Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety.

Bone sialoprotein (BSP) and osteopontin (OPN) are secreted glycoproteins with a conserved Arg-Gly-Asp (RGD) integrin-binding motif and are expressed predominantly in bone. The RGD tripeptide is commonly present in extracellular attachment proteins and has been shown to mediate the attachment of osteosarcoma cells and osteoclasts. To determine the origin and incidence of BSP and OPN mRNA expression in primary tumor, a cohort of archival, primary invasive breast carcinoma specimens was analyzed. BSP transcripts were detected in 65% and OPN transcripts in 77% of breast cancers examined. In general, BSP and OPN transcripts were detected in both invasive and in situ carcinoma components. The transcripts were not detected in surrounding stromal cells or in peritumoral macrophages. Despite its abundance in carcinomas, BSP expression was not detected in a panel of 11 human breast cancer cell lines (MCF-7, T47D, SK-Br-3, MDA-MB-453, MDA-MB- 231, MDA-MB-436, BT549, MCF-7(AOR), Hs578T, MDA-MB-435, and LCC15-MB) and OPN expression was detected only in two of these (MDA-MB-435 and LCC15-MB). To examine the possibility that expression of these genes was down-regulated in cell culture, several cell lines were grown as nude mouse xenografts in vivo; however, these tumors also failed to express BSP. OPN expression was identified in all cell lines grown as nude mouse xenografts. Our data suggest that in human primary breast tumors, the origin of BSP and OPN mRNA is predominantly the breast cancer cells and that expression of these transcripts is influenced by the tumor environment.

Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer

COVID-19 is a novel coronavirus that causes a severe infection in the respiratory system. Nigella sativa L. (Ranunculaceae) is an annual flowering plant used traditionally as a natural food supplem...

Possible therapeutic effects of Nigella sativa and its thymoquinone on COVID-19.

Targeting RAGE to prevent SARS-CoV-2-mediated multiple organ failure: Hypotheses and perspectives.

Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies.

Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain.

Parkinson's disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches.

The Gut-Brain Axis: Two Ways Signaling in Parkinson’s Disease

COVID-19, emerged at the end of 2019 have dramatically threatened the health, economy, and social mobility of people around the world and till date no medication is available for its treatment. An amazing herb, Nigella sativa, having antiviral, antihypertensive, anti- diarrhoeal, analgesics, and anti-bacterial properties, needs to be explored for its efficacy against SARS-CoV-2, the causative agent of COVID-19. In-silico studies were carried out to understand the role of its bioactive constituents in COVID-19 treatment and prevention. Firstly, the disease network was prepared by using ACE2 (Angiotensin-II receptor), as it is the entry site for virus. It was used to decipher the mechanism of SARS-COV-2 infection in humans. Second, the target receptors for N. sativa were predicted and protein interaction studies were conducted. Further, docking studies were also performed to analyse it for treatment purpose as well. This study concludes that pathways undertaken by N. sativa bioactive constituents were similar to the pathways followed in SARS-COV-2 pathology, like renin-angiotensin system, kidney functions, regulation of blood circulation, blood vessel diameter, etc. Also, in docking studies, the constituents of N. sativa, α-hederin, Thymohydroquinone and Thymoquinone were observed to be efficiently binding to ACE2. Also, the bioactive phytoconstituents are involved in molecular pathways like HIF1, VEGF, IL-17, AGE-RAGE, chemokine and calcium signaling pathways which can be majorly helpful in combating hypoxia and inflammation caused due to compromised immune system and oxidative stress. Therefore, N. sativa standardized extract having the above phytoconstituents could be useful in COVID-19 and hence opens a new treatment line.

Deciphering underlying mechanism of Sars-CoV-2 infection in humans and revealing the therapeutic potential of bioactive constituents from Nigella sativa to combat COVID19: in-silico study.

The earlier that hepatocellular carcinoma (HCC) is identified, the better the opportunity for a cure. As of now, HCC is diagnosed once it has metastasized all through the body. Operative, precise techniques of HCC detection and clinical analysis are required now. Biosensors and sensors are the biological devices intended to distinguish a definite natural analyte by essentially transforming a biological material (like RNA, DNA, cells, tissue, protein) into an electrical signal that can be distinguished and detected. The utilization of biosensors in HCC detection and monitoring holds immense potential due to their portability and miniaturized form. Biosensor innovation can possibly provide quick and precise detection, consistent imaging of malignant growth cells, monitoring of angiogenesis, and the capability to determine the efficacy of anticancer chemotherapy agents. This chapter outlines and correlates the explanatory performance of biosensors recently utilized in clinical examination and summarizes the hurdles to early HCC detection. It also discusses extending the utilization of biosensors as a diagnostic device along with future applications of biosensor innovation.

Biosensor-based early diagnosis of hepatic cancer

CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease

Hepatocellular carcinoma (HCC) is the second most important cause of liver cancer mortality across the globe. More than 7,00,000 new cases occur every year of HCC. Liver cirrhosis, mostly occurs due to chronic hepatitis B and C infection, is a major cause of hepatocarcinogenesis. The occurrence of HCC is usually associated with three different stages—nonalcoholic fatty acid, nonalcoholic steatohepatitis, and cirrhosis. Most of the patients are observed with advanced stages of HCC at the time of screening. Despite its high prevalence, its etiology is unclear, and also the disease-adjusting medications are inaccessible for patients with an advanced stage of HCC. Hence, there is an immediate urgency of improving the early detection and also the prognostication of patients suffering from HCC. Pharmacodynamic biomarkers are indicators for the assessment of the molecular linkage between drug regimen and target response. Recently, some novel pharmacodynamic biomarkers such as hepatocyte growth factor and fibroblast growth factor have been developed in response to sorafenib (an FDA-approved drug for HCC treatment). But the survival rates posttreatment with sorafenib are limited (2–5 months), and the other drugs such as lenvatinib, cabozantinib, and ramucirumab are still under clinical trials. Therefore it is imperative to focus on new potential pharmacodynamic biomarkers to study the pharmacokinetic–pharmacodynamic responses of the latest and existing drugs to have an effective treatment for advanced-stage HCC. In addition to this, the advancement of new therapies specific to target pathways involved in the progression of HCC should be the main aim for future research perspectives. In this chapter, we have discussed the utility and effectiveness of pharmacodynamic biomarkers using various animal models, and we have also analyzed the association of drug-target interaction and biological response against HCC.

Nitu Dogra

Papers

The Gut-Brain Axis: Two Ways Signaling in Parkinson’s Disease

Deciphering underlying mechanism of Sars-CoV-2 infection in humans and revealing the therapeutic potential of bioactive constituents from Nigella sativa to combat COVID19: in-silico study.

Biosensor-based early diagnosis of hepatic cancer

CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease

Pharmacodynamic biomarker for Hepatocellular carcinoma C: Model-based evaluation for pharmacokinetic–pharmacodynamic responses of drug