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Lupeol and Its Role in Chronic Diseases

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Drug Discovery from Mother Nature

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 929))

Abstract

Lupeol belongs to pentacyclic lupane-type triterpenes and exhibits in edible vegetables, fruits and many plants. Many researches indicated that lupeol possesses many beneficial pharmacological activities including antioxidant, anti-inflammatory, anti-hyperglycemic, anti-dyslipidemic and anti-mutagenic effects. From various disease-targeted animal models, these reports indicated that lupeol has anti-diabetic, anti-asthma, anti-arthritic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective and anticancer efficiency under various routes of administration such as topical, oral, subcutaneous, intraperitoneal and intravenous. It is worth mentioning that clinical trials of lupeol were performed to treat canine oral malignant melanoma and human moderate skin acne in Japan and Korea. The detailed mechanism of anti-inflammatory, anti-diabetic, hepatoprotective and anticancer activities was further reviewed from published papers. These evidence indicate that lupeol is a multi-target agent to exert diverse pharmacological potency with many potential targeting proteins such as α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP 1B) and TCA cycle enzymes and targeting pathway such as IL-1 receptor-associated kinase-mediated toll-like receptor 4 (IRAK-TLR4), Bcl-2 family, nuclear factor kappa B (NF-kB), phosphatidylinositol-3-kinase (PI3-K)/Akt and Wnt/β-catenin signaling pathways. This review also provides suggestion that lupeol might be a valuable and potential lead compound to develop as anti-inflammatory, anti-diabetic, hepatoprotective and anticancer drugs.

Fan-Shiu Tsai and Li-Wei Lin have equally contributed.

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References

  1. Agarwal SK, Kumar S (2003) An improved process for the extraction of lupeol, an antiurotithic compound from Crateva nurvala. Indian. INXXAPIN 191625 A1 20031206: 11

    Google Scholar 

  2. Agra LC, Ferro JN, Barbosa FT, Barreto E (2015) Triterpenes with healing activity: a systematic review. J Dermatol Treat 26:465–470

    Article  CAS  Google Scholar 

  3. Ahmad SF, Pandey A, Kour K, Bani S (2010) Downregulation of pro-inflammatory cytokines by lupeol measured using cytometric bead array immunoassay. Phytotherapy Res 24:9–13

    Article  CAS  Google Scholar 

  4. AI-Rehaily AJ, El-Tahir KEH, Mossa JS, Rafatullah S (2001) Pharmacological studies of various extracts and the major constituent, lupeol, obtained from hexane extract of Teclea nobilis in Rodents. Nat Prod Sci 7:76–82

    Google Scholar 

  5. Akihisa T, Kojima N, Kikuchi T, Yasukawa K, Tokuda H, Masters E, Manosroi A, Manosroi J (2010) Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat. J Oleo Sci 59:273–280

    Google Scholar 

  6. Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, Kumaki K, Tamura T (1996) Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry 43:1255–1260

    Article  CAS  PubMed  Google Scholar 

  7. Alqahtani A, Hamid K, Kam A, Wong KH, Abdelhak Z, Razmovski-Naumovski V, Chan K, Li KM, Groundwater PW, Li GQ (2013) The pentacyclic triterpenoids in herbal medicines and their pharmacological activities in diabetes and diabetic complications. Curr Med Chem 20:908–931

    CAS  PubMed  Google Scholar 

  8. Ambasta RK, Jha SK, Kumar D, Sharma R, Jha NK, Kumar P (2015) Comparative study of anti-angiogenic activities of luteolin, lectin and lupeol biomolecules. J Transl Med 13:307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Annabi B, Vaillancourt-Jean E, Beliveau R (2013) MT1-MMP expression level status dictates the in vitro action of lupeol on inflammatory biomarkers MMP-9 and COX-2 in medulloblastoma cells. Inflammopharmacology 21:91–99

    Article  CAS  PubMed  Google Scholar 

  10. Ardiansyah YE, Shirakawa H, Hata K, Hiwatashi K, Ohinata K, Goto T, Komai M (2012) Lupeol supplementation improves blood pressure and lipid metabolism parameters in stroke-prone spontaneously hypertensive rats. Biosci Biotechnol Biochem 76:183–185

    Google Scholar 

  11. Asha R, Devi VG, Abraham A (2016) Lupeol, a pentacyclic triterpenoid isolated from Vernonia cinerea attenuate selenite induced cataract formation in Sprague Dawley rat pups. Chem Biol Interact 245:20–29

    Google Scholar 

  12. Ashalatha K, Venkateswarlu Y, Priya AM, Lalitha P, Krishnaveni M, Jayachandran S (2010) Anti inflammatory potential of Decalepis hamiltonii (Wight and Arn) as evidenced by down regulation of pro inflammatory cytokines-TNF-alpha and IL-2. J Ethnopharmacol 130:167–170

    Article  CAS  PubMed  Google Scholar 

  13. Badshah H, Ali T, Rehman SU, Amin FU, Ullah F, Kim TH, Kim MO (2016) Protective effect of lupeol against lipopolysaccharide-induced neuroinflammation via the p38/c-Jun N-terminal kinase pathway in the adult mouse Brain. J Neuroimmune Pharmacol 11:48–60

