European Medicines Agency Evaluation of Medicines for Human Use

London, 15 September 2008 Doc Ref.: EMEA/HMPC/464551/2008

Background

The Committee on Herbal Medicinal Products (HMPC) was established in September 2004, in accordance with Regulation (EC) No 726/2004. The duties of HMPC are laid down in Directive 2004/24/EC amending, as regards traditional herbal medicinal products, Directive 2001/83/EC. They aim at enhancing the harmonisation of procedures and provisions concerning herbal medicinal products laid down in EU Member States, and further integrating herbal medicinal products in the European regulatory framework.

The establishment of Community herbal monographs as well as a draft Community ‘list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products’ are among the core duties of the HMPC. Public calls for submission of relevant scientific data represent an important part of the HMPC’s efforts to obtain the best possible basis for the related assessment work.

Call for scientific data

The HMPC invites all interested parties¹ to submit any scientific data, which may be used in the assessment of Centellae asiaticae herba as part of the establishment of Community herbal monographs, and/or entries to the Community ‘list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products’.

The Rapporteur is seeking to receive copies of scientific contributions other than those referred to in the annex to this call for submission of scientific data.

¹ Such as pharmaceutical industry associations, health care professional groups, learned societies, consumers and patients’ associations, governmental institutions as well as EU and EEA-EFTA Member States.

7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 75 23 70 51 E-mail: mail@emea.europa.eu http://www.emea.europa.eu © European Medicines Agency, 2008. Reproduction is authorised provided the source is acknowledged

Conditions for data submissions

Scientific contributions should be relevant to the purpose of the assessment, and their scope should address either:

1.    Well-established medicinal use: Submitted data should provide evidence that the constituent or the constituents of the medicinal product has or have a well-established medicinal use with recognised efficacy and an acceptable level of safety within the meaning of Directive 2001/83/EC as amended.

2.    Traditional use: Submitted data should provide evidence that the medicinal product in question, or a corresponding product, has been in medicinal use throughout a period of at least 30 years preceding the date of the application, including at least 15 years within the Community.

Furthermore, the acceptance of scientific contributions will be based on compliance with the following general criteria:

1.    The name and contact details of the party providing the scientific contribution is required.

2.    Scientific contributions should be classified by the interested party as (i) peer-reviewed data; or (ii) non peer-reviewed data. The EMEA encourages submission of peer-reviewed data/publications (not just the reference) as the most relevant and reliable documents. Non peer-reviewed data such as references from older standard books of phytotherapy or comparable scientific sources can be taken into consideration provided that they are of an adequate quality.

3.    A document providing a specification of the literature search strategy, the date of the search, search terms (inclusion/exclusion terms) as well as a listing of databases used for the search should be enclosed.

4.    All contributions should be provided in either electronic format (e.g. via e-mail or a CD-Rom) or paper format (2 copies) and a list of attached documents and their references should be enclosed.

Non-compliance with any of these requirements for data submission may result in the rejection of the contribution provided.

To facilitate an effective handling of incoming documents and/or CD-Roms etc., interested parties are requested to submit documents:

either to the following email address: hmpc.secretariat@emea.europa.eu. or by post:

European Medicines Agency (EMEA)

7 Westferry Circus Canary Wharf London E14 4HB United Kingdom Att.: HMPC secretariat

or by fax: (44-20) 75 23 70 51, Att.: HMPC secretariat.

Please note, that in order for the Rapporteur to respect assessment deadlines, any submissions are kindly requested by 30 November 2008 at the latest.

Copyright

The use by the HMPC of bibliographic material is entirely for a non-commercial purpose. As its noncommercial use by the Committee is guaranteed, any interested party will not incur in any liability as to the use intended by the HMPC by forwarding bibliographic literature to the Committee. The HMPC is in all cases willing to confirm in writing the non-commercial use of documents sent in by interested parties.

Confidentiality

Unpublished data may be included. Confidentiality will be lifted in cases where the contributor has given its consent. In other cases where confidential data are presented, it should be duly justified why these data are protected and how transparency in the procedure of assessment can be assured. The HMPC will consider such submissions on a case-by-case basis. The contributor should also take duly into account the rights of interested parties, as the documentation provided will be used for the development of Community list entries and Community herbal monographs. Such development is underpinned by assessment reports, which will be made public in accordance with measures taken by the EMEA to ensure an appropriate level of transparency.

Language requirements

Documents should be submitted in English where possible since this is the working language of the HMPC, but documents in other official Community languages will be accepted. In order to facilitate the assessment, the HMPC strongly recommends the submission of an abstract in English when original references are provided.

