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Professor 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: 51漫画, The Gateway, Leicester, LE1 9BH

T: +44 (0)116 250 6386

E: rrjarroo@dmu.ac.uk

W: /hls

 

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Publications and outputs

 


  • dc.title: Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei dc.contributor.author: Bhambra, Avninder S.; Taylor, Annie; Hering, Moritz; Elsegood, Mark R. J.; Teat, Simon J.; Weaver, George W.; Arroo, R. R. J.; Kaiser, Marcel; Maeser, Pascal dc.description.abstract: Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 碌M against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the <1 碌M range. We have demonstrated that substituted 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidines present promising antitrypanosomal hit molecules with potential for further preclinical development. dc.description: open access article

  • dc.title: CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues dc.contributor.author: Ruparelia, K. C.; Zeka, K.; Beresford, Kenneth J. M.; Wilsher, Nicola E.; Potter, Gerard A.; Androutsopoulos, V. P.; Brucoli, Federico; Arroo, R. R. J. dc.description.abstract: Naturally occurring stilbenoids, such as the (E)-stilbenoid resveratrol and the (Z)-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were assessed, using the MTT cell proliferation assay on a panel of human breast cell lines. Breast tumour cell lines that express CYP1 were significantly more strongly affected by the resveratrol analogues than the cell lines that did not have CYP1 activity. Metabolism studies using isolated CYP1 enzymes provided further evidence that (E)-stilbenoids can be substrates for these enzymes. Structures of metabolic products were confirmed by comparison with synthetic standards and LC-MS co-elution studies. The most promising stilbenoid was (E)-4,3鈥�,4鈥�,5鈥�-tetramethoxystilbene (51漫画212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, 51漫画212 selectively affects proliferation of cells that express CYP1 enzymes. dc.description: open access article

  • dc.title: Thermal degradation of (2R, 3R)-dihydromyricetin in neutral aqueous solution at 100 鈩� dc.contributor.author: Zhang, Haolin; Lin, Shiye; Xie, Ruiwei; Zhong, Weizhi; Wang, Hui; Farag, Mohamed A.; Hussain, H,; Arroo, R. R. J.; Chen, Xiaojia; Xiao. Jianbo dc.description.abstract: In the field of thermal degradation of flavonoids, most current studies have been mainly focused on the flavonols. However, the thermal degradation of dihydroflavonols in aqueous solution have been limited studied compared to flavonols. Different from the C2-C3 double bonds of flavonols, the single C2-C3 bonds of dihydroflavonols may cause different degradation mechanisms. Dihydromyricetin (DMY) is a typical dihydroflavonol with six hydroxyl groups, and possesses various health effects. We explored the thermal degradation of DMY in neutral aqueous solution (pH 7) at 100 鈩�. Ultra-performance liquid chromatography combined with photodiode array and electrospray ionization quadrupole-time-of-flight tandem mass spectrometric detection (UPLC-PDA ESI-QTOF鈥揗S/MS) provided suitable platform for exploring DMY degradation pathways, and negative ion mode was applied. Thermal treatment led to a decline in DMY level with time, accompanied by the appearance of various degradation products of DMY. Degradation mechanisms of DMY included isomerization, oxidation, hydroxylation, dimerization and ring cleavage. The pyrogallol-type ring B of DMY might be initially oxidized into ortho-quinone, which could further attack another DMY to form dimers. Besides, hydroxylation is likely to occur at C-2, C-3 of DMY or DMY dimers, and then further to yield ring-cleavage products via breakage of the O1-C2 bond, C2-C3 bond, or C3-C4 bond. The 3-hydroxy-5-(3,3,5,7-tetrahydroxy-4-oxochroman-2-yl) cyclohexa-3,5-diene-1, 2-dione (m/z 333.0244) and unknown compounds m/z 435.0925 were annotated as key intermediates in DMY degradation. Four phenolic acids, including 3,4,5-trihydroxybenzoic acid (m/z 169.0136, RT 1.4 min), 2,4,6-trihydroxyphenylglyoxylic acid (m/z 197.0084, RT 1.7 min), 2-oxo-2-(2,4,6-trihydroxyphenyl) acetaldehyde (m/z 181.0132, RT 2.4 min), and 2,4,6-trihydroxybenzoic acid (m/z 169.0139, RT 2.5 min) were identified as the major end products of DMY degradation. In addition, 5-((3,5dihydroxyphenoxy) methyl)-3-hydroxycyclohexa-3,5-diene-1,2-dione (m/z 261.0399, RT 11.7 min) and unidentified compound with m/z 329.0507 (RT 1.0 min) were also suggested to be end products of DMY degradation. These results provided novel insights on DMY stability and degradation products. Moreover, the heating treatment on DMY aqueous solution was found to gradually reduce the antioxidant activities of DMY, and even destroy the beneficial effect of DMY on the gut microbiota composition. dc.description: 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. Collaboration: Institute of Chinese Medical Sciences, University of Macau, Macao, China Universidade de Vigo, Department of Analytical and Food Chemistry, Faculty of Sciences, 32004, Ourense, Spain Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo, Egypt Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany Leicester School of Pharmacy, 51漫画, The Gateway, Leicester LE1 9BH, United Kingdom

