Phytochemistry Reviews

, Volume 17, Issue 3, pp 573–609 | Cite as

Rheum australe, an endangered high-value medicinal herb of North Western Himalayas: a review of its botany, ethnomedical uses, phytochemistry and pharmacology

  • Shahzad A. Pandith
  • Riyaz Ahmad Dar
  • Surrinder K. Lattoo
  • Manzoor A. Shah
  • Zafar A. Reshi
Article
  • 85 Downloads

Abstract

Rheum australe (Himalayan Rhubarb) is a multipurpose, endemic and endangered medicinal herb of North Western Himalayas. It finds extensive use as a medicinal herb since antiquity in different traditional systems of medicine to cure a wide range of ailments related to the circulatory, digestive, endocrine, respiratory and skeletal systems as well as to treat various infectious diseases. The remedying properties of this plant species are ascribed to a set of diverse bioactive secondary metabolite constituents, particularly anthraquinones (emodin, chrysophanol, physcion, aloe-emodin and rhein) and stilbenoids (piceatannol, resveratrol), besides dietary flavonoids known for their putative health benefits. Recent studies demonstrate the pharmacological efficacy of some of these metabolites and/or their derivatives as lead molecules for the treatment of various human diseases. Present review comprehensively covers the literature available on R. australe from 1980 to early 2018. The review provides up-to-date information available on its botany for easy identification of the plant, and origin and historical perspective detailing its trade and commerce. Distribution, therapeutic potential in relation to traditional uses and pharmacology, phytochemistry and general biosynthesis of major chemical constituents are also discussed. Additionally, efficient and reproducible in vitro propagation studies holding vital significance in preserving the natural germplasm of the plant and for its industrial exploitation have also been highlighted. The review presents a detailed perspective for future studies to conserve and sustainably make use of this endangered plant species at a commercial scale.

Keywords

Rheum australe Anthraquinone Stilbenoid Flavonoid Anticancer Antidiabetic Antimicrobial Antioxidative Anti-inflammatory 

