Dr Randolph Arroo

Job: School of Pharmacy Head of Research

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Research group(s): Chemistry for Health

Address: De Montfort University, The Gateway, Leicester, LE1 9BH

T: +44 (0)116 250 6386

E: rrjarroo@dmu.ac.uk

W: www.dmu.ac.uk/hls

 

Publications and outputs 

 

  • Over 3 decades of research on dietary flavonoid antioxidants and cancer prevention: What have we achieved?
    Over 3 decades of research on dietary flavonoid antioxidants and cancer prevention: What have we achieved? Alfa, Hajara H.; Arroo, R. R. J. Epidemiological studies keep confirming that the so-called Mediterranean Diet, which is characterised by a relatively high intake of fruit and vegetables, enhances health and provides protection against cancer. The first step in carcinogenesis, and possibly in a range of other degenerative diseases such as heart disease or degenerative dementia, is most likely damage to DNA and other macromolecules. Radical oxygen species - i.e. superoxide anion, hydrogen peroxide, and the hydroxyl radical - are generally considered a major cause of damage to macromolecules. It was long suggested that the antioxidant properties of food ingredients are essential to understanding the mechanism of action of what constitutes a healthy diet, i.e. a diet that prevents the onset of degenerative diseases. However, since the levels of antioxidants in blood plasma required to see any health benefits is much higher that what we get through our diet, the role of dietary phytochemicals acting as anti-oxidants is now in in doubt. Nevertheless, a correlation between presence of flavonoids in the diet and prevention of degenerative diseases has remained. Though there is a putative role for dietary flavonoids in the prevention of degenerative diseases, the exact mechanism of action of these phytonutrients is still a matter of debate. The human body has its own defences against oxidative stress in the form of the enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced glutathione (GSH). Rather than being antioxidants in their own right, plant constituents are more likely to act as triggers or inducers of expression of the human antioxidants SOD, CAT, and GSH. HHA was supported via IBB University, Faculty of Natural Sciences, Lapai, Niger State, Nigeria The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Use of Natural Products in the Prevention and Management of Type 2 Diabetes
    Use of Natural Products in the Prevention and Management of Type 2 Diabetes Zeka, Keti; Alfa, Hajara H; Ruparelia, Ketan C; Arroo, R. R. J. Metabolic syndrome is an umbrella term for a group of disorders related to imbalance of energy utilization and storage. It includes obesity, hypertension, increased triglyceride levels, aberrant cholesterol levels, and insulin resistance with resulting elevated fasting blood glucose levels that usually result in diabetes. Metabolic syndrome is associated with chronic low-grade local tissue inflammation and increased susceptibility to a variety of degenerative diseases. Lifestyle changes, e.g. more physical exercise, a diet rich in fruits and vegetables, etc. can help prevent or delay metabolic syndrome related problems. In addition, certain food supplements or herbal extracts are commonly believed to make an important contribution to a healthy life style, i.e glucomannan. Whereas there is a consensus that a vegetable-rich diet contributes to a lower occurrence of metabolic syndrome related disorders, the exact nature of the compounds in the diet that contribute to the prevention of degenerative diseases is still a matter of debate. This chapter book sets out to evaluate several natural products that are currently considered to play a role in the prevention or management of type 2 diabetes. Phytochemicals with antioxidant activity were long believed to be a major contributing factor in the suppression of chronic inflammation. However, not all antioxidant compounds have anti-inflammatory properties. Further, the peroxisome proliferator-activated receptor gamma (PPARγ)-activating potential of a wide range of natural products has been explored in great detail, and resulted in a credible model. A third model considers the potential role of phytoestrogens on human physiology. These compounds are known to interact with oestrogen receptors and can modulate a range of cell signalling pathways, either as agonists or as antagonists. The efficacy of several of the identified pharmaceutically active compounds and plant extracts, either as supplements, dietary factors or as part of a healthy life style, may be supported by laboratory results. However, caution is justified when considering food supplements in doses that greatly exceed the amounts that would be obtained through a regular diet. Book chapter, jointly written with authors from University of Cambridge, UK (Department of Haematology) and IBB University, Nigeria (Faculty of Natural Sciences)
  • The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells
    The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells Lodhi, Sabahat; Ankrett, Dyan N.; Wilsher, Nicola E.; Potter, Gerard A.; Beresford, Kenneth J. M.; Arroo, R. R. J.; Ruparelia, K. C. As part of a programme to develop anticancer prodrugs which are activated by cytochrome P450 (CYP)1B1, a library of 4,6-diaryl-2-pyridones was synthesised in yields of 6-60% from the corresponding chalcones. A number of these derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing little toxicity towards a non-tumour breast cell line with no CYP expression. Metabolism studies provided evidence supporting the involvement of CYP1 enzymes in the bioactivation of these compounds. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • New resveratrol analogues for potential use in diabetes and cancer.
    New resveratrol analogues for potential use in diabetes and cancer. Zeka, K.; Arroo, R. R. J.; Hasa, Dritan; Beresford, Kenneth J. M.; Ruparelia, K. C. Resveratrol is a well notorious compound that may play a role in the prevention of diabetes complications and different cancers. Along, resveratrol, a naturally occurring phytoalexin, is known to exert numerous beneficial effects in the organism. Isolation of resveratrol from plants, however, has been proved being difficult. Importantly, the bioavailability in the body is poor therefore capability is reduced and not enough resveratrol reaches the target organ. In this study we generated different methoxylated resveratrol analogues using Wittig reaction. Trans stilbene obtained was 0.08 g and the cis one was 0.01 g. Additionally with the Horner-Witting method a yield of 0.15 g trans stilbene was obtained. By substituting the hydroxyl group with methoxy group at different positions on the aromatic rings, we could increase the efficacy and bioavailability of the Trans form of resveratrol. open access journal
  • Chemical properties of thymoquinone, a monoterpene isolated from the seeds of Nigella sativa Linn.