    Google Scholar 

  14. Baliga MS, Thilakchand KR, Rai MP, Rao S, Venkatesh P (2013) Aegle marmelos (L.) Correa (Bael) and its phytochemicals in the treatment and prevention of cancer. Integr Cancer Ther 12:187–196

    Article  CAS  PubMed  Google Scholar 

  15. Bani S, Kaul A, Khan B, Ahmad SF, Suri KA, Gupta BD, Satti NK, Qazi GN (2006) Suppression of T lymphocyte activity by lupeol isolated from Crataeva religiosa. Phytotherapy Res 20:279–287

    Article  CAS  Google Scholar 

  16. Beveridge TH, Li TS, Drover JC (2002) Phytosterol content in American ginseng seed oil. J Agric Food Chem 50:744–750

    Article  CAS  PubMed  Google Scholar 

  17. Bhandari P, Patel NK, Bhutani KK (2014) Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors. Bioorg Med Chem Lett 24:3596–3599

    Article  CAS  PubMed  Google Scholar 

  18. Chappell J (2002) The genetics and molecular genetics of terpene and sterol origami. Curr Opin Plant Biol 5:151–157

    Article  CAS  PubMed  Google Scholar 

  19. Chatterjee I, Chakravarty AK, Gomes A (2006) Daboia russellii and Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br. J Ethnopharmacol 106:38–43

    Article  CAS  PubMed  Google Scholar 

  20. Chen YF, Ching C, Wu TS, Wu CR, Hsieh WT, Tsai HY (2012) Balanophora spicata and lupeol acetate possess antinociceptive and anti-inflammatory activities in vivo and in vitro. Evid Based Complement Altern Med 2012:371273

    Google Scholar 

  21. Connolly JD, Hill RA (2008) Triterpenoids. Nat Prod Rep 25:794–830

    Article  CAS  PubMed  Google Scholar 

  22. Correa RS, Coelho CP, dos Santos MH, Ellena J, Doriguetto AC (2009) Lupeol. Acta Crystallogr C 65:O97–O99

    Article  CAS  PubMed  Google Scholar 

  23. de Lima FO, Alves V, Barbosa Filho JM, Almeida JR, Rodrigues LC, Soares MB, Villarreal CF (2013) Antinociceptive effect of lupeol: evidence for a role of cytokines inhibition. Phytotherapy Res 27:1557–1563

    Google Scholar 

  24. de Miranda AL, Silva JR, Rezende CM, Neves JS, Parrini SC, Pinheiro ML, Cordeiro MC, Tamborini E, Pinto AC (2000) Anti-inflammatory and analgesic activities of the latex containing triterpenes from Himatanthus sucuuba. Planta Med 66:284–286

    Article  PubMed  Google Scholar 

  25. Deutschlander MS, Lall N, Van de Venter M, Hussein AA (2011) Hypoglycemic evaluation of a new triterpene and other compounds isolated from Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark. J Ethnopharmacol 133:1091–1095

    Article  CAS  PubMed  Google Scholar 

  26. Duke JA (1992) Handbook of phytochemical constituents of GRAS herbs and other economic plants, vol CRC. Press, Boca Raton

    Google Scholar 

  27. Fernandez A, Alvarez A, Garcia MD, Saenz MT (2001a) Anti-inflammatory effect of Pimenta racemosa var. ozua and isolation of the triterpene lupeol. Farmaco 56:335–338

    Google Scholar 

  28. Fernandez MA, de las Heras B, Garcia MD, Saenz MT, Villar A (2001b) New insights into the mechanism of action of the anti-inflammatory triterpene lupeol. J Pharm Pharmacol 53:1533–1539

    Google Scholar 

  29. Fotie J, Bohle DS, Leimanis ML, Georges E, Rukunga G, Nkengfack AE (2006) Lupeol long-chain fatty acid esters with antimalarial activity from Holarrhena floribunda. J Nat Prod 69:62–67

    Article  CAS  PubMed  Google Scholar 

  30. Furukawa S, Takagi N, Ikeda T, Ono M, Nafady AM, Nohara T, Sugimoto H, Doi S, Yamada H (2002) Two novel long-chain alkanoic acid esters of lupeol from alecrim-propolis. Chem Pharm Bull (Tokyo) 50:439–440

    Article  CAS  Google Scholar 

  31. Gandhi GR, Ignacimuthu S, Paulraj MG (2012) Hypoglycemic and beta-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats. Food Chem Toxicol 50:1667–1674

    Article  CAS  PubMed  Google Scholar 

  32. Geetha T, Varalakshmi P (1999) Effect of lupeol and lupeol linoleate on lysosomal enzymes and collagen in adjuvant-induced arthritis in rats. Mol Cell Biochem 201:83–87

    Article  CAS  PubMed  Google Scholar 

  33. Geetha T, Varalakshmi P (2001) Anti-inflammatory activity of lupeol and lupeol linoleate in rats. J Ethnopharmacol 76:77–80

    Article  CAS  PubMed  Google Scholar 

  34. Geetha T, Varalakshmi P, Latha RM (1998) Effect of triterpenes from Crataeva nurvala stem bark on lipid peroxidation in adjuvant induced arthritis in rats. Pharmacol Res 37:191–195