Abbreviations

4CL

Coumaric acid: CoA ligase

Δψm

Mitochondrial membrane potential

2,4-D

2,4-Dichlorophenoxyacetic acid

ALP

Alkaline phosphatase

ACC

Acetyl-CoA carboxylase

AP-1

Activator protein-1

AG

α-Glucosidase

AAE

Ascorbic acid equivalents

AST

Glutamate oxaloacetate transaminase

ALT

Glutamate pyruvate transaminase

BHA

Butylated hydroxyanisole

BHT

Butylated hydroxytoluene

BAP

6-Benzylaminopurine

C4H

Cinnamic acid 4-hydroxylase

CHS

Chalcone synthase

CHI

Chalcone isomerase

CSN

COP9 signalosome

CKII

Casein kinase II

DPPH

2,2-Diphenyl-1-picrylhydrazyl

ER

Estrogen receptor

F-1,6-bP

Fructose-1,6-diphosphatase

F3H

Flavanone 3-hydroxylase

F3′H

Flavonoid 3′-hydroxylase

F3′5′H

Flavonoid 3′,5′-hydroxylase

FLS

Flavonol synthase

GPT

Glutamate pyruvate transaminase

GLUT-2

Glucose transporter 2

G,6-P

Glucose-6-phosphatase

H2O2

Hydrogen peroxide

HPLC

High-performance liquid chromatography

IBA

3-Indolebutyric acid

IAA

Indole-3-acetic acid

IPP

Isopentenyl diphosphate

IL

Interleukin

LDH

Lactate dehydrogenase

MEP

2-C-methyl-d-erythritol 4-phosphate pathway

MVA

Mevalonic acid pathway

MIC

Minimum inhibitory concentration

MMPs

Matrix metalloproteinases

MAO

Monoamine oxidase

NF-κB

Nuclear factor κB

NAA

1-Naphthaleneacetic acid

OSB

O-Succinylbenzoic acid

PAL

Phenylalanine ammonia lyase

PKSs

Polyketide synthases

PPAR’s

Peroxisome proliferator-activated receptors

PNP’s

Plant natural products

QOL

Quality of life

ROS

Reactive oxygen species

Rb

Retinoblastoma

SARS

Severe acute respiratory syndrome

SPP

Safoof-e-Pathar phori

TCA cycle

Tricarboxylic acid cycle

TPA

12-O-Tetradecanoylphorbol-13-acetate

TNF-α

Tumor necrosis factor alpha

VAS

Visual analog scale

VMSS

Verbal multidimensional scoring system

WHO

World Health Organization

Notes

Acknowledgements

Work in the SP laboratory is supported by Department of Science and Technology (DST), India, under the INSPIRE Faculty Scheme [DST/INSPIRE/04/2016/001059]. S.K.L., M.S. and Z.A.R are acknowledged for their useful comments and discussions. We thank R.A.D. for assistance with manuscript writing.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Abou-Agag LH, Aikens ML, Tabengwa EM, Benza RL, Shows SR, Grenett HE, Booyse FM (2001) Polyphenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells. Alcohol Clin Exp Res 25:155–162PubMedGoogle Scholar
  2. Acharya KP, Rokaya MB (2005) Ethnobotanical survey of medicinal plants traded in the streets of Kathmandu valley. Sci World 3:44–48Google Scholar
  3. Agarwal S, Singh SS, Verma S, Kumar S (2000) Antifungal activity of anthraquinone derivatives from Rheum emodi. J Ethnopharmacol 72:43–46PubMedGoogle Scholar
  4. Agarwal SK, Singh SS, Lakshmi V, Verma S, Kumar S (2001) Chemistry and pharmacology of rhubarb (Rheum species)—a review. J Sci Ind Res India 60:1–9Google Scholar
  5. Ahmad W, Zaidi SMA, Mujeeb M, Ansari SH, Ahmad S (2013) HPLC and HPTLC methods by design for quantitative characterization and in vitro anti-oxidant activity of polyherbal formulation containing Rheum emodi. J Chromatogr Sci 52:911–918PubMedGoogle Scholar
  6. Akhtar MS, Habib A, Ali A, Bashir S (2016) Isolation, identification, and in vivo evaluation of flavonoid fractions of chloroform/methanol extracts of Rheum emodi roots for their hepatoprotective activity in Wistar rats. Int J Nutr Pharmacol Neurol Dis 6:28Google Scholar
  7. Akula R, Ravishankar GA (2011) Influence of abiotic stress signals on secondary metabolites in plants. Plant Signal Behav 6:1720–1731Google Scholar
  8. Alam MA, Javed K, Jafri M (2005) Effect of Rheum emodi (Revand Hindi) on renal functions in rats. J Ethnopharmacol 96:121–125PubMedGoogle Scholar
  9. Alves DS, Pérez-Fons L, Estepa A, Micol V (2004) Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol 68:549–561PubMedGoogle Scholar
  10. Anand S, Muthusamy V, Sujatha S, Sangeetha K, Bharathi Raja R, Sudhagar S, Poornima Devi N, Lakshmi B (2010) Aloe emodin glycosides stimulates glucose transport and glycogen storage through PI3K dependent mechanism in L6 myotubes and inhibits adipocyte differentiation in 3T3L1 adipocytes. FEBS Lett 584:3170–3178PubMedGoogle Scholar
  11. Arvindekar A, Laddha K (2016) An efficient microwave-assisted extraction of anthraquinones from Rheum emodi: optimisation using RSM, UV and HPLC analysis and antioxidant studies. Ind Crops Prod 83:587–595Google Scholar
  12. Arvindekar A, More T, Payghan PV, Laddha K, Ghoshal N, Arvindekar A (2015) Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi. Food Funct 6:2693–2700PubMedGoogle Scholar
  13. Aslam M, Dayal R, Javed K, Fahamiya N, Mohd Mujeeb HAP (2012) Phytochemical evaluation of Rheum emodi wall. Curr Pharma Res 2:471–479Google Scholar
  14. Austin MB, Noel JP (2003) The chalcone synthase superfamily of type III polyketide synthases. Nat Prod Rep 20:79–110PubMedGoogle Scholar
  15. Austin C, Patel S, Ono K, Nakane H, Fisher L (1992) Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives. Biochem J 282:883–889PubMedPubMedCentralGoogle Scholar
  16. Azelmat J, Larente JF, Grenier D (2015) The anthraquinone rhein exhibits synergistic antibacterial activity in association with metronidazole or natural compounds and attenuates virulence gene expression in Porphyromonas gingivalis. Arch Oral Biol 60:342–346PubMedGoogle Scholar
  17. Babu KS, Srinivas P, Praveen B, Kishore KH, Murty US, Rao JM (2003) Antimicrobial constituents from the rhizomes of Rheum emodi. Phytochemistry 62:203–207PubMedGoogle Scholar
  18. Babu KS, Tiwari AK, Srinivas PV, Ali AZ, Raju BC, Rao JM (2004) Yeast and mammalian α-glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi Wall. ex Meisson. Bioorg Med Chem Lett 14:3841–3845Google Scholar
  19. Babu PVA, Liu D, Gilbert ER (2013) Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 24:1777–1789PubMedGoogle Scholar
  20. Bandele OJ, Osheroff N (2007) Bioflavonoids as poisons of human topoisomerase IIα and IIβ. Biochemistry 46:6097–6108PubMedPubMedCentralGoogle Scholar
  21. Bano H, Siddique M, Gupta R, Bhat MA, Mir S (2017) Response of Rheum australe L. (rhubarb), (Polygonaceae) an endangered medicinal plant species of Kashmir Himalaya, to organic-inorganic fertilization and its impact on the active component Rhein. J Med Plants Res 11:118–128Google Scholar
  22. Bernard F-X, Sable S, Cameron B, Provost J, Desnottes J-F, Crouzet J, Blanche F (1997) Glycosylated flavones as selective inhibitors of topoisomerase IV. Antimicrob Agents Ch 41:992–998Google Scholar
