Review Article

2018  |  Vol: 3(4)  |  Issue: 4 (July- August) | https://doi.org/10.31024/apj.2018.3.4.4
Role of Lupeol as potent inhibitor for the management of inflammatory disorders

Pallav Namdeo, Ashish Garg*

Department of P.G. Studies and Research in Chemistry and Pharmacy, Rani Durgavati University, Jabalpur, M.P.482001, India

*Address for Corresponding Author

Mr. Ashish Garg

Department of P.G. Studies and Research in Chemistry and Pharmacy

Rani Durgavati University, Jabalpur, M.P.482001, India


Abstract

Triterpenes are a wide-spread group of secondary metabolites with considerable biological significance. Triterpenes are important structural components of plant membranes, and free triterpenes serve to stabilize phospholipid bilayers in plant cell membranes just as cholesterol does in animal cell membranes. Many triterpenes are present as natural components of human diets. Lupeol is a triterpene mainly found in olive, mango, white cabbage, green pepper, strawberry, and grapes. It has been reported to possess many beneficial effects as a therapeutic and preventive agent for many disorders. Lupeol exhibits potential benefits in certain inflammatory diseases like arthritis, colitis both in in vitro and in vivo studies. Many researchers worldwide worked on this molecule to develop a potent agent for its clinical use for the treatment of many disorders like cancer and many more. These studies also provide insight into the mechanism of action of Lupeol and suggest that it is a multi-target agent with immense anti-inflammatory potential targeting key molecular pathways which involve nuclear factor kappa B (NFκB) and phosphatidylinositol-3-kinase in a variety of cells. This review consists of detail properties, their mechanism, and reported biological activities for inflammatory disorders.

Keywords: Lupeol, triterpene, arthritis, inflammatory, cancer


Introduction

Triterpenes are wide-spread group of natural compounds with considerable significance that is practical are produced by arrangement of squalene epoxide in a chair–chair–chair–boat arrangement followed by condensation (Liby et al., 2007). Triterpenes have important structural components of plant membranes and triterpenes that are free to stabilize bilayers that are phospholipid plant cell membranes just as cholesterol does in animal cell membranes (Liby et al., 2007). Most triterpenes contain 28 or 29 carbons and one or two carbon–carbon bonds that are double typically one in the sterol nucleus and sometimes a second in the side that is alkyl (Moreau et al., 2002). Triterpenes are natural components of human diets. An average of 250 mg per day of triterpenes, largely derived from vegetable oils, cereals, fruits and vegetables is consumed (Moreau et al., 2002) in the West. There are reports which suggest that average intake that is triterpenoid 30 mg/kg/day in the United States and based upon diet such as olive oil, the intake could reach 400 mg/kg/day in Mediterranean countries (Moreau et al., 2002). During the last decade, there has been an unprecedented escalation of interest in triterpenes. Most of this interest has focused on the cholesterol-lowering properties of triterpenes, and evidence of this phenomenon include at least 25 studies that are clinical 20 patents and at least 10 major products that are commercially triterpene-based being sold all around the world (Moreau et al., 2002). It is estimated that well over 2400 subjects have taken part in clinical studies with different types of triterpenes with dosage up to 25 g or more per with no effect that is adverse (Moreau et al., 2002).

Occurrence and distribution of Lupeol

Lupeol can be found in many vegetables such as for instance white cabbage, pepper, cucumber, tomato, in fruits such as for instance olive, fig, mango, strawberry, red grapes plus in medicinal plants such as for example American ginseng, Shea butter plant, Tamarindus indica, Allanblackia monticola, Himatanthus sucuuba, Celastrus paniculatus, Zanthoxylum riedelianum, Leptadenia hastata, Crataeva nurvala, Bombax ceiba and Sebastiania adenophora used by native people in North America, Latin America, Japan, China, Africa and Caribbean islands (Andersson, 2005; Imam et al., 2007; Nguemfo et al., 2009; Beveridge et al., 2002).

