Login Register Cart 0
Generic placeholder image

Current Indian Science

Editor-in-Chief

ISSN (Print): 2210-299X
ISSN (Online): 2210-3007

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Promising Anticancer Stand-ins of Phyllanthus Species

Author(s): Simran, Vani, Priyanka Kriplani* and Kumar Guarve

Volume 1, 2023

Published on: 14 September, 2023

Article ID: e060923220756 Pages: 12

DOI: 10.2174/2210299X01666230906092220

open_access

Open Access Journals Promotions 2
Abstract

Background: Phyllanthus species plants along with their active constituent phyllanthin, are the most widely used plants to cure various diseases. Present studies indicate their applicability as anti-diabetic, anti-malarial, antiplasmodial, anti-viral, anti-inflammatory, antibacterial, antioxidant, antineoplastic, diuretic, nephroprotective, hypolipidemic, and hepatoprotective properties.

Objective: The objective of the present review is to study the recent literature and patents, including the various methods of extraction and isolation of phyllanthin along with its pharmacokinetics and clinical trials and mainly focussing on their anticancer potential along with a brief on other pharmacological activities.

Methods: Recent prose and patents focussing on the anticancer potential of mainly P. amarus and P. niruri have been highlighted with special emphasis on scientific novelty and impact.

Results: Both P.amarus and P.niruri displayed good anticancer potential in multiple tumors and synergistic effects when combined with other anticancer drugs. Ne isolation/extraction methods, clinical trials, and pharmacokinetic studies have been discussed.

Conclusion: The anticancer potential of P.amarus and P.niruri has opened new avenues for further research. Clinical trials are the need of the hour to validate and confirm the tumor-suppressing properties of both plants.

Keywords: Anticancer, Clinical trials, Phyllanthus species, P. amarus, P. niruri, Phyllanthin.

