The Premier Natural Animal Therapy Organisation

Professional insurance for HATO members

For details, please click here






A nebulized complex traditional Chinese medicine inhibits Histamine and IL-4 production by ovalbumin in guinea pigs and can stabilize mast cells in vitro

Hung-Chou Chang 3 1, Cheng-Chung Gong 1 2, Chi-Lim Chan 1 and Oi-Tong Mak 1 4

1  Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan, ROC

2  Department of Medical Technology, Chung Hwa University of Medicine Technology, Jen-Te, Tainan, Taiwan, ROC

3  Office of Academic Affairs, Tainan Tzu-Chi Senior High School, Tainan, Taiwan, ROC

4  Department of Healthcare Management, University of Kang Ning, 188, Sec. 5, An Chung Rd. A Nan District, Tainan, Taiwan, ROC



Traditional Chinese medicines have been used for anti-asthma treatment for several centuries in many Asian countries, and have been shown to effectively relieve symptoms. Our previous study demonstrated that a complex traditional Chinese medicine (CTCM) administered in nebulized form through the intratracheal route is effective against early-phase air-flow obstruction and can inhibit IL-5 production in ovalbumin (OVA)-sensitized guinea pigs. However, the antiasthmatic mechanisms of CTCMs are still unclear.


In this study, we examined the underlying mechanism of a CTCM that we used in our previous study in order to Guinea Pig ~ CREDIT: renascertain its function in the early-phase response to OVA challenge.

In each group, 10–12 unsensitized or OVA-sensitized guinea pigs were treated with nebulized CTCM before OVA challenge, and the airway responses of the animals to OVA were recorded. Bronchoalveolar lavage fluid (BALF) samples were collected 5 min after OVA challenge, and the histamine and IL-4 contents in the BALF were measured. P815 cells (a mouse mast cell line) were untreated or pretreated with CTCM or cromolyn sodium (a mast cell stabilizer), and incubated with Compound 48/80 (mast cell activator) for 9 hr. The levels of histamine and IL-4 released from the cells were quantified.


We found that the inhibition of bronchoconstriction by the CTCM was attenuated by pretreatment with propranolol, suggesting that the CTCM has a bronchodilator effect that is associated with beta-adrenergic receptor. Our results also showed that the CTCM inhibited histamine and IL-4 secretion in the OVA-induced airway hypersensitivity in guinea pigs at 5 min post-OVA challenge, and in vitro study revealed that the CTCM is able to stabilize mast cells.


In conclusion, our results suggested that the CTCM is a kind of bronchodilator and also a mast cell stabilizer. Our findings provide useful information regarding the possible mechanism of the CTCM, and show its potential for application in the treatment of allergenic airway disease.

CITATION: BMC Complementary and Alternative Medicine 2013, 13:174 doi:10.1186/1472-6882-13-174

Published: 13 July 2013


SOURCE: This is an Open Access article courtesy of BioMed Central - Creative Commons Attribution 2.0 License



Effect of Semisolid Formulation of Persea Americana Mill (Avocado) Oil on Wound Healing in Rats

Ana Paula de Oliveira, 1 Eryvelton de Souza Franco, 2 Rafaella Rodrigues Barreto, 2 Daniele Pires Cordeiro, 2 Rebeca Gonçalves de Melo, 2 Camila Maria Ferreira de Aquino, 2 Antonio Alfredo Rodrigues e Silva, 2 Paloma Lys de Medeiros, 3 Teresinha Gonçalves da Silva, 4 Alexandre José da Silva Góes, 4 and Maria Bernadete de Sousa Maia 2 , 5 

1 Department of Pathology, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil

2 Department of Physiology and Pharmacology, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil

3 Department of Histology and Embryology, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil

4 Department of Antibiotics, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil

5 Department of Physiology and Pharmacology, Laboratory of Pharmacology of Bioactive Products, Federal University of Pernambuco, 50670-901 Recife, PE, Brazil


The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

1. Introduction

Wound healing is a complex process involving different cell types, cytokines, growth factors, and the extracellular matrix with the purpose of swiftly reestablishing skin integrity [1–3]. This wound healing process occurs in three overlapping phases: inflammation, proliferation, and remodeling [4–11].

Avocado (Persea americana) Oil ~ CREDIT: Itineranttrader; Wikimedia Commons, public domainHemostasis is followed after several hours by an inflammatory stage, during which cytokines and growth factors are secreted, and leucocytes and to a lesser extent other cell types are recruited to clean the wound. In the proliferative phase tissue repair occurs in response to the factors produced initially. Endothelial cells proliferate to form new blood vessels that are essential for supplying blood to the wound site. A proliferation of fibroblasts also occurs, thus establishing a proper wound bed for reepithelialization, which starts with the proliferation and centripetal migration of keratinocyte from the wound edges or from hair follicles and sweat glands in the remaining dermis. During the last phase, the following events occur: regression of capillaries, reorganization of the extracellular matrix, and restructuring of scar tissue, which may take many months if not years [12–14].

Previous studies have shown that the healing process may be modulated by fatty acids [8, 10]. Linolenic (18:3 ω-3), linoleic (18:2 ω-6), and oleic (18:1 ω-9) acids are precursors of eicosapentaenoic (EPA) (20:5 ω-3), arachidonic (AA) (20:4 ω-6), and eicosatrienoic acids (ETA) (20:3 ω-9) which are part of the structure of cell membrane phospholipids and serve as substrates for the synthesis of eicosanoids (inflammatory mediators), such as prostaglandins, thromboxanes, prostacyclins (via cyclooxygenase), and leukotrienes (via lipooxygenase) [15–20]. Eicosanoids formed from arachidonic acid, prostaglandin E2, thromboxane B2, and leukotriene B4 are proinflammatory inducers, more potent than those formed from EPA, prostaglandin E3, thromboxane B3, and leukotriene B5, which have anti-inflammatory effects [15, 18, 19, 21]. Considering that these families of fatty acids compete for the same enzyme, the proper balance between ω3, ω6, and ω9 is of great importance [18]. Depending on the ω3 : ω6 : ω9 ratio of the diet more proinflammatory or anti-inflammatory eicosanoids can be synthesized. Besides modulating the inflammatory response, eicosanoids also act in immunological responses, platelet aggregation, and cell growth and differentiation [22].

Avocado (P. americana) extract or oil in natura has been used in wound healing [23, 24], the treatment of psoriasis [25], wrinkles, and stretch marks [26, 27], as well as for their hepatoprotective actions [28]. The unsaponifiable fraction of this oil has regenerative properties of the epidermis [26, 27], besides improving scleroderma [29].

Avocado oil extracted from the pulp of the fruit is rich in polyunsaturated fatty acids (PUFAs), linoleic (6.1–22.9%) and linolenic acids (0.4–4.0%), and the monounsaturated fatty acid (MUFA), oleic acid (31.8–69.6%). It also contains β-sitosterol, β-carotene, lecithin, minerals, and vitamins A, C, D, and E [23, 30–34]. Therefore, the aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura on incisional and excisional cutaneous wound models in Wistar rats and to characterize the fatty acids present in avocado oil.

2. Materials and Methods

2.1. Extraction and Fatty Acid Characterization of the In Natura Avocado Oil

The in natura oil of avocado (fruit), Margarida variety, was extracted using hexane as extraction solvent, following the method described by Salgado et al. [33]. The phytochemical characterization of the oil in natura in terms of its composition of fatty acids was determined after converting them into methyl esters [35]. The sample was analyzed using a Thermo Trace Ultra GC (SHIMADZU, model GC-14B) apparatus equipped with a flame ionization detector and HP-20 (carbowax 20m) capillary column (25m × 0.32mm × 0.3μm). The column temperature was initially set to 40°C for 1min, then increased to 150°C at heating to 55°C/min, and finally increased to 220°C at 1.7°C/min. The injector and detector temperatures were 200 and 220°C, respectively. Nitrogen was used as the carrier gas at a flow rate of 1.0mL/min; injection was in split mode (1:20), and the injection volume was 1.0μL of the test sample. A standard fatty acid methyl ester mixture (Supelco, USA) was used to identify fatty acid methyl esters by their retention time. Fatty acid data were expressed as percent of total peak area.

2.2. Pharmaceutical Formulation

The semisolid formulation of avocado oil, SSFAO 50%, was composed of avocado oil and a vehicle (petroleum jelly), in sufficient amount to daily treatment, order of ensures formulation stability. This manipulation met the standards and quality control for medicines from the Synthesis of Substances of Therapeutic Interest Laboratory, Department of Antibiotics of the Federal University of Pernambuco. As a negative control, the formulation vehicle (petroleum jelly) was used, and as a positive control, an oil rich in essential fatty acids (EFA) (Curatec EFA). The pre-clinical toxicity tests conducted in our laboratory to evaluate the dermal and ocular irritation, sensitization, and toxicity (acute and subchronic) of an SSFAO or in natura avocado oil in rodents and lagomorphs did not show any clinical signs of toxicity.

2.3. Animals

A total of 64 adult Wistar rats, male and female, with ages between 3-4 months and weighing between 200–250g, were used. The animals came from the vivarium of the Department of Physiology and Pharmacology of the Federal University of Pernambuco. The rats were kept individually in metabolic cages, in 12h light/dark cycle and at a constant temperature (20 ± 2°C), with water and food ad libitum, throughout the experiment. The experiments were approved by the Ethics Committee for Animal Experimentation (number 23076.027831/2010-21) of the Federal University of Pernambuco, Recife, Brazil.


4. Discussion

Extracts of avocado (P. americana Mill.) have been used in wound healing [23, 24]. We note that the in natura avocado oil is rich in monounsaturated fatty acids, with oleic acid being the most prevalent, which corroborates with the results obtained by Tango et al. [31]. The linoleic and oleic acid contents are just shy of those described by Salgado et al. [33]; however, the amount of linolenic acids are above those verified by these authors. This fact can be caused by the anatomical region of the fruit, maturation stage, and geographic location of the growth of the plant [44, 45].

Fatty acids (oleic, linoleic, and linolenic) have been the subject of several studies, because they seem to be active in the healing process [10, 38]. The healing process can be monitored by assessing the rate of contraction of the wound, period of reepithelialization, tensile strength, and histopathology in different wound models [46]. We note that the rate of contraction of excisional wounds of animals treated with SSFAO 50% or avocado oil (fifth day) was slower than that present in the EFA control. A result similar to that was described by Franco et al. [38], who reported a significant delay in the contraction of the wounds, in the inflammatory stage of healing, in experimental groups compared to the EFA control. Probably, the delay in the contraction rate is related to the easy absorption of avocado oil through the skin [26, 27] allowing the wound bed to remain more exposed to the environment, increasing the chances of dehydration [38].

The best profile in the rate of contraction of wounds of animals treated with 50% SSFAO or avocado oil (13th and 14th days) is probably related to the properties of the avocado oil (PUFA, MUFA, β-sitosterol, β-carotene, lecithin, minerals, and vitamins A, C, D, and E), which encouraged the migration, proliferation, and cell differentiation during the proliferative phase of wound healing. This finding corroborates those of Nayak et al. [23] and Vega et al. [24], which demonstrated the effectiveness of topical or oral administration of an extract from avocado fruit in different types of wounds using rats.

Cat paw with small skin wound ~ CREDIT: EmmiPIn this study, the presence of devitalized tissue (slough) was not verified in animals treated with SSFAO 50% or avocado oil, unlike animals treated with petroleum jelly. Hess and Kirsner [47] attributed the presence of devitalized tissue in the wound bed to tissue changes caused by oxygen, drying of the wound bed, or high microbial density. We suggest that the lack of development of slough in the groups treated with 50% SSFAO or avocado oil is associated with the antimicrobial activity attributed to linoleic acid [38, 48], as well as the proper maintenance of hydration and oxygen stress in the wound bed.

The histopathological assessment revealed that the animals treated with 50% SSFAO or avocado oil in natura showed a significant increase in the presence of epithelial tissue. The possible pharmacological effects attributed to avocado oil, in regard to the healing process, can be associated with its phytochemical compounds, such as vitamins (A and E) and fatty acids (oleic, linoleic, and linolenic acids). As these fatty acids are precursors of pharmacologically active substances, such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes [15–20] that are involved in regulating cell division and differentiation, angiogenesis and synthesis of the extracellular matrix [22, 40, 49]. As does linoleic acid [50], vitamin E has important antioxidant functions [51] in combating free radicals that are responsible for the cytotoxicity and delay in tissue healing [52]. The adequate availability of these products provides a favorable environment to reepithelialization when administered to the wound bed.

Topical application of 50% SSFAO or avocado oil in natura promoted a reduction in the number of inflammatory cells in the scar tissue, characterizing anti-inflammatory activity. The modulation of the inflammatory response can be attributed to the high availability of oleic acid present in the SSFAO, since this fatty acid induces a less intense local inflammatory response, and competes with linoleic and linolenic acids for the same enzymes (cyclooxigenases and lipooxigenases) synthesizing less powerful inflammatory mediators than those formed by arachidonic acid [15, 18, 19, 21].

A significant decrease was observed in the number of fibroblast cells in animals treated with 50% SSFAO or in natura avocado oil; however, the collagen deposition was inversely proportional, characterizing the maturing of scar tissue (remodeling phase).

There is a view that, in the physiological process of healing, collagen accumulates in the area of the wound until the 21st day after the injury; after this period, the balance between synthesis and degradation of collagen is restored [53], with a rapid disappearance (apoptosis) of fibroblastic cells [54].

A significant increase was observed in the tensile strength; this was proportional; the deposition of collagen, in animals treated with 50% SSFAO or in natura avocado oil. This finding is backed by Nunes et al. [55], Stoff et al. [56], Deodhar [57], and Udupa et al. [58], who reported that the resistance of the skin is related to formation, concentration, and chemical reorganization of the collagen fibers during the remodeling stage. According to Hunt [59], Stoff et al. [56], and López et al. [60], the tensile strength test is used to describe the quality of the healing from incisional wounds, this being one of the most reliable ways. Thus, the increase in tensile strength observed in this study may be due to increased collagen synthesis or due to a change in the maturation process, result of the action of mono- and polyunsaturated fatty acids present in avocado oil.


1. Templin C, Grote K, Schledzewski K, et al. Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms. Experimental Dermatology. 2009;18(5):445–453. [PubMed]

2. Yamaguchi Y, Yoshikawa K. Cutaneous wound healing: an update. Journal of Dermatology. 2001;28(10):521–534. [PubMed]

3. Heilborn JD, Weber G, Grönberg A, Dieterich C, Ståhle M. Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo. Experimental Dermatology. 2010;19(4):332–338. [PubMed]

4. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiological Reviews. 2003;83(3):835–870. [PubMed]

5. Lau K, Paus R, Tiede S, Day P, Bayat A. Exploring the role of stem cells in cutaneous wound healing. Experimental Dermatology. 2009;18(11):921–933. [PubMed]

6. Martin P. Wound healing-aiming for perfect skin regeneration. Science. 1997;276(5309):75–81. [PubMed]

7. Rahban SR, Garner WL. Fibroproliferative scars. Clinics in Plastic Surgery. 2003;30(1):77–89. [PubMed]

8. McDaniel JC, Belury M, Ahijevych K, Blakely W. Omega-3 fatty acids effect on wound healing. Wound Repair and Regeneration. 2008;16(3):337–345. [PMC free article] [PubMed]

9. Novotný M, Vasilenko T, Varinská L, et al. ER-α agonist induces conversion of fibroblasts into myofibroblasts, while ER-? agonist increases ECM production and wound tensile strength of healing skin wounds in ovariectomised rats. Experimental Dermatology. 2011;20(9):703–708. [PubMed]

10. Cardoso CR, Souza MA, Ferro EAV, Favoreto S, Pena JDO. Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. Wound Repair and Regeneration. 2004;12(2):235–243. [PubMed]

11. Araújo LU, Grabe-Guimarães A, Mosqueira VCF, Carneiro CM, Silva-Barcellos NM. Profile of wound healing process induced by allantoin1. Acta Cirurgica Brasileira. 2010;25(5):460–466. [PubMed]

12. Schreml S, Landthaler M, Schaferling M, Babilas P. A new star on the H2O2 rizon of wound healing? Experimental Dermatology. 2011;20(3):229–231. [PubMed]

13. Deiters U, Barsig J, Tawil B, Mühlradt PF. The macrophage-activating lipopeptide-2 accelerates wound healing in diabetic mice. Experimental Dermatology. 2004;13(12):731–739. [PubMed]

14. Groeber F, Holeiter M, Hampel M, et al. Skin tissue engineering-In vivo and vitro applications. Advanced Drug Delivery Reviews. 2011;128(1):352–366. [PubMed]

15. Cherian G. Metabolic and cardiovascular diseases in poultry: role of dietary lipids. Poultry Science. 2007;86(5):1012–1016. [PubMed]

16. Martins JM, Gruezo ND. Ácidos graxos ω6 na etiologia do câncer de cólon e reto/ω-6 fatty acid and colorectal câncer. Revista Brasileira De Cancerologia. 2009;55(1):69–74.

17. Costea I, Mack DR, Israel D, et al. Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn’s disease in children & young adults. PLoS ONE. 2010;5(12)e15672 [PMC free article] [PubMed]

18. Garófolo A, Petrilli AS. Omega-3 and 6 fatty acids balance in inflammatory response in patients with cancer and cachexia. Revista de Nutricao. 2006;19(5):611–621.

19. Andrade PMM, Carmo MGT. N-3 fatty acids: a link between eicosanoids, inflammation and immunity. Nm-metabólica. 2006;08(3):135–143.

20. Astudillo AM, Balgoma D, Balboa MA, Balsinde J. Dynamics of arachidonic acid mobilization by inflammatory cells. Biochim Biophys Acta. 2012;1821(2):249–256. [PubMed]

21. Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukotrienes and Essential Fatty Acids. 2006;75(3):197–202. [PubMed]

22. Carmo MCNS, Correia MITD. The role of omega-3 fatty acids in cancer. Revista Brasileira de Cancerologia. 2009;55(3):279–287.

23. Nayak BS, Raju SS, Chalapathi Rao AV. Wound healing activity of Persea americana (avocado) fruit: a preclinical study on rats. Journal of Wound Care. 2008;17(3):123–126. [PubMed]

24. Vega RMG, Rivero RR, Moreiro RG. Study of avocado action on the process healing in burnt rats. Archivo Médico Camaguey. 2000;4(2):39–43.

25. Stücker M, Memmel U, Hoffmann M, Hartung J, Altmeyer P. Vitamin B12 cream containing avocado oil in the therapy of plaque psoriasis. Dermatology. 2001;203(2):141–147. [PubMed]

26. Tango JS, Turatti JM. Abacate: Cultura, Matéria-Prima, Processamento e Aspectos Econômicos. Vol. 1. Campinas, Brazil: ITAL; 1992. Óleo de abacate; pp. 156–192.

27. Crizel GR, Mendonça CRB. Abacate: variedades, produção e aspectos nutricionais. Conhecimento sem fronteiras. XVII Congresso de Iniciação Científica X Encontro de Pós-Graduação-UFPEL; 2008.

28. Kawagishi H, Fukumoto Y, Hatakeyama M, et al. Liver injury suppressing compounds from avocado (Persea americana) Journal of Agricultural and Food Chemistry. 2001;49(5):2215–2221. [PubMed]

29. Gaby AR. Natural remedies for scleroderma. Alternative Medicine Review. 2006;11(3):188–195. [PubMed]

30. Soares SE, Mancini Filho J, Della Modesta RC. Sensory detection limits of avocado oil in mixtures with olive oil. Revista Española de Ciencia y Tecnologia de Alimentos. 1992;32(5):509–516.

31. Tango JS, Carvalho CRL, Soares NB. Physical and chemical characterization of avocado fruits aiming at its potencial for oil extration. Revista Brasileira de Fruticultura. 2004;26(1):17–23.

32. Ortiz MA, Dorantes AL, Gallndez MJ, Cárdenas SE. Effect of a novel oil extraction method on avocado (Persea americana Mill) pulp microstructure. Plant Foods for Human Nutrition. 2004;59(1):11–14. [PubMed]

33. Salgado JM, Danieli F, Regitano-D’Arce MAB, Frias A, Mansi DN. The avocado oil (Persea americana Mill) as a raw material for the food industry. Ciencia e Tecnologia de Alimentos. 2008;28:20–26.

34. Massafera G, Costa TMB, Oliveira JED. Fatty acids of mesocarp and seed oils of avocados (Persea americana Mill.) from Ribeirão Preto, SP. Alimentos e Nutrição. 2010;21(1):325–331.

35. Hartman L. Rapid preparation of fatty acid methyl esters from lipids. Laboratory Practive. 1973;22(7):475–476. [PubMed]

36. Davidson JM. Animal models for wound repair. Archives of Dermatological Research. 1998;290(1):S1–S11. [PubMed]

37. Galiano RD, Michaels J, Dobryansky M, Levine JP, Gurtner GC. Quantitative and reproducible murine model of excisional wound healing. Wound Repair and Regeneration. 2004;12(4):485–492. [PubMed]

38. Franco ES, Aquino CMF, Medeiros PL, et al. Effect of a semisolid formulation of Linum usitatissimum L., (Linseed) oil on the repair of skin wounds. Evidence-Based Complementary and Alternative Medicine. 2012;2012:p. 7.270752 [PMC free article] [PubMed]

39. Andrade SF. Manual de Terapêutica Veterinária. São Paulo, Brazil: Roca; 2002.

40. Zhang Z, Wang S, Diao Y, Zhang J, Lv D. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity. Lipids in Health and Disease. 2010;9:p. 24. [PMC free article] [PubMed]

41. Luna LG. Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. 3rd edition. New York, NY, USA: McGraw-Hill; 1968.

42. Li P, Liu P, Xiong RP, et al. Ski, a modulator of wound healing and scar formation in the rat skin and rabbit ear. Journal of Pathology. 2011;223(5):659–671. [PubMed]

43. Michalany J. Técnica Histológica Em Anatomia Patológica. 1st edition. São Paulo, Brasil: Editora Pedagogica e Universitaria; 1980.

44. Tango JS, Costa SI, Antunes AJ, Figueiredo IB. Composition du fruit et de l’huile de différentes variétés d’avocats cultivés dans l’Etat de São Paulo. Fruits. 1972;27(1):143–146.

45. Ahmed EM, Barmore CR. Avocado. In: Nagy S, Shaw PE, Wardowski WF, editors. Fruits of Tropical and sub Tropical Origin: Composition, Properties and Uses. Vol. 1. Lake Alfred, Fla, USA: AVI Publishing; 1990. pp. 121–156.

46. Gupta N, Jain UK. Prominent wound healing properties of indigenous medicines. Journal of Natural Pharmaceuticals. 2010;1(1):2–13.

47. Hess CT, Kirsner RS. Orchestrating wound healing: assessing and preparing the wound bed. Advances in Skin & Wound Care. 2003;16(5):246–258. [PubMed]

48. Declair V. Treatmento of chronics ulcers of difficult cicatrization with linoleic acid. Jornal Brasileiro de Medicina. 2002;82(6):36–41.

49. Elias PM, Brown BE. The mammalian cutaneous permeability barrier. Defective barrier function in essential fatty acid deficiency correlates with abnormal intercellular lipid deposition. Laboratory Investigation. 1978;39(6):574–583. [PubMed]

50. Park NY, Valacchi G, Lim Y. Effect of dietary conjugated linoleic acid supplementation on early inflammatory responses during cutaneous wound healing. Mediators of Inflammation. 2010;2010:8 pages.342328 [PMC free article] [PubMed]

51. Musalmah M, Nizrana MY, Fairuz AH, et al. Comparative effects of palm vitamin E and α-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats. Lipids. 2005;40(6):575–580. [PubMed]

52. Shetty S, Udupa S, Udupa L. Evaluation of antioxidant and wound healing effects of alcoholic and aqueous extract of Ocimum sanctum Linn in rats. Evidence-based Complementary and Alternative Medicine. 2008;5(1):95–101. [PMC free article] [PubMed]

53. Mack JA, Abramson SR, Ben Y, et al. Hoxb13 knockout adult skin exhibits high levels of hyaluronan and enhanced wound healing. The FASEB Journal. 2003;17(10):1352–1354. [PubMed]

54. Balbino CA, Pereira LM, Curi R. Mechanisms involved in wound healing: a revision. Brazilian Journal of Pharmaceutical Sciences. 2005;41(1):27–51.

55. Nunes JAT, Ribas-Filho JM, Malafaia O, et al. Evaluation of the hydro-alcoholic Schinus terebinthifolius raddi (Aroeira) extract in the healing process of the alba linea in rats. Acta Cirurgica Brasileira. 2006;21(3):8–15. [PubMed]

56. Stoff A, Rivera AA, Banerjee NS, et al. Promotion of incisional wound repair by human mesenchymal stem cell transplantation. Experimental Dermatology. 2009;18(4):362–369. [PMC free article] [PubMed]

57. Deodhar AK. Surgical physiology of wound healing: a review. Journal of Postgraduate Medicine. 1997;43(2):52–56. [PubMed]

58. Udupa SL, Udupa AL, Kulkarni DR. Studies on the anti-inflammatory and wound healing properties of Moringa oleifera and Aegle marmelos. Fitoterapia. 1994;65(2):119–123.

59. Hunt TK. Basic principles of wound healing. Journal of Trauma. 1990;30(12):122–128. [PubMed]

60. López HS, Camberos LO, Ocampo AA. Evaluación comparativa de la mezcla propoleo zabila con cicatrizantes comerciales. Veterinaria Mexico. 1989;20(1):407–413.

CITATION: Evid Based Complement Alternat Med. 2013; 2013: 472382.

Published online 2013 March 19. doi:  10.1155/2013/472382. PMCID: PMC3614059


SOURCE: Open access article from Evidence-based Complementary and Alternative Medicine : eCAM are provided here courtesy of Hindawi Publishing Corporation



Effects of Laser Acupuncture on Longitudinal Bone Growth in Adolescent Rats

Mijung Yeom,1 Sung-Hun Kim,1,2 Bina Lee,2 Xiuyu Zhang,1,2 Hyangsook Lee,1 Dae-Hyun Hahm,1,2 Youngjoo Sohn,2 and Hyejung Lee1,2

1Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea2Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea 


Longitudinal bone growth is the results of chondrocyte proliferation and hypertrophy and subsequent endochondral ossification in the growth plate. Recently, laser acupuncture (LA), an intervention to stimulate acupoint with low-level laser irradiation, Human Acupuncture Points ~ Credit: priyanphoenixhas been suggested as an intervention to improve the longitudinal bone growth. This study investigated the effects of laser acupuncture on growth, particularly longitudinal bone growth in adolescent male rats. Laser acupuncture was performed once every other day for a total of 9 treatments over 18 days to adolescent male rats. Morphometry of the growth plate, longitudinal bone growth rate, and the protein expression of BMP-2 and IGF-1 in growth plate were observed. The bone growth rate and the heights of growth plates were significantly increased by laser acupuncture. BMP-2 but not IGF-1 immunostaining in growth plate was increased as well. In conclusion, LA promotes longitudinal bone growth in adolescent rats, suggesting that laser acupuncture may be a promising intervention for improving the growth potential for children and adolescents.

CITATION: Mijung Yeom, Sung-Hun Kim, Bina Lee, et al., “Effects of Laser Acupuncture on Longitudinal Bone Growth in Adolescent Rats,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 424587, 7 pages, 2013. doi:10.1155/2013/424587


SOURCE: Open Access article courtesy of Hindawi - Creative Commons Attribution 3.0 Unported Licence



Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling

 Xiaobai Liu 1 2 3, Zhenhua Wang3 4, Ping Wang 2 3, Bo Yu 5, Yunhui Liu 5 and Yixue Xue 2 3

† Equal contributors

1 The 96th Class, 7-year Program, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China

2 Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China

3 Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China

4 Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China

5 Department of Neurosurgery, Shengjing Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110004, People’s Republic of China



It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs’ protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia.

Green Tea ~ CREDIT: KeyseekerMethods

Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated.


GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia.


These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

Additional conclusions from extended article

In conclusion, we have reported for the first time that pre-treatment with GTPs alleviated MCAO-induced BBB damage by protecting the TJ barrier intact and inhibiting PKCα signaling in rats. The results have given another insight into the thinking that GTPs could be chosen as a potential multi-targeted neuroprotective agent in the treatment of early cerebral ischemia.

CITATION: BMC Complementary and Alternative Medicine 2013, 13:187 doi:10.1186/1472-6882-13-187. Published: 21 July 2013


SOURCE: This is an Open Access article courtesy of BioMed Central - Creative Commons Attribution 2.0 License



Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

Hen-Yu Liu,1,2 Ming-Che Liu,3,4 Ming-Fu Wang,5 Wei-Hong Chen,1,2 Ching-Yu Tsai,1,2 Kuan-Hsien Wu,1,2 Che-Tong Lin,6 Ying-Hua Shieh,7 Rong Zeng,8 and Win-Ping Deng1,2,9,10

1Stem Cell Research Center, Taipei Medical University, Taipei, Taiwan2Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan3School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan4Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan5Department of Food and Nutrition, Providence University, Taichung, Taiwan6Graduate Institute of Oral Rehabilitation Sciences, Taipei Medical University, Taipei, Taiwan7Department of Family Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan8Department of Orthopedic Surgery, The Affiliated Hospital, Guangdong Medical College, Zhanjiang 524001, China9Translational Research Laboratory, Cancer Center, Taipei Medical University, Taipei, Taiwan10Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan


The aim of this study is to examine the therapeutic potential of deep sea water (DSW) on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8) and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP). Dog in ocean ~ Credit: hotblackDeep sea water at hardness (HD) 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3) by MTT assay. For in vivo animal study, bone mineral density (BMD) was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP) activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs) were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM).


In this study, the potential effects of DSW on bone regeneration in osteoporosis recovery were investigated; we found that DSW promoted osteoblast viability and increased BMD scores, trabecular bone numbers, and ameliorated symptoms of osteoporosis. These findings suggest that DSW could be a useful treatment for preventing osteoporosis in the near future.

CITATION: Hen-Yu Liu, Ming-Che Liu, Ming-Fu Wang, et al., “Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 161976, 11 pages, 2013. doi:10.1155/2013/161976. Accepted 27 June 2013


SOURCE: Open Access article courtesy of Hindawi - Creative Commons Attribution 3.0 Unported Licence