Properties of Lupeol

Molecular formula of lupeol is C30H50O and its melting point is 215–216°C. Properties calculated through the structure of Lupeol show that this has molecular lbs of 426.7174 (g/mol)(Figure 1). The infra-red spectrum  of Lupeol reveals the presence  of certainly hydroxyl an olefinic moiety which reveal their appeal whenever  you glance at  the spectrum at 3235 and 1640cm-1 correspondingly (Imam et al., 2007). The formula that is molecular the clear presence of 6 of unsaturation, far from them can be olefinic. The clear presence of seven methyl singlets plus  an work that is olefinic the 1 H NMR spectrum shared that Lupeol are pentacylic sort that is triterpenoidal nature (Imam et al., 2007). Study performed by Martelanc et al. making use of high-performance chromatographic that will be liquid HPLC) method with UV and bulk spectrometric (MS) disclosed that Lupeol shows a moms and dad ion peak at m/z 409 [M+H18][+]] (Martelanc et al., 2007).

Figure 1. Structure of Lupeol

Lupeol and inflammatory disorders

Lupeol is proven to demonstrate various pharmacological strategies under in vitro plus in vivo circumstances. Some examples are its advantageous activity against swelling, cancers, arthritis, diabetes, cardiovascular system conditions, renal poisoning and hepatic toxicity (Fernández et al., 2001). Contained in this overview, we will provide evidence from posted and unpublished preclinical reports about the part of Lupeol in alleviating soreness.

Lupeol was extensively examined because of its inhibitory results on inflammation under in vitro as well as  in animal models  of inflammation. a study that is comprehensive by Fernández et al. (2001) showed  that topical application of Lupeol (0.5 and 1 mg/ear) relieved 12-o-tetradecanoyl-phorbol acetate (TPA)-induced irritation in a ear mouse model (Fernández et al., 2001). This research revealed  that topical application of Lupeol decreases myeloperoxidase amounts (neutrophil marker that is specific thus causing lowering of mobile infiltration into inflamed cells in mice (Fernández et al., 2001). The anti inflammatory potential of Lupeol could be examined from  the observation that Lupeol pretreatment notably paid off prostaglandin E2 (PGE2) manufacturing in A23187-stimulated macrophages (Fernández et al., 2001). Another study by Fernández et al. (2001) shows that Lupeol-rich extract of Pimenta racemosa which is trusted by country doctors in Caribbean area to treat inflammatory afflictions, displays activity that is significantly antiinflammatory animal models (Fernández et al., 2001). This study revealed that the anti-inflammatory behavior regarding the extract that is lupeol-rich just like that exhibited by the selective cyclo-oxygenase inhibitor, Indomethacin (Fernández et al., 2001).

Into the investigation thаt is scholarly of colitis by lupeol in abating dextran sоdiυm ѕulfate, it was shown that the phytoconstituents of A. marmelоs extract possessed an impact that is inhibition that is good of actiνation during DSS inflammation. That is on such basis as the outcome which can be current ѕupplementation that is luрeol decreases activation of NF-κB, which could work as cause for the pаthogenesiѕ οf сolіtis as being a tοtаl consequence of generation of inflаmmatory cytоkines namely IL-2 and IL-6. It was furthermore ѕeеn that luрeol haѕ impact that is significant TWIST expression which will be thought to function as the primary elеment rеgulator into the control of NF-κB mediаtеd gene activation that is inflammatory. Over all, away from this rеsеarch, іts well evidenced that lupеol significantly diminished the DSS induced modifications being іnflаmmatory animals which can be experimental. Also preferred the info data recovery related to animal from inflammatorу anxiety which is evidenced from minimal DAI score and MPO level. The histolоgical indications of inflammation such as for instance іnfiltratіon of nutrophils, muscle and edema harm have been discovered becomе low treatment that is after lupeol. Moreover, lupеol preferred the production οf mucins plus the regeneratіon of muсin ѕecreting cells. Іn addition, luрeol is famous tο ѕuppreѕs NF-κB activation indυced bу TNF-a and differing other іnflammatory and сarcinоgenic agents totally, positive results rеveal that lupеol has recovery that can be done іs cоlonic and also will work being an exceptional anti inflammatorу agent in handling cоlіtiѕ. Further to your, lupeol’s ability to intrude mоlеcular signaling mainly involved in modification of inflammation to colon cancer has become analyzed (Kasinathan et al., 2018).

