Role of Unani Medicine in Prevention and Treatment of Waba (Epidemics) including COVID-19: A Review

Mankind has faced many hardships like natural disaster, drought and epidemics. Study focuses on epidemics caused by microbes.Unani medicine has a long experience in treating epidemic diseases because its history is as old as the history of human being itself. More or less entire of the civilisations throughout the history became the basis for evolution of Unani medicine. Hippocrates (460-380BC) regarded it asbothart and science, discussed the epidemics and wrote a book on Epidemics. Body is assumed healthy when the humours are balanced. So, Unani scholars have rightly said Fa’il (Active agent) is not able to produce any change (Actions & Reactions) in the body without the prior presence of Munfa’il(Pertinent) having the capacity to accept it like in Waba(epidemic). The aim is to explore the fundamental concept of Waba from the Unani literature and understand COVID-19 in reference to existing literature of Unani medicine. The literature of Unani medicine was surveyed for concept of Waba(Epidemic) & related concepts. Internet was used to access indexed papers using search engines like Medline, PubMed, Science Direct, etc. Logical preventive strategies like quarantine, and useof fumigants, prophylactic drugs are mentioned in Unani literature that have been used in epidemics with flue like symptoms. This knowledge and experience may be used for achieving methods for prophylaxis, cure or add on therapeutic measures for COVID-19 epidemic.

Targeting Itch/p73 pathway by thymoquinone as a novel therapeutic strategy for cancers with p53 mutation

The tumor suppressor p73 is a member of p53 family and has a high degree of similarity with p53 function and structure. Like p53, p73 can also induce the expression of several genes involved in cell cycle and apoptosis. p73 expression is downregulated in many tumors by several mechanisms including the ubiquitination pathway. Thus, understanding the ubiquitin-proteasome pathway in p73 regulation will help in targeting this later and develop a new promising therapeutic strategy for cancer with p53 mutations. The aim of this study was to evaluate the effect of Thymoquinone (TQ), the major biologically active compound of the black seed oil on the expression of several E3 ubiquitin ligase enzymes known to be regulators of p73 and the related events in cancer cells with p53 mutation, such as the human acute lymphoblastic leukemia Jurkat cells, the human triple-negative breast cancer (MDA-MB-468 cells) and human promyelocytic leukemia HL60 cells. RNA-seq data showed that several E3 ubiquitin-ligase enzymes, well documented to be involved in the degradation of p73 including Itch, Pirh2, E3s Pin2, Mdm2, TRIM32 and SCFFBXO45 were downregulated in Jurkat cells. Among the target genes, Itch was significantly downregulated in TQ-treated Jurkat cells as compared with control cells. TQ-induced Itch downregulation was confirmed by real-time RT-PCR in Jurkat cells, MDA-MB-468 cells and HL60. Treating Jurkat cells with either TQ or the proteasome inhibitor MG132 induced an upregulation of p73. The present study indicates that TQ could be a promising inhibitor of the E3-ubiquitin ligase Itch leading to the upregulation of tumor suppressor p73 in cancers expressing mutant p53.

An update on the effectiveness of metformin alone and with chemotherapy drugs on tumor cells

Cancer and diabetes are critical risks that reveal many complications. Metformin has long been used in herbal medicine as an anti-diabetes medicine. It is one of the first-line therapies for type two (T2D that has gained use across different healthcare systems. It is the most preferred form of treatment due to its safety, being readily available, and widely used because it has fewer and affordable side effects for many users. The repurposing of metformin used in other treatments to treat cancer patients or the combination of targeted treatments with metformin can reduce the side effects of chemotherapy drugs, enhance the effectiveness, and may reduce resistance to targeted drugs. The mechanism of metformin has been demonstrated and its association with other drugs. It Inhibits cell growth and stops the cell cycle, and stimulates programmed cell death and autophagy of various cancer cells. Patients with diabetes and different kinds of malignancies such as colorectal, hepatic, and ovarian cancers have better response rates after metformin treatment. A combination of metformin and new medications has had a significant effect on those who do not receive metformin. On the other hand, prevailing evidence has greatly proved the benefit of using metformin as an adjuvant agent in medical oncology practice.