  23. Bhat WW, Dhar N, Razdan S, Rana S, Mehra R, Nargotra A, Dhar RS, Ashraf N, Vishwakarma R, Lattoo SK (2013) Molecular characterization of UGT94F2 and UGT86C4, two glycosyltransferases from Picrorhiza kurrooa: comparative structural insight and evaluation of substrate recognition. PLoS ONE 8:e73804PubMedPubMedCentralGoogle Scholar
  24. Bhat WW, Rana S, Dhar N, Razdan S, Pandith SA, Vishwakarma R, Lattoo SK (2014) An inducible NADPH–cytochrome P450 reductase from Picrorhiza kurrooa—an imperative redox partner of cytochrome P450 enzymes. Funct Integr Genomic 14:381–399Google Scholar
  25. Bhatia A, Arora S, Singh B, Kaur G, Nagpal A (2011) Anticancer potential of Himalayan plants. Phytochem Rev 10:309–323Google Scholar
  26. Bhatt V, Negi G (2006) Ethnomedicinal plant resources of Jaunsari tribe of Garhwal Himalaya, Uttaranchal. Indian J Tradit Know 5:331–335Google Scholar
  27. Bhattarai K, Ghimire M (2006) Cultivation and sustainable harvesting of commercially important medicinal and aromatic plants of Nepal. Heritage Research and Development Forum, Nepal, pp 369–372Google Scholar
  28. Bhojwani SS, Razdan MK (1986) Plant tissue culture: theory and practice. Elsevier, AmsterdamGoogle Scholar
  29. Bisht C, Badoni A (2009) Medicinal strength of some alpine and sub-alpine zones of western Himalaya, India. NY Sci J 2:41–46Google Scholar
  30. Boege F, Straub T, Kehr A, Boesenberg C, Christiansen K, Andersen A, Jakob F, Köhrle J (1996) Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I. J Biol Chem 271:2262–2270PubMedGoogle Scholar
  31. Bogs J, Ebadi A, McDavid D, Robinson SP (2006) Identification of the flavonoid hydroxylases from grapevine and their regulation during fruit development. Plant Physiol 140:279–291PubMedPubMedCentralGoogle Scholar
  32. Boss PK, Davies C, Robinson SP (1996) Analysis of the expression of anthocyanin pathway genes in developing Vitis vinifera L. cv Shiraz grape berries and the implications for pathway regulation. Plant Physiol 111:1059–1066PubMedPubMedCentralGoogle Scholar
  33. Brown EG (1997) In: Dey PM, Harborne JB (eds) Plant biochemistry. Academic Press, London. ISBN 0-12-214674-3Google Scholar
  34. Cantero G, Campanella C, Mateos S, Cortes F (2006) Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin. Mutagenesis 21:321–325PubMedGoogle Scholar
  35. Casagrande F, Darbon J-M (2001) Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol 61:1205–1215PubMedGoogle Scholar
  36. Castellarin SD, Di Gaspero G (2007) Transcriptional control of anthocyanin biosynthetic genes in extreme phenotypes for berry pigmentation of naturally occurring grapevines. BMC Plant Biol 7:1–10Google Scholar
  37. Cha T-L, Qiu L, Chen C-T, Wen Y, Hung M-C (2005) Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Res 65:2287–2295PubMedGoogle Scholar
  38. Chai Y, Wang F, Y-l Li, Liu K, Xu H (2012) Antioxidant activities of stilbenoids from Rheum emodi Wall. Evid Based Compl Altern Med 2012:1–7Google Scholar
  39. Chauhan NS (1999) Medicinal and aromatic plants of Himachal Pradesh. Indus Publishing, DelhiGoogle Scholar
  40. Chauhan N, Kaith BS, Mann S (1992) Anti-inflammatory activity of Rheum australe roots. Int J Pharmacogn 30:93–96Google Scholar
  41. Chen Y-C, Yang L-L, Lee TJ (2000) Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-κB activation. Biochem Pharmacol 59:1445–1457PubMedGoogle Scholar
  42. Chen H, Hsieh W, Chang W, Chung J (2004) Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells. Food Chem Toxicol 42:1251–1257PubMedGoogle Scholar
  43. Chen Y-Y, Chiang S-Y, Lin J-G, Ma Y-S, Liao C-L, Weng S-W, Lai T-Y, Chung J-G (2010a) Emodin, aloe-emodin and rhein inhibit migration and invasion in human tongue cancer SCC-4 cells through the inhibition of gene expression of matrix metalloproteinase-9. Int J Oncol 36:1113–1120PubMedGoogle Scholar
  44. Chen Y-Y, Chiang S-Y, Lin J-G, Yang J-S, Ma Y-S, Liao C-L, Lai T-Y, Tang N-Y, Chung J-G (2010b) Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res 30:945–951PubMedGoogle Scholar
  45. Chen Z, Zhang L, Yi J, Yang Z, Zhang Z, Li Z (2012) Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity. J Cell Biochem 113:3547–3558PubMedGoogle Scholar
  46. Chien S-C, Wu Y-C, Chen Z-W, Yang W-C (2015) Naturally occurring anthraquinones: chemistry and therapeutic potential in autoimmune diabetes. Evid Based Compl Altern Med 2015:1–13Google Scholar
  47. Choi M, Jung U, Yeo J, Kim M, Lee M (2008) Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non-obese diabetic (NOD) mice. Diabetes Metab Res 24:74–81Google Scholar
  48. Choi RJ, Ngoc TM, Bae K, Cho H-J, Kim D-D, Chun J, Khan S, Kim YS (2013) Anti-inflammatory properties of anthraquinones and their relationship with the regulation of P-glycoprotein function and expression. Eur J Pharm Sci 48:272–281PubMedGoogle Scholar
  49. Constantinou A, Mehta R, Runyan C, Rao K, Vaughan A, Moon R (1995) Flavonoids as DNA topoisomerase antagonists and poisons: structure–activity relationships. J Nat Prod 58:217–225PubMedGoogle Scholar
  50. Cushnie TT, Lamb AJ (2005) Antimicrobial activity of flavonoids. Int J Antimicrob Ag 26:343–356Google Scholar
  51. Debeaujon I, Peeters AJ, Léon-Kloosterziel KM, Koornneef M (2001) The TRANSPARENT TESTA12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium. Plant Cell 13:853–871PubMedPubMedCentralGoogle Scholar
  52. Dev S (2001) Ancient-modern concordance in Ayurvedic plants: some examples. Development of plant-based medicines: conservation, efficacy and safety. Springer, Berlin, pp 47–67Google Scholar
  53. Dhar N, Rana S, Razdan S, Bhat WW, Hussain A, Dhar RS, Vaishnavi S, Hamid A, Vishwakarma R, Lattoo SK (2014) Cloning and functional characterization of three branch point oxidosqualene cyclases from Withania somnifera (L.) dunal. J Biol Chem 289:17249–17267PubMedPubMedCentralGoogle Scholar
  54. Didry N, Dubreuil L, Pinkas M (1994) Activity of anthraquinonic and naphthoquinonic compounds on oral bacteria. Pharmazie 49:681–683PubMedGoogle Scholar
  55. Dymock W, Warden C, Hooper D (1890) Pharmacographica indica a history of the principal drugs of vegetable origin met with in British India Part III, publ. London, pp 46–47Google Scholar
  56. Fang F, J-b Wang, Y-l Zhao, Jin C, W-j Kong, H-p Zhao, H-j Wang, X-h Xiao (2011) A comparative study on the tissue distributions of rhubarb anthraquinones in normal and CCl 4-injured rats orally administered rhubarb extract. J Ethnopharmacol 137:1492–1497PubMedGoogle Scholar
  57. Farooq U, Pandith SA, Saggoo MIS, Lattoo SK (2013) Altitudinal variability in anthraquinone constituents from novel cytotypes of Rumex nepalensis Spreng—a high value medicinal herb of North Western Himalayas. Ind Crop Prod 50:112–117Google Scholar