  • dc.title: Developing Artemisia annua L. for the production of artemisinin to treat multi-drug resistant malaria dc.contributor.author: Arroo, R. R. J. dc.description.abstract: Sweet wormwood (Artemisia annua L.) is the commercial source of the sesquiterpene compound artemisinin 鈥� the key ingredient for several first-line antimalarial drugs. Currently artemisinin-based combination therapy (ACT) is recommended for the treatment of P. falciparum malaria. Fast acting artemisinin-based compounds are combined with a drug from a different class. The benefits of ACTs are their high efficacy, fast action and the reduced likelihood of resistance developing. A. annua also produces several polymethoxyflavones which are currently not in clinical use, but show some interesting pharmacological properties. The plants are grown as a medicinal crop, and the leaves are harvested for artemisinin extraction. Several attempts have been made to create varieties of A. annua that yield increased amounts of artemisinin; the efforts range from classical breeding to biotechnological approaches to use of genetic modification of crops. In a parallel development, key genes of the artemisinin biosynthetic pathways have been expressed in yeast, though full biosynthesis of the compound through yeast fermentation has not yet been achieved. At present, plant crops remain the only commercial source of artemisinin. In addition to its immediate pharmaceutical applications, over-the-counter available herbal preparations of Artemisia annua are widely promoted on-line as health supplements to fight inflammation or, even more controversially, as prophylactic against malaria for travellers to tropical countries.

  • dc.title: Advances in the natural 伪鈥恎lucosidase inhibitors dc.contributor.author: 艦枚hreto臒lu, Didem; Renda, G眉lin; Arroo, R. R. J.; Xiao, Jianbo; Sari, Suat dc.description.abstract: 伪鈥怗lucosidase (AG) inhibitors, one of the classes of oral antidiabetics used to treat type 2 diabetes mellitus, delay digestion and absorption of glucose, which in turn, has a lowering effect on postprandial blood glucose and insulin levels. Natural products are a great source for the development of new AG inhibitory drug candidates. We aim to summarize advances in natural AG inhibitors according to their secondary metabolite groups in the last decade. Their mechanisms of action and structure鈥揳ctivity relationships will especially be discussed. dc.description: open access article

  • dc.title: The protective effects of flavonoids and carotenoids against diabetic complications鈥擜 review of in vivo evidence dc.contributor.author: Jin, Yannan; Arroo, R. R. J. dc.description.abstract: Diabetes mellitus is a chronic metabolic disorder caused either by inadequate insulin secretion, impaired insulin function, or both. Uncontrolled diabetes is characterized by hyperglycemia which over time leads to fatal damage to both macro-and microvascular systems, causing complications such as cardiovascular diseases, retinopathy and nephropathy. Diabetes management is conventionally delivered through modifications of diet and lifestyle and pharmacological treatment, using antidiabetic drugs, and ultimately insulin injections. However, the side effects and financial cost of medications often reduce patient compliance to treatment, negatively affecting their health outcomes. Natural phytochemicals from edible plants such as fruits and vegetables (F&V) and medicinal herbs have drawn a growing interest as potential therapeutic agents for treating diabetes and preventing the onset and progression of diabetic complications. Flavonoids, the most abundant polyphenols in the human diet, have shown antidiabetic effects in numerous in vitro and preclinical studies. The underlying mechanisms have been linked to their antioxidant, anti-inflammatory and immunomodulatory activities. Carotenoids, another major group of dietary phytochemicals, have also shown antidiabetic potential in recent in vitro and in vivo experimental models, possibly through a mechanism of action similar to that of flavonoids. However, scientific evidence on the efficacy of these phytochemicals in treating diabetes or preventing the onset and progression of its complications in clinical settings is scarce, which delays the translation of animal study evidence to human applications and also limits the knowledge on their modes of actions in diabetes management. This review is aimed to highlight the potential roles of flavonoids and carotenoids in preventing or ameliorating diabetes-related complications based on in vivo study evidence, i.e., an array of preclinical animal studies and human intervention trials. The current general consensus of the underlying mechanisms of action exerted by both groups of phytochemicals is that their anti-inflammatory action is key. However, other potential mechanisms of action are considered. In total, 50 in vivo studies were selected for a review after a comprehensive database search via PubMed and ScienceDirect from January 2002 to August 2022. The key words used for analysis are type-2 diabetes (T2DM), diabetic complications, flavonoids, carotenoids, antioxidant, anti-inflammatory, mechanisms of prevention and amelioration, animal studies and human interventions. dc.description: open access article