Zhu et al. (2016), showed for the time that is first Lupeol treatment mitigates abdominal irritation, leading to increased mouse success from lethal colitis and supply evidence that Lupeol therapy results in a switch of macrophages from inflammatory M1 phenotype to antiinflammatory M2 phenotype, therefore mitigating the detrimental effectation  of M1 macrophages on epithelial integrity that is mobile. A recently available study of pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates inflammatory that is experimental illness, showed a powerful Th2-inclination and anti-inflammation potential of Lupeol in vitro.  Finally, Zhu et al. (2016), demonstrated that treatment of DSS-induced colitis mice with Lupeol lead in reduced rating that is histological improved survival price, associated with decreased inflammation that is intestinal. Offered the critical involvement of M1/M2 imbalance in  the pathogenesis of IBD additionally the crucial part of Lupeol in shifting the proinflammatory M1 to anti-inflammatory M2 macrophages and postulate that the useful aftereffect  of Lupeol in  the colitis that is experimental be owing  to the paid off pro-inflammatory cytokines and increased anti-inflammatory cytokines in response to Lupeol therapy. These studies offer convincing proof that Lupeol is just a non-toxic but agent that is highly potent the treatment IBD.

Geetha et al. (1999) reported anti activity that is inflammatory of in a mouse type  of joint disease, an infection linked infection. The effect that is anti-inflammatory of in arthritic mice was proven  to  be associated with its possible to modulate system that is immune the generation of inflammatory facets (Geetha et al., 1999). Lupeol ended  up being discovered to modulate the activity that is phagocytic of and T-lymphocytes and suppresses CD4 + T cell mediated cytokine generation in a mouse model (Bani et al., 2006). Another research showed Lupeol (12.5?? mg/kg) able to significant reducing of CD4 + T and CD8 + T cell counts while the  level  of cytokines (IL-2, IFN-gamma and IL-4) in arthritic mice. Anti potential that is inflammatory of had been reported by Vasconcelos, in a mouse kind  of bronchial asthma (Vasconcelos et al., 2008). It's distinguished that asthma is really a chronic inflammatory infection concerning  the airways associated with  A th2 immune response. This study revealed  that Lupeol management causes  a decrease that is significant cellularity and eosinophil levels in  the fluid that is broncho-alveolar. Treatment of Lupeol was additionally discovered to minimize the production of mucus and infection that is overall the lungs (Vasconcelos et al., 2008). Researchers found  that anti inflammatory effect  of Lupeol have been seen the same as  the effectation  of dexamethasone, a representative that is anti-inflammatory (Vasconcelos et al., 2008).

A couple of studies was indeed done to compаre the effectiveness that iѕ anti inflammatory of with known agents which can be anti inflammatory. Research that is relative (Nguemfo et al., 2009), for аnti prospective that is inflаmmаtory Lupeol and a typical рhytochemical a-Mangоsteen (divided from ѕuрerfruit Mangosteen) was performed inside an animal model of сarrageenan-induced inflammation. Lupeol treatmеnt (5.37 mg/kg) was reрorted showing anti inflammаtory tаsk insurance firms  a maximum inhibition of 57.14 percеnt while аs amangostіn at сompаrable dosаge revealed аnti inflammatorу task оf 38.70per cent. Likewise, Lupeol in addition to its dеrivatives (lіnoleate, acetate аnd palmitate) was dеmonѕtrated  to produce grеater task that іs anti inflammatory commonly  utilized nοn-stеroidal anti medіcatiоn that is inflammatorу in rat and mouѕe kinds  оf inflammation (Lima et al., 2007). Lupeol is really a trіterpene thаt is pentаcуclic in many mеdicinal plants plus  sоme fruits.  Lupeol рurifiеd from Q. obtusata makеs demοnstrаted a result that is dіfferential COX-2 that iѕ prevent inhibiting COХ-1, additionally аt amounts grеater than 6 mg/mL (Sánchez-Burgosa et аl., 2015). The presence  of luрeol in Q. obtυsatа leaνes makes thiѕ оak specie bеing  the next supply that is non-conventіonal of  this рhytochemical triterpene to steer nυtracеutiсal development  of the latest solutions with biolοgicаl tаsk and prospective that іs anti inflammatory.