[1]
Sibiya, A.M.; Ramya, A.K.; Vaseeharan, B. Bioactive molecules from phyllanthus niruri and investigating their effects against diabetes. MedDocs eBooks., 2020, 1-7.
[2]
National herbal medicine is writing the group volumeNational herbal medicine compilation; People's Health Publisher: Beijing, 1978, First Volume, p. 263.
[3]
Li, P.T. A revision of Chinese phyllanthus (Euphorbiaceae). J. Syst. Evol., 1987, 25(5), 371-383.
[4]
Mao, X.; Wu, L.F.; Guo, H.L.; Chen, W.J.; Cui, Y.P.; Qi, Q.; Li, S.; Liang, W.Y.; Yang, G.H.; Shao, Y.Y.; Zhu, D.; She, G.M.; You, Y.; Zhang, L.Z. The genus phyllanthus: An ethnopharmacological, phytochemical, and pharmacological review. Evid. Based Complement. Alternat. Med., 2016, 2016, 1-36.
[http://dx.doi.org/10.1155/2016/7584952] [PMID: 27200104]
[5]
Bagalkotkar, G.; Sagineedu, S.R.; Saad, M.S.; Stanslas, J. Phytochemicals from phyllanthus niruri Linn. and their pharmacological properties: A review. J. Pharm. Pharmacol., 2010, 58(12), 1559-1570.
[http://dx.doi.org/10.1211/jpp.58.12.0001] [PMID: 17331318]
[6]
Basavaraju, M.; Gunashree, B. S.; Bagalkotkar, G. phyllanthus niruri L: A holistic medicinal plant with modern therapeutics; Scientist R Academy, 2022, 1, p. 12.
[7]
Patel, J.R.; Tripathi, P.; Sharma, V.; Chauhan, N.S.; Dixit, V.K. phyllanthus amarus: Ethnomedicinal uses, phytochemistry and pharmacology: A review. J. Ethnopharmacol., 2011, 138(2), 286-313.
[http://dx.doi.org/10.1016/j.jep.2011.09.040] [PMID: 21982793]
[8]
Sharma, A.; Singh, R.T.; Handa, S.S. Estimation of phyllanthin and hypophyllanthin by high performance liquid chromatography inphyllanthus amarus.. Phytochem. Anal., 1993, 4(5), 226-229.
[http://dx.doi.org/10.1002/pca.2800040507]
[9]
Yanyun, C.; Yirao, Z.; Guanghui, K.N. phyllanthus embical fruit tablet and preparation method thereof. CN105166883B, 2019.
[10]
Yadav, N.P.; Pal, A.; Shanker, K.; Bawankule, D.U.; Gupta, A.K.; Darokar, M.P.; S Khanuja, S.P. Synergistic effect of silymarin and standardized extract of phyllanthus amarus against CCl4-induced hepatotoxicity in Rattus norvegicus. Phytomedicine., 2008, 15(12), 1053-1061.
[http://dx.doi.org/10.1016/j.phymed.2008.08.002] [PMID: 18848770]
[11]
Syamasundar, K.V.; Singh, B.; Singh Thakur, R.; Husain, A.; Yoshinobu, K.; Hiroshi, H. Antihepatotoxic principles of phyllanthus niruri herbs. J. Ethnopharmacol., 1985, 14(1), 41-44.
[http://dx.doi.org/10.1016/0378-8741(85)90026-1] [PMID: 4087921]
[12]
Baskaran, M.A.; Periyasamy, L.A.; Rajagopalan, R.U. Effect of phyllanthus niruri on alcohol and polyunsaturated fatty acid induced oxidative stress in Liver. Int. J. Pharm. Pharm. Sci., 2010, 2(4), 58-62.
[13]
Suresh, V.; Sojan, J.; Krishna Radhika, N.; Asha, V.V. Anti-HBV activity of the different extracts from phyllanthus rheedei wight in cell culture based assay systems. J. Ethnopharmacol., 2014, 156, 309-315.
[http://dx.doi.org/10.1016/j.jep.2014.08.028] [PMID: 25219604]
[14]
Krithika, R.; Jyothilakshmi, V.; Verma, R.J. Phyllanthin inhibits CCl 4 -mediated oxidative stress and hepatic fibrosis by down-regulating TNF-α/NF-κB, and pro-fibrotic factor TGF-β1 mediating inflammatory signaling. Toxicol. Ind. Health., 2016, 32(5), 953-960.
[http://dx.doi.org/10.1177/0748233714532996] [PMID: 24817434]
[15]
Pradit, W.; Chomdej, S.; Nganvongpanit, K.; Ongchai, S. Chondroprotective potential of phyllanthus amarus Schum. & Thonn. in experimentally induced cartilage degradation in the explants culture model. In Vitro Cell. Dev. Biol. Anim., 2015, 51(4), 336-344.