Eruca sativa L-A promising source of drug lead for antimicrobial, neuroprotective and anticancer treatment regimens: Pharmacological properties of medicinal plant “Eruca sativa”

Rocket (Eruca sativa) is a low-calorie leafy vegetable of the family Brassicaceae under the genera Eruca mostly consumed raw in salads. It has been used since ancient times from food to medicine and cosmetics without any knowledge of the mechanism or the targets involved. However, presently, the production and cultivation of rocket have significantly increased owing to its different biological effects. Erucin and Sulforaphane are the most commonly studied isothiocyanates obtained from the plant parts of Eruca sativa. Over time, with continuous usage of conventional and synthetic drugs, the drug resistant and off-target toxicities rapidly increase, which necessitates for alternative medicine with increased specificity and minimal detrimental effects. It is interesting to note that many previous studies have reported the antimicrobial impact of E. sativa against the pathogenic bacterial species like Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, etc. Moreover, Erucin obtained from E. sativa has shown significant inhibitory and protective effect against different human cancer cell lines and xenograft animal models. The present review gives a brief overview of the antimicrobial, neuroprotective and anticancer effects of the various plant parts of E. sativa and the most bioactive isothiocyanates. It is exciting to note that epigenetic modulation of gene expression has also been reported in some studies which could be a new direction of research on the path of naturopathy.

The role of zinc deficiency in endothelial dysfunction

Endothelial dysfunction is the key element for developing cardiovascular disease. The crucial role of endothelium mandate searching for possible reversible causes of its dysfunction. Zinc is one of trace elements and essential micronutrients and enters in the component of more than 300 metalloenzymes which have roles in the degradation of carbohydrates, lipids, proteins and nucleic acids. Moreover, Zinc exerts antioxidant properties through different mechanisms including the induction of potent antioxidant metallothionein. The zinc supplementation can prevent endothelial dysfunction via several mechanisms such as the inhibition of the increase in NF-κB-induced inflammatory markers, the induction of an increase in eNOS expression levels and NO availability, the activation of PPAR receptor and the inhibition of TNFα activation-induced apoptosis. Thus, screening for zinc deficiency in general population especially, people with chronic diseases and with nutritional problems is highly recommended. This review describes the role of zinc deficiency in endothelial dysfunction.

Inaugural Issue Editorial Note

Welcome to the Inaugural Issue of European Journal of Cell Science, launched in June 2019!

Thymoquinone induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells: role of apoptosis-related WT1 and BCL2 genes

Acute myeloid leukemia (AML) is an aggressive and heterogeneous disease characterized by an abnormal proliferation and impaired differentiation of the myeloid precursor cells. The outcome for most AML patients remains poor with high relapse rates and chemotherapy remains the first line treatment for AML. The Wilms tumor wt1 and the anti-apoptotic BCL2 genes are upregulated in AML and are known to be involved in apoptosis inhibition. In the present study we evaluated the molecular mechanisms underlie the anti-proliferative and pro-apoptotic activities exerted by thymoquinone (TQ), the major biologically active compound of the black seed oil on acute myeloid leukemia (AML) cell line-HL60. Cell proliferation was determined by WST-1 assay and apoptosis rate was assessed by flow cytometry using annexin-V/7AAD staining. The expression of target genes was analyzed by real-time RT–PCR analysis. TQ significantly reduced HL60 cell viability and induced apoptosis in a dose and time-dependent manner. In order to decipher the molecular mechanisms underlie the anti-cancer activities induced by TQ in AML cells, we investigated its effect on the expression of WT1 and BCL2 genes. TQ significantly decreased the expression of WT1 and BCL2 genes in a dose and time-dependent manner. In summary, these findings suggest that TQ induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells most likely through targeting the apoptosis-related WT1 and BCL2 genes and also suggest that TQ could be a promising strategy for AML therapy.

Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

Human hepatocellular carcinoma (HCC) is the most prevalent and recurrent type of primary adult liver cancer without any effective therapy. Thus, there is an increase demands for finding new drugs and treatment strategies with selective and potent effects towards HCC. Plant-derived compounds acting as anti-cancer agents can induce apoptosis through targeting several signaling pathways. Thymoquinone (TQ), the major biologically active compound of the black seed oil (Nigella sativa) has demonstrated inhibitory activities on various cancers by targeting several pathways. In the present study, we have evaluated the molecular mechanisms that underlie the anti-proliferative, anti-metastatic, and pro-apoptotic activities exerted by TQ on liver cancer cell lineHepG2, a well-documented HCC in vitro model. Cell proliferation was determined by WST-1 assay, apoptosis rate was assessed by flow cytometry using annexin-V/7AAD staining, wound healing assay to investigate the metastasis, and the expression of target genes was assessed by Real-time RT–PCR analysis. We found that TQ significantly reduced HepG2 cell viability and induced apoptosis in a dose-dependent manner. Migration of HepG2 cells was suppressed in response to TQ. Moreover, TQ decreased the expression of several angiogenesis-related genes including versican (VCAN), growth factor receptor-bound protein 2 (Grb2), and the histone methyltransferase for lysine 27 of histone 3 (EZH2). The findings suggest that TQ exerts inhibitory effects on HCC most likely through targeting key genes involved in the invasiveness and