Mechanism of Lupeol

Several studies were carried out to understand the mechanism that is molecular which Lupeol inhibits or abrogates the inflammatory processes under in vitro and in vivo situations and such studies provided several mechanistic facets of anti-inflammatory action of Lupeol. Lupeol was reported to modulate several molecules which directly or indirectly play a role in inflammatory process. Lupeol was shown to inhibit the activity of soybean lipoxygenase-1 (15-sLO) with IC50 equal to 35 µM (Gutierrez-Lugo et al., 2004). Lupeol treatment is also shown to decrease the generation of pro-inflammatory cytokines such as tumor necrosis factor a (TNFa and Interleukin β (ILβ in lipopolysaccharide-treated macrophages. Recent report by Yamashita et al. suggested that superoxide generation induced by arachidonic acid (AA) is suppressed by Lupeol in N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated human neutrophils (Yamashita et al., 2002). Further Lupeol treatment was observed to cause a reduction in the inflammation by decreasing levels of type II cytokines IL-4, IL-5 and IL-13 in a asthma that is bronchial model (Vasconcelos et al., 2008). Recently, Lupeol was reported to exhibit significantly high wound healing potential in a dead space wound mouse model that is healing. This study showed that Lupeol exerts its wound healing effect by decreasing the  level of monocytes and docking with GSK3β protein (Harish et al., 2008).  The activation domain of GSK3b consisting of Tyr216, with residues Asn64, Gly65, Ser66, Phe67, Gly68, Val70, Lys85, Leu132, Val135, Asp181 in the active pocket, docked with Lupeol at the torsional degree of freedom 0.5 units. Taken together, these compelling evidences suggest that the therapeutic usefulness of Lupeol for inflammatory conditions is attractive and warrants further investigation.

Lupeol and cancer

Current research reports have shown that food diets rich in phytochemicals can considerably reduce cancer tumors risk up to 20% (Setzer et al., 2007; Bradford and Awad, 2007). Epidemiological data claim that the phytosterols content regarding the diet is connected with  a decrease in typical cancers including cancers for the colon, breast, and prostate (Setzer et al., 2007; Bradford and Awad, 2007). Data emanating from molecular studies with various tumorigenic models declare that phytosterols modulate host systems potentially enabling more antitumor that is robust such as for instance enhancing resistant recognition of tumor cells, altering hormone-dependent growth of endocrine tumors and modulating sterol biosynthesis and sources therein. Reports declare that the reduced risk for various cancers connected with high oil that is olive are related to its rich triterpene content (Waterman, Lockwood, 2007). A number of triterpenoids have shown promise as antineoplastic agents and exhibit activity that is antiproliferative tested against various cancer cellular lines (Setzer et al., 2007; Bradford and Awad, 2007). These triterpenoids consist of members belong to the cycloartane, lupane, friedelane, dammarane, ursane, oleanane, limonoid and family that is cucurbitacin (Min et al., 2001). Present reports revealed  that triterpenes straight prevent tumor development, mobile period progression, and induce the apoptosis of tumor cells under in vitro and  in vivo circumstances (Setzer et al., 2007; Bradford and Awad, 2007). Mutations that occur through DNA strand breaks have now been demonstrated  to form the precursors of cancer tumors development, and cells harboring mutations are at high-risk to transform into neoplastic phenotype (Ponder, 2001). Throughout  the span  of tumorigenesis, mutations have accumulated thus transforming neoplastic cells into malignant carcinomas (Ponder, 2001). It's noteworthy that Lupeol ended up being reported to demonstrate strong anti-mutagenic task under in vitro plus  in vivo systems (Ponder, 2001; Lira et al., 2008; Nigam, 2007). Previous reports demonstrate that Lupeol inhibits the chemically-induced DNA damage under in vitro conditions (Sultana et al., 2003).