  58. Fay MF (1992) Conservation of rare and endangered plants using in vitro methods. In Vitro Cell Dev Biol Plant 28:1–4Google Scholar
  59. Ferrali M, Signorini C, Caciotti B, Sugherini L, Ciccoli L, Giachetti D, Comporti M (1997) Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Lett 416:123–129PubMedGoogle Scholar
  60. Füllbeck M, Huang X, Dumdey R, Frommel C, Dubiel W, Preissner R (2005) Novel curcumin-and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells. BMC Cancer 5:97PubMedPubMedCentralGoogle Scholar
  61. Gao F, Liu W, Guo Q, Bai Y, Yang H, Chen H (2017) Physcion blocks cell cycle and induces apoptosis in human B cell precursor acute lymphoblastic leukemia cells by downregulating HOXA5. Biomed Pharmacother 94:850–857PubMedGoogle Scholar
  62. García-Mediavilla V, Crespo I, Collado PS, Esteller A, Sánchez-Campos S, Tuñón MJ, González-Gallego J (2007) The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol 557:221–229PubMedGoogle Scholar
  63. Geahlen RL, Koonchanok Nm Fau - McLaughlin JL, McLaughlin Jl Fau - Pratt DE, Pratt DE (1989) Inhibition of protein–tyrosine kinase activity by flavanoids and related compounds. J Nat Prod 52:982–986PubMedGoogle Scholar
  64. Ghimire S (2007) Developing a community-based monitoring system and sustainable harvesting guidelines for non-timber forest products (NTFP) in Kangchenjunga Conservation Area (KCA), East Nepal. Final Report submitted to WWF Nepal Program, Baluwatar, Kathmandu, NepalGoogle Scholar
  65. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 45673:1–10Google Scholar
  66. Hameed I, Dastagir G, Hussain F (2008) Nutritional and elemental analyses of some selected medicinal plants of the family Polygonaceae. Pak J Bot 40:2493–2502Google Scholar
  67. Han N-N, Li X, Tao L, Zhou Q (2018) Doxorubicin and rhein loaded nanomicelles attenuates multidrug resistance in human ovarian cancer. Biochem Biophys Res Commun (In press)Google Scholar
  68. Hao K, Qi Q, Wan P, Zhang J, Hao H, Liang Y, Xie L, Wang G, Sun J (2014) Prediction of human pharmacokinetics from preclinical information of rhein, an antidiabetic nephropathy drug, using a physiologically based pharmacokinetic model. Basic Clin Pharmacol 114:160–167Google Scholar
  69. Haq F, Ullah R (2011) Comparative determination of trace elements from Allium sativum, Rheum australe and Terminalia chebula by atomic absorption spectroscopy. Int J Biosci 1:77–82Google Scholar
  70. Hashemi M, Behrangi N, Borna H, Entezari M (2012) Protein tyrosine kinase (PTK) as a novel target for some natural anti-cancer molecules extracted from plants. J Med Plant Res 6:4375–4378Google Scholar
  71. Hatano T, Uebayashi H, Ito H, Shiota S, Tsuchiya T, Yoshida T (1999) Phenolic constituents of Cassia seeds and antibacterial effect of some naphthalenes and anthraquinones on methicillin-resistant Staphylococcus aureus. Chem Pharm Bull 47:1121–1127PubMedGoogle Scholar
  72. He Z-H, He M-F, Ma S-C, But PP-H (2009) Anti-angiogenic effects of rhubarb and its anthraquinone derivatives. J Ethnopharmacol 121:313–317PubMedGoogle Scholar
  73. Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure–activity relationships. J Nutr Biochem 13:572–584PubMedGoogle Scholar
  74. Hilliard JJ, Krause HM, Bernstein JI, Fernandez JA, Nguyen V, Ohemeng KA, Barrett JF (1995) A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase. In: Antimicrobial resistance, 390. Springer, Boston, MA, pp 59–69Google Scholar
  75. Ho T-Y, Wu S-L, Chen J-C, Li C-C, Hsiang C-Y (2007) Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antivir Res 74:92–101PubMedGoogle Scholar
  76. Hong J-Y, Chung H-J, Bae SY, Trung TN, Bae K, Lee SK (2014) Induction of cell cycle arrest and apoptosis by physcion, an anthraquinone isolated from rhubarb (rhizomes of Rheum tanguticum), in MDA-MB-231 human breast cancer cells. J Cancer Prev 19:273–278PubMedPubMedCentralGoogle Scholar
  77. Hsu S-C, Chung J-G (2012) Anticancer potential of emodin. BioMedicine 2:108–116Google Scholar
  78. Hu L, Chen N-N, Hu Q, Yang C, Yang Q-S, Wang F-F (2014) An unusual piceatannol dimer from Rheum australe D. Don with antioxidant activity. Molecules 19:11453–11464PubMedGoogle Scholar
  79. Huang Q, Shen H-M, Ong C-N (2004) Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-κB. Biochem Pharmacol 68:361–371PubMedGoogle Scholar
  80. Huang Q, Shen H-M, Ong C-N (2005) Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway. Cell Mol Life Sci 62:1167–1175PubMedGoogle Scholar
  81. Huk I, Brovkovych V, Nanobash Vili J, Weigel G, Neumayer C, Partyka L, Patton S, Malinski T (1998) Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia–reperfusion injury: an experimental study. Brit J Surg 85:1080–1085PubMedGoogle Scholar
  82. Hussain F, Ahmad B, Hameed I, Dastagir G, Sanaullah P, Azam S (2010) Antibacterial, antifungal and insecticidal activities of some selected medicinal plants of polygonaceae. Afr J Biotechnol 9:5032–5036Google Scholar
  83. Hussain H, Al-Harrasi A, Al-Rawahi A, Green IR, Csuk R, Ahmed I, Shah A, Abbas G, Rehman NU, Ullah R (2015) A fruitful decade from 2005 to 2014 for anthraquinone patents. Expert Opin Ther Pat 25:1053–1064PubMedGoogle Scholar
  84. Ibrahim M, Khan AA, Tiwari SK, Habeeb MA, Khaja M, Habibullah C (2006) Antimicrobial activity of Sapindus mukorossi and Rheum emodi extracts against H pylori: in vitro and in vivo studies. World J Gastroenterol 12:7136–7142PubMedPubMedCentralGoogle Scholar
  85. Ibrahim M, Khaja MN, Aara A, Khan AA, Habeeb MA, Devi YP, Narasu ML, Habibullah CM (2008) Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J Gastroenterol 14:2566–2571PubMedPubMedCentralGoogle Scholar
  86. Ikigai H, Nakae T, Hara Y, Shimamura T (1993) Bactericidal catechins damage the lipid bilayer. BBA-Biomembranes 1147:132–136PubMedGoogle Scholar
  87. Jassim S, Naji MA (2003) Novel antiviral agents: a medicinal plant perspective. J Appl Microbiol 95:412–427PubMedGoogle Scholar
  88. Jayasuriya H, Koonchanok NM, Geahlen RL, McLaughlin JL, Chang C-J (1992) Emodin, a protein tyrosine kinase inhibitor from Polygonum cuspidatum. J Nat Prod 55:696–698PubMedGoogle Scholar
  89. Jiang W, Yin Q, Wu R, Zheng G, Liu J, Dixon RA, Pang Y (2015) Role of a chalcone isomerase-like protein in flavonoid biosynthesis in Arabidopsis thaliana. J Exp Bot 66:7165–7179PubMedPubMedCentralGoogle Scholar
  90. Jiang J, Wang R-P, Hou M-H, Liu H-Y, Zhang H, Jiang C-S (2017) Hydromethanolic extract of Rehum emodi exhibits significant antimicrobial activity against acute gastroenteriti bacterial strains. Microb Pathog 115:179–182PubMedGoogle Scholar