    Article  CAS  PubMed  Google Scholar 

  35. Golechha M, Sarangal V, Ojha S, Bhatia J, Arya DS (2014) Anti-inflammatory effect of Emblica officinalis in rodent models of acute and chronic inflammation: involvement of possible mechanisms. Int J Inflamm 2014:178408

    Article  Google Scholar 

  36. Gupta R, Sharma AK, Sharma MC, Dobhal MP, Gupta RS (2012) Evaluation of antidiabetic and antioxidant potential of lupeol in experimental hyperglycaemia. Nat Prod Res 26:1125–1129

    Article  CAS  PubMed  Google Scholar 

  37. Hao J, Pei Y, Ji G, Li W, Feng S, Qiu S (2011) Autophagy is induced by 3β-O-succinyl-lupeol (LD9-4) in A549 cells via up-regulation of Beclin 1 and down-regulation mTOR pathway. Eur J Pharmacol 670:29–38

    Article  CAS  PubMed  Google Scholar 

  38. Harish BG, Krishna V, Santosh Kumar HS, Khadeer Ahamed BM, Sharath R, Kumara Swamy HM (2008) Wound healing activity and docking of glycogen-synthase-kinase-3-β-protein with isolated triterpenoid lupeol in rats. Phytomedicine 15:763–767

    Article  CAS  PubMed  Google Scholar 

  39. Hata K, Hori K, Takahashi S (2003) Role of p38 MAPK in lupeol-induced B16 2F2 mouse melanoma cell differentiation. J Biochem 134:441–445

    Article  CAS  PubMed  Google Scholar 

  40. Hata K, Mukaiyama T, Tsujimura N, Sato Y, Kosaka Y, Sakamoto K, Hori K (2006) Differentiation-inducing activity of lupane triterpenes on a mouse melanoma cell line. Cytotechnology 52:151–158

    Article  CAS  PubMed  Google Scholar 

  41. Hata K, Ogihara K, Takahashi S, Tsuka T, Minami S, Okamoto Y (2010) Effects of lupeol on melanoma in vitro and in vivo: fundamental and clinical trials. Anim Cell Technol Basic Appl Aspects 16:339–344

    Google Scholar 

  42. He Y, Liu F, Zhang L, Wu Y, Hu B, Zhang Y, Li Y, Liu H (2011) Growth inhibition and apoptosis induced by lupeol, a dietary triterpene, in human hepatocellular carcinoma cells. Biol Pharm Bull 34:517–522

    Article  CAS  PubMed  Google Scholar 

  43. Itoh H, Mukaiyama T, Goto T, Hata K, Azuma K, Tsuka T, Osaki T, Imagawa T, Okamoto Y (2014) Non-surgical treatment of canine oral malignant melanoma: a case study of the application of complementary alternative medicine. Oncol Lett 7:1829–1830

    PubMed  PubMed Central  Google Scholar 

  44. Jin Y, Lyu Y, Tang X, Zhang Y, Chen J, Zheng D, Liang Y (2015) Lupeol enhances radiosensitivity of human hepatocellular carcinoma cell line SMMC-7721 in vitro and in vivo. Int J Radiat Biol 91:202–208

    Article  CAS  PubMed  Google Scholar 

  45. Jyotshna, Srivastava P, Killadi B, Shanker K (2015) Uni-dimensional double development HPTLC-densitometry method for simultaneous analysis of mangiferin and lupeol content in mango (Mangifera indica) pulp and peel during storage. Food Chem 176:91–98

    Google Scholar 

  46. Kahlos K, Kangas L, Hiltunen R (1989) Ergosterol peroxide, an active compound from Inonotus radiatus. Planta Med 55:389–390

    Article  CAS  PubMed  Google Scholar 

  47. Kardar MN, Zhang T, Coxon GD, Watson DG, Fearnley J, Seidel V (2014) Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis. Phytochemistry 106:156–163

    Article  CAS  PubMed  Google Scholar 

  48. Katkar GD, Sharma RD, Vishalakshi GJ, Naveenkumar SK, Madhur G, Thushara RM, Narender T, Girish KS, Kemparaju K (2015) Lupeol derivative mitigates Echis carinatus venom-induced tissue destruction by neutralizing venom toxins and protecting collagen and angiogenic receptors on inflammatory cells. Biochim Biophys Acta 1850:2393–2409

    Article  CAS  PubMed  Google Scholar 

  49. Katzung BG, Masters SB, Trevor AJ (2012) Nosteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, nonopoid analgesics, and drugs used in gout. Basic and clinical pharmacology. McGraw-Hill Medical, pp 635–636

    Google Scholar 

  50. Khan MF, Maurya CK, Dev K, Arha D, Rai AK, Tamrakar AK, Maurya R (2014) Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells. Bioorg Med Chem Lett 24:2674–2679

    Article  CAS  PubMed  Google Scholar 

  51. Kim MJ, Bae GS, Choi SB, Jo IJ, Kim DG, Shin JY, Lee SK, Kim MJ, Song HJ, Park SJ (2015) Lupeol protects against cerulein-induced acute pancreatitis in mice. Phytotherapy Res 29:1634–1639