List of references already acquired by the Rapporteur:

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3.    Ahshawat MS, Saraf S. Preparation and characterization of herbal creams for improvement of skin viscoelastic properties. Int J Cosmet Sci 2008, 30:183-93

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5.    Aziz ZA, Davey MR, Lowe KC, Power JB. Isolation and culture of protoplasts from the medicinal plant Centella asiatica. Rev Bras Pl Med 2006, 8:105-9

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9.    Bouhouche N, Solet JM, Simon-Ramiasa A, Bonaly J, Cosson L. Conversion of 3-demethylthiocolchicine into thiocolchicoside by Centella asiatica suspension cultures. Phytochemistry 1998, 47:743-7

10.    Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000, 20:680-4

11.    Brinkhaus B, Linder M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine 2000, 7:427-48

12.    Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine 2000, 7:427-48

13.    Bunpo P, Kataoka K, Arimochi H, Nakayama H, Kuwahara T, Bando Y et al. Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats. Food Chem Toxicol 2004, 42:1987-97

14.    Caldas ED, Machado LL. Cadmium, mercury and lead in medicinal herbs in Brazil. Food Chem Toxicol 2004, 42:599-603

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16.    Chen SW, Wang WJ, Li WJ, Wang R, Li YL, Huang YN et al. Anxiolytic-like effect of asiaticoside in mice. Pharmacol Biochem Behav 2006, 85:339-44

17.    Chen Y, Han T, Qin L, Rui Y, Zheng H. [Effect of total triterpenes from Centella asiatica on the depression behaviour and concentration of amino acid in forced swimmin mice]. Journal of Chinese medicinal materials 2003, 26:870-3

18.    Chen Y, Qin LP, Zheng HC, Zhang ZH. [Resources distribution and pharmacognostic identification of Centella asiatica (L.) urban produced in China]. China journal of Chinese materia medica 2000, 25:199-202

19.    Chen YJ, Dai YS, Chen BF, Chang A, Chen HC, Lin YC et al. The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats. Biol Pharm Bull 1999, 22:703-6

20.    Cheng CL, Guo JS, Luk J, Koo MW. The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci 2004, 74:2237-49

21.    Cheng CL, Koo MW. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats. Life Sci 2000, 67:2647-53

22.    Chitturi S, Farrell GC. Hepatotoxic slimming aids and other herbal hepatotoxins. J Gastroenterol Hepatol 2008, 23:366-73

23.    Coldren CD, Hashim P, Ali JM, Oh SK, Sinskey AJ, Rha C. Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids. Planta Med 2003, 69:725-32

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26.    Edwin D, Geetha VR, Vishwanathan H, Usha Rani MV. Studies on antimutagenic effects of Centella asiatica, Alternanthera sessilis and Emblica officinalis in somatic cells of mice. J. Environ. Biol. 2000, 21:75-8

27.    Ernst E. Herbal remedies for anxiety a systematic review of controlled clinical trials. Phytomedicine 2006, 13:205-8.

28.    Gadahad MR, Rao M, Rao G. Enhancement of hippocampal CA3 neuronal dendritic arborization by Centella asiatica (Linn) fresh leaf extract treatment in adult rats. J Chin Med Assoc 2008, 71:6-13

29.    Gautam R, Saklani A, Jachak SM. Indian medicinal plants as a source of antimycobacterial agents. J Ethnopharmacol 2007, 110:200-34

30.    Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T. Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. Life Sci 2004, 76:585-97

31.    Govindan G, Sambandan TG, Govindan M, Sinskey A, Vanessendelft J, Adenan I, et al. A bioactive polyacetylene compound isolated from Centella asiatica. Planta Med 2007, 73: 597-9

32.    Gupta YK, Veerendra Kumar MH, Srivastava AK. Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav 2003, 74:579-85

33.    Haftek M, Mac Mary S, Bitoux MA, Creidi P, Seite S, Rougier A et al. Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin. Exp Dermatol. 2008, [Epub ahead of print]

34.    Herbert D, Paramasivan CN, Prabhakar R, Swaminathan G. In vitro experiments with Centella asiatica: investigation to elucidate the effect of an indigenously prepared powder of this plant on the acid-fastness and viability of M. tuberculosis. Indian J Lepr 1994, 66:65-8

35.    Hong SS, Kim JH, Li H, Shim CK. Advanced formulation and pharmacological activity of hydrogel of the titrated extract of Centella asiatica. Arch Pharm Res 2005, 28:502-8

36.    Huang YH, Zhang SH, Zhen RX, Xu XD, Zhen YS. [Asiaticoside inducing apoptosis of tumour cells and enhancing anti-tumour activity of vincristine.]. Ai Zheng 2004, 23:1599604

37.    Husain GM, Mishra D, Singh PN, Rao CV, Kumar V. Ethnopharmacological review of native traditional medicinal plants for brain disorders. Pharmacognosy Reviews 2007, 1:1928

38.    Hussin M, Abdul-Hamid A, Mohamad S, Saari N, Ismail M, Hair Bejo M. Protective effect of Centella asiatica extract and powder on oxidative stress in rats. Food Chemistry 2007, 100:535-41

39.    Inamdar PK, Yeole RD, Ghogare AB, de Souza NJ. Determination of biologically active constituents in Centella asiatica. Journal of Chromatography A 1996, 742:127-30