  91. Kabir Dar A, Siddiqui M, Wahid-ul H, Lone A, Manzoor N, Haji A (2015) Threat status of rheum emodi—a study in selected cis-Himalayan regions of Kashmir Valley Jammu & Kashmir India. Med Aromat Plants 4:183Google Scholar
  92. Kapoor L (2000) Handbook of Ayurvedic medicinal plants: herbal reference library. CRC Press/Taylor and Francis Group, Boca RatonGoogle Scholar
  93. Kaul TN, Middleton E, Ogra PL (1985) Antiviral effect of flavonoids on human viruses. J Med Virol 15:71–79PubMedGoogle Scholar
  94. Kaur A, Kumar S, Sharma R (2012) Assessment of anti-ulcer activity of Rheum emodi rhizomes extract. I G J Pharm Sci 2:333–341Google Scholar
  95. Khan SA, Ahmad A, Khan MI, Yusuf M, Shahid M, Manzoor N, Mohammad F (2012) Antimicrobial activity of wool yarn dyed with Rheum emodi L. (Indian Rhubarb). Dyes Pigm 95:206–214Google Scholar
  96. Khan MA, Shahid-ul-Islam, Mohammad F (2017) Investigating the combined effect of natural and metal salt mordants on coloring potential of Indian Rhubarb (Rheum emodi) natural dye. J Nat Fibers 14:196–204Google Scholar
  97. Kim JW, Jin YC, Kim YM, Rhie S, Kim HJ, Seo HG, Lee JH, Ha YL, Chang KC (2009) Daidzein administration in vivo reduces myocardial injury in a rat ischemia/reperfusion model by inhibiting NF-kB activation. Life Sci 84:227–234PubMedGoogle Scholar
  98. Kim S-J, Kim M-C, Lee B-J, Park D-H, Hong S-H, Um J-Y (2010) Anti-Inflammatory activity of chrysophanol through the suppression of NF-kB/caspase-1 activation in vitro and in vivo. Molecules 15:6436–6451PubMedGoogle Scholar
  99. Kobori M, Masumoto S, Akimoto Y, Takahashi Y (2009) Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice. Mol Nutr Food Res 53:859–868PubMedGoogle Scholar
  100. Kong L, Cheng CH, Tan R (2004) Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones. J Ethnopharmacol 91:351–355PubMedGoogle Scholar
  101. Kounsar F, Afzal ZM (2010) Rheum emodi induces nitric oxide synthase activity in murine macrophages. Am J Biomed Sci 2:155–163Google Scholar
  102. Kounsar F, Rather MA, Ganai BA, Zargar MA (2011) Immuno-enhancing effects of the herbal extract from Himalayan rhubarb Rheum emodi Wall. ex Meissn. Food Chem 126:967–971Google Scholar
  103. Krenn L, Presser A, Pradhan R, Bahr B, Paper DH, Mayer KK, Kopp B (2003) Sulfemodin 8-O-β-d-glucoside, a new sulfated anthraquinone glycoside, and antioxidant phenolic compounds from Rheum emodi. J Nat Prod 66:1107–1109PubMedGoogle Scholar
  104. Krenn L, Pradhan R, Presser A, Reznicek G, Kopp B (2004) Anthrone C-glucosides from Rheum emodi. Chem Pharm Bull 52:391–393PubMedGoogle Scholar
  105. Kritikar K, Basu B (2003) Indian medicinal plants with illustrations, 2nd ed. Sri Satguru Publications, India, pp 2093–2096Google Scholar
  106. Kumar M, Paul Y, Anand V (2009) An ethnobotanical study of medicinal plants used by the locals in Kishtwar, Jammu and Kashmir, India. Ethnobot Leafl 2009:5Google Scholar
  107. Kumar DN, Shikha DS, George VC, Suresh P, Kumar RA (2012) Anticancer and anti-metastatic activities of Rheum emodi rhizome chloroform extracts. Asian J Pharm Clin Res 5:189–194Google Scholar
  108. Kumar DN, George VC, Suresh P, Kumar RA (2013) Acceleration of pro-caspase-3 maturation and cell migration inhibition in human breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts. EXCLI J 12:462–478PubMedPubMedCentralGoogle Scholar
  109. Kumar N, Ragupathi D, George VC, Suresh PK, Kumar RA (2015) Cancer-specific chemoprevention and anti-metastatic potentials of Rheum emodi rhizome ethyl acetate extracts and identification of active principles through HPLC and GC-MS analysis. Pak J Pharm Sci 28:83–93PubMedGoogle Scholar
  110. Kunwar RM, Adhikari N (2005) Ethnomedicine of Dolpa district, Nepal: the plants, their vernacular names and uses. Lyonia 8:43–49Google Scholar
  111. Kuo P-L, Lin T-C, Lin C-C (2002) The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci 71:1879–1892PubMedGoogle Scholar
  112. Kwak HJ, Park MJ, Park CM, Moon SI, Yoo DH, Lee HC, Lee SH, Kim MS, Lee HW, Shin WS (2006) Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation. Int J Cancer 118:2711–2720PubMedGoogle Scholar
  113. Lahlou M (2013) The success of natural products in drug discovery. Pharmacol Pharm 4:17–31Google Scholar
  114. Lal N, Ahuja PS (1989) Propagation of Indian Rhubarh (Rheum emodi Wall.) using shoot-tip and leaf explant culture. Plant Cell Rep 8:493–496PubMedGoogle Scholar
  115. Lal N, Ahuja PS (1993) Assessment of liquid culture procedures for in vitro propagation of Rheum emodi. Plant Cell Tiss Org 34:223–226Google Scholar
  116. Lal B, Singh K (2008) Indigenous herbal remedies used to cure skin disorders by the natives of Lahaul-Spiti in Himachal Pradesh. Int J Trad Know 7:237–241Google Scholar
  117. Latif A, Shinwari Z, Hussain J, Murtaza S (2006) NTFPS: an alternative to forest logging in Minadam and Sultanar Valley Swat. Lyonia 11:15–21Google Scholar
  118. Lee H-Z, Hsu S-L, Liu M-C, Wu C-H (2001) Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma. Eur J Pharmacol 431:287–295PubMedGoogle Scholar
  119. Leistner E (1971) A second pathway leading to anthraquinones in higher plants. Phytochemistry 10:3015–3020Google Scholar
  120. Leistner E (1995) Morinda species: biosynthesis of quinones in cell cultures. In: Bajaj YPS (ed) Biotechnology in Agriculture and Forestry—Vol. 33; Medicinal and aromatic plants, VIII. Springer, Berlin, pp 296–307Google Scholar
  121. Lin J-G, Chen G-W, Li T-M, Chouh S-T, Tan T-W, Chung J-G (2006) Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53 dependent apoptotic pathway. J Urol 175:343–347PubMedGoogle Scholar
  122. Lin C-W, Wu C-F, Hsiao N-W, Chang C-Y, Li S-W, Wan L, Lin Y-J, Lin W-Y (2008) Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71. Int J Antimicrob Ag 32:355–359Google Scholar
  123. Lin M-L, Lu Y-C, Chung J-G, Li Y-C, Wang S-G, Sue-Hwee N, Wu C-Y, Su H-L, Chen S-S (2010) Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway. Cancer Lett 291:46–58PubMedGoogle Scholar
  124. Liu J, Gao X, Lian T, Zhao A, Li K (2003) Apoptosis of human hepatoma HepG2 cells induced by emodin in vitro. Ai Zheng Chin J Cancer 22:1280–1283Google Scholar
  125. Liu B, Yang J, Wang S (2007) The chemical constituents in rhubarb rhizomes and roots derived from Rheum emodi Wall. W Chin J Pharm Sci 22:33Google Scholar
  126. Liu W, Tang L, Ye L, Cai Z, Xia B, Zhang J, Hu M, Liu Z (2010) Species and gender differences affect the metabolism of emodin via glucuronidation. AAPS J 12:424–436PubMedPubMedCentralGoogle Scholar
  127. Lloyd JU (1921) Origin and history of all the pharmacopeial vegetable drugs, chemicals and preparations with bibliography. Caxton Press, CaldwellGoogle Scholar