    Article  CAS  Google Scholar 

  52. Kim SJ, Cho HI, Kim SJ, Kim JS, Kwak JH, Lee DU, Lee SK, Lee SM (2014) Protective effects of lupeol against d-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice. J Nat Prod 77:2383–2388

    Article  CAS  PubMed  Google Scholar 

  53. Kumar A, Tantry BA, Rahiman S, Gupta U (2011) Comparative study of antimicrobial activity and phytochemical analysis of methanolic and aqueous extracts of the fruit of Emblica officinalis against pathogenic bacteria. J Tradit Chin Med 31:246–250

    PubMed  Google Scholar 

  54. Kumari A, Kakkar P (2012) Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade. Life Sci 90:561–570

    Article  CAS  PubMed  Google Scholar 

  55. Kumari A, Kakkar P (2012) Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes. Food Chem Toxicol 50:1781–1789

    Article  CAS  PubMed  Google Scholar 

  56. Kwon HH, Yoon JY, Park SY, Min S, Kim YI, Park JY, Lee YS, Thiboutot DM, Suh DH (2015) Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne. J Invest Dermatol 135:1491–1500

    Article  CAS  PubMed  Google Scholar 

  57. Lakshmi V, Gupta P, Tiwari P, Srivastava AK (2006) Antihyperglycemic activity of Rhizophora apiculata Bl. in rats. Nat Prod Res 20:1295–1299

    Article  CAS  PubMed  Google Scholar 

  58. Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO (2011) Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Hepatology 53:160–170

    Article  CAS  PubMed  Google Scholar 

  59. Li W, Hao J, Xiao Y (2013) Synthesis and in vitro antitumor activities of lupeol dicarboxylic acid monoester derivatives. Arch Pharm Res 36:1447–1453

    Article  CAS  PubMed  Google Scholar 

  60. Lima LM, Perazzo FF, Tavares Carvalho JC, Bastos JK (2007) Anti-inflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark. J Pharm Pharmacol 59:1151–1158

    Article  CAS  PubMed  Google Scholar 

  61. Lira SR, Rao VS, Carvalho AC, Guedes MM, de Morais TC, de Souza AL, Trevisan MT, Lima AF, Chaves MH, Santos FA (2009) Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism. Inflammopharmacology 17:221–228

    Article  CAS  PubMed  Google Scholar 

  62. Liu Y, Bi T, Dai W, Wang G, Qian L, Shen G, Gao Q (2015a) Lupeol induces apoptosis and cell cycle arrest of human osteosarcoma cells through PI3K/AKT/mTOR Pathway. Technol Cancer Res Treat pii: 1533034615609014

    Google Scholar 

  63. Liu Y, Bi T, Shen G, Li Z, Wu G, Wang Z, Qian L, Gao Q (2016) Lupeol induces apoptosis and inhibits invasion in gallbladder carcinoma GBC-SD cells by suppression of EGFR/MMP-9 signaling pathway. Cytotechnology 68:123–133

    Google Scholar 

  64. Liu Y, Bi T, Wang G, Dai W, Wu G, Qian L, Gao Q, Shen G (2015b) Lupeol inhibits proliferation and induces apoptosis of human pancreatic cancer PCNA-1 cells through AKT/ERK pathways. Naunyn Schmiedebergs Arch Pharmacol 388:295–304

    Google Scholar 

  65. Lucetti DL, Lucetti EC, Bandeira MA, Veras HN, Silva AH, Leal LK, Lopes AA, Alves VC, Silva GS, Brito GA, Viana GB (2010) Anti-inflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel. J Inflamm (Lond) 7:60

    Google Scholar 

  66. Malini MM, Lenin M, Varalakshmi P (2000) Protective effect of triterpenes on calcium oxalate crystal-induced peroxidative changes in experimental urolithiasis. Pharmacol Res 41:413–418

    Article  CAS  PubMed  Google Scholar 

  67. Manjula K, Rajendran K, Eevera T, Kumaran S (2012) Effect of Costus igneus stem extract on calcium oxalate urolithiasis in albino rats. Urol Res 40:499–510

    Article  CAS  PubMed  Google Scholar 

  68. Manoharan S, Palanimuthu D, Baskaran N, Silvan S (2012) Modulating effect of lupeol on the expression pattern of apoptotic markers in 7, 12-dimethylbenz(a)anthracene induced oral carcinogenesis. Asian Pac J Cancer Prev 13:5753–5757

    Article  CAS  PubMed  Google Scholar 

  69. Martelanc M, Vovk I, Simonovska B (2009) Separation and identification of some common isomeric plant triterpenoids by thin-layer chromatography and high-performance liquid chromatography. J Chromatogr A 1216:6662–6670

    Article  CAS  PubMed  Google Scholar 

  70. Murtaza I, Saleem M, Adhami VM, Hafeez BB, Mukhtar H (2009) Suppression of cFLIP by lupeol, a dietary triterpene, is sufficient to overcome resistance to TRAIL-mediated apoptosis in chemoresistant human pancreatic cancer cells. Cancer Res 69:1156–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Na M, Kim BY, Osada H, Ahn JS (2009) Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta. J Enzyme Inhib Med Chem 24:1056–1059