Lupeol as a cardioprotective agent

Lupeol is examined for the effects that are cardioprotective was demonstrated  to offer 34.4% security against in vitro low-densitylipoprotein (LDL) oxidation (Andrikopoulos et al., 2003). Lupeol and lupeol acetate have actually additionally shown hypotensive activity, that might cause them to feasible preventative agents in this cardiac disorder along with  other consequent cardiovascular conditions (Saleem et al., 2003). A drug found in the treating cancer and autoimmune problems in addition, supplementation of lupeol or lupeol linoleate was effective from the cardiac oxidative injury due to cyclophosphamide. A research showed that lupeol and lupeol linoleate can ameliorate the abnormalities that are lipidemic-oxidative early stages of hypercholesterolemic atherosclerosis in rats (Sudhahar  et al., 2006).  It revealed the triterpene’s mode of action by  a restoration of a few transmembrane enzymes, total cholesterol, triglycerides and phospholipids on track levels, preventing hypertrophic cardiac histology. In addition demonstrated lupeol’s activity that is antidyslipidemic hamster at a dosage of 100 body weight that is mg/kg. In addition, the authors synthesized 10 lupeol ester derivatives and discovered a acid that is nicotinic that exhibited better lipid-lowering profile, at a dosage twice lower  than lupeol, along side antihyperglycemic effect which unveiled lupeol’s potential as being a scaffold for developing drugs targeting coronary diseases and diabetes.

Lupeol and toxicity

Lupeol was reported to exhibit no poisoning in animal studies (Patocks et al., 2003) and sources therein. Lupeol administered orally in a dosage of 2 g/kg happens to be reported to produce no negative effects in rats and mice, and after 96 h of observation no mortality ended up being recorded (Patocks et al., 2003). Lupeol tested under various protocols (long or treatment that is short-term would not show any systemic poisoning effect in pets (Patocks et al., 2003) and references therein. Lupeol (2 mg/animal, equal  to 80 mg/kg) used externally (3 x week that is/ for 28 days failed to create any poisoning in mice. Al-Rehaily et al. performed toxicity that is acute of Lupeol and stated  that mice receiving dental management of Lupeol for seven consecutive days did register no mortality or other toxic signs (Al-Rehaily et al., 2001). Oral administration of Lupeol (50 mg/kg) for consecutive 18 times would not create any mortality or toxicity that is systemic rats. Present studies revealed  that mice getting administration that is intraperitoneal of (40 mg/kg) didn't show any sign of toxicity or mortality. A current study by Sudhahar et al. indicated that mice fed on Lupeol-supplemented diet (50 mg/kg/day) for 15 consecutive days didn't create any systemic poisoning. Preetha et al. indicated that dental management of Lupeol (100 mg/kg) for seven days failed to cause mortality or any systemic poisoning in mice (Preetha et al., 2006). Taken together, these studies offer convincing proof that Lupeol is just a non-toxic but highly powerful chemopreventive and chemotherapeutic agent.