    Chemical properties of thymoquinone, a monoterpene isolated from the seeds of Nigella sativa Linn. Arroo, R. R. J.; Alfa, H.H. Thymoquinone is the main ingredient of the essential oil extracted from the seeds of Nigella sativa L. (Ranunculaceae). The monoterpene is considered to be the active pharmaceutical ingredient in the seeds, which have traditionally been highly prized for their medicinal properties. The compound has been the focus of a considerable number of pharmacological investigations and has been reviewed regularly for its action against a variety of inflammatory diseases, its effect on metabolic syndrome, and its potential anticancer properties. While discussing the chemical and pharmacological properties of thymoquinone, recent reviews have reflected on the keto-enol tautomerism of thymoquinone. Specifically, thymoquinone is described as a tautomeric compound, where the keto-form is said to be the major configuration that is responsible for its pharmacological properties [1, 2]. In both reviews, reference is made to a 2005 review by Salem [3]. The latter review discusses a range of activities of thymoquinone, mainly on cell signalling and antioxidant (scavenging) molecular mediators involved in the process of inflammation. However, no mention is made in this review of keto- or enol forms of thymoquinone. Moreover, the chemical structure of thymoquinone does not allow keto-enol tautomerism. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Recent advances in chemistry, therapeutic properties and sources of polydatin
    Recent advances in chemistry, therapeutic properties and sources of polydatin Arroo, R. R. J.; Sohretoglu, D.; Yuzbasioglu, B.M.; Kuruuzum-Uz, A. Polydatin (PLD), the 3-O-β-glucopyranoside of the well-known stilbenoid compound resveratrol, is a major compound of Fallopia japonica (Houtt.) R. Decr. (Japanese knotweed), which is widely used in traditional Chinese medicine to treat infection, inflammatory diseases and circulatory problems. It has shown a wide range of biological activities including anti-inflammatory, anti-oxidant, anti-cancer, neuroprotective, hepatoprotective, nephroprotective and immunostimulatory effects. Although resveratrol has similar beneficial effects, its low bioavailability has remained a problem. Glycosylation increases solubility of resveratrol in an aqueous environment, thus improving its bioavailability. This has led to a growing interest in PLD. Promising results obtained from bioactivity studies have boosted an intense research on this compound. The aim of this review is to give a comprehensive overview of the botanical sources, pharmacology, biosynthesis, biotechnological production, and bioactivities of PLD, and to discuss clinical studies on this compound. Joint review by Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy and De Montfort University, Leicester School of Pharmacy.
  • Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin
    Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin Surichan, Somchaiya; Arroo, R. R. J.; Tsatsakis, A. M.; Androutsopoulos, V. P. Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism and further antiproliferative activity of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA–MB–468 and the normal breast cell line MCF10A. Tangeretin was converted to 4ʹ OH tangeretin by recombinant CYP1 enzymes and in MCF7 and MDA–MB–468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25±0.15 μM) in MDA–MB–468 cells, whereas it was less active in MCF7 cells (13.5±0.8 μM) and completely inactive in MCF10A cells (>100 μM). In MDA–MB–468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70–fold increase was noted in the IC50 (18±1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4ʹ OH tangeretin was significantly reduced in MDA–MB–468 cells (2.55±0.19 μM vs. 6.33±0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA–MB–468 cells, whereas the cell cycle of MCF10A cells was unaffected by 10 μM of tangeretin treatment for 24 and/or 48 h. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA–MB–468 cells. Taken collectively, the results suggest that tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4ʹ hydroxy tangeretin. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.
    Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans. Arroo, R. R. J.; Hano, C.; Renouard, S.; Corbin, C.; Drouet, S.; Medvedec, B.; Doussot, J.; Colas, C.; Maunit, B.; Bhambra, A. S.; Gontier, E.; Jullian, N.; Mesnard, F.; Boitel, M.; Abbasi, B. H.; Lainé, E. Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands. Collaboration with: Université d’Orléans, 28000 Chartres, France, Université de Picardie Jules Verne, F-80037 Amiens, France De Montfort University Open access article
  • New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification
    New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification Zeka, K.; Ruparelia, K. C.; Sansone, C.; Macchiarelli, G.; Continenza, M. A.; Arroo, R. R. J. Saffron extracts have a long history of application as skin protectant, possibly due to their ability to scavenge free radicals. In this work, the performance of a hydrogel enriched with antioxidant compounds isolated from saffron crocus (Crocus sativus L.) petals was tested. These hydrogels could be considered as new drug delivery system. Hydrogels are crosslinked polymer networks that absorb large quantities of water but retain the properties of a solid, thus making ideal dressings for sensitive skin. We tested antioxidant-en- riched hydrogels on primary mouse fibroblasts. Hydrogels enriched with kaempferol and crocin extracted from saffron petals showed good biocompatibility with in vitro cultured fibroblasts. These new types of hydrogels may find applications in wound treatment and/or beautification. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes.
    Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes. Surichan, Somchaiya; Arroo, R. R. J.; Ruparelia, K. C.; Tsatsakis, A. M.; Androutsopoulos, V.P. Nobiletin is a fully methoxylated flavone that has demonstrated anticancer activity via multiple modes of action. In the present study, the metabolism and further antiproliferative activity of nobiletin was evaluated in the CYP1 expressing human breast cancer cell line MDA–MB–468 and the normal breast cell line MCF10A. Nobiletin was metabolized in MDA–MB–468 cells to a single-demethylated derivative assigned NP1. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Nobiletin exhibited submicromolar IC50 (0.1±0.04 μM) in MDA–MB–468 cells, whereas it was considerably less active in MCF10A cells (40 μM). In the presence of the CYP1 inhibitor acacetin, the conversion of nobiletin to NP1 was significantly reduced in MDA–MB–468 cells. Furthermore, a significant increase was noted in the population of the cells at the G1 phase, following treatment with nobiletin (10 μM) for 24 h compared with the control cells treated with DMSO (0.1%) alone (55.9±0.14 vs. 45.6±1.96), whereas the cell cycle of MCF10A cells was not significantly altered under the same treatment conditions. Taken collectively, the results suggest that nobiletin is selectively bioactivated in MDA–MB–468 breast cancer cells via metabolism by the CYP1 family of enzymes. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link