    Article  CAS  PubMed  Google Scholar 

  72. Nagaraj M, Sunitha S, Varalakshmi P (2000) Effect of lupeol, a pentacyclic triterpene, on the lipid peroxidation and antioxidant status in rat kidney after chronic cadmium exposure. J Appl Toxicol 20:413–417

    Article  CAS  PubMed  Google Scholar 

  73. Narvaez-Mastache JM, Garduno-Ramirez ML, Alvarez L, Delgado G (2006) Antihyperglycemic activity and chemical constituents of Eysenhardtia platycarpa. J Nat Prod 69:1687–1691

    Article  CAS  PubMed  Google Scholar 

  74. Nazaruk J, Borzym-Kluczyk M (2015) The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem Rev 14:675–690

    Article  CAS  PubMed  Google Scholar 

  75. Nguemfo EL, Dimo T, Dongmo AB, Azebaze AG, Alaoui K, Asongalem AE, Cherrah Y, Kamtchouing P (2009) Anti-oxidative and anti-inflammatory activities of some isolated constituents from the stem bark of Allanblackia monticola Staner L.C (Guttiferae). Inflammopharmacology 17:37–41

    Article  CAS  PubMed  Google Scholar 

  76. Nigam N, Prasad S, George J, Shukla Y (2009) Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin. Biochem Biophys Res Commun 381:253–258

    Article  CAS  PubMed  Google Scholar 

  77. Nigam N, Prasad S, Shukla Y (2007) Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin. Food Chem Toxicol 45:2331–2335

    Article  CAS  PubMed  Google Scholar 

  78. Nikiema JB, Vanhaelen-Fastre R, Vanhaelen M, Fontaine J, De Graef C, Heenen M (2001) Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation. Phytotherapy Res 15:131–134

    Article  CAS  Google Scholar 

  79. Nitta M, Azuma K, Hata K, Takahashi S, Ogiwara K, Tsuka T, Imagawa T, Yokoe I, Osaki T, Minami S, Okamoto Y (2013) Systemic and local injections of lupeol inhibit tumor growth in a melanoma-bearing mouse model. Biomed Rep 1:641–645

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Nkobole N, Houghton PJ, Hussein A, Lall N (2011) Antidiabetic activity of Terminalia sericea constituents. Nat Prod Commun 6:1585–1588

    CAS  PubMed  Google Scholar 

  81. Ogihara K, Naya Y, Okamoto Y, Hata K (2014) Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells. Springerplus 3:632

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Ogiwara K, Hata K (2009) Melanoma cell differentiation induced by lupeol separates into two stages: morphological and functional changes. J Nat Med 63:323–326

    Article  CAS  PubMed  Google Scholar 

  83. Omoyeni OA, Hussein A, Meyer M, Green I, Iwuoha E (2015) Pleiocarpa pycnantha leaves and its triterpenes induce apoptotic cell death in Caco-2 cells in vitro. BMC Complement Altern Med 15:224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Ortiz-Andrade RR, Garcia-Jimenez S, Castillo-Espana P, Ramirez-Avila G, Villalobos-Molina R, Estrada-Soto S (2007) alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent. J Ethnopharmacol 109:48–53

    Article  CAS  PubMed  Google Scholar 

  85. Palanimuthu D, Baskaran N, Silvan S, Rajasekaran D, Manoharan S (2012) Lupeol, a bioactive triterpene, prevents tumor formation during 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis. Pathol Oncol Res 18:1029–1037

    Article  CAS  PubMed  Google Scholar 

  86. Papi Reddy K, Singh AB, Puri A, Srivastava AK, Narender T (2009) Synthesis of novel triterpenoid (lupeol) derivatives and their in vivo antihyperglycemic and antidyslipidemic activity. Bioorg Med Chem Lett 19:4463–4466

    Article  CAS  PubMed  Google Scholar 

  87. Patocka J (2003) Biologically active pentacyclic triterpenes and their current medicine signification. J Appl Biomed 1:7–12

    CAS  Google Scholar 

  88. Pereira AC, Pereira AB, Moreira CC, Botion LM, Lemos VS, Braga FC, Cortes SF (2015) Hancornia speciosa Gomes (Apocynaceae) as a potential anti-diabetic drug. J Ethnopharmacol 161:30–35

    Article  PubMed  Google Scholar 

  89. Phillips DR, Rasbery JM, Bartel B, Matsuda SP (2006) Biosynthetic diversity in plant triterpene cyclization. Curr Opin Plant Biol 9:305–314

    Article  CAS  PubMed  Google Scholar 

  90. Piaulino CA, Carvalho FC, Almeida BC, Chaves MH, Almeida FR, Brito SM (2013) The stem bark extracts of Cenostigma macrophyllum attenuates tactile allodynia in streptozotocin-induced diabetic rats. Pharm Biol 51:1243–1248

    Article  PubMed  Google Scholar 

  91. Poumale HM, Awoussong KP, Randrianasolo R, Simo CC, Ngadjui BT, Shiono Y (2012) Long-chain alkanoic acid esters of lupeol from Dorstenia harmsiana Engl. (Moraceae). Nat Prod Res 26:749–755