[http://dx.doi.org/10.1007/s11626-014-9846-y] [PMID: 25515248]
[16]
Ilangkovan, M.; Jantan, I.; Bukhari, S.N.A. Phyllanthin from phyllanthus amarus inhibits cellular and humoral immune responses in Balb/C mice. Phytomedicine., 2016, 23(12), 1441-1450.
[http://dx.doi.org/10.1016/j.phymed.2016.08.002] [PMID: 27765364]
[17]
Murugaiyah, V.; Chan, K.L. Mechanisms of antihyperuricemic effect of phyllanthus niruri and its lignan constituents. J. Ethnopharmacol., 2009, 124(2), 233-239.
[http://dx.doi.org/10.1016/j.jep.2009.04.026] [PMID: 19397979]
[18]
Gowrishanker, B.; Vivekanandan, O.S. In vivo studies of a crude extract of phyllanthus amarus L. in modifying the genotoxicity induced in Vicia faba L. by tannery effluents. Mutat Res., 1994, 322(3), 185-192.
[http://dx.doi.org/10.1016/0165-1218(94)90005-1] [PMID: 7521518]
[19]
Meselhy, M.R.; Abdel-Sattar, O.E.; El-Mekkawy, S.; EL-Desoky, A.M.; Mohamed, S.O.; Mohsen, S.M.; Abdel-Sattar, E.; El-Halawany, A. Preparation of Lignan-Rich Extract from the Aerial Parts of phyllanthus niruri Using Nonconventional Methods. Molecules., 2020, 25(5), 1179.
[http://dx.doi.org/10.3390/molecules25051179] [PMID: 32151037]
[20]
Murugaiyah, V.; Chan, K.L. Determination of four lignans in phyllanthus niruri L. by a simple high-performance liquid chromatography method with fluorescence detection. J. Chromatogr. A, 2007, 1154(1-2), 198-204.
[http://dx.doi.org/10.1016/j.chroma.2007.03.079] [PMID: 17418855]
[21]
Thakur, I.; Bigoniya, P. Radioprotective and free radicals scavenging activity of phyllanthin: Isolated from phyllanthus niruri.. Int. J. Pharm. Biol. Sci., 2014, 4, 1-10.
[22]
Row, L.R.; Srinivasulu, C.; Smith, M.; Rao, G.S.R.S. Crystalline constituents of euphorbiaceae—V. Tetrahedron., 1966, 22(8), 2899-2908.
[http://dx.doi.org/10.1016/S0040-4020(01)99083-0]
[23]
Liquon, R. Method for separating and purifying phyllanthin from common leaf flower herb. CN101898940A, 2010.
[24]
Zhenguo, Z.; Xuejian, L.; Mingjiao, D. Phyllanthus emblica leaf or fruit anticancer Chinese medicine and preparation method and use thereof. CN101391961A, 2009.
[25]
Tang, Y.Q.; Jaganath, I.B.; Sekaran, S.D. phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis. PLoS One., 2010, 5(9), e12644.
[http://dx.doi.org/10.1371/journal.pone.0012644] [PMID: 20838625]
[26]
de Araújo Júnior, R.F.; de Souza, T.P.; Pires, J.G.L.; Soares, L.A.L.; de Araújo, A.A.; Petrovick, P.R.; Mâcedo, H.D.O.; de Sá Leitão Oliveira, A.L.C.; Guerra, G.C.B. A dry extract of phyllanthus niruri protects normal cells and induces apoptosis in human liver carcinoma cells. Exp. Biol. Med., 2012, 237(11), 1281-1288.
[http://dx.doi.org/10.1258/ebm.2012.012130] [PMID: 23239439]
[27]
Tang, Y.Q.; Jaganath, I.; Manikam, R.; Sekaran, S.D. Phyllanthus Suppresses Prostate Cancer Cell, PC-3, Proliferation and Induces Apoptosis through Multiple Signalling Pathways (MAPKs, PI3K/Akt, NFκB, and Hypoxia). Evid. Based Complement. Alternat. Med., 2013, 2013, 1-13.
[http://dx.doi.org/10.1155/2013/609581] [PMID: 23690850]
[28]
Tang, Y.Q.; Jaganath, I.B.; Manikam, R.; Sekaran, S.D. Inhibition of MAPKs, Myc/Max, NFκB, and hypoxia pathways by phyllanthus prevents proliferation, metastasis and angiogenesis in human melanoma (MeWo) cancer cell line. Int. J. Med. Sci., 2014, 11(6), 564-577.
[http://dx.doi.org/10.7150/ijms.7704] [PMID: 24782645]
[29]
Lee, S.H.; Jaganath, I.B.; Atiya, N.; Manikam, R.; Sekaran, S.D. Suppression of ERK1/2 and hypoxia pathways by four phyllanthus species inhibits metastasis of human breast cancer cells. J. Food Drug. Anal., 2016, 24(4), 855-865.