  • dc.title: Use of herbal appetite suppressants to aid weight loss dc.contributor.author: Kuntawala, Dhivani H.; Arroo, R. R. J.; Jin, Yannan dc.description.abstract: Aim: Obesity has become a common health problem worldwide and is a major risk factor for noncommunicable diseases such as cardiovascular diseases, diabetes, musculoskeletal disorders, and some cancers. Thus, weight loss has become a hot topic within the general discussion on health and well-being, and many products are marketed as aids in weight loss. This presentation aims to raise awareness about the role herbal supplements may play in weight management as part of a healthy lifestyle. Methodology: A systematic review of recent peer-reviewed literature on the application of herbal materials or specialised plant metabolites in weight management. Results: A range of herbal products and specialised metabolites is used in weight loss: some increase human metabolic rate, others act as inhibitors of digestion of either fats or carbohydrates, whereas a third group affects the process appetite. The latter can be achieved through creating the sensation of satiety or by other mechanisms that suppress appetite. Conclusions: Whereas various products are commonly marketed as aids to weight loss, there is currently little scientific consensus on their efficacy or on potential adverse effects of herbal supplements.

  • dc.title: Interactions of Candida tropicalis pH-related antigen 1 with Complement Proteins C3, C3b, factor-H, C4BP and Complement Evasion dc.contributor.author: Valand, Nisha; Gazioglu, Ozcan; Yesilkaya, Hasan; Shivkumar, Maitreyi; Horley, Neill; Arroo, R. R. J.; Wallis, Russell; Kishore, Uday; Venkatraman Girija, U. dc.description.abstract: Candida, as a part of the human microbiota, can cause opportunistic infections that are either localised or systemic candidiasis. Emerging resistance to the standard antifungal drugs is associated with increased mortality rate due to invasive Candida infections, particularly in immunocompromised patients. While there are several species of Candida, an increasing number of Candida tropicalis isolates have been recently reported from patients with invasive candidiasis or inflammatory bowel diseases. In order to establish infections, C. tropicalis has to adopt several strategies to escape the host immune attack. Understanding the immune evasion strategies is of great importance as these can be exploited as novel therapeutic targets. C. albicans pH-related antigen 1 (CaPra1), a surface bound and secretory protein, has been found to interact strongly with the immune system and help in complement evasion. However, the role of C. tropicalis Pra1 (CtPra1) and its interaction with the complement is not studied yet. Thus, we characterised how pH-related antigen 1 of C. tropicalis (CtPra1) interacts with some of the key complement proteins of the innate immune system. CtPra1 was recombinantly produced using a Kluyveromyces lactis yeast expression system. Recombinant CtPra1, was found to bind human C3 and C3b, central molecules of the complement pathways that are important components of the innate immune system. It was also found to bind human complement regulatory proteins factor-H and C4b-binding protein (C4BP). CtPra1-factor-H and CtPra1-C4BP interactions were found to be ionic in nature as the binding intensity affected by high sodium chloride concentrations. CtPra1 inhibited functional complement activation with different effects on classical (鈭�20 %), lectin (鈭�25 %) and alternative (鈭�30 %) pathways. qPCR experiments using C. tropicalis clinical isolates (oral, blood and peritoneal fluid) revealed relatively higher levels of expression of CtPra1 gene when compared to the reference strain. Native CtPra1 was found to be expressed both as membrane-bound and secretory forms in the clinical isolates. Thus, C. tropicalis appears to be a master of immune evasion by using Pra1 protein. Further investigation using in-vivo models will help ascertain if these proteins can be novel therapeutic targets. dc.description: 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.