    Article  CAS  PubMed  Google Scholar 

  92. Prabhu B, Balakrishnan D, Sundaresan S (2015) Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats. Hum Exp Toxicol (in press)

    Google Scholar 

  93. Prasad S, Kalra N, Shukla Y (2007) Hepatoprotective effects of lupeol and mango pulp extract of carcinogen induced alteration in Swiss albino mice. Mol Nutr Food Res 51:352–359

    Article  CAS  PubMed  Google Scholar 

  94. Prasad S, Kumar Yadav V, Srivastava S, Shukla Y (2008) Protective effects of lupeol against benzo[a]pyrene induced clastogenicity in mouse bone marrow cells. Mol Nutr Food Res 52:1117–1120

    Google Scholar 

  95. Prasad S, Madan E, Nigam N, Roy P, George J, Shukla Y (2009) Induction of apoptosis by lupeol in human epidermoid carcinoma A431 cells through regulation of mitochondrial, Akt/PKB and NFkappaB signaling pathways. Cancer Biol Ther 8:1632–1639

    Article  CAS  PubMed  Google Scholar 

  96. Preetha SP, Kanniappan M, Selvakumar E, Nagaraj M, Varalakshmi P (2006) Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats. Comp Biochem Physiol C Toxicol Pharmacol 143:333–339

    Article  CAS  PubMed  Google Scholar 

  97. Rahman K (2007) Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2:219–236

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Ramirez Apan AA, Perez-Castorena AL, de Vivar AR (2004) Anti-inflammatory constituents of Mortonia greggii Gray. Z Naturforsch C 59:237–243

    PubMed  Google Scholar 

  99. Righi AA, Alves TR, Negri G, Marques LM, Breyer H, Salatino A (2011) Brazilian red propolis: unreported substances, antioxidant and antimicrobial activities. J Sci Food Agric 91:2363–2370

    Article  CAS  PubMed  Google Scholar 

  100. Ruiz-Montanez G, Ragazzo-Sanchez JA, Calderon-Santoyo M, Velazquez-de la Cruz G, de Leon JA, Navarro-Ocana A (2014) Evaluation of extraction methods for preparative scale obtention of mangiferin and lupeol from mango peels (Mangifera indica L.). Food Chem 159:267–272

    Article  CAS  PubMed  Google Scholar 

  101. Rutters F, Pilz S, Koopman AD, Rauh SP, Te Velde SJ, Stehouwer CD, Elders PJ, Nijpels G, Dekker JM (2014) The association between psychosocial stress and mortality is mediated by lifestyle and chronic diseases: the Hoorn Study. Soc Sci Med 118:166–172

    Article  PubMed  Google Scholar 

  102. Saleem M (2009) Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. Cancer Lett 285:109–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Saleem M, Afaq F, Adhami VM, Mukhtar H (2004) Lupeol modulates NF-kappaB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene 23:5203–5214

    Article  CAS  PubMed  Google Scholar 

  104. Saleem M, Alam A, Arifin S, Shah MS, Ahmed B, Sultana S (2001) Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin. Pharmacol Res 43:127–134

    Article  CAS  PubMed  Google Scholar 

  105. Saleem M, Kaur S, Kweon MH, Adhami VM, Afaq F, Mukhtar H (2005) Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway. Carcinogenesis 26:1956–1964

    Article  CAS  PubMed  Google Scholar 

  106. Saleem M, Kweon MH, Yun JM, Adhami VM, Khan N, Syed DN, Mukhtar H (2005) A novel dietary triterpene lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model. Cancer Res 65:11203–11213

    Article  CAS  PubMed  Google Scholar 

  107. Saleem M, Maddodi N, Abu Zaid M, Khan N, bin Hafeez B, Asim M, Suh Y, Yun JM, Setaluri V, Mukhtar H (2008) Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Clin Cancer Res 14:2119–2127

    Google Scholar 

  108. Saleem M, Murtaza I, Tarapore RS, Suh Y, Adhami VM, Johnson JJ, Siddiqui IA, Khan N, Asim M, Hafeez BB, Shekhani MT, Li B, Mukhtar H (2009) Lupeol inhibits proliferation of human prostate cancer cells by targeting beta-catenin signaling. Carcinogenesis 30:808–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Saleem M, Murtaza I, Witkowsky O, Kohl AM, Maddodi N (2009) Lupeol triterpene, a novel diet-based microtubule targeting agent: disrupts survivin/cFLIP activation in prostate cancer cells. Biochem Biophys Res Commun 388:576–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Santiago LA, Mayor AB (2014) Lupeol: an antioxidant triterpene in Ficus pseudopalma Blanco (Moraceae). Asian Pac J Trop Biomed 4:109–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Saratha V, Subramanian SP (2012) Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and secondary complications of FCA induced adjuvant disease in experimental rats. Inflammopharmacology 20:27–37

    Article  CAS  PubMed  Google Scholar 

  112. Siddique HR, Mishra SK, Karnes RJ, Saleem M (2011) Lupeol, a novel androgen receptor inhibitor: implications in prostate cancer therapy. Clin Cancer Res 17:5379–5391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Siddique HR, Saleem M (2011) Beneficial health effects of lupeol triterpene: a review of preclinical studies. Life Sci 88:285–293