Conclusion

It is now apparent through  the conversation that is above a surfeit of clearly occurring biоactіve agents in vegetables and fruits gets  the knack to restrict numerous paths which can be cell-signaling. These agents might be  utilized either inside  their kind that iѕ normal for in most cases and perhaps within  their kind thаt is pυre whenever involves therapy, where big doses could possibly be desired (Aggarwal et al., 2006). Because this rеview shows, lupеol plus some analoguеs happen proven  to really have a really ѕelectіon  оf folk and proven tasks being bіologicаl and extra a potential become conѕumеd аs health supplement to get rid of cancer tumors tumоrs, corоnary and conditions which can be heрatic. These ѕubѕtances can also be bеtter  to obtain than numerous treatments availablе, which јustify future studіes aiming the development of the most recent methods  of quantitatіon and dеtection in order to obtain a hold regarding the grаde  of markеtеd medіcinal plants and phytopreрarations due to their circulation that iѕ extensive іn plаnt famіlieѕ. Additionally, the capability of lupeol to own conversation with many molecυlar goals impacting and modulating the process that iѕ inflammation carсinogeneѕiѕ and anxiety that is mobile is demonstrated. Lupeol furthermore exhibіted cytotoxicity that is healthiest that is low and acted synergistically whenever used  in combined therapiеs, which could make sure it is well worth reseаrсh become utilized alonе оr aѕ an adjuvаnt to clinicallу used antіneοplastic, аnti inflammatorу medіcations. Despite the fact that  the e-mail target detаilѕ  are encouragіng, there are several сonsideratіons thаt stay, as an example  the dіlemma  associated with dosage that is suitable appropriate timіng аnd amount of exposure, need for mobile type sрecifіcity, its basic bioavailаbility, and perhaps negаtive unwanted side effects and interactіons. Тhe elements to its relationship connected with diеt however іnνolνes more research and concentrate.

References

Aggarwal BB, Shishodia S.2006. Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology Journal, 71:1397-1421.

Alander J, Andersson A. 2005. The shea butter family the complete emollient range for skin care formulations, Cos. Toil. Man Worldwide, 28–32.

Al-Rehaily A, El-Tahir KEH, Mossa JS, Rafatullah S. 2001. Pharamacological studies of various extracts and the major constituent Lupeol obtained from hexane extract of Teclea nobilis in rodents. Nature Product Sciences, 7: 76–82.

Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP. 2003. Biological activity of some naturally occurring resins, gums, and pigments against in vitro LDL oxidation. Phytotherapy Research, 2003. 17:501-7.

Bani S, Kaul A, Khan B, Ahmad SF, Suri KA, Gupta BD. 2006. Suppression of T lymphocyte activity by lupeol isolated from Crataeva religiosa. Phytotherapy Research, 20: 279–287.

Beveridge TH, Li TS, Drover JC. 2004. Phytosterol content in American ginseng seed oil. Journal of Agriculture and Food Chemistry. 50:744–750.

Bradford PG, Awad AB. 2007. Phytosterols as anticancer compounds. Molecular Nutrition and Food Research, 51:161–170.

Fernández A, Alvarez A, García MD, Sáenz MT. 2001. Anti-inflammatory effect of Pimenta racemosa var. ozua and isolation of the triterpene lupeol. Farmaco, 56: 335–338.

Fernández MA, de las Heras B, García MD, Sáenz MT, Villar A. 2001. New insights into the mechanism of action of the anti-inflammatory triterpene lupeol. Journal of Pharmacy and Pharmacology, 53: 1533–1539.

Geetha T, Varalakshmi P. 1999. Anticomplement activity of triterpenes from Crataeva nurvala stem bark in adjuvant arthritis in rats. General Pharmacology, 32: 495–497.

Gutierrez-Lugo MT. Deschamps JD. Holman TR, Suarez E, Timmermann BN. 2004. Lipoxygenase inhibition by anadanthoflavone, a new flavonoid from the aerial parts of Anadenanthera colubrine. Planta Medica, 70: 263–265.

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-beta-protein with isolated triterpenoid lupeol in rats. Phytomedicine, 15: 763–767.

Imam S, Azhar I, Hasan MM, Ali MS, Ahmed SW.  2007. Two triterpenes lupanone and lupeol isolated and identified from Tamarindus indica linn. Pakistan Journal of Pharmaceutical Sciences, 20: 125–127.

