element of the immobilized receptor. The binding of three specific ligands to 5-HT1A receptor was investigated by two different methods. Moreover, we examined the feasibility of 5-HT1A receptor colume in high throughput screening of new ligands from complex systems as exemplified by Curcuma wenyujin Y. H. Chen et C. Ling. Gweicurculactone, 2-hydroxy-1-(3,4-dihydroxybenzene)-7-(4'-hydroxybezene)-heptane and curcuminol F were identified as the ligands of 5-HT1A receptor with the binding energies of -7.06 kcal/mol, -7.77 kcal/mol and -5.26 kcal/mol, respectively. Collectively, these results indicated that the immobilized 5-HT1A receptor was capable of screening bioactive compound from complex system, providing an effective methodology for high throughput screening.

Indian spices: past, present and future challenges as the engine for bio-enhancement of drugs: impact of COVID-19.

Spices are natural plant products enriched with the history of being used as herbal medicine for prevention of diseases. India is also known as the 'Land of Spices'. Out of 109 spices recognized by the International Organization for Standardization (ISO) more than 52-60 spice crops are grown in India. The major spices exported by India are turmeric, cumin, coriander, fenugreek, peppers, etc. The Indian spices are divided into three era viz. early period, middle age and early modern period. Spices are used in beverages, liquors, and pharmaceutical, cosmetic and perfumery products. The major issue with spices is their handling and storage. This review article mainly focuses on two aspects: at the outset the handling and storage of the spices is an essential factor as spices are available in different forms like raw, processed, fresh, whole dried, or pre-ground dried. Therefore, the need of processing, packaging, storage and handling of the spices is important as the deterioration of spices can lead to the loss of therapeutic activity. Furthermore, many herbal constituents have the capability to enhance the bioavailability of drugs. Therefore, an attempt has been made to throw a light on the bioenhancer activity and therapeutic activity along with their mechanism of action of some Indian spices which are regularly used for cooking purpose on a daily basis to enhance the taste of food. The spices suggested by ministry of AYUSH which is relevant to its medicinal and biological property in treatment and prevention from COVID-19 are discussed. © 2022 Society of Chemical Industry.

Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Currently, there are no particular antivirals available to battle with COVID-19. The RNA-dependent RNA polymerase (RdRp) has emerged as a novel drug target due to its essential role in virus replication. In this study, turmeric-derived compounds were chosen and subjected to in-silico analysis to evaluate their binding affinity against the RdRp-RNA complex of SARS-CoV-2. Our in-silico approach included the analysis of protein-ligand interactions by molecular docking and molecular dynamics simulations, followed by free energy calculations by molecular mechanics Poisson-Boltzmann surface area analysis. Curcumin and diacetylcurcumin showed stability and good binding affinity at the active site of the SARS-CoV-2 RdRp-RNA complex. Furthermore, to validate the potency of selected compounds, we compared them with Favipiravir and Remdesivir antiviral drugs from our previous analysis on targeting tea bioactive molecules to inhibit RdRp-RNA complex. The comparative analysis revealed that the selected compounds showed higher potential to be developed as RdRp-RNA inhibitors than antiviral medicines Remdesivir and Favipiravir. However, these compounds need to be further validated by in-vitro and in-vivo investigations.

Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products.

Impacts of the COVID-19 Pandemic on Food Security and Diet-Related Lifestyle Behaviors: An Analytical Study of Google Trends-Based Query Volumes.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 disease (COVID)-19 is having profound effects on the global economy and food trade. Limited data are available on how this pandemic is affecting our dietary and lifestyle-related behaviors at the global level. Google Trends was used to obtain worldwide relative search volumes (RSVs) covering a timeframe from before the COVID-19 pandemic 1 June 2019 to 27 April 2020. Spearman's rank-order correlation coefficients were used to measure relationships between daily confirmed cases and aforementioned RSVs between 31 December 2019 and 15 April 2020. RSV curves showed increased interest in multiple keywords related to dietary and lifestyle behaviors during the COVID-19 lockdown period in March and April 2020. Spearman's correlation analysis showed that the strongest variables in each keyword category were (1) food security (food shortage: r = 0.749, food bank: r = 0.660, and free food: r = 0.555; all p < 0.001), (2) dietary behaviors (delivery: r = 0.780, restaurant: r = -0.731, take-away: r = 0.731, and food-delivery: r = 0.693; all p < 0.001), (3) outdoor-related behaviors (resort: r = -0.922, hotel: r = -0.913, cinema: r = -0.844, park: r = -0.827, fitness: r = -0.817, gym: r = -0.811; plant: r = 0.749, sunbathing: r = 0.668, and online: r = 0.670; all p < 0.001), and (4) immune-related nutrients/herbs/foods (vitamin C: r = 0.802, vitamin A: r = 0.780, zinc: r = 0.781, immune: r = 0.739, vitamin E: r = 0.707, garlic: r = 0.667, omega-3 fatty acid: r = -0.633, vitamin D: r = 0.549, and turmeric: r = 0.545; all p < 0.001). Restricted movement has affected peoples' dietary and lifestyle behaviors as people tend to search for immune-boosting nutrients/herbs and have replaced outdoor activities with sedentary indoor behaviors.

EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study.

Inspired by the 'There is no scientific evidence that turmeric prevents COVID-19' statement made by WHO, the protective or therapeutic potential of the compounds in turmeric contents was investigated against COVID-19 with in silico methodology. The drugs used for experimental COVID-19 therapies were included in this study using the same method for comparison with turmeric components. The 30 turmeric compounds and nine drugs were performed in the docking procedure for vital proteins of COVID-19. With evaluations based on docking scores, the Prime MMGBSA binding free energy and protein-ligand interactions were identified in detail. The 100 ns MD simulations were also performed to assess the stability of the ligands at the binding site of the target proteins. The Root Mean Square Deviation (RMSD) is used to obtain the average displacement for a particular frame concerning a reference frame. The results of this study are suggesting that turmeric spice have a potential to inhibit the SARS-CoV-2 vital proteins and can be use a therapeutic or protective agent against SARS-CoV-2 via inhibiting key protein of the SARS-CoV-2 virus. The compound 4, 23 and 6 are the most prominent inhibitor for the main protease, the spike glycoprotein and RNA polymerase of virus, respectively. The MD simulation validated the stability of ligand-protein interactions. The compactness of the complexes was shown using a radius of gyration. ADME properties of featured compounds are in range of 95% drug molecules. It is hoped that the outputs of this study will contribute to the struggle of humanity with COVID-19.Communicated by Ramaswamy H. Sarma.

Effect of the Phytochemical Agents against the SARS-CoV and Some of them Selected for Application to COVID-19: A Mini-Review.

BACKGROUND: The aim of the present review is to provide basic knowledge regarding the treatment of Coronavirus via medicinal plants. Coronavirus (COVID-19, SARS-CoV, and MERS-CoV) as a viral pneumonia causative agent, has infected thousands of people in China and worldwide. Currently, there is no specific medicine or vaccine available that can treat or prevent this virus and this has posed a severe threat to human health; therefore, there is an urgent need to develop a novel drug or anticoronavirus vaccine. However, natural compounds to treat coronaviruses are the most effective alternative and complementary therapies due to their diverse range of biological and therapeutic properties. METHODS: We performed an open-ended, English restricted search of Scopus database, Web of Science, and Pubmed for all available literature from Jan-March, 2020, using terms related to phytochemical compounds, medicinal plants and coronavirus. RESULTS: The view on anti-coronavirus (anti-CoV) activity in the plant-derived phytochemicals and medicinal plants gives a strong base to develop a novel treatment employing these compounds for coronavirus. Various phytochemicals and medicinal plant extracts have been revised and are considered as potential anti-CoV agents for effective control of the virus and future drug development. Herein, we discuss some important plants (Scutellaria baicalensis, Psorothamnus arborescens, Glycyrrhiza radix, Glycyrrhiza uralensis, Lycoris radiate, Phyllanthus emblica, Camellia sinensis, Hyptis atrorubens Poit, Fraxinus sieboldiana, Erigeron breviscapus, Citri Reticulatae Pericarpium, Amaranthus tricolor, Phaseolus vulgaris, Rheum palmatum, Curcuma longa and Myrica cerifera) that have emerged to have broad-spectrum antiviral activity. CONCLUSION: Nigella sativa has potent anti-SARS-CoV activity and it might be a useful source for developing novel antiviral therapies for coronavirus.

A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis.

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.