  • dc.title: Best Practice in the chemical characterisation of extracts used in pharmacological and toxicological research鈥擳he ConPhyMP鈥擥uidelines dc.contributor.author: Heinrich, Michael; Jalil, Banaz; Abdel-Tawab, Mona; Echeverria, Javier; Kuli膰, 沤arko; McGaw, Lyndy J.; Pezzuto, John M.; Potterat, Olivier; Wang, Jia-Bo; Appendino, Giovanni; Arroo, R. R. J.; Atanasov, Atanas G.; Barron, Denis; Bauer, Rudolf; Ca帽igueral, Salvador; Efferth, Thomas; F眉rst, Robert; Izzo, Angelo A.; Kelber, Olaf; Kemper, Kathi; Monagas, Maria; Pendry, Barbara; Pereda-Miranda, Rogelio; Rollinger, Judith; Russo, Alessandra; Verpoorte, Robert; Visioili, Francesco; Vollmer, G眉nter; Wohlmuth, Hans dc.description.abstract: Background: Research onmedicinal plants and extracts derived fromthem differs from studies performed with single compounds. Extracts obtained from plants, algae, fungi, lichens or animals pose some unique challenges: they are multicomponent mixtures of active, partially active and inactive substances, and the activity is often not exerted on a single target. Their composition varies depending on the method of preparation and the plant materials used. This complexity and variability impact the reproducibility and interpretation of pharmacological, toxicological and clinical research. Objectives: This project develops best practice guidelines to ensure reproducibility and accurate interpretations of studies using medicinal plant extracts. The focus is on herbal extracts used in pharmacological, toxicological, and clinical/intervention research. Specifically, the consensus-based statement focuses on defining requirements for: 1) Describing the plant material/herbal substances, herbal extracts and herbal medicinal products used in these studies, and 2) Conducting and reporting the phytochemical analysis of the plant extracts used in these studies in a reproducible and transparent way. The process and methods: We developed the guidelines through the following process: 1) The distinction between the three main types of extracts (extract types A, B, and C), initially conceptualised by the lead author (MH), led the development of the project as such; 2) A survey among researchers of medicinal plants to gather global perspectives, opportunities, and overarching challenges faced in characterising medicinal plant extracts under different laboratory infrastructures. The survey responses were central to developing the guidelines and were reviewed by the core group; 3) A core group of 9 experts met monthly to develop the guidelines through a Delphi process; and. 4) The final draft guidelines, endorsed by the core group, were also distributed for feedback and approval to an extended advisory group of 20 experts, including many journal editors. Outcome: The primary outcome is the 鈥淐onsensus statement on the Phytochemical Characterisation of Medicinal Plant extracts鈥� (ConPhyMP) which defines the best practice for reporting the starting plant materials and the chemical methods recommended for defining the chemical compositions of the plant extracts used in such studies. The checklist is intended to be an orientation for authors in medicinal plant research as well as peer reviewers and editors assessing such research for publication dc.description: The Advisory group on Consensus statement on the Phytochemical Characterisation of Medicinal Plant extracts (ConPhyMP) is a consortium of experts on Pharmacognosy and Phytochemistry open access article

  • dc.title: Effect of the Citrus Flavone Nobiletin on Circadian Rhythms and Metabolic Syndrome dc.contributor.author: Neba Ambe, Gael Noel Neh; Breda, Carlo; Bhambra, Avninder S.; Arroo, R. R. J. dc.description.abstract: The importance of the circadian clock in maintaining human health is now widely acknowledged. Dysregulated and dampened clocks may be a common cause of age-related diseases and metabolic syndrome Thus, circadian clocks should be considered as therapeutic targets to mitigate disease symptoms. This review highlights a number of dietary compounds that positively affect the maintenance of the circadian clock. Notably the polymethoxyflavone nobiletin has shown some encouraging results in pre-clinical experiments. Although many more experiments are needed to fully elucidate its exact mechanism of action, it is a promising candidate with potential as a chronotherapeutic agent. dc.description: Invited review paper for a special issue of Molecules on "Biological Activities of Natural Products III" (Halina Ekiert & Agnieszka Szopa, eds.) open access article

 

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.