The Science

The Science Behind 8 Action Cold Sore Management

1. Anti-Inflammatory

1. Flavonoids’ from Australian Manuka Honey​

Manuka Honey is a natural product that could be useful for treating cold sores. The safety and efficacy of honey in herpes infection is also proved in a few small clinical trials. A study conducted on 16 adult patients with a history of recurrent herpetic lesions showed that the pain and duration of attacks, the occurrence of crusting, and the healing period with topical administration of honey were much better than with acyclovir treatment.The flavonoids present in honey contribute to its antiviral properties.1-4

2. Arginine blockers from Lysine

Lysine, with its arginine blocking property, may help slow down or prevent the growth of HSV-1. In-vitro studies have shown arginine deficiency to suppress HSV-1 replication and hamper viral development. A study that evaluated the effects of lysine for the prevention and treatment of recurrent herpes simplex infection found lysine to be effective for reducing occurrence, severity and healing time for recurrent HSV infection. 5-8

Lysine may help prevent HSV from being more active. A study on guinea pigs found that lysine-treated skin remained clinically normal; whereas, untreated controls displayed clinical symptoms for nearly three days post-inoculation.9

Lysine also accelerates recovery from herpes simplex infection and suppresses disease recurrence. A study comprising 30 subjects measured the safety and effectiveness of a cream containing lysine, zinc, and herbal-based product in cold sores. The study found that the cream cleared cold sores in 40 percent of the participants by the third day and 87 percent by the end of the sixth day.10,11

3. Zinc ions as inhibitors of the enzyme DNA polymerase

Zinc can coat HSV virion (single virus particle) and prevent infection by inhibiting virion glycoprotein function. Zinc inhibits HSV in every point of the viral life cycle – viral polymerase function, protein production and processing, and free virus inactivation.12

In-vitro studies show that zinc ions selectively inhibit the enzyme DNA polymerase, a key enzyme required for viral replication and transcription. Zinc ions can inhibit virus replication completely at concentrations as low as just 0.1 mM. Apart from in-vitro studies, several human studies involving topical zinc application have shown a significantly reduced recurrence and duration of infection. 13-16

Zinc oxide – Shorten the duration of cold sores

Zinc oxide cream may also shorten the duration of cold sores. Cold sores treated with zinc oxide were found to clear sooner than those treated with placebo. The time until recovery was 5.0 days in patients who received treatment with the zinc oxide cream, while the recovery period was 6.5 days in placebo.15

Zinc oxide also reduces cold sores symptoms such as blistering, soreness, itching, and tingling. Use of a topical formulation containing zinc oxide, l-lysine, and 14 other ingredients was associated with a decrease in symptoms and duration of cold sore lesions in 30 patients. By day 6, 87% of patients were cured, and by day 11, all the participants were cured.17

4. The virus's entry blockers from Propolis 4. The virus's entry blockers from Propolis

Propolis exerts antiviral action by blocking partly the virus’s entry within the cells, which, in turn, affects viral replication. The antiviral effect of propolis extracts and selected constituents were analyzed in a cell culture study. Propolis extracts were found to exhibit high levels of antiviral activity against HSV-1 – plaque formation (regions of cell destruction by the virus) was significantly reduced by >98%. The study showed that propolis extracts might be suitable for topical application against herpes infection.18