  128. López-Lázaro M, Willmore E, Austin CA (2010) The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat Res-Gen Tox En 696:41–47Google Scholar
  129. Lu J, Papp LV, Fang J, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A (2006) Inhibition of mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res 66:4410–4418PubMedGoogle Scholar
  130. Lu CC, Yang JS, Huang AC, Hsia TC, Chou ST, Kuo CL, Lu HF, Lee TH, Wood WG, Chung JG (2010) Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res 54:967–976PubMedPubMedCentralGoogle Scholar
  131. Lu C, Wang H, Lv W, Xu P, Zhu J, Xie J, Liu B, Lou Z (2011) Antibacterial properties of anthraquinones extracted from rhubarb against Aeromonas hydrophila. Fish Sci 77:375Google Scholar
  132. Malik S, Kumar R, Vats SK, Bhushan S, Sharma M, Ahuja PS (2009) Regeneration in Rheum emodi Wall.: a step towards conservation of an endangered medicinal plant species. Eng Life Sci 9:130–134Google Scholar
  133. Malik S, Sharma N, Sharma UK, Singh NP, Bhushan S, Sharma M, Sinha AK, Ahuja PS (2010) Qualitative and quantitative analysis of anthraquinone derivatives in rhizomes of tissue culture-raised Rheum emodi Wall. plants. J Plant Physiol 167:749–756PubMedGoogle Scholar
  134. Malik AH, Khuroo AA, Dar G, Khan Z (2011) Ethnomedicinal uses of some plants in the Kashmir Himalaya. Ind J Tradit Know 10:362–366Google Scholar
  135. Malik MA, Bhat SA, Fatima B, Ahmad SB, Sidiqui S, Shrivastava P (2016) Rheum emodi as a valuable medicinal plant. Int J Gen Med Pharm 5:35–44Google Scholar
  136. Marzocchella L, Fantini M, Benvenuto M, Masuelli L, Tresoldi I, Modesti A, Bei R (2011) Dietary flavonoids: molecular mechanisms of action as anti-inflammatory agents. Recent Pat Inflamm Allergy Drug Discov 5:200–220PubMedGoogle Scholar
  137. Mijatovic S, Maksimovic-Ivanic D, Radovic J, Miljkovic D, Kaludjerovic G, Sabo T, Trajkovic V (2005) Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin. Cell Mol Life Sci 62:1275–1282PubMedGoogle Scholar
  138. Mirzoeva O, Grishanin R, Calder P (1997) Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria. Microbiol Res 152:239–246PubMedGoogle Scholar
  139. Mishra V (2016) Potent gastroprotective effect chrysophanol and emodin from Rheum emodi via H+K+Atpase inhibition and increasing the Pge2 level in rats. Nat Prod Indian J 12:1–12Google Scholar
  140. Mishra SK, Tiwari S, Shrivastava A, Srivastava S, Boudh GK, Chourasia SK, Chaturvedi U, Mir SS, Saxena AK, Bhatia G (2014) Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats. J Nat Med 68:363–371PubMedGoogle Scholar
  141. Mori A, Nishino C, Enoki N, Tawata S (1987) Antibacterial activity and mode of action of plant flavonoids against Proteus vulgaris and Staphylococcus aureus. Phytochemistry 26:2231–2234Google Scholar
  142. Nadkarni KM (2010) Indian plants and drugs. Ajay Book Service, IndiaGoogle Scholar
  143. Narender T, Sukanya P, Sharma K, Bathula SR (2013) Preparation of novel antiproliferative emodin derivatives and studies on their cell cycle arrest, caspase dependent apoptosis and DNA binding interaction. Phytomedicine 20:890–896PubMedGoogle Scholar
  144. Nautiyal S, Maikhuri R, Rao K, Saxena K (2003) Ethnobotany of the Tolchha Bhotiya tribe of the buffer zone villages in Nanda Devi Biosphere Reserve, IndiaGoogle Scholar
  145. Naveena B, Sen A, Vaithiyanathan S, Babji Y, Kondaiah N (2008) Comparative efficacy of pomegranate juice, pomegranate rind powder extract and BHT as antioxidants in cooked chicken patties. Meat Sci 80:1304–1308PubMedGoogle Scholar
  146. Nerland DE (2007) The antioxidant/electrophile response element motif. Drug Metab Rev 39:235–248PubMedGoogle Scholar
  147. Nin S, Morosi E, Schiff S, Bennici A (1996) Callus cultures of Artemisia absinthium L.: initiation, growth optimization and organogenesis. Plant Cell Tiss Org 45:67–72Google Scholar
  148. Ohemeng K, Schwender C, Fu K, Barrett J (1993) DNA gyrase inhibitory and antibacterial activity of some flavones (1). Bioorg Med Chem Lett 3:225–230Google Scholar
  149. Pandey S, Malik S, Sharma S, Sharma M (2008) Studies on differential growth behaviour of two alpine herbs of Western Himalaya from different altitudes under in vitro conditions. Ind J Biotechnol 7:137–140Google Scholar
  150. Pandey A, Misra P, Choudhary D, Yadav R, Goel R, Bhambhani S, Sanyal I, Trivedi R, Trivedi PK (2015) AtMYB12 expression in tomato leads to large scale differential modulation in transcriptome and flavonoid content in leaf and fruit tissues. Sci Rep 5:12412PubMedPubMedCentralGoogle Scholar
  151. Pandith SA, Hussain A, Bhat WW, Dhar N, Qazi AK, Rana S, Razdan S, Wani TA, Shah MA, Bedi Y (2014) Evaluation of anthraquinones from Himalayan rhubarb (Rheum emodi Wall. ex Meissn.) as antiproliferative agents. S Afr J Bot 95:1–8Google Scholar
  152. Pandith SA, Dhar N, Rana S, Bhat WW, Kushwaha M, Gupta AP, Shah MA, Vishwakarma R, Lattoo SK (2016) Functional promiscuity of two divergent paralogs of Type III plant polyketide synthases. Plant Physiol 171:2599–2619PubMedPubMedCentralGoogle Scholar
  153. Park M-Y, Kwon H-J, Sung M-K (2009) Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages. Biosci Biotechnol Biochem 73:828–832PubMedGoogle Scholar
  154. Parveen S, Kamili A, Shah A (2012) Impact of BAP and different auxins on in vitro shoot proliferation of Rheum emodi Wall. J Pharm Biol Sci 4:47–52Google Scholar
  155. Phondani PC, Maikhuri RK, Rawat LS, Farooquee NA, Kala CP, Vishvakarma SR, Rao K, Saxena K (2010) Ethnobotanical uses of plants among the Bhotiya tribal communities of Niti Valley in Central Himalaya, India. Ethnobot Res Appl 8:233–244Google Scholar
  156. Plaper A, Golob M, Hafner I, Oblak M, Šolmajer T, Jerala R (2003) Characterization of quercetin binding site on DNA gyrase. Biochem Bioph Res Co 306:530–536Google Scholar
  157. Pradhan R, Krenn L, Presser A, Haslinger E, Kopp B (2002) New natural compounds from Rheum emodi Wall. In: Watanabe T et al (eds) The Himalayan Plants–can they save us? Proceedings of Nepal-Japan Joint Symposium on Conservation and Utilization of Himalayan Medicinal Resources, Society for the Conservation and Development of Himalayan Medicinal Resources, Japan, pp 134–137Google Scholar
  158. Pratheeshkumar P, Budhraja A, Son Y-O, Wang X, Zhang Z, Ding S, Wang L, Hitron A, Lee J-C, Xu M (2012) Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR-2 regulated AKT/mTOR/P70S6 K signaling pathways. PLoS ONE 7:e47516PubMedPubMedCentralGoogle Scholar
  159. Press JR, Shrestha KK, Sutton DA (2000) Annotated checklist of the flowering plants of Nepal. Natural History Museum Publications, LondonGoogle Scholar