    Article  CAS  PubMed  Google Scholar 

  114. Siveen KS, Nguyen AH, Lee JH, Li F, Singh SS, Kumar AP, Low G, Jha S, Tergaonkar V, Ahn KS, Sethi G (2014) Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells. Br J Cancer 111:1327–1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Slimen IB, Najar T, Ghram A, Dabbebi H, Ben Mrad M, Abdrabbah M (2014) Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperth 30:513–523

    Article  CAS  Google Scholar 

  116. Sousa AF, Pinto PC, Silvestre AJ, Pascoal Neto C (2006) Triterpenic and other lipophilic components from industrial cork byproducts. J Agric Food Chem 54:6888–6893

    Article  CAS  PubMed  Google Scholar 

  117. Srivastava S, Sonkar R, Mishra SK, Tiwari A, Balaramnavar VM, Mir S, Bhatia G, Saxena AK, Lakshmi V (2013) Antidyslipidemic and antioxidant effects of novel Lupeol-derived chalcones. Lipids 48:1017–1027

    Article  CAS  PubMed  Google Scholar 

  118. Stork G, Uyeo S, Wakamatsu T, Grieco P, Labovitz J (1971) Total synthesis of lupeol. J Am Chem Soc 93:4945–4947

    Article  CAS  Google Scholar 

  119. Sudhahar V, Ashok Kumar S, Varalakshmi P, Sujatha V (2008) Protective effect of lupeol and lupeol linoleate in hypercholesterolemia associated renal damage. Mol Cell Biochem 317:11–20

    Article  CAS  PubMed  Google Scholar 

  120. Sudhahar V, Ashokkumar S, Varalakshmi P (2006) Effect of lupeol and lupeol linoleate on lipemic–hepatocellular aberrations in rats fed a high cholesterol diet. Mol Nutr Food Res 50:1212–1219

    Article  CAS  PubMed  Google Scholar 

  121. Sudhahar V, Kumar SA, Sudharsan PT, Varalakshmi P (2007) Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia. Vascul Pharmacol 46:412–418

    Article  CAS  PubMed  Google Scholar 

  122. Sudhahar V, Kumar SA, Varalakshmi P (2006) Role of lupeol and lupeol linoleate on lipemic-oxidative stress in experimental hypercholesterolemia. Life Sci 78:1329–1335

    Article  CAS  PubMed  Google Scholar 

  123. Sudhahar V, Kumar SA, Varalakshmi P, Sundarapandiyan R (2007) Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia. Mol Cell Biochem 295:189–198

    Article  CAS  PubMed  Google Scholar 

  124. Sudhahar V, Veena CK, Varalakshmi P (2008) Antiurolithic effect of lupeol and lupeol linoleate in experimental hyperoxaluria. J Nat Prod 71:1509–1512

    Article  CAS  PubMed  Google Scholar 

  125. Sudharsan PT, Mythili Y, Selvakumar E, Varalakshmi P (2005) Cardioprotective effect of pentacyclic triterpene, lupeol and its ester on cyclophosphamide-induced oxidative stress. Hum Exp Toxicol 24:313–318

    Article  CAS  PubMed  Google Scholar 

  126. Sudharsan PT, Mythili Y, Selvakumar E, Varalakshmi P (2006) Lupeol and its ester ameliorate the cyclophosphamide provoked cardiac lysosomal damage studied in rat. Mol Cell Biochem 282:23–29

    Article  CAS  PubMed  Google Scholar 

  127. Sudharsan PT, Mythili Y, Selvakumar E, Varalakshmi P (2006) Lupeol and its ester exhibit protective role against cyclophosphamide-induced cardiac mitochondrial toxicity. J Cardiovasc Pharmacol 47:205–210

    Article  CAS  PubMed  Google Scholar 

  128. Sultana N, Saify ZS (2012) Naturally occurring and synthetic agents as potential anti-inflammatory and immunomodulants. Antiinflammatory Antiallergy Agents Med Chem 11:3–19

    Article  CAS  Google Scholar 

  129. Sultana S, Saleem M, Sharma S, Khan N (2003) Lupeol, a triterpene, prevents free radical mediated macromolecular damage and alleviates benzoyl peroxide induced biochemical alterations in murine skin. Indian J Exp Biol 41:827–831

    CAS  PubMed  Google Scholar 

  130. Sunitha S, Nagaraj M, Varalakshmi P (2001) Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats. Fitoterapia 72:516–523

    Article  CAS  PubMed  Google Scholar 

  131. Surendra K, Corey EJ (2009) A short enantioselective total synthesis of the fundamental pentacyclic triterpene lupeol. J Am Chem Soc 131:13928–13929

    Article  CAS  PubMed  Google Scholar 

  132. Suzuki M, Ikekawa N (1966) Studies on the sterol of Bombyx mori. V. Lupeol in silkworm blood. Chem Pharm Bull (Tokyo) 14:1049–1051

