Botanical cosmeceutical solutions

BOTANICAL COSMECEUTICAL SOLUTIONS

THE BEST OF NATURE AND SCIENCE Prepared by: Alix Wride, Applied Research Specialist Josh Beaty, Marketing Director Adrienne Le, Creative Brand Strategist

Astragalus membranaceus Herbal skincare to rejuvenate & restore

Astragalus membranaceus is no stranger to the world of herbal healing.

This well known plant has been referenced in Chinese medicinal writings over 2,000 years old, and is still commonly used today. In the world of Chinese medicine it is said to nourish and replenish the Qi while helping the body adapt to stress by normalizing body processes (4, 6).

Its first appearance was in Shen Nong Ben Cao Jing, one of three foundational books of Chinese medicine, now translated to The Divine Farmer’s Materia Medica (6). It was valued for its ability to strengthen the primary energy of the body (the immune system), as well as the metabolic, respiratory, and eliminative functions in the body (6).

Today with a quick search, you’ll see statements of immune boosting, cardiovascular aid, blood glucose regulation, anti-aging, wound healing and many more; but how can one herb accomplish all of those very different tasks?

A. membranaceus has over 200 isolated compounds, including polysaccharides, saponins, and flavonoids, which when isolated can work towards accomplishing these various functions within the body (6). A. membranaceus is a very well studied and well known herb for all of these reasons but has only more recently found its way into the mainstream skincare scene.

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WHAT MAKES THIS HERB SO GOOD FOR OUR SKIN? Simply put, the use of Astragalus membranaceus in a skincare formula can lead to decreased MMP-1 responsible for the breakdown of collagen, increased hyaluronic acid responsible for skin hydration, and decreased melanin production due to UV damage (4, 7). It has been also found to have wound healing properties by various parties (6, 11). All of these together lead to the overall anti-aging effect of this herb, and good reason to consider adding it to a skincare regimen.

MMP-1 One of the major active components extracted from Astragalus membranaceus is Astragaloside IV (AST), which has been found to decrease the rate of environmentally induced breakdown of collagen in the skin (1). What causes this environmental breakdown? One major factor is ultraviolet radiation.

As commonly known, UV can be very damaging to the skin. This UV radiation has been shown to impair vital signaling pathways necessary for healthy skin function, particularly the TGF-β/Smad signaling pathway. TGF-β (Transforming growth factor-β) is the primary regulator of collagen synthesis in human skin, and smads are intracellular proteins that deliver DNA signals from TGF-β molecules to the cells to activate gene transcription (3).

It has been reported that UV radiation impairs TGF-β/Smad signaling (1). This impairment is a major reason for the reduced collagen synthesis in human skin fibroblasts,which are responsible for the production of collagen and other fibers. This damage from this UV radiation then leads to the appearance of matrix metalloproteinases (MMPs) in skin cells which are responsible for the degradation of many extracellular matrix proteins. Collagenase-1, also known as MMP-1, is the specific MMP responsible for the breakdown of collagen (1,2,4).

Astragalus membranaceus, as previously mentioned, is comprised of saponins