  160. Procházková D, Boušová I, Wilhelmová N (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia 82:513–523PubMedGoogle Scholar
  161. Rafiq RA, Quadri A, Nazir LA, Peerzada K, Ganai BA, Tasduq SA (2015) A potent inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase signalling, quercetin (3,3′,4′,5,7-Pentahydroxyflavone) promotes cell death in ultraviolet (UV)-B-irradiated B16F10 melanoma cells. PLoS ONE 10:e0131253PubMedPubMedCentralGoogle Scholar
  162. Rajkumar V, Guha G, Ashok Kumar R (2011a) Antioxidant and anti-cancer potentials of Rheum emodi rhizome extracts. Evid Based Compl Altern Med 2011:1–9Google Scholar
  163. Rajkumar V, Guha G, Kumar RA (2011b) Apoptosis induction in MDA-MB-435S, Hep3B and PC-3 cell lines by Rheum emodi rhizome extracts. Asian Pac J Cancer Prev 12:1197–1200PubMedGoogle Scholar
  164. Ramos S (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 18:427–442PubMedGoogle Scholar
  165. Rana C, Sharma A, Kumar N, Dangwal L, Tiwari J (2010) Ethnopharmacology of some important medicinal plants of Nanda Devi national park (NDNP) Uttarakhand, India. Nat Sci 8:9–14Google Scholar
  166. Rana S, Lattoo SK, Dhar N, Razdan S, Bhat WW, Dhar RS, Vishwakarma R (2013) NADPH-cytochrome P450 reductase: molecular cloning and functional characterization of two paralogs from Withania somnifera (L.) Dunal. PLoS ONE 8:e57068PubMedPubMedCentralGoogle Scholar
  167. Rana S, Bhat WW, Dhar N, Pandith SA, Razdan S, Vishwakarma R, Lattoo SK (2014) Molecular characterization of two A-type P450s, WsCYP98A and WsCYP76A from Withania somnifera (L.) Dunal: expression analysis and withanolide accumulation in response to exogenous elicitations. BMC Biotechnol 14:89PubMedPubMedCentralGoogle Scholar
  168. Rather GA, Sharma A, Pandith SA, Kaul V, Nandi U, Misra P, Lattoo SK (2017) De novo transcriptome analyses reveals putative pathway genes involved in biosynthesis and regulation of camptothecin in Nothapodytes nimmoniana (Graham) Mabb. Plant Mol Biol 1–19Google Scholar
  169. Ravindran R, Dorairaj S (2017) In silico identification of potent PPAR agonists from Rheum emodi. Plant Comp. 6:2693–2700Google Scholar
  170. Ravishankar D, Rajora AK, Greco F, Osborn HM (2013) Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell B 45:2821–2831Google Scholar
  171. Rawlings BJ (1999) Biosynthesis of polyketides (other than actinomycete macrolides). Nat Prod Rep 16:425–484PubMedGoogle Scholar
  172. Razdan S, Bhat WW, Dhar N, Rana S, Pandith SA, Wani TA, Vishwakarma R, Lattoo SK (2017) Molecular characterization of DWF1 from Withania somnifera (L.) Dunal: its implications in withanolide biosynthesis. J Plant Biochem Biot 26:52–63Google Scholar
  173. Rehman H, Begum W, Anjum F, Tabasum H, Zahid S (2015) Effect of rhubarb (Rheum emodi) in primary dysmenorrhoea: a single-blind randomized controlled trial. J Complement Integr Med 12:61–69PubMedGoogle Scholar
  174. Roggemans J, Claes M-C (1979) Rapid clonal propagation of rhubarb by in vitro culture of shoot-tips. Sci Hort 11:241–246Google Scholar
  175. Rokaya MB, Münzbergová Z, Timsina B, Bhattarai KR (2012) Rheum australe D. Don: a review of its botany, ethnobotany, phytochemistry and pharmacology. J Ethnopharmacol 141:761–774PubMedGoogle Scholar
  176. Romagni J (2009) Biosynthesis of chemical signals—de novo synthesis and secondary metabolites. EOLSS Publications, Oxford, pp 393–414Google Scholar
  177. Saito ST, Silva G, Pungartnik C, Brendel M (2012) Study of DNA–emodin interaction by FTIR and UV–Vis spectroscopy. J Photochem Photobiol B 111:59–63PubMedGoogle Scholar
  178. Saito K, Yonekura-Sakakibara K, Nakabayashi R, Higashi Y, Yamazaki M, Tohge T, Fernie AR (2013) The flavonoid biosynthetic pathway in Arabidopsis: structural and genetic diversity. Plant Physiol Biochem 72:21–34PubMedGoogle Scholar
  179. Scambia G, Ranelletti F, Panici PB, De Vincenzo R, Bonanno G, Ferrandina G, Piantelli M, Bussa S, Rumi C, Cianfriglia M (1994) Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 34:459–464PubMedGoogle Scholar
  180. Semple SJ, Pyke SM, Reynolds GD, Flower RL (2001) In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus. Antivir Res 49:169–178PubMedGoogle Scholar
  181. Semwal D, Saradhi PP, Kala C, Sajwan B (2010) Medicinal plants used by local Vaidyas in Ukhimath block, Uttarakhand. Ind J Trad Know 9:480–485Google Scholar
  182. Seo EJ, Ngoc TM, Lee S-M, Kim YS, Jung Y-S (2012) Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. J Pharmacol Sci 118:245–254PubMedGoogle Scholar
  183. Sharma RK, Sharma S (2017) Seed longevity, germination and seedling vigour of Rheum australe D. Don: a step towards conservation and cultivation. J Appl Res Med Arom Plants 5:47–52Google Scholar
  184. Sharma AD, Singh P (2002) Germinability, productivity and economic viability of Rheum emodi Wall. ex Meissn. cultivated at lower altitude. Curr Sci India 84: 143Google Scholar
  185. Sharma PK, Chauhan N, Lal B (2004) Observations on the traditional phytotherapy among the inhabitants of Parvati valley in western Himalaya, India. J Ethnopharmacol 92:167–176PubMedGoogle Scholar
  186. Sharma PK, Thakur SK, Manuja S, Rana R, Kumar P, Sharma S, Chand J, Singh A, Katoch KK (2011) Observations on traditional phytotherapy among the inhabitants of Lahaul Valley through amchi system of medicine—a cold desert area of Himachal Pradesh in north western Himalayas, India. Chin Med 2:93–102Google Scholar
  187. Shi P, Huang Z, Chen G (2008) Rhein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma BEL-7402 cells. Am J Chin Med 36:805–813PubMedGoogle Scholar
  188. Shieh D-E, Chen Y-Y, Yen M-H, Chiang L-C, Lin C-C (2004) Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells. Life Sci 74:2279–2290PubMedGoogle Scholar
  189. Shuangsuo D, Zhengguo Z, Yunru C, Xin Z, Baofeng W, Lichao Y, Yan’an C (2006) Inhibition of the replication of hepatitis B virus in vitro by emodin. Med Sci Monit 12:302–306Google Scholar
  190. Simpson T (1987) The biosynthesis of polyketides. Nat Prod Rep 4:339–376PubMedGoogle Scholar
  191. Singh R, Chauhan S (2004) 9, 10-anthraquinones and other biologically active compounds from the genus rubia. Chem Biodivers 1:1241–1264PubMedGoogle Scholar
  192. Singh SS, Pandey SC, Singh R, Agarwal SK (2005) 1, 8-Dihydroxyanthraquinone derivatives from rhizomes of Rheum emodi Wall. Ind J Chem 43B:1494–1496Google Scholar
  193. Singh P, Negi JS, Rawat MS, nee Pant GJ (2010) Quantification of mineral elements of Rheum emodi Wall. (Polygonaceae). Biol Trace Elem Res 138:293–299PubMedGoogle Scholar
  194. Singh PP, Ambika, Chauhan S (2013) Activity-guided isolation of antioxidants from the roots of Rheum emodi. Nat Prod Res 27:946–949PubMedGoogle Scholar
