skin wound healing: from mediterranean ethnobotany to evidence

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3 rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens Skin wound healing: from Mediterranean ethnobotany to evidence based Phytotherapy Efthymia Eleni Tsioutsiou [email protected] Department of Physical Sciences, Earth and Environment University of Siena

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Page 1: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Skin wound healing: from Mediterranean ethnobotany to evidence based Phytotherapy

Efthymia Eleni Tsioutsiou

[email protected]

Department of Physical Sciences, Earth and Environment

University of Siena

Page 2: Skin wound healing: from Mediterranean ethnobotany to evidence

Ethnobotany: science that studies the uses of herbal species in a human society

Many medicinal plants known in ethnobotanical tradition

worldwide are nowadays used for:

• skin inflammation

• minor wounds

• small burns

3rd Annual International Conference on Pharmaceutical Sciences,

2-5 May 2016, Athens

Page 3: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Phytotherapy

Medicinal plants only resource of remedies for

wound care, for thousands of years

Multitasking features possessed by the plant

phytocomplex

Page 4: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Wound healing is a multifactorial process

Influenced by:

• oxygenation

• hydration

• bacterial infections

• nutrition

• diseases

• assumption of drugs

Necessary to act on more targets contemporarily!

Page 5: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Ethnobotanical study

Aims of the study:

• Evaluate the present status of the medicinal flora in specific regions of Italy and Greece

• Appraise the viability of folk medicine tradition

• Notice similarities and differences in the use of plants in the various zones

Page 6: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Ethnobotanical study

• Study areas: Italy, Greece (coastal and mountainous zones)

Page 7: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Ethnobotanical study

Considering

• Bibliographic data

• Relevant literature

• Vokou et al., 1993

• Malamas and Marselos, 1992

• Hanlidou et al., 2014 (Herbal market of Thessaloniki)

Zagori

Page 8: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Materials and methods

• Visits and interviews made with subjects (mostly old people) who had personal experience in self-medication using herbs

• The informants were requested to indicate vernacular names of plants, folk uses, parts used, preparation procedures, and possible species associations (including the description of recipes and their sources)

Page 9: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Materials and methods

Collection and botanical identification

The collection and identification of the most common taxa were carried out in the field; some specimens were identified in the laboratory according to more recent taxonomic revision

Page 10: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Results regarding species

• 105 species are used in the study areas for the indication of skin disorders and minor wounds

• 3 species are used in common in all 4 study areas

• The majority of species are reported in single areas

29% of taxa in the montane Greece

The information collected is mainly referred to wild species, whereas semi-cultivated or cultivated

species are less frequently used

Page 11: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Results regarding plant families

• The plant families of Asteraceae and Lamiaceae were reported in all four survey areas and were the most represented in terms of number of species

• Asteraceae (13 species) and Lamiaceae (11 species)

• More than 20% of the plant families are used at least in 3 out of 4 considered zones

Page 12: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Results

Percentages of sharing for taxa (families and species) used for treating skin diseases in Greece and Italy

Page 13: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Hypericum perforatum L.

Herbal substance: dried flowering tops

Preparation used in wound healing: St. John's wort oil, obtained by maceration of fresh flowering tops in vegetable oil (DER 1-4:20) for 30-40 days until the oil’s color becomes intensively red

Mechanism of action: increase of collagen granule number in fibroblasts

Flavonoids, hypericins and phloroglucinols: anti-inflammatory and antibacterial activity

Page 14: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Juglans regia L.

Herbal substance: leaves Preparation applied: wash, cataplasm or poultice

Used in skin disorders such as acne, eczema, herpes, scrofulous disease, excessive perspiration of the hands and feet and slow healing wounds

Species mentioned and described for being used in wound healing in the coastal zones

Astringent activity assigned to the tannin content

Page 15: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Plantago lanceolata L.

Herbal substance: leaves

Preparation used in wound healing: leaves after the nerves have been pulled out of them

For superficial wounds: application of the plant’s juice

Page 16: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Ophioglossum vulgatum L.