Click here for a full listing of Randolph Arroo's publications and outputs. 

Research interests/expertise

  • Phytochemistry
  • Natural products
  • Pharmacognosy 
  • Alkaloids
  • Lignans
  • Sesquiterpenes
  • Anticancer drugs
  • Malaria 

Areas of teaching

  • Chemistry of medicinal natural products
  • Phytotherapy, complementary and alternative medicine 

Membership of professional associations and societies

Conference attendance

International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015), Shanghai, China, June 26-29 2015 – Invited key note lecture: ‘Dietary Flavonoids and The Prevention of Degenerative Diseases’.

 

University of L'Aquila, Department of Life, Health & Environmental Sciences, L’Aquila, Italy, 13-15 April 2015 – Visiting professor lecture: ‘Chemopreventive effects of orange peel extract’.

 

International Conference on Natural products in Cancer Therapy. Naples, 25-28 June 2013 – Invited key note lecture: ‘Phytoestrogens as natural prodrugs in cancer prevention: Towards a mechanistic model’.

 

Dana Centre/Science Museum, London, 8 November 2012 – Public lecture: ‘Shakespeare's Medicine Cabinet’.

 

International Conference on Natural Anticancer Drugs. Olomouc, Czech Republic, 30 June – 4 July, 2012 – Invited key note lecture: ‘Plant cell factories: Industrial revolution or green revolution?’

 

International Conference of Folk and Herbal Medicine. Udaipur (Rajasthan), 25-27 November, 2010 – Invited key note lecture: ‘Self treatment of malaria with preparations of Artemisia annua Linn.’

Current research students

Saeed Nazir (1st supervisor)

Externally funded research grants information

February 2011 - July 2011 Removal of Chewing Gum using Nut-based Compounds, funded by the EMDA Innovation Fellowship

October 2009 - July 2010 Phytochemicals Conference 2010, funded by paying delegates

July 2009 - August 2009 Antibacterial Compounds from Osha root (Ligusticum porteri), funded by the Nuffield Foundation

August 2008 - September 2008 Exploration of Cow Parsley (Anthriscus Sylvestris) funded by the Nuffield Foundation

March 2006 - April 2010 Development of Artemisia annua Linn as a UK crop for the production of antimalarial medicine, funded by DEFRA-LINK

Professional esteem indicators

  • Phytotherapy Research - Editorial Board
  • Phytochemical Analysis - Editorial Board
  • Plant Resources of Tropical Africa / Medicinal Plants - Co-editor

Case studies

High-artemisia-yielding Artemisia annua cultivars developed in Dr. Arroo's DEFRA-LINK project (see Externally funded research grants information) are now commercially grown in Madagascar.

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