40.    Jagetia GC. Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation. J. Clin. Biochem. Nutr. 2007, 40:74-81

41.    Jayashree G, Kurup Muraleedhara G, Sudarslal S, Jacob VB. Anti-oxidant activity of Centella asiatica on lymphoma-bearing mice. Fitoterapia 2003, 74:431-4

42.    Jayathirtha MG, Mishra SH. Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica. Phytomedicine 2004, 11:361-5

43.    Jia G, Lu X. Enrichment and purification of madecassoside and asiaticoside from Centella asiatica extracts with macroporous resins. J Chromatogr A 2008, 1193:136-41

44.    Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005, 97:115-24

45.    Kavindra Nath Tiwari, Nilesh Chandra Sharma, Vaibhav Tiwari, Brahma Deo Singh. Micropropagation of Centella asiatica (L.), a valuable medicinal herb. Plant Cell, Tissue and Organ Culture 2000, 63:179-85

46.    Kim C, Hwang YY, Chang JY, Choi HG, Lim SJ, Lee MK. Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system. International Journal of Pharmaceutics 2001, 220:141-7

47.    Kim OT, Ahn JC, Hwang SJ, Hwang B. Cloning and expression of a farnesyl diphosphate synthase in Centella asiatica (L.) Urban. Mol Cells 2005, 19:294-9

48.    Kim OT, Bang KH, Shin YS, Lee MJ, Jung SJ, Hyun DY et al. Enhanced production of asiaticoside from hairy root cultures of Centella asiatica (L.) Urban elicited by methyl jasmonate. Plant Cell Rep 2007, 26:1941-9

49.    Kim OT, Kim MY, Hong MH, Ahn JC, Hwang B. Stimulation of asiaticoside accumulation in the whole plant cultures of Centella asiatica (L.) urban by elicitors. Plant Cell Rep 2004, 23:339-44

50.    Kim OT, Kim MY, Huh SM, Bai DG, Ahn JC, Hwang B. Cloning of a cDNA probably encoding oxidosqualene cyclase associated with asiaticoside biosynthesis from Centella asiatica (L.) Urban. Plant Cell Rep 2005, 24:304-11

51.    Kuroda M, Mimaki Y, Harada H, Sakagami H, Sashida Y. Five new triterpene glycosides from Centella asiatica. Nat. Med. 2001, 55:134-8

52.    Laugel C, Baillet A, Ferrier D, Grossiord JL, Marty JP. Incorporation of triterpenic derivatives within an o/w/o multiple emulsion: structure and release studies. International Journal of Cosmetic Science 1998, 20:183-91

53.    Lee J, Jung E, Kim Y, Park J, Park J, Hong S et al. Asiaticoside Induces Human Collagen I Synthesis through TGFp Receptor I Kinase (TpRI Kinase)-Independent Smad Signaling. Planta Med 2006, 72:324-8

54.    Liu M, Dai Y, Li Y, Luo Y, Huang F, Gong Z et al Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice. Planta Med 2008, 74:809-15

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56.    Mamtha B, Kavitha K, Srinivasan KK, Shivananda PG. An in vitro study of the effect of Centella asiatica [Indian pennywort] on enteric pathogens. Indian J Pharmacol 2004, 36:41-4

57.    Maquart FX, Bellon G, Giller P, Randoux A, Borel JP. Stimulation of Collagen synthesis in fibroblast cultures using triterpene extracts of Centella asiatica. Sem. Hop. Paris 1989, 65:1571-4

58.    Matsuda, H.; Morikawa, T.; Ueda, H.; Yoshikawa, M. Masayuki. Medicinal foodstuffs. XXVI. Inhibitors of aldose reductase and new triterpene and its oligoglycoside, centellasapogenol A and centellasaponin A, from Centella asiatica (Gotu Kola). Heterocycles 2001, 55:1499-504

59.    Mauri P, Pietta P. Electrospray characterization of selected medicinal plant extracts. J Pharm Biomed Anal 2000, 23:61-8

60.    Ming ZJ, Liu SZ, Cao L. [Effect of total glycosides of Centella asiatica on antagonizing liver fibrosis induced by dimethylnitrosamine in rats]. Chinese journal of integrated traditional and Western medicine 2004, 24:731-4

61.    Mohandas RAO KG, Muddanna RAO S, Gurumadhva RAO S. Centella asiatica (Linn) induced behavioural changes during growth spurt period in neonatal rats. Neuroanatomy 2005, 4:18-23

62.    Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S. Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats. Evid Based Complement Alternat Med 2006, 3:349-57

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68.    Rajkumar S, Jebanesan A. Larvicidal and Adult Emergence Inhibition Effect of Centella asiatica Brahmi (Umbelliferae) against Mosquito Culex quinquefasciatus Say (Diptera: Culicidae). African Journal of Biomedical Research 2005, 8:31-3

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