  195. Sobolev VS, Horn BW, Potter TL, Deyrup ST, Gloer JB (2006) Production of stilbenoids and phenolic acids by the peanut plant at early stages of growth. J Agric Food Chem 54:3505–3511PubMedGoogle Scholar
  196. Srinivas G, Anto RJ, Srinivas P, Vidhyalakshmi S, Senan VP, Karunagaran D (2003) Emodin induces apoptosis of human cervical cancer cells through poly (ADP-ribose) polymerase cleavage and activation of caspase-9. Eur J Pharmacol 473:117–125PubMedGoogle Scholar
  197. Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P (2007) Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev 27:591–608PubMedGoogle Scholar
  198. Stafford HA (1990) Flavonoid metabolism. CRC Press/Taylor and Francis Group, Boca RatonGoogle Scholar
  199. Stapleton PD, Shah S, Hamilton-Miller JM, Hara Y, Nagaoka Y, Kumagai A, Uesato S, Taylor PW (2004) Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins. Int J Antimicrob Ag 24:374–380Google Scholar
  200. Suboj P, Babykutty S, Gopi DRV, Nair RS, Srinivas P, Gopala S (2012) Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB. Eur J Pharm Sci 45:581–591PubMedGoogle Scholar
  201. Sukanya P, Gunjan S, Tripathi R, Tadigoppula N (2014) Anti-malarial activity of new emodin derivatives against Plasmodium falciparum chloroquine resistant strain. Nat Prod Chem Res 2:1–6Google Scholar
  202. Sydiskis R, Owen D, Lohr J, Rosler K, Blomster R (1991) Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 35:2463–2466PubMedPubMedCentralGoogle Scholar
  203. Tali BA, Ganie AH, Nawchoo IA, Wani AA, Reshi ZA (2015) Assessment of threat status of selected endemic medicinal plants using IUCN regional guidelines: a case study from Kashmir Himalaya. J Nat Conserv 23:80–89Google Scholar
  204. Taylor LP, Grotewold E (2005) Flavonoids as developmental regulators. Curr Opin Plant Biol 8:317–323PubMedGoogle Scholar
  205. Tian B, Hua Y (2005) Concentration-dependence of prooxidant and antioxidant effects of aloin and aloe-emodin on DNA. Food Chem 91:413–418Google Scholar
  206. Ubbink-Kok T, Anderson JA, Konings W (1986) Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli. Antimicrob Agents Ch 30:147–151Google Scholar
  207. Uniyal SK, Singh K, Jamwal P, Lal B (2006) Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. J Ethnobiol Ethnomed 2:1–8Google Scholar
  208. Walkey D, Matthews K (1979) Rapid clonal propagation of rhubarb (Rheum rhaponticum L.) from meristem-tips in tissue culture. Plant Sci Lett 14:287–290Google Scholar
  209. Wang H-H, Chung J-G (1997) Emodin-induced inhibition of growth and DNA damage in the Helicobacter pylori. Curr Microbiol 35:262–266PubMedGoogle Scholar
  210. Wang HH, Chung JG, Ho CC, Wu LT, Chang SH (1998) Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium Helicobacter pylori. Planta Med 64:176–178PubMedGoogle Scholar
  211. Wang C, Wu X, Chen M, Duan W, Sun L, Yan M, Zhang L (2007) Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells. Toxicology 231:120–128PubMedGoogle Scholar
  212. Wang A, Li J, Li J (2010) Chemical constituents of Rheum emodi. Zhongcaoyao Chin Trad Herb Drugs 41:343–347Google Scholar
  213. Wang J, Liu S, Yin Y, Li M, Wang B, Yang L, Jiang Y (2015) FOXO3-mediated up-regulation of Bim contributes to rhein-induced cancer cell apoptosis. Apoptosis 20:399–409PubMedGoogle Scholar
  214. Wani TA, Pandith SA, Gupta AP, Chandra S, Sharma N, Lattoo SK (2017) Molecular and functional characterization of two isoforms of chalcone synthase and their expression analysis in relation to flavonoid constituents in Grewia asiatica L. PLoS ONE 12:e0179155PubMedPubMedCentralGoogle Scholar
  215. Wayne P (2002) National committee for clinical laboratory standards. Performance standards for antimicrobial disc susceptibility testing 12Google Scholar
  216. Xiong H-R, Luo J, Hou W, Xiao H, Yang Z-Q (2011) The effect of emodin, an anthraquinone derivative extracted from the roots of Rheum tanguticum, against herpes simplex virus in vitro and in vivo. J Ethnopharmacol 133:718–723PubMedGoogle Scholar
  217. Xue J, Ding W, Liu Y (2010) Anti-diabetic effects of emodin involved in the activation of PPARγ on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice. Fitoterapia 81:173–177PubMedGoogle Scholar
  218. Yang Y, Shang W, Zhou L, Jiang B, Jin H, Chen M (2007) Emodin with PPARγ ligand-binding activity promotes adipocyte differentiation and increases glucose uptake in 3T3-Ll cells. Biochem Biophys Res Commun 353:225–230PubMedGoogle Scholar
  219. Ye M, Han J, Chen H, Zheng J, Guo D (2007) Analysis of phenolic compounds in rhubarbs using liquid chromatography coupled with electrospray ionization mass spectrometry. J Am Soc Mass Spectr 18:82–91Google Scholar
  220. Yim H, Lee YH, Lee CH, Lee SK (1999) Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor. Planta Med 65:9–13PubMedGoogle Scholar
  221. Youl E, Bardy G, Magous R, Cros G, Sejalon F, Virsolvy A, Richard S, Quignard J, Gross R, Petit P (2010) Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway. Brit J Pharmacol 161:799–814Google Scholar
  222. Zargar BA, Masoodi MH, Ahmed B, Ganie SA (2011) Phytoconstituents and therapeutic uses of Rheum emodi wall. ex Meissn. Food Chem 128:585–589Google Scholar
  223. Zhang Y, Liu D (2011) Flavonol kaempferol improves chronic hyperglycemia-impaired pancreatic beta-cell viability and insulin secretory function. Eur J Pharmacol 670:325–332PubMedGoogle Scholar
  224. Zhang L, Lau Y-K, Xi L, Hong R-L, Kim DS, Chen C-F, Hortobagyi GN, C-j Chang, Hung M-C (1998) Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene 16:2855–2863PubMedGoogle Scholar
  225. Zhang T, Wu Z, Du J, Hu Y, Liu L, Yang F, Jin Q (2012) Anti-Japanese-encephalitis-viral effects of kaempferol and daidzin and their RNA-binding characteristics. PLoS ONE 7:e30259PubMedPubMedCentralGoogle Scholar
  226. Zhao P, Iwamoto Y, Kouno I, Egami Y, Yamamoto H (2004) Stimulating the production of homoisoflavonoids in cell suspension cultures of Caesalpinia pulcherrima using cork tissue. Phytochemistry 65:2455–2461PubMedGoogle Scholar
  227. Zheng JM, Zhu JM, Li LS, Liu ZH (2008) Rhein reverses the diabetic phenotype of mesangial cells over-expressing the glucose transporter (GLUT1) by inhibiting the hexosamine pathway. Brit J Pharmacol 153:1456–1464Google Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Shahzad A. Pandith
    • 1
  • Riyaz Ahmad Dar
    • 1
  • Surrinder K. Lattoo
    • 2
  • Manzoor A. Shah
    • 1
  • Zafar A. Reshi
    • 1
  1. 1.Department of BotanyUniversity of KashmirSrinagarIndia
  2. 2.Plant Biotechnology DivisionCSIR-Indian Institute of Integrative MedicineJammu TawiIndia

Personalised recommendations