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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: 草榴视频, 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: Aminated Polyphenols From Strecker Degradation of Amino Acids in Food Processing: A Class of Novel Bioactive Components dc.contributor.author: Li, Chunlin; Arroo, R. R. J.; Shpigelman, Avi; Xiao, Jianbo dc.description.abstract: Polyphenols tend to be oxidized to form o-quinones (1,2-carbonyl), significantly catalyzed by elevated temperatures, like the ones occurring during thermal processing. During food processing, both Strecker degradation鈥攑rimarily involving 伪-dicarbonyl compounds reacting with amino acids鈥攁nd polyphenol oxidation鈥攚here o-quinones can react with amino acids鈥攕pontaneously occur. These distinct pathways each contribute to the formation of characteristic aroma compounds and browning pigments, thereby influencing the final quality and sensory properties of the food. The aminated derivatives of polyphenols from Strecker degradation have long been ignored by the researchers. This review highlights the occurrence, mechanism, significance, and benefits of the aminated polyphenols formed during food processing to provide a perspective on the development of new functional components. Temperature significantly affects Strecker degradation. In the presence of complex polyphenols with a pyrogallol group, Strecker degradation can happen at room temperature (25掳C) or body temperature (37掳C). For example, tea catechins readily take place Strecker degradation with amino acids at 37掳C to yield aminated polyphenols. Although the aminated polyphenols have not been reported in food raw materials, the aminated polyphenols metabolites (4鈥�-NH2-EGCG, 4鈥�-NH2-myricetin, 3鈥�-methyl-4鈥�-NH2-myricetin, 5-NH2-baicalein and 6-NH2-baicalein) have been discovered in vivo. There is no data on the functions of NH2-flavonoids in vivo. NH2-flavonoids are much more stable than their precursor flavonoids, potentially providing longer interaction time with the body. dc.description: open access article Research collaboration: Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Instituto de Agroecolox铆a e Alimentaci贸n (IAA) 鈥� CITEXVI, Universidade de Vigo, Vigo, Spain Faculty of Biotechnology & Food Engineering, Technion, Israel Institute of Technology, Haifa, Israel Leicester School of Pharmacy, 草榴视频, Leicester, United Kingdom

  • dc.title: Chemopreventive properties of naturally occurring methoxylated resveratrol analogues dc.contributor.author: Brucoli, Federico; Neba Ambe, Gael Noel Neh; Bhambra, Avninder; Arroo, R. R. J. dc.description.abstract: Whereas thousands of papers have been published on the cancer chemopreventive properties of resveratrol (3,5,4鈥�-trihydroxy-trans-stilbene) and related monomeric stilbenoids, there still is no consensus on their mechanism of action in a dietary setting. A widely held assumption is that the naturally occurring trans stilbenoids act as phytoestrogens, and thus affect cell metabolism of estrogen sensitive cells. This is known to be the mechanism of action for Tamoxifen, a synthetic drug with a stilbene moiety at its core, which is now approved as a chemopreventive agent. The bioavailability of resveratrol is low, which means that the doses known to inhibit cell proliferation in vitro (IC50 in the range 3鈥�30鈥礛) are never reached in vivo. The cytotoxic activity of a methoxylated analogue of resveratrol, pterostilbene (3,5-dimethoxy-4鈥�-hydroxy trans stilbene), is in the same range as resveratrol. However, the methoxylated trans stilbenoid appears have better pharmacokinetic properties. Still, its overall bioavailability in vivo seems insufficient to make it have any significant effect on modulation of carcinogenesis. Polymethoxylated cis-stilbenoids (combretastatins), in contrast to the trans-stilbenoids, are too cytotoxic to be considered as chemopreventive agents. Combretastatin A4 has been considered as a cancer therapeutic agent; it inhibits tubulin polymerization by interacting at the colchicine binding site of microtubules, a mechanism of action that is fundamentally different from that of the trans-stilbenoids. It may be speculated that naturally occurring trans stilbenoids selectively accumulate in precancerous cells, thus locally reaching sufficiently high levels. This hypothesis may be difficult to prove experimentally. Further clues on the material properties of stilbenoids will most likely come from synthetic chemistry, where a wide range of analogues can be investigated for structure鈥揳ctivity relationships. dc.description: open access article

  • dc.title: Amination of Flavonoids Possessing a Pyrogallol Group in Cell Culture Medium at 37鈼 dc.contributor.author: Zhang, Haolin; Zhang, Jingjing; Cao, Hui; H枚gger, Petra; Arroo, R. R. J.; Farag, Mohamed A.; Shpigelman, Avi; Xiao, Jianbo; Li, Chunlin dc.description.abstract: A class of flavonoid aminated derivatives that had been consistently overlooked in literaturewas shown to be formed as artefacts in cell culturemedium. In this study, 34 flavonoids from different subclasses were incubated in Dulbecco鈥檚 modified Eagle鈥檚Medium (DMEM) at 37鈼 for 2 h to identify the reaction mechanism behind aminated derivatives formation from flavonoids. Baicalein, scutellarein, dihydromyricetin, (鈭�)-gallocatechin (GC), (鈭�)-epigallocatechin (EGC), (鈭�)-GC gallate, and (鈭�)-EGC gallate were found to yield corresponding nitrogenous derivatives in both DMEM and amino acid solution. The nitrogen source of these seven flavonoid -aminated derivatives was revealed to be amino acids in DMEM. The pyrogallol group of the flavonoids was a key structural motif, being first oxidized into quinone and then further reacting with amino acids (Strecker degradation) to yield aminated flavonoids and corresponding aldehydes. A slightly alkaline environment accelerated the amination of flavonoids, possibly via the formation of flavonoid quinone. These results provide the mechanistic evidence for the in vitro generation of flavonoid -aminated derivatives, yet to be tested using in vivo assays. dc.description: open access article

  • dc.title: Herbal appetite suppressants used to aid weight loss. dc.contributor.author: Malik, Sonia; Kuntawala, Dhivani H.; Neba Ambe, Gael Noel Neh; Jin, Yannan; Bhambra, Avninder S.; Arroo, R. R. J. dc.description.abstract: Overweight and obesity are global health challenges associated with an increased risk of life-threatening comorbidities. Whereas a healthy diet and a lifestyle with a sufficient amount of exercise is the first recommendation to avert complications arising from overweight, a variety of prescription medicines is recognised as potential aids in weight loss. However, concerns about adverse effects of many prescription weight-loss agents has made that may drugs are now prohibited in some countries, though not in all countries. This has given rise to a clandestine market which has made proper monitoring of safety of products on sale increasingly complex. In addition to pharmaceutical products, a wide range of food substitutes or food supplements that are marketed as aids in weight loss is available. Regulation of food ingredients is considerably less stringent than regulation for pharmaceutical products; whereas pharmaceutical companies need to provide evidence of safety and efficacy before they are allowed marketing of any products, manufacturers of herbal and dietary supplements are just expected to ensure safety of their products. A sustainable reduction in food intake can be a major challenge, and people on weight-loss programmes have to fight cravings and hunger pangs. Appetite suppression-based therapies are the novel and promising treatments to control obesity. Recently, the peptide Semaglutide (Wegovy庐, Ozempic庐) has emerged as a very popular appetite suppressing prescription drug, which is administered by injection, though oral formulations have been developed too. Appetite suppressing herbal supplements have often been used traditionally since ages and are therefore generally regarded as safe. The aim of present review is to reflect on the most popular herbal supplements that are currently marketed as appetite suppressants, and that are widely promoted as aids in weight loss exercises. Notably, members of the family Apocynaceae, e.g. Caralluma spp. and Hoodia spp. contain pregnane glycosides that have been shown to restore sensitivity to the appetite suppressant hormone leptin in obese mice. The anti-obesity effect of Garcinia spp. (Clusiaceae) has been attributed to the presence of hydroxycitric acid (HCA), which inhibits fatty acid and triglyceride biosynthesis. In addition, HCA administration has been shown to increase serotonin levels, which in turn results in reduced appetite. A similar mechanism of action is seen with extracts of Griffonia simplicifolia (Fabaceae) that are particularly rich in the serotonin precursor 5-hydroxytryptophan. A third mechanism of action is seen in Gymnema sylvestre (Apocynaceae) which contains gymnemic acids that selectively inhibit oral sweet taste sensation in humans, thus lessening the appeal of sweets and pastries. dc.description: This is an extended version of a plenary lecture presented by Randolph Arroo at the conference 'Natural Products in Drug Discovery and Development 鈥� Advances and Perspectives', 19-22 September 2022, Ia艧i, Romania. Full-text access to a view-only version of the paper is available through the following SharedIt link: https://rdcu.be/dZL4e

  • 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 (草榴视频212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, 草榴视频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, 草榴视频, 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

 

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.