    Article  CAS  Google Scholar 

  133. Tarapore RS, Siddiqui IA, Adhami VM, Spiegelman VS, Mukhtar H (2013) The dietary terpene lupeol targets colorectal cancer cells with constitutively active Wnt/β-catenin signaling. Mol Nutr Food Res 57:1950–1958

    Article  CAS  PubMed  Google Scholar 

  134. Tarapore RS, Siddiqui IA, Saleem M, Adhami VM, Spiegelman VS, Mukhtar H (2010) Specific targeting of Wnt/β-catenin signaling in human melanoma cells by a dietary triterpene lupeol. Carcinogenesis 31:1844–1853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Thimmappa R, Geisler K, Louveau T, O’Maille P, Osbourn A (2014) Triterpene biosynthesis in plants. Annu Rev Plant Biol 65:225–257

    Article  CAS  PubMed  Google Scholar 

  136. Tomosaka H, Koshino H, Tajika T, Omata S (2001) Lupeol esters from the twig bark of Japanese pear (Pyrus serotina Rehd.) cv. Shinko. Biosci Biotechnol Biochem 65:1198–1201

    Article  CAS  PubMed  Google Scholar 

  137. Vasconcelos JF, Teixeira MM, Barbosa-Filho JM, Lucio AS, Almeida JR, de Queiroz LP, Ribeiro-Dos-Santos R, Soares MB (2008) The triterpenoid lupeol attenuates allergic airway inflammation in a murine model. Int Immunopharmacol 8:1216–1221

    Article  CAS  PubMed  Google Scholar 

  138. Vidya L, Lenin M, Varalakshmi P (2002) Evaluation of the effect of triterpenes on urinary risk factors of stone formation in pyridoxine deficient hyperoxaluric rats. Phytotherapy Res 16:514–518

    Article  CAS  Google Scholar 

  139. von Ruesten A, Feller S, Bergmann MM, Boeing H (2013) Diet and risk of chronic diseases: results from the first 8 years of follow-up in the EPIC-Potsdam study. Eur J Clin Nutr 67:412–419

    Article  Google Scholar 

  140. Wu XT, Liu JQ, Lu XT, Chen FX, Zhou ZH, Wang T, Zhu SP, Fei SJ (2013) The enhanced effect of lupeol on the destruction of gastric cancer cells by NK cells. Int Immunopharmacol 16:332–340

    Article  CAS  PubMed  Google Scholar 

  141. Xue Z, Li J, Cheng A, Yu W, Zhang Z, Kou X, Zhou F (2015) Structure identification of triterpene from the mushroom Pleurotus eryngii with inhibitory effects against breast cancer. Plant Foods Hum Nutr 70:291–296

    Article  CAS  PubMed  Google Scholar 

  142. Yasukawa K, Yu S, Yamanouchi S, Takido M, Akihisa T, Tamura T (1995) Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Phytomedicine 1:309–313

    Article  CAS  PubMed  Google Scholar 

  143. Yoder RA, Johnston JN (2005) A case study in biomimetic total synthesis: polyolefin carbocyclizations to terpenes and steroids. Chem Rev 105:4730–4756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yokoe I, Azuma K, Hata K, Mukaiyama T, Goto T, Tsuka T, Imagawa T, Itoh N, Murahata Y, Osaki T, Minami S, Okamoto Y (2015) Clinical systemic lupeol administration for canine oral malignant melanoma. Mol Clin Oncol 3:89–92

    PubMed  Google Scholar 

  145. Yokozawa T, Kim HY, Kim HJ, Okubo T, Chu DC, Juneja LR (2007) Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process. Br J Nutr 97:1187–1195

    Article  CAS  PubMed  Google Scholar 

  146. Yoon YP, Lee HJ, Lee DU, Lee SK, Hong JH, Lee CJ (2015) Effects of lupenone, lupeol, and taraxerol derived from Adenophora triphylla on the gene expression and production of airway MUC5AC mucin. Tuberc Respir Dis (Seoul) 78:210–217

    Article  Google Scholar 

  147. Yunusov MS, Komissarova NG, Belenkova NG (2006) Method for preparing betulin and lupeol from white from white-stem brich bark. Russian. RUXXE7 RU 2270202 C1 20060220: 6

    Google Scholar 

  148. Zhang L, Tu Y, He W, Peng Y, Qiu Z (2015) A novel mechanism of hepatocellular carcinoma cell apoptosis induced by lupeol via brain-derived neurotrophic factor inhibition and glycogen synthase kinase 3 beta reactivation. Eur J Pharmacol 762:55–62

    Article  CAS  PubMed  Google Scholar 

  149. Zhang L, Zhang Y, Zhang L, Yang X, Lv Z (2009) Lupeol, a dietary triterpene, inhibited growth, and induced apoptosis through down-regulation of DR3 in SMMC7721 cells. Cancer Invest 27:163–170

    Article  CAS  PubMed  Google Scholar 

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Tsai, FS., Lin, LW., Wu, CR. (2016). Lupeol and Its Role in Chronic Diseases. In: Gupta, S., Prasad, S., Aggarwal, B. (eds) Drug Discovery from Mother Nature. Advances in Experimental Medicine and Biology, vol 929. Springer, Cham. https://doi.org/10.1007/978-3-319-41342-6_7

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