Herbal substance: aerial parts

Preparation used traditionally in wound healing: ointment obtained by the maceration of the aerial parts in olive oil

Used in Northern Italy mainly as wound poultice, particularly as haemostatic

The lipophilic compounds confer the tissue repair properties

Page 17: Skin wound healing: from Mediterranean ethnobotany to evidence

In vitro studies on the wound healing activity (Clericuzio et al., 2012)

Aim: Isolation of two new glycosylated and acylated flavonols from the aerial parts of the plant

Results: These compounds, along with the yet known quercetin-3-O-methyl ether were all found to be active in scratch-wound healing assays on keratinocytes

Quercetin-3-O-methyl ether

Maximum activity at 20 μM

3rd Annual International Conference on Pharmaceutical Sciences,

2-5 May 2016, Athens

Ophioglossum vulgatum L.

Page 18: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Ophioglossum vulgatum L. In vitro studies on the wound healing activity

(Clericuzio et al., 2014)

Aims:

• Isolation and characterization of a galactosyldiacylglycerol mixture from the fern frond dichloromethane extract

• Test of the wound healing properties of the mixture in vitro on human keratinocytes

Results:

• Increased wound closure rates in keratinocyte monolayers (5 μg/ml)

• Modulation of intracellular calcium levels and ERK1/2 MAP kinase activation

Page 19: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Momordica charantia L.

Herbal substance: leaves, fruits and seeds

Preparation used traditionally in wound healing: ointment obtained by the maceration of the fruit in olive oil

Common in the region Macedonia (Greece) for being used in wound healing replacing almost completely the use of conventional drugs such as silver sulfadiazine

Page 20: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Momordica charantia L. Clinical studies on the wound healing activity

(Teoh et al., 2009)

Aim: observation of the topical effect of bitter melon extract on the wound healing process in rats with diabetes induced by streptozotocin

Diabetic group: delayed wound healing compared to the normal group

Diabetic group treated with M. charantia extract: acceleration of the wound healing process as compared to the non-treated group

Results

Page 21: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Momordica charantia L. Clinical studies on the wound healing activity

(Prasad et al., 2006)

Aim: evaluation of the fruit powder ointment for wound healing in

an excision, incision and dead space wound model in rats

Results: Powder ointment showed a statistically significant response, in terms of:

1) wound-contracting ability

2) wound closure time, period of epithelization

3) tensile strength of the wound

4) regeneration of tissues at wound site

Page 22: Skin wound healing: from Mediterranean ethnobotany to evidence

European Medicines Agency (EMA)

Skin disorders and minor wounds are among the most frequent indications

• Only 12% (13 of the 105) of the species cited at least once are catalogued in the EMA list.

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

From Mediterranean ethnobotany to evidence-based Phytotherapy

Page 23: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Largely shared (used in 3 out of 4 areas) Hypericum perforatum L.

Only in coastal areas of both countries

Juglans regia L.

Only in Greece Agrimonia eupatoria L.

Urtica dioica L.

Only in coastal Greece Achillea millefolium L.

Hamamelis virginiana L. Origanum dictamnus L.

Urtica urens L.

Only in coastal Italy Arctium lappa L.

Quercus pubescens Willd.

Only in montane Greece Matricaria chamomilla L.

Salvia officinalis L.

Only in montane Italy Calendula officinalis L.

Taxa cited by informants and included in the EMA list

Page 24: Skin wound healing: from Mediterranean ethnobotany to evidence

The study of the medicinal plants with an official therapeutic role in wound healing is based on:

• Ethnobotanical knowledge

• Medical tradition

And is developed through: the contemporary clinical and experimental investigations aimed at understanding their mechanisms of action

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Conclusions

Page 25: Skin wound healing: from Mediterranean ethnobotany to evidence

Ethnobotanical data

• Mediterranean basin self-medication practices are still present

• Significant use of a large number of wild and/or semi-cultivated Mediterranean species, for therapeutic applications related to the treatment of skin disorders (burns, ulcers and small wounds)

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Conclusions

Page 26: Skin wound healing: from Mediterranean ethnobotany to evidence

• Only 12% of these species are catalogued by EMA for this type of indication

• More opportunities for scientific studies on the use of new principles derivable from these species

Further aim of our study:

1. examine more sample areas

2. create a list of Mediterranean species potentially useful in wound healing and in the treatment of other skin problems

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Conclusions

Page 27: Skin wound healing: from Mediterranean ethnobotany to evidence

3rd Annual International Conference on Pharmaceutical Sciences, 2-5 May 2016, Athens

Thank you for your attention

Efthymia Eleni Tsioutsiou [email protected]

Department of Physical Sciences, Earth and Environment

University of Siena

Elisabetta Miraldi, Paolo Governa, Marco Biagi, Paolo Giordani, Laura Cornara