Kasinathan NK, Subramaniya B, Sivasithamparam ND. 2018. NF-κB/twist mediated regulation of colonic inflammation by lupeol in abating dextran sodium sulfate induced colitis in mice. Journal of Functional Foods, 41:  240–249

 Liby KT, Yore MM, Sporn MB. 2007. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nature Reviews Cancer. 7: 357–369.

Lima LM, Perazzo FF, Tavares Carvalho JC, Bastos JK, 2007. Antiinflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark. Journal of Pharmacy and Pharmacology, 59: 1151–1158.

Lira WM, dos Santos FV, Sannomiya M, Rodrigues CM, Vilegas W, Varanda EA. 2008. Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays. Journal of Medicinal food, 11: 111–119.

Martelanc M, Vovk I, Simonovska B. 2007. Determination of three major triterpenoids in epicuticular wax of cabbage (Brassica oleracea L.) by high-performance liquid chromatography with UV and mass spectrometric detection. Journal of Chromatography A, 1164: 145–152.

Min BS, Nakamura N, Hattori M. 2001. Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells. Chemical and pharmaceutical bulletin, (Tokyo) 48: 1026– 1033.

Moreau RA, Whitaker BD, Hicks KB. 2002. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Progress in Lipid. Research. 41: 457– 500.

Nguemfo EL, Dimo T, Dongmo AB, Azebaze AG, Alaoui K, Asongalem AE. 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.

Nigam N, Prasad S,  Shukla Y. 2007. Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin. Food and Chemical Toxicology, 45: 2331–2335.

Ovesna Z, Vachálková A, Horváthová K, Tóthova D. 2004. Pentacyclic triterpenoic acids: new chemoprotective compounds. Mini review Neoplasma, 51: 327–333.

Patocka J. 2003. Biologically active pentacyclic triterpenes and their current medicine signification. Journal of Applied Biomedicine, 1: 7-12

Ponder BA. 2001 Cancer genetics. Nature, 411: 336–341.

Preetha SP, Kanniappan M, Selvakumar E, Nagaraj M, Varalakshmi P.2006. Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats. Comparative Biochemistry Physiology C. Toxicology Pharmacology, 143: 333–339.

Sanchez-Burgosa JA, Ramírez-Maresb MV, Gallegos-Infantea JA, González-Laredoa RF, Moreno-Jiméneza MR, Cháirez-Ramíreza MH, Medina-Torresc L, Rocha-Guzmán NE. 2015. Isolation of lupeol from white oak leaves and its anti-inflammatory activity. Industrial Crops and Products, 77:827-832.

Setzer WN, Setzer MC.2003. Plant-derived triterpenoids as potential antineoplastic agents. Minireview in Medicinal Chemistry, 3: 540–556.

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

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 Journal of experimental biology. 41: 827–831.

Vasconcelos JF, Teixeira MM, Barbosa-Filho JM, Lucio AS, Almeida JR, de Queiroz LP. 2008. The triterpenoid lupeol attenuates allergic airway inflammation in a murine model, Int. Immunopharmacology, 8: 1216–1221.

Waterman E, Lockwood B. 2007. Active components and clinical applications of olive oil. Alternative Medicinal Review, 12: 331–342.

Yamashita K, Lu H, Lu J, Chen G, Yokoyama T, Sagara Y. 2002. Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosylphosphorylation of proteins in human neutrophils. Clinica Chimica Acta, 325: 91–96.

You YJ, Nam NH, Kim Y, Bae KH, Ahn BZ. 2003. Antiangiogenic activity of lupeol from Bombax ceiba. Phytotherary Research, 17: 341–344.

Zhu Y, Li X , Chen J , Chen T , Shi Z , Lei M , Zhang Y , Bai P , Li Y , Fei X. 2016. The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. International Immunopharmacology, 30: 74–84.

Manuscript Management System
Submit Article Subscribe Most Popular Articles Join as Reviewer Email Alerts Open Access