[http://dx.doi.org/10.1016/j.jfda.2016.03.010] [PMID: 28911625]
[30]
Jose, J.; Sudhakaran, S.; Kumar, S.; Jayaraman, S.; Variyar, E.J. A comparative evaluation of anticancer activities of flavonoids isolated from mimosa pudica, aloe vera and phyllanthus niruri against human breast carcinoma cell line (Mcf-7) using mtt assay. Int. J. Pharm. Pharm. Sci., 2014, 6(2), 319-322.
[31]
Hermansyah, D.; Putra, A.; Munir, D.; Lelo, A.; Amalina, N.D.; Alif, I. Synergistic effect of Curcuma longa extract in combination with Phyllanthus niruri extract in regulating Annexin A2, epidermal growth factor receptor, matrix metalloproteinases, and pyruvate kinase M1/2 signaling pathway on breast cancer stem cell. Open Access Maced. J. Med. Sci., 2021, 9(A), 271-285.
[32]
Parvathaneni, M.; Battu, G.R.; Gray, A.I.; Gummalla, P. Investigation of anticancer potential of hypophyllanthin and phyllanthin against breast cancer by in vitro and in vivo methods. Asian Pac. J. Trop. Dis., 2014, 4, S71-S76.
[http://dx.doi.org/10.1016/S2222-1808(14)60417-5]
[33]
Guo, J.; Jiang, Z.; Liu, B; Wang, C; Zhang, W. Synergistic combination of a Phyllanthus amarus extract and 5-fluorouracil for treatment of subjects with cancer. AU2016101447A4, 2016.
[34]
Deliang, L.; Pingkang, G.; Artemisia, C.; Zhong, C.; Hui, Y.H. Application of traditional Chinese medicine composition containing Phyllanthus urinaria, corious versicolor, salvia miltiorrhiza and lithospermum in preparation of medicine for inhibiting postoperative recurrence of liver cancer. CN114699441A, 2022.
[35]
Chunquan, L; Yicun, C; Chaosheng, C; Xiuying, C Preparation method and application of Phyllanthus emblica L. polysaccharide. CN104262504A, 2016.
[36]
Mohamed, S.I.A.; Jantan, I.; Nafiah, M.A.; Seyed, M.A.; Chan, K.M. Lignans and polyphenols of phyllanthus amarus schumach and thonn induce apoptosis in hct116 human colon cancer cells through caspases-dependent pathway. Curr. Pharm. Biotechnol., 2021, 22(2), 262-273.
[http://dx.doi.org/10.2174/1389201021666200612173029] [PMID: 32532192]
[37]
Raphael, K.R.; Kuttan, R. Inhibition of experimental gastric lesion and inflammation by phyllanthus amarus extract. J. Ethnopharmacol., 2003, 87(2-3), 193-197.
[http://dx.doi.org/10.1016/S0378-8741(03)00120-X] [PMID: 12860307]
[38]
Júnior, R.F.A.; Soares, L.A.; da Costa Porto, C.R.; de Aquino, R.G.; Guedes, H.G.; Petrovick, P.R.; de Souza, T.P.; Araújo, A.A.; Guerra, G.C. Growth inhibitory effects of phyllanthus niruri extracts in combination with cisplatin on cancer cell lines. World J. Gastroenterol., 2012, 18(31), 4162-6168.
[http://dx.doi.org/10.3748/wjg.v18.i31.4162] [PMID: 22919249]
[39]
Sayuti, M.; Riwanto, I.; Boediono, B.P.; Akbar, T.I. Anticancer Activity of phyllanthus niruri Linn Extract in Colorectal Cancer Patients: A phase II Clinical Trial. Studies, 2020, 10, 17.
[40]
Puspita, N.A.; Alhebshi, H. The effect of phyllanthus niruri L extracts on human leukemic cell proliferation and apoptosis induction. Indones. J. Pharm., 2019, 30(4), 241.
[http://dx.doi.org/10.14499/indonesianjpharm30iss4pp241]
[41]
Sharma, P.; Parmar, J.; Verma, P.; Sharma, P.; Goyal, P.K. Anti-tumor activity of phyllanthus niruri (a medicinal plant) on chemical-induced skin carcinogenesis in mice. Asian Pac. J. Cancer Prev., 2009, 10(6), 1089-1094.
[PMID: 20192590]
[42]
Unni, R.; Shah, G.; Snima, K.S.; Kamath, C.R.; Nair, S.; Lakshmanan, V.K. Enhanced delivery of phyllanthus niruri nanoparticles for prostate cancer therapy. J. of Bionanoscience., 2014, 8(2), 101-107.