Reference (Anti-Inflammatory Activity)
  1. Watanabe K, Rahmasari R, Matsunaga A, et al . Anti-influenza viral effects of honey in vitro: potent high activity of manuka honey. Arch Med Res. 2014;45:359–65.
  2. Shahzad A, Cohrs RJ. In vitro antiviral activity of honey against varicella zoster virus (VZV): A translational medicine study for potential remedy for shingles. Transl Biomed. 2012;3:1–5.
  3. Zeina B , Othman O , al-Assad S . Effect of honey versus thyme on Rubella virus survival in vitro. J Altern Complement Med. 1996;2:345–8.
  4. Al-Waili NS. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions. Med Sci Monit. 2004;10(8):MT94-MT98.
  5. Griffith RS, DeLong DC, Nelson JD. Relation of arginine-lysine antagonism to Herpes simplex growth in tissue culture. Chemotherapy. 1981;27:209-213.
  6. Mailoo VJ, Rampes S. Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence. Integr Med (Encinitas). 2017;16(3):42-46.
  7. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175(4):183-90.
  8. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol. 1984;58(6):659-666.
  9. Ayala E, Krikorian D. Effect of L-lysine monohydrochloride on cutaneous herpes simplex virus in the guinea pig. J Med Virol. 1989;28:16-20.
  10. Griffith RS, Norins AL, Kagan C. A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica. 1978;156(5):257-67.
  11. Singh BB, Udani J, Vinjamury SP, et al. Safety and effectiveness of an L-lysine, zinc, and herbal-based product on the treatment of facial and circumoral herpes. Altern Med Rev. 2005;10(2):123-127.
  12. Read SA, Obeid S, Ahlenstiel C, et al. The Role of Zinc in Antiviral Immunity. Adv Nutr. 2019;10(4):696-710.
  13. Shlomai J, Asher Y, Gordon YJ, et al. Effect of zinc ions on the synthesis of Herpes simplex virus DNA in infected BSC-1 cells. Virology. 1975;66:330-335.
  14. Fridlender B, Chejanovsky N, Becker Y. Selective inhibition of Herpes simplex virus type I DNA polymerase by zinc ions. Virology. 1978;84:551- 554.
  15. Godfrey HR, Godfrey NJ, Godfrey JC, et al. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med. 2001;7(3):49-56.
  16. Arens M, Travis S. Zinc salts inactivate clinical isolates of herpes simplex virus in vitro. J Clin Microbiol. 2000;38(5):1758-1762.
  17. Singh BB, Udani J, Vinjamury SP, et al. Safety and effectiveness of an L-lysine, zinc, and herbal-based product on the treatment of facial and circumoral herpes. Altern Med Rev. 2005;10(2):123-127.
  18. Schnitzler P, Neuner A, Nolkemper S, et al. Antiviral activity and mode of action of propolis extracts and selected compounds. Phytother Res. 2010;24 Suppl 1:S20-S28.

2. Pro-Wound Healing

1. The increase of the release of oxygen from hemoglobin - Manuka Honey

Manuka Honey possesses a multitude of properties that can help speed up the healing process in cold sores. The acidity of honey increases the release of oxygen from hemoglobin and discourages the proliferation of harmful proteases. Proteases are known to delay wound healing.1

Another important property of honey is its high osmolarity or high sugar content. The high osmolarity of honey helps drain fluid out of the wounds, which assists the clearance of lymph, and this mechanism promotes wound healing.1

2. The maintenance of collagen's triple helix structure – Glycine

Glycine is the smallest amino acid, and thus when topically applied, it can penetrate and repair the skin easily. Glycine may help repair damaged tissue and promote skin healing. Glycine also helps maintain skin firmness. Glycine residues are necessary to maintain collagen’s triple-helix structure and hence support the production of healthy collagen. The role of glycine to stimulate collagen synthesis and repair damaged skin has been shown in many studies.2

When used in combination with two other amino acids, leucine and proline, glycine can improve wrinkles and retard skin aging.3

3. The stimulating effect on skin fibroblast growth – Folic Acid

Folic acid has skin regeneration and anti-photoaging properties and is a popular ingredient in skin products. Folic acid-containing creams improve skin condition in patients with skin damage from UV radiation.4,5

Folic acid also shows beneficial effects on skin fibroblast. Skin fibroblasts are cells within the inner layer of skin that are responsible for generating connective tissue. Skin fibroblasts also allow the skin to recover from injury. Treatment of cultured skin fibroblasts with folic acid stimulates cellular DNA repair capacity, demonstrating that this essential vitamin may be a useful treatment option for photo-aged skin. DNA damage from UV radiation can cause cell death if no repair mechanism is in place.6,7

A study by Debowska et al. found that treatment with folic acid increased the repair rate of UV-induced DNA damage. The study showed that a 30-day treatment with folic acid cream improved skin moisturization and decreased water loss (Transepidermal water loss). Skin elasticity was almost two times greater after using the tested cream. A decrease of skin roughness and desquamation index (linked to the level of skin dryness) was also observed.6

4. The stimulative effect of Propolis on mast cells (participants in all three phases of wound healing - inflammatory, proliferative, and remodelling)

Propolis helps speed up healing time and reduces the symptoms in cold sores. Jautová et al. tested a lip cream containing propolis extract against acyclovir in patients with herpes labialis. The study found that healing was reached after three days with Propolis and four days with acyclovir. Symptoms relief such as pain, burning, itching, tension, and swelling were more in the propolis group.8

A study that assessed the efficacy of propolis ointment in patients with cold sores recurrences found that the rate of lesion healing was significantly faster among the patients treated with propolis ointment (6 days) compared to those treated with placebo (9 days). The patients who applied the Propolis ointment experienced pain relief earlier than those who applied the placebo ointment. At the end of the treatment, 81.8% of the patients in the propolis ointment group judged their treatment ‘very effective’.9 

The anti-inflammatory and antimicrobial properties of Propolis make it useful in wound healing. Wound healing is categorized into three phases: inflammatory, proliferative, and remodeling – and mast cells participate in all three phases. A study by Barroso et al. found that topical Propolis was more effective than a popular steroid cream, dexamethasone, in reducing mast cells in oral surgery wounds. Mast cells are specialized immune cells associated with inflammation and slowed wound healing. The anti-inflammatory action of Propolis mediated by mast cells was more effective than dexamethasone in the inflammatory phase of healing.10

5. The increase of re-epithelisation – Zinc oxide

A well-known property of zinc oxide is its healing capacity. The benefits of zinc in wound healing are supported by reports of delayed wound healing in patients with zinc deficiency. When these zinc-deficient patients were supplemented with zinc therapy, normalization of the wound healing mechanisms was observed.11 

Topical zinc oxide increases wound healing and reepithelialization. The various processes associated with the initiation, maintenance, and completion of epithelialization is essential for proper wound closure. The topical use of zinc oxide improves the rate of wound healing in patients, regardless of their zinc status.11

Zinc oxide also enhances the ability of matrix metalloproteinases (MMPs) to break down collagen fragments enzymatically.11

6. Collagen synthesis requires hydroxylation of lysine and proline, and co-factors such as ferrous iron and vitamin C

Wound healing is a complex phenomenon that requires different minerals, vitamins, and other factors. Lysine is required for collagen formation and plays a crucial role in wound healing. Collagen is an essential protein that gives structure to the skin and affects wound repair. During biosynthesis, collagen acquires several post-translational modifications, including lysine modifications, which are vital to collagen’s structure and biological functions.12

Apart from supporting collagen formation, lysine also acts as a binding agent, increasing the number of new cells at a wound. Animal studies indicate that lysine may speed up wound healing and reduce recovery time. In animal tissue, lysine was found to become more active at the site of a wound. This process activated cell function as well as regulated gene expression to promote tissue repair. Lysine may also promote the formation of new blood vessels.13

7. Coenzyme Q10 increases levels of collagen-like polymer (CLP) treated with coenzyme Q1

Coenzyme Q10 also possesses anti-inflammatory and wound healing properties. A mice study found the collagen-like polymer levels (CLP) to be significantly higher with coenzyme Q10 compared to the control group. Coenzyme Q10 group also showed significant inhibition on inflammatory markers, myeloperoxidase, and phospholipase A2, compared to the control group. These data indicate that coenzyme Q10 may have an anti-inflammatory and a wound-healing effect.14

Reference (Pro-wound healing)
  1. Johnston M, McBride M, Dahiya D, et al. Antibacterial activity of Manuka honey and its components: An overview. AIMS Microbiol. 2018;4(4):655-664.
  2. de Paz-Lugo P, Lupiáñez JA, Meléndez-Hevia E. High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids. 2018;50(10):1357-1365.
  3. Kawashima M, Yokose U, Hachiya A, et al. Improvement of crow’s feet lines by topical application of 1-carbamimidoyl-L-proline (CLP). Eur J Dermatol. 2013;23(2):195-201.
  4. Knott A, Koop U, Mielke H, et al. A novel treatment option for photoaged skin. J Cosmet Dermatol. 2008;7(1):15-22.
  5. Pustisek N, Situm M. UV-radiation, apoptosis and skin. Coll Antropol. 2011;35 Suppl 2:339-341.
  6. Debowska R, Rogiewicz K, Iwanenko T, et al. Folic acid (Folacin) – new application of a cosmetic ingredient. Kosmetische Medizin. 2005;3:16–22.
  7. Gisondi P, Fantuzzi F, Malerba M, Girolomoni G. Folic acid in general medicine and dermatology. J Dermatolog Treat. 2007;18(3):138-146.
  8. Jautová J, Zelenková H, Drotarová K, et al. Lip creams with propolis special extract GH 2002 0.5% versus aciclovir 5.0% for herpes labialis (vesicular stage): Randomized, controlled double-blind study. Wien Med Wochenschr. 2019;169(7-8):193-201.
  9. Hoheisel O. The effects of Herstat (3% propolis ointment ACF) application in cold sores: a double-blind placebo-controlled clinical trial. Journal of Clinical Research. 2001;4(65‐75): 65‐75.
  10. Barroso PR, Lopes-Rocha R, Pereira EM, et al. Effect of propolis on mast cells in wound healing. Inflammopharmacology. 2012;20(5):289-294.
  11. Agren MS. Studies on zinc in wound healing. Acta Derm Venereol Suppl (Stockh). 1990;154:1-36.
  12. Yamauchi M, Sricholpech M. Lysine post-translational modifications of collagen. Essays Biochem. 2012;52:113-133.
  13. Guo S, Luisa A. DiPietro LA. Factors affecting wound healing. J Dent Res. 2010 Mar; 89(3): 219–229.
  14. Choi BS, Song HS, Kim HR, et al. Effect of coenzyme Q10 on cutaneous healing in skin-incised mice. Arch Pharm Res. 2009;32(6):907-913.

3. Soothing

1. Zinc oxide - Astringent, soothing and protective properties

In addition to its healing properties, zinc oxide has astringent, soothing, and protective properties. Zinc oxide provides a physical barrier, which helps prevent skin irritation and helps heal damaged skin. Zinc oxide is a key ingredient in skin products for eczema, slight excoriations, wounds, and hemorrhoids.1

2. Aloe vera – Well known for its soothing effect

The soothing effects of Aloe vera are well known. Aloe vera is beneficial for all forms of burn, be it radiation, thermal, or solar. It has also been demonstrated that it has a prophylactic effect if used before, during, and after these skin damaging events. The polysaccharides, mannose-6-phosphate, and complex anthraquinones all contribute synergistically to the benefits of this material.2

Reference (Soothing)
  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 14806, Zinc oxide. Accessed Oct. 2, 2020.
  2. Korać RR, Khambholja KM. Potential of herbs in skin protection from ultraviolet radiation. Pharmacogn Rev. 2011;5(10):164-173.

4. Cooling

1. Menthol effect on neuronal receptors called TRP melastatin 8 receptor (TRPM8)

Topical menthol is well known for its cooling and soothing property. Menthol creates a cooling sensation by attaching to a neuronal receptor called TRP melastatin 8 receptor (TRPM8), a low temperature-sensing receptor in the skin and mucosa. TRP’s are present throughout the body, but TRPM8 is found mainly within thermosensitive neurons, which, apart from responding to temperature reductions, are specifically sensitive to menthol.1,2

In a study of 10 healthy male volunteers, menthol was applied topically in three concentrations (0.5%, 4.6%, and 10.0%) to the left thigh. The skin‐cooling effects were measured using a digital infrared camera and were also collected as patient self‐reports. The study found that all three concentrations of menthol gel significantly decreased skin temperature for at least one hour.3

References (Cooling)
  1. Yang S, Wang R, Wan G, et al. A Multiscale Study on the Penetration Enhancement Mechanism of Menthol to Osthole. J Chem Inf Model. 2016;56(11):2234-2242.
  2. Wang H, Meng F. The permeability enhancing mechanism of menthol on skin lipids: a molecular dynamics simulation study. J Mol Model. 2017;23(10):279.
  3. Lasanen R, Julkunen P, Airaksinen O, et al. Menthol concentration in topical cold gel does not have significant effect on skin cooling. Skin Res Technol. 2016;22(1):40-45.

5. Antiseptic effect

1. Menthol - Stimulation of thermosensitive neurons associated with pain relief

In addition to its cooling and soothing effects, menthol also acts as a counterirritant to reduce pain sensation. Topically applied menthol gels result in a cooling sensation and are reported to act as a counterirritant to reduce pain sensation. Topical products containing menthol are commonly used in the management of pain. The ability of menthol to stimulate TRP melastatin 8 receptor (TRPM8) is responsible for its pain relief effect.1-3

Ice or cold packs have been used as pain relievers for years. Like ice or cold packs, menthol gel decreases arterial blood flow and provides pain relief.4

The pain relief activity of menthol was compared to ice or cold packs. Study participants were randomly assigned to four treatment groups – ice, menthol, ice-plus-menthol, and no treatment. The treatments were randomly applied for 20 minutes to the right forearm on four different days. The study found that ice, menthol, and ice-plus-menthol treatments all reduced blood flow compared with the “no treatment” group. The ice-plus-menthol treatment resulted in a more rapid and more significant reduction in blood flow. Menthol was also associated with significantly less discomfort than the ice.4

2. Melissa officinalis - Analgesic effect due to effects on the cholinergic system and nitric oxide pathway

Melissa officinalis is known to impart analgesic properties. The analgesic properties of Melissa officinalis are exerted through the cholinergic system and nitric oxide pathway.5

References (Analgesic effect)
  1. Yang S, Wang R, Wan G, et al. A Multiscale Study on the Penetration Enhancement Mechanism of Menthol to Osthole. J Chem Inf Model. 2016;56(11):2234-2242.
  2. Wang H, Meng F. The permeability enhancing mechanism of menthol on skin lipids: a molecular dynamics simulation study. J Mol Model. 2017;23(10):279.
  3. Lasanen R, Julkunen P, Airaksinen O, et al. Menthol concentration in topical cold gel does not have significant effect on skin cooling. Skin Res Technol. 2016;22(1):40-45.
  4. Topp R, Ledford ER, Jacks DE. Topical menthol, ice, peripheral blood flow, and perceived discomfort. J Athl Train. 2013;48(2):220-225.
  5. Bounihi A, Hajjaj G, Alnamer R, et al. In Vivo Potential Anti-Inflammatory Activity of Melissa officinalis L. Essential Oil. Adv Pharmacol Sci. 2013;2013:101759.

6. Reginerative

1. The anti-inflammatory activity of citral from Melissa officinalis essential oil

Melissa officinalis has antioxidant or radical scavenging effects, so studies were done to explore its anti-inflammatory activities further. A study by Guginski et al. used the “paw swelling” method to assess the inflammatory properties of Melissa officinalis. The study found that pre-treatment with Melissa officinalis significantly reduced inflammation-induced paw swelling or edema in rats and diminished the nociceptive response in mice. As per experts, the anti-inflammatory activity of melissa officinalis essential oil is due to the presence of citral.1-3

2. The inhibitory effect of Tea Tree constituents on the production of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-10

Besides antiviral and antibacterial properties, tea tree oil has anti-inflammatory properties that can come in handy when treating a cold sore. The anti-inflammatory effect of tea tree oil helps to soothe and relieve painful and irritated skin. It may also help reduce redness and swelling.4

Tea tree oil affects a range of immune responses. Tea tree oil can inhibit the production of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-10.5

3. Carnosol and carnosic acid in Rosemary oil and their anti-inflammatory activity

Rosemary oil has also demonstrated anti-inflammatory actions. Anti-inflammatory activity is mainly due to its components, carnosol, and carnosic acid. Rosemary essential oil and extract were found to significantly inhibit leukocyte migration, which, in turn, reduced the number of leukocytes or white blood cells at the site of inflammation, resulting in an anti-inflammatory response. Rosemary extract also inhibited other pro-inflammatory substances, such as nitric oxide and genes involved in the inflammatory cascade.6-8

4. Aloe vera juice and the inhibition of Interleukin 6 (IL-6) and IL-8, the reduction of leukocyte adhesion, an increase of IL-10 levels, and decrease of tumor necrosis factor (TNF) alpha levels

Apart from wound healing, Aloe vera also possesses anti-inflammatory activities. Aloe vera effectively inhibits inflammatory reactions by the inhibition of Interleukin 6 (IL-6) and IL-8, the reduction of leukocyte adhesion, an increase of IL-10 levels, and decrease of Tumor necrosis factor (TNF) alpha levels.9

5. Rhubarb components rhaponticin and the aglycone rhapontigenin and inhibition of enzymes cyclooxygenase and lipoxygenase and activation of hyaluronoglucosaminidase

Rhubarb, one of the most ancient and important herbs, is well known for its anti-inflammatory effects. Kolodziejczyk-Czepas et al. reviewed the anti-inflammatory effects of Rhubarb components rhaponticin and the aglycone rhapontigenin. The anti-inflammatory effects were found to be due to the inhibition of enzymes cyclooxygenase and lipoxygenase and activation of hyaluronoglucosaminidase. Apart from rhaponticin, other Rhubarb components known to possess anti-inflammatory effects include emodin, rhein, chrysophanol, and aloe-emodin.10,11

6. Rosmarinic acid, carnosic acid and salvianolic acid have a high antioxidant activity and are very significant scavenger of free radicals

Sage acts as a powerful antioxidant and anti-inflammatory agent. A study investigating the anti-inflammatory and antioxidant activity of Sage found the herb to have beneficial effects on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in rats. In vivo, extracts from sage leaf dose-dependently inhibited croton oil-induced ear swelling in mice.12,13

The antioxidant properties of sage are due to rosmarinic acid, ursolic acid, and carnosic acid. In addition, salvianolic acid, a rosmarinic acid dimer isolated from the sage extract, also has a high antioxidant activity and is a very significant scavenger of free radicals. Oleanolic acid also exhibited anti-inflammatory activity, but it is less active.12,14

The topical application of rosmarinic acid inhibits epidermal inflammation, while the anti-inflammatory action of ursolic acid is twofold more potent than that of indomethacin.14 

In a clinical study, the anti-inflammatory potency of sage extract was tested using the ultraviolet (UV) erythema test. The study found that compared to placebo, sage extract significantly reduced the ultraviolet-induced erythema to a similar extent as hydrocortisone.15

7. Calendula - Inhibition of pro-inflammatory cytokines and Cox-2 and subsequent prostaglandin synthesis

Calendula officinalis belonging to the family Asteraceae possess significant anti-inflammatory activity. A study on Calendula officinalis flower’s anti-inflammatory properties found that a combination of carotenoids, flavonoids, and triterpenoids was capable of mediating acute and chronic inflammation in mice. The inflammatory response of Calendula officinalis extract might be mediated by the inhibition of pro-inflammatory cytokines and COX-2 and subsequent prostaglandin synthesis.16

8. Glycyrrhizic acid from Liquorice sequesters HMGB1 and regulates the production of inflammatory cytokines, which, in turn, prevents contact dermatitis

Liquorice or Glycyrrhiza glabra has significant anti-inflammatory activity. Most of glycyrrhiza’s anti-inflammatory activity is due to its cortisol-like effects.17,18

Glycyrrhizic acid, extracted from the root of the licorice plant is useful in inflammatory skin diseases such as atopic dermatitis. In a mice model of atopic dermatitis, glycyrrhizic acid inhibited the release of the cytokines interleukins. By inhibiting the inflammatory factor HMGB1 (High-Mobility Group protein B1), glycyrrhizic acid improves the symptoms of atopic dermatitis. Glycyrrhizic acid sequesters HMGB1 and regulates the production of inflammatory cytokines, which, in turn, prevents contact dermatitis.19,20

Glycyrrhetinic acid, another important component of liquorice, exerts an effect similar to topical hydrocortisone in the treatment of eczema, contact and allergic dermatitis, and psoriasis. In many studies, glycyrrhetinic acid was found to be superior to topical cortisone, especially in chronic cases.21,22

9. Chlorophyll-a and its degradation products are good anti-inflammatory agents and can be used to treat inflammation and related diseases

Chlorophyll-a and its degradation products are good anti-inflammatory agents and can be used to treat inflammation and related diseases. A study by Subramoniam et al. evaluated the anti-inflammatory property of chlorophylls and their degradation products. Chlorophyll a and pheophytin-a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll-a inhibited bacterial lipopolysaccharide-induced TNF-α (a pro-inflammatory cytokine).23

References (Anti-inflammatory effect)
  1. Bounihi A, Hajjaj G, Alnamer R, et al. In Vivo Potential Anti-Inflammatory Activity of Melissa officinalis L. Essential Oil. Adv Pharmacol Sci. 2013;2013:101759.
  2. Miraj S, Rafieian-Kopaei, Kiani S. Melissa officinalis L: A Review Study With an Antioxidant Prospective. J Evid Based Complementary Altern Med. 2017;22(3):385-394.
  3. Guginski G, Luiz AP, Silva MD, et al. Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacol Biochem Behav. 2009;93(1):10-16.
  4. Carson CF, Hammer KA, Riley TV. Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006; 19(1): 50–62.
  5. Pearce AL, Finlay-Jones JJ, Hart PH. Reduction of nickel-induced contact hypersensitivity reactions by topical tea tree oil in humans. Inflamm Res. 2005;54(1):22-30.
  6. Nogueira de Melo GA, Grespan R, Fonseca JP, et al. Rosmarinus officinalis L. essential oil inhibits in vivo and in vitro leukocyte migration. J Med Food. 2011;14(9):944-946.
  7. Mengoni ES, Vichera G, Rigano LA, et al. Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia. 2011;82(3):414-421.
  8. Benincá JP, Dalmarco JB, Pizzolatti MG, et al.  Analysis of the anti-inflammatory properties of Rosmarinus officinalis L. in mice. Food Chemistry. 2011;124: 468-475.
  9. Rezazadeh F, Moshaverinia M, Motamedifar M, Alyaseri M. Assessment of Anti HSV-1 Activity of Aloe Vera Gel Extract: an In Vitro Study. J Dent (Shiraz). 2016;17(1):49-54.
  10. Xiang H, Zuo J, Guo F, et al. What we already know about rhubarb: a comprehensive review. Chin Med. 2020;15:88.
  11. Kolodziejczyk-Czepas J, Czepas J. Rhaponticin as an anti-inflammatory component of rhubarb: a minireview of the current state of the art and prospects for future research. Phytochem Rev. 2019;18(5):1375–1386.
  12. Kolac UK, Ustuner MC, Tekin N, et al. The Anti-Inflammatory and Antioxidant Effects of Salvia officinalis on Lipopolysaccharide-Induced Inflammation in Rats. J Med Food. 2017;20(12):1193-1200.
  13. Dawid-Pać R. Medicinal plants used in treatment of inflammatory skin diseases. Postepy Dermatol Alergol. 2013;30(3):170-177.
  14. Ghorbani A, Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. J Tradit Complement Med. 2017;7(4):433-440.
  15. Reuter J, Jocher A, Hornstein S, et al. Sage extract rich in phenolic diterpenes inhibits ultraviolet-induced erythema in vivo. Planta Med. 2007;73(11):1190-1.
  16. Preethi KC, Kuttan G, Kuttan R. Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action. Indian J Exp Biol. 2009;47(2):113-120.
  17. Kuroyanagi T, Saito M. Effect of prednisolone and glycyrrhizin on passive transfer of experimental allergic encephalomyelitis. Arerugi. 1966;15:67–74. 
  18. Cyong J, Otsuka Y. A pharmacological study of the anti-inflammatory activity of Chinese herbs. A review. Acupunct Electrother Res. 1982;7:173–202.
  19. Lee S.H, Bae I.H, Choi H, et al. Ameliorating effect of dipotassium glycyrrhizinate on an IL-4- and IL-13-induced atopic dermatitis-like skin-equivalent model. Archives of Dermatology Research. 2019;311:131–140.
  20. Wang Y, Zhang Y, Peng G, et al. Glycyrrhizin ameliorates atopic dermatitis-like symptoms through inhibition of HMGB1. International Immunopharmacology. 2018;60:9–17.
  21. Nokhodchi A, Nazemiyeh H, Ghafourian T. The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations. Farmaco. 2002;57:883–888.
  22. Saeedi M, Morteza-Semnani K, Ghoreishi M.R. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003;14:153–157.
  23. Subramoniam A, Asha VV, Nair SA, et al. Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α gene by the same. Inflammation. 2012;35(3):959-966.

7. Anti-Itch Effect

1. Tea tree oil due to its antiseptic properties can help heal infections that cause itchy skin

Tea tree oil can help soothe dry skin by reducing itching and irritation. Wallengren et al. found tea tree oil to be more effective than zinc oxide and clobetasone butyrate creams in treating eczema.1

Due to its antiseptic properties, tea tree oil can also help heal infections that cause itchy skin. A study conducted on 24 people found that tea tree oil was effective in reducing itchy eyelids. While 16 of the 24 participants were totally free of itching, the remaining showed some improvements.2

References (Anti-itch effect)
  1. Wallengren J. Tea tree oil attenuates experimental contact dermatitis. Arch Dermatol Res. 2011;303(5):333-338.
  2. Gao YY, Xu DL, Huang lJ, et al. Treatment of ocular itching associated with ocular demodicosis by 5% tea tree oil ointment. Cornea. 2012;31(1):14-17.

8. Moisturising

1. Polysaccharide component of Aloe vera is responsible for its moisturizing properties

A well-known property that makes Aloe vera a key ingredient in dermatological preparations is its moisturizing properties. Aloe vera extract improves skin hydration, possibly through a humectant mechanism. The polysaccharide component of Aloe vera is responsible for the moisturizing properties. When applied to the forearm of 20 female subjects, formulations containing Aloe vera extract increased the water content of the stratum corneum.1 

The retention of water and the hydration balance in the superficial skin layers ensures the skin’s elasticity and flexibility. The moisturizing effect of Aloe vera supports its use in the treatment of dry skin.2,3

2. Glycine is part of the skin’s "natural moisturizing factors"

Water-soluble substances called natural moisturizing factors (NMF) are responsible for maintaining the skin’s moisture balance and various skin functions. Natural moisturizing factors are composed of amino acids, sugars, and electrolytes that work to keep the skin’s surface intact, supple, and hydrated. Glycine is part of the “natural moisturizing factors.” Amino acids present in the “natural moisturizing factors” work together with aquaporins or the body’s water transport system to transport moisture throughout the skin. Hence, the use of amino acids like glycine in topical preparations helps improve moisture retention and promote skin hydration.4,5

3. Calendula – Promotes skin hydration and firmness

Calendula is an effective moisturizer and is useful for preventing dry skin, soothing the discomfort of dry skin, and healing the dry skin symptoms.6

Studies show that calendula extract promotes skin hydration and firmness. A study involving 21 healthy human volunteers investigated the effects of a topical cream of Calendula officinalis extract on the skin’s mechanical parameters. The cream was applied to the cheeks of the volunteers for a period of eight weeks. The cream containing Calendula extract induced skin tightness. The cream also increased the hydration of the skin; hydration is vital for normal skin metabolism and may even prevent skin alteration and early aging. It also showed some improvement in some elastic and viscoelastic parameters.7

Calendula extract also improves blood flow to the affected area. As per a case report study, topical Calendula officinalis ointment can be used to treat exfoliative cheilitis, a rare condition presenting as dry lips with scaling and crusting. When used continuously for 15 days, Calendula ointment completely cleared the cheilitis.8

References (Moisturising)
  1. Dal’Belo SE, Gaspar LR, Maia Campos PM. Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques. Skin Res Technol. 2006;12(4):241-246.
  2. Fox LT, du Plessis J, Gerber M, et al. In Vivo skin hydration and anti-erythema effects of Aloe vera, Aloe ferox and Aloe marlothii gel materials after single and multiple applications. Pharmacogn Mag. 2014;10(Suppl 2):S392-S403.
  3. Saraf S, Sahu S, Kaur CD, et al. Comparative measurement of hydration effects of herbal moisturizers. Pharmacognosy Res. 2010;2(3):146-151. 8490.65508.
  4. Razak MA, Begum PS, Viswanath B, et al. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701.
  5. Maeno K. Direct Quantification of Natural Moisturizing Factors in Stratum Corneum using Direct Analysis in Real Time Mass Spectrometry with Inkjet-Printing Technique. Sci Rep. 2019;9(1):17789.
  6. Akhtar N, Zaman SU, Khan BA, et al, Ebrahimzadeh MA. Calendula extract: effects on mechanical parameters of human skin. Acta Pol Pharm. 2011;68(5):693-701.
  7. Roveroni-Favaretto LH, Lodi KB, Almeida JD. Topical Calendula officinalis L. successfully treated exfoliative cheilitis: a case report. Cases J. 2009;2:9077.
  8. Kang CH, Rhie SJ, Kim YC. Antioxidant and Skin Anti-Aging Effects of Marigold Methanol Extract. Toxicol Res. 2018;34(1):31-39.

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