How Active Ingredients in CELSUS Bio Work in Reducing the Appearance of Scars

The following are clinical trials and studies related to our ingredients providing evidence for their efficacy in reducing the appearance of scars, stretch marks, and signs of aging.

Palmitoyl Tripeptide-5

In vitro efficacy study in human fibroblasts has shown excellent collagen building capacity of Palmitoyl Tripeptide-5 (PT-5) compared to the positive standard Tissue Growth Factor (TGF) and increase of collagen synthesis by 119% compared to the positive standard TGF. In vivo clinical study of anti-wrinkle effect of PT-5 on 60 healthy volunteers has been performed. Various concentrations of PT-5 (1% and 2.5% respectively) were applied twice daily for 84 days. Effect on wrinkles is a 350% improvement compared to placebo. Clinical trials have thus shown that PT-5 is capable of reducing and changing the type and aspect of wrinkles that add years to your appearance. Pentapharm Ltd, Basel, Switzerland

See also: J.E. Murphy-Ullrich, M. Poczatek, Cytokine & Growth Factor Reviews, 11, 2000, 59–69

Tamanu Oil – Calophyllum inophyllum

The Australian Society of Cosmetic Chemists has researched Tamanu oil chemical compounds and the beneficial effects in the role of anti-ageing and improvement of scars. The Bioscience Laboratories concluded that Tamanu oil’s ability to improve the appearance of scars was significant after a nine week study was completed on six subjects with obvious scars for one year or more. Tamanu oil was applied twice daily for nine weeks on obviously improvement appeared after six weeks and continued throughout the nine week test. Quantitative measurements of skin color for melanin (darkness) and hemoglobin (redness) were made on the scar and surrounding normal skin areas, as well scars were rated for roughness, length and width. The subjects' scar length was reduced by an average 0.28 centimeters, and width was reduced by an average 0.12 centimeters. "Calophyllum inophyllum – Tamanu oil the African, Asian, Polynesian and Pacific Panacea". Dweck, A.C. International Journal of Cosmetic Science 24, 6, 1-8 (2002).

“Tamanu or Calophyllum inophyllum has proved that its virtues not only withstand the scrutiny of independent traditional use, but also can be proven in modern in vivo studies to be as effective as its legend suggested.” A.C. Dweck. International Journal of Cosmetic Science, 2002, 24, p1.

In a search for anti-tumor-promoting agents, Faculty of Pharmacy, Meijo University, Tempaku, Nagoya (Japan) carried out a primary screening of ten 4-phenylcoumarins isolated from Calophyllum Inophyllum, by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-Otetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without any cytotoxicity. CalocoumarinA (5) showed more potent activity than any of the other compounds tested. The results of the present investigation indicate that some of these 4-phenylcoumarins might be valuable as potential cancer chemopreventive agents (anti-tumor-promoters). "The Cancer Chemopreventative Agents, 4-Phenylcoumarins from Calophyllum". M. Itoigawa. Cancer Letters, Volume 169, Issue 1, Pages 15-19 

Cotton Thistle

This study demonstrates the restructuring power of cotton thistle, when it is used for the treatment of damaged skin. The study measures the expression of the biological markers of keratinocyte differentiation; Involucrin, Loricrin, and LEKTI (Lympho-Epithelial Kazal Type related Inhibitor). The results clearly show that Cotton Thistle effectively repairs damaged skin, by stimulating keratinocyte differentiation. The expression of protein bio-markers, Loricrin and Involucrin, demonstrates good cell differentiation, from the supra-basal layer up to the terminal stage. Good expression of the marker LEKTI shows that cotton thistle will help strengthen cellular cohesion thereby improving the protective barrier effect of the skin.

The repairing performance of cotton thistle has been evaluated in a model of severe epidermal damage. The repairing performance can be estimated by measuring the formation of a neo-epidermis under the burned surface or around the edges of the wound, corresponding to the early stages of epidermal reparation. Result: In severely damaged skin cotton thistle stimulates the processes of cutaneous repair.

Another study carried out on skin explants proves the potential of Cotton Thistle as a dermal regenerator. The study monitored collagen neo-synthesis in skin explant samples maintained in living conditions for several days. Newly synthesized pro-collagen was measured by immuno-enzymatic assay. All the results are statistically significant. Cotton thistle promotes in-depth skin regeneration, replenishes strength and firmness and leads to the effective repair of damaged skin.

Gattefossé : 36 chemin de Genas - BP 603 - F-69804 Saint-Priest Cedex – France.

Aloe Vera - Aloe barbadensis

In this work, we report the influence of Aloe Vera on the collagen content and its characteristics in a healing wound. It was observed that Aloe Vera increased the collagen content of the granulation tissue as well as its degree of cross linking as seen by increased aldehyde content and decreased acid solubility. The type I/type III collagen ratio of treated groups were lower than that of the untreated controls, indicating enhanced levels of type III collagen. Wounds were treated either by topical application or oral administration of Aloe Vera to rats and both treatments were found to result in similar effects. “Influence of Aloe vera on collagen characteristics in healing dermal wounds in rats.” P Chithra, G B Sajithlal, G Chandrakasan. Molecular and Cellular Biochemistry, 181: 1-2, 71-76.

In the present work, we have studied the influence of Aloe Vera on the content of glycosaminoglycan (GAG) and its types in the granulation tissue of healing wounds. We have also reported the levels of a few enzymes involved in matrix metabolism. The amount of ground substance synthesized was found to be higher in the treated wounds, and in particular, hyaluronic acid and dermatan sulphate levels were increased. The levels of the reported glycohydrolases were elevated on treatment with Aloe Vera, indicating increased turnover of the matrix. Both topical and oral treatments with Aloe Vera were found to have a positive influence on the synthesis of GAGs and thereby beneficially modulate wound healing. P Chithra, G.B Sajithlal, Gowri Chandrakasan, (1998) Influence of Aloe Vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. Journal of Ethnopharmacology, 59: 179-186. Doi: 10.1016/S0378-874(97)00112-8

Objective: To demonstrate the microcirculatory and wound healing effects of Aloe Vera on induced second degree burn wounds in rats. Conclusion: Aloe Vera could exhibit the actions of both anti-inflammation and wound healing promotion when applied on a second-degree burn wound. “Therapeutic effects of Aloe Vera on cutaneous microcirculation and wound healing in second degree burn model in rats”. Somboonwong J, Thanamittramanee S, Jariyapongskul A, et al. J Med Assoc Thai. 2000 Apr;83(4):417-25. PMID: 10808702

In this topical study the influence of Aloe Vera, on the wound healing process was investigated with microscopic and cell count methods. The results show that the number of neutrophil, macrophage, and fibroblast cells and the wound thickness in the control group were statistically different from the experimental groups. It was found that the wound diameter thickness in the experimental group was greatly lower due to twice administration of gel and the power of wound healing was more than other groups. “Influence of Aloe Vera gel on dermal wound healing process in rat”. Nasrin Takzare, Mir-Jamal Hosseini, Gholamreza Hasanzadeh, Hamideh Mortazavi, Alireza Takzare, Parisa Habibi. Toxicology Mechanisms and Methods (2009), Volume: 19, Issue: 1, Pages: 73-77

"Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model". Heggers JP, Elzaim H, Garfield R, et al. (1997). Journal of alternative and complementary medicine 3 (2): 149–53.doi:10.1089/acm.1997.3.149. PMID 9395704.

"Wound healing. Oral and topical activity of Aloe vera". Davis RH, Leitner MG, Russo JM, Byrne ME (November 1989). Journal of the American Podiatric Medical Association 79 (11): 559–62. PMID 2607423.

"The efficacy of aloe vera for burn wound healing: a systematic review". Maenthaisong R, Chaiyakunapruk N, Niruntraporn S et al. (2007). Burns 33 (6): 713–718. doi:10.1016/j.burns.2006.10.384. PMID 17499928.

Gotu Kola - Centella asiatica

Scar Management (Hypertrophic and Keloid): Centella has long been recommended for the treatment of keloids and/or hypertrophic scars. In one open clinical trial, 227 patients were divided into two groups and treated with oral Centella alone or surgical scar revision plus Centella at doses of 60-150 mg daily for up to 18 months. In the Centella-only group, 116 of 139 patients (82%) experienced relief of symptoms and disappearance of inflammation. In the 88 subjects in the combined surgery and Centella group, 72 percent demonstrated improvement. “Clinical study of a new antikeloid agent”. Bosse JP, Papillon J, Frenette G, et al. Ann Plast Surg 1979;3:13-21.

In addition to its oral use, Centella has been used as a topical cream in a comprehensive scar management program. Observationally, it was found to improve scar maturity from an average of six months without treatment to three months with treatment. “New innovations in scar management”. Widgerow AD, Chait LA, Stals R, Stals PJ. Aesthetic Plast Surg 2000;24:227-234.

Objective: To investigate the effects of asiaticoside on the expression of Smad protein by hypertrophic scar fibroblasts (HSFs) and to clarify the mechanism of asiaticoside in scar treatment. Result: Asiaticoside inhibits scarring probably by enhancing the expression of inhibitory Smad7, and is a potential treatment for scarring. “Effects of asiaticoside on the expression of Smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts”. Qi SH, Xie JL, Pan S, Xu YB, Li TZ, et al. Clin Exp Dermatol. 2008 Mar;33(2):171-5. PMID: 18201262

Asiaticoside (ATS) isolated from the leaves of Centella asiatica possesses strong wound-healing properties and reduces scar formation. However, the specific effects of asiaticoside on the formation of keloidal scars remain unknown. In the present study, we evaluated the in vitro effects of asiaticoside on the proliferation, collagen expression, and transforming growth factor (TGF)-β/Smad signaling of keloid-derived fibroblasts. Taken together, these results suggest that asiaticoside could be of potential use in the treatment and/or prevention of hypertrophic scars and keloids. “Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts”. Tang B, Zhu B, Liang Y, Bi L, Hu Z, Chen B, et al. Arch Dermatol Res. 2011 Oct;303(8):563-72.

Anti-aging/Wrinkles: A randomized double-blind study on the skin of female volunteers to investigate the effects of topically applied madecassoside (a key compound in Gotu Kola) on structural skin properties. After six months of treatment, they detected significant improvements in deep and superficial wrinkles, suppleness, firmness, roughness and skin hydration. The study found that two-thirds of the subjects showed improvement in skin regeneration and aesthetics. "Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin”. M Haftek et al. Experimental Dermatology. November 2008.

Wound healing: Centella has several pharmacological actions, based primarily on in vivo experiments. Compared to control wounds, rats treated with gotu kola had a higher degree of epithelialization and a significantly more rapid rate of wound contraction. “Effects of Centella asiatica extract on dermal wound healing in rats”. Suguna L, Sivakumar P, Chandrakasan G. Indian J Exp Biol 1996;34:1208-1211. and “Effect of Centella asiatica on normal and dexamethasone-suppressed wound healing in Wistar Albino rats”Shetty BS, Udupa SL, Udupa AL, Somayaji SN.. Int J Low Extrem Wounds 2006;5:137-143.

Examination of gene expression to determine gene activation in human dermal fibroblast in the presence of asiaticoside (a key compound in Gotu Kola). Fifty-four genes with known functions of cell growth and synthesis of the extracellular matrix were investigated and it was found that all were significantly activated at various time points. Result: there is a close correlation among the beneficial cellular gene activation and protein production in response to asiaticoside treatment. "Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts." L Lu et al. International Journal of Dermatology. November 2004.

A June 2008 study appearing in the periodical "Planta Medica" was designed to investigate the effect of madecassoside (a key compound in Gotu Kola) on burn wound healing and its possible mechanism of action. The researchers found that wound closure reached its peak effect after twenty days in the group receiving the highest dose. Further analysis revealed that madecassoside alleviated infiltration of inflammatory cells as well as enhanced dermal proliferation caused by endothelial cell growth. The authors concluded that these data suggest madecassoside has significant wound-healing activity and the use of Gotu kola leads to successful treatment of burn injury. Additionally, results from this study signify that the effect of madecassoside on wound healing may involve several mechanisms including anti-oxidative activity, collagen synthesis and angiogenesis (formation of new blood vessels) in burns. "Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice”. M liu et al. Planta Medica. June 2008.

“Effect of the triterpenoid fraction of Centella asiatica on macromolecules of the connective matrix in human skin fibroblast cultures”. Tenni R, Zanaboni G, De Agostini MP, Rossi A, Bendotti C, Cetta G. Italian Journal of Biochemistry. 1988 Mar-Apr; 37(2):69-77.

Antioxidant properties: Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance. “Asiaticoside-induced elevation of antioxidant levels in healing wounds”. Shukla A et al. Phytotherapy Research Journal. 1999 Feb;13(1):50-4

Calendula - Calendula officinalis

Wounds were covered with 5% unguentum containing fractions C1 and C5, isolated from the flowers of Calendula officinalis in combination with allantoin. The combination applied markedly stimulates physiological regeneration and epithelialization. This effect is assumed to be due to more intensive metabolism of glycoproteins, nucleoproteins and collagen proteins during the regenerative period in the tissues. “Influence of the physiological regeneration and epithelialization using fractions isolated from Calendula officinalis”. Klouchek-Popova E, Popov A, Pavlova N, Krusteva S. Acta Physiol Pharmacol Bulg. 1982;8(4):63-7. PMID:7185264

The effects of oral and topical application of Calendula officinalis flower extract on excision wounds were checked. The parameters assessed were the days needed for re-epithelization and percentage of wound closure. The hydroxy proline and hexosamine content in the granuloma tissue of the wound was also measured. The percentage of wound closure was 90.0% in the extract-treated group, whereas the control group showed only 51.1% on the eighth day of wounding (p < .01). The days needed for re-epithelization were 17.7 for the control animals; extract treatment at a dose of 20 or 100 mg/kg b.wt reduced the period to 14 and 13 days, respectively. A significant increase was observed in the hydroxy proline and hexosamine content in the extract-treated group compared with the untreated animals. The data indicate potent wound healing activity of Calendula officinalis extract. “Wound healing activity of flower extract of Calendula officinalis”. Preethi KC, Kuttan R. J Basic Clinic Physiol Pharmacol. 2009;20(1):73-9. PMID: 19601397

Comfrey - Symphytum officinale

Two concentrations of comfrey creams were evaluated for the treatment of fresh abrasions among 278 patients. 29 A 10% comfrey formulation was compared to a 1% comfrey formulation, which was considered the reference or placebo cream. The topical application of 10% comfrey led to significantly faster wound healing than the reference cream after 2 to 3 days of application. No adverse effects or problems with drug tolerability occurred. Specifically, cutaneous reactions were observed in none of the patients throughout the 10-day observation phase. Conclusion: Symphytum herb extract can be attributed distinct wound healing effects, effects that can explicitly be used in paediatry. “Wound healing effects of a Symphytum herb extract cream (Symphytum x uplandicum): results of a randomized, controlled double-blind study”. Barna M, Kucera A, Hladivoca M, Kucera M. Wein Med Wochenschr. 2007;157(21-22):569-74.

Plantain - Plantago major

Proteins with physicochemical properties and biological activity similar to those of membranotropic homeostatic tissue-specific bioregulators that had been found earlier in various animal tissues were discovered in leaves of the common plantain (Plantago major L.). To study the specific activity of these plant proteins, we developed an experimental model for organotypic roller cultivation of newt (Pleurodeles waltl) skin tissue in vitro. We showed that the plant proteins of interest exert the wound-healing effect, which is characteristic of this plant, on the skin of vertebrates both in vitro and in vivo. “Study of a new group of bioregulators islolated from the greater Plantain (Plantago Major L.)” M.S. Krasnov, V.P. Yamskova, D.V. Margasyuk, et al. Applied Biochemistry and Microbiology, 2011, Vol. 47, No. 2, pp. 128-135.

Eclipta Alba - Eclipta prostrata

Wound Healing: Ethanolic extracts of the leaves Eclipta Alba has been evaluated for its wound healing activity in wistar rats. Enhanced wound healing activity may be due to free radical scavenging action of the plant and the enhanced level of antioxidant enzymes in granuloma tissue. “Phytochemical and Pharmacological potential of Eclipta Alba: A Review”. R.M. Thorat, V.M. Jadhav, D.D. Gaikwad, S.L. Jadhav. International Research Journal of Pharmacy, 2010 pp. 77-80.

Analgesic: The results reflects that analgesic effects and therapeutic efficacy of the extract on animal models which are comparable with those of standard drugs such as Aspirin and Morphine. “Analgesic activities of the medicinal plants of Wedelia trilobata, Wedelia biflora and Eclipta alba in standard experimental animal models”, S Sureshkumar, S Bhama. Biosciences, Biotechnology Research Asia, Volume 04 Number(1)

Anti-inflammatory: Anti-inflammatory activity of the tested extract was comparable with that of the standard drug indomethacin (10 mgkg ) and cyproheptadine (8 mgkg ). The results lend support to the traditional use of E. prostrata in the treatment of inflammatory diseases. “Anti-inflammatory activity of methanolic extract of Eclipta prostrata L. (Astearaceae)” G. Arunachalam, N. Subramanian, G. P. Pazhani and V. Ravichandran, African Journal of Pharmacy and Pharmacology Vol. 3(3). pp. 097-100, March, 2009

Anti-oxidant: Eclipta prostrata Linn (Compositae), a traditional medicine has been used for treatment of diverse symptoms e.g. hyperlipidemia, atherosclerosis and skin diseases. This study, hexane extract of E. prostrata Linn was evaluated for bioactivities. The extract showed its new action as a potential vasorelaxant. Moreover, antioxidative and cytotoxic activities of the extract were also observed. All the fractions exhibited antimicrobial activity with minimum inhibitory concentration (MIC) range of 64-256 μg/mL. The results imply therapeutic value of the plant species as an alternative medicinal source of potential vasorelaxants. “Bioactivity Evaluation of Eclipta prostrata Linn: A Potential Vasorelaxant”. Supaluk Prachayasittikul, Orapin Wongsawatkul, Thummaruk Suksrichavalit, Somsak Ruchirawat and Virapong Prachayasittikul. European Journal of Scientific Research. Aug 2010. Volume 44 Issue 2

Onion Bulb Extract - Allium cepa

“The ability of onion extract gel to improve the cosmetic appearance of postsurgical scars”. Zoe Diana Draelos MD. Journal of Cosmetic Dermatology. June 2008. Volume 7, Issue 2, pages 101–104.