[http://dx.doi.org/10.1166/jbns.2014.1204]
[43]
Kalidindi, S.R. Phyllanthus emblica and shilajit have synergistic benefits when used with chromium-containing compositions to improve endothelial function and cardiovascular health. US10183047B2, 2019.
[44]
Ying, F; Zhang, S.G; Chen, H.; Zhang, X.; Zheng, W.; Jin, H.G; Hou, L.K; Min, B.Z. Phyllanthus emblica fruit wine preparation method and Phyllanthus emblica fruit wine prepared through method. CN105462743A, 2014.
[45]
Kaur, S.; Mahmood, K.; Southall, M.D. Extracts of Phyllanthus niruri. US8075931B2, 2011.
[46]
Ott Manns, MP Inventor. use of phyllanthus constituents for treating or preventing infections caused by hepatitis b viruses. US7829124B2, 2010.
[47]
Van, N; Kiang, H.T. Fructose Phyllanthus emblica juice and production method there of. CN103519263A, 2014.
[48]
Li, X.Y.; Huang, M.; Shi, S.; Min, W.Z.; Yi, Z.; Yi, D. A kind of Phyllanthus emblica Nectar wine and preparation method thereof. CN103484293B, 2016.
[49]
Changan, P.; Weihua, W. Production method of Phyllanthus emblica and Athyrium multidentatum fruit-vegetable chewable tablets. CN106036617A, 2016.
[50]
Yang, C.G.; Changyi, P.Y.; Chuanhai, S. Low sugar beverage of Phyllanthus emblica and preparation method thereof. CN108925794A, 2018.
[51]
Dongliang, Y.Y.L.; Zongze, G. Phyllanthus emblica targeted refined substance, preparation method and application thereof in cigarettes. CN111772227B, 2022.
[52]
Lingxiao, W.; Bitao, W. kind of preparation method of Phyllanthus embical fruit sprouted unpolished rice vegetable protein dew. CN109363022A, 2019.
[53]
Wu, L.Y.; Zhengping, S.L.; Wang, L.J.; Liang, F.L.; Wenting, W. Method for preparing nano-silver composite particles from Phyllanthus emblica polysaccharide. CN107309438B, 2021.
[54]
Jun, Z. Phyllanthus emblica-containing pearl-shaped ball and processing method thereof. CN103393044A, 2013.
[55]
Kalidindi, S R Phyllanthus emblica compositions for reduction of blood glucose levels. WO2015191206A1, 2015.
[56]
Liguo, Z.; Jiaping, Z. 2014.
[57]
Cui Taomei Double Happiness Su Mei Zhou Lin Cha Yufeng Yang and Kim Li Xueqin Wang Dayuan Gao Ying. preparation method of phyllanthus emblica extract for removing freckles and whitening skin. CN108186456B, 2020.
[58]
Minghao, Z.; Jindan, Z.; Ruffa, Z. Quality control method and application of Phyllanthus urinaria capsules. CN113447598A, 2021.
[59]
Keudell, C.V.; Giessen, R.V. Use of phyllanthus component for the treatment or prophylaxis of infections triggered by flaviviridae. US20040028754A1, 2004.
[60]
Keudell, C.V. Compositions comprising Phyllanthus extract for use in the treatment or prevention of a sars-cov-2 infection and/or at least one symptom of covid-19. EP3954379A1, 2022.
[61]
Nishiura, J.L.; Campos, A.H.; Boim, M.A.; Heilberg, I.P.; Schor, N. phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients. Urol. Res., 2004, 32(5), 362-366.
[http://dx.doi.org/10.1007/s00240-004-0432-8] [PMID: 15221244]
[62]
Sarisetyaningtyas, P.V.; Hadinegoro, S.R.; Munasir, Z. Randomized controlled trial of phyllanthus niruri linn extract. Paediatr. Indones., 2016, 46(2), 77-81.
[http://dx.doi.org/10.14238/pi46.2.2006.77-81]
[63]
Dirjomuljono, M.; Kristyono, I.; Tjandrawinata, R.R.; Nofiarny, D. Symptomatic treatment of acute tonsillo-pharyngitis patients with a combination of Nigella sativa and phyllanthus niruri extract. Int. J. Clin. Pharmacol. Ther., 2008, 46(6), 295-306.
[http://dx.doi.org/10.5414/CPP46295] [PMID: 18541126]
[64]
Schuler, T.D.; Shahani, R.; Honey, R.J.D.A.; Pace, K.T. Medical expulsive therapy as an adjunct to improve shockwave lithotripsy outcomes: A systematic review and meta-analysis. J. Endourol., 2009, 23(3), 387-393.
[http://dx.doi.org/10.1089/end.2008.0216] [PMID: 19245302]
[65]
Boim, M.A.; Heilberg, I.P.; Schor, N. phyllanthus niruri as a promising alternative treatment for nephrolithiasis. Int. Braz J Urol, 2010, 36(6), 657-664.
[http://dx.doi.org/10.1590/S1677-55382010000600002] [PMID: 21176271]
[66]
Colpo, E.; Vilanova, C.D.D.A.; Pereira, R.P.; Reetz, L.G.B.; Oliveira, L.; Farias, I.L.G.; Boligon, A.A.; Athayde, M.L.; Rocha, J.B.T. Antioxidant effects of phyllanthus niruri tea on healthy subjects. Asian Pac. J. Trop. Med., 2014, 7(2), 113-118.
[http://dx.doi.org/10.1016/S1995-7645(14)60005-5] [PMID: 24461523]
[67]
Shanmugam, K.; Shanmugam, B.; Ravi, S.; Subbaiah, G.; Ramakrishana, C.; Mallikarjuna, K.; Reddy, K. Exploratory studies of (-)-Epicatechin, a bioactive compound of phyllanthus niruri, on the antioxidant enzymes and oxidative stress markers in D-galactosamine-induced hepatitis in rats: A study with reference to clinical prospective. Pharmacogn. Mag., 2017, 13(49)(Suppl. 1), 56.
[http://dx.doi.org/10.4103/0973-1296.203973] [PMID: 28479727]
[68]
Pucci, N.D.; Marchini, G.S.; Mazzucchi, E.; Reis, S.T.; Srougi, M.; Evazian, D.; Nahas, W.C. Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: A perspective for disease prevention. Int. Braz J. Urol., 2018, 44(4), 758-764.
[http://dx.doi.org/10.1590/s1677-5538.ibju.2017.0521] [PMID: 29617079]
[69]
Baiguera, C.; Boschetti, A.; Raffetti, E.; Zanini, B.; Puoti, M.; Donato, F. <b><i>phyllanthus niruri</i></b> versus Placebo for Chronic Hepatitis B Virus Infection: A Randomized Controlled Trial. Complement. Med. Res., 2018, 25(6), 376-382.
[http://dx.doi.org/10.1159/000484927] [PMID: 30372693]
[70]
Girish, C.; Sowjanya, K.; Bammigatti, C.; Prasanna Lakshmi, N. Efficacy of phyllanthus niruri on improving liver functions in patients with alcoholic hepatitis: A double-blind randomized controlled trial. Indian J. Pharmacol., 2021, 53(6), 448-456.
[http://dx.doi.org/10.4103/ijp.IJP_540_20] [PMID: 34975132]
[71]
Decha, P.; Kanokwan, K.; Khanittha, W.; Pisittawoot, A. Phonophoresis of phyllanthus amarus nanoparticle gel improves functional capacity in individuals with knee osteoarthritis: A randomized controlled trial. 2020, 24(1), 15-18.
[72]
George, A.; Udani, J.K.; Yusof, A. Effects of phyllanthus amarus PHYLLPRO TM leaves on hangover symptoms: A randomized, double-blind, placebo-controlled crossover study. Pharm. Biol., 2019, 57(1), 145-153.
[http://dx.doi.org/10.1080/13880209.2019.1585460] [PMID: 30922154]
[73]
Hanh, N.D.; Sinchaipanid, N.; Mitrevej, A. Physicochemical characterization of phyllanthin from phyllanthus amarus Schum. et Thonn. Drug Dev. Ind. Pharm., 2014, 40(6), 793-802.
[http://dx.doi.org/10.3109/03639045.2013.788010] [PMID: 23594304]
[74]
Parvathaneni, M.; Rao Battu, G.; Jangiti, R.; Diyya, K. Pharmacokinetic study of phyllanthin and hypophyllanthin after oral administration to rats. Pharmacogn. J., 2014, 6(2), 45-51.
[http://dx.doi.org/10.5530/pj.2014.2.8]
[75]
Sethiya, N.K.; Shah, P.; Rajpara, A.; Nagar, P.A.; Mishra, S.H. Antioxidant and hepatoprotective effects of mixed micellar lipid formulation of phyllanthin and piperine in carbon tetrachloride-induced liver injury in rodents. Food Funct., 2015, 6(11), 3593-3603.
[http://dx.doi.org/10.1039/C5FO00947B] [PMID: 26333006]

Rights & Permissions Print Cite
Article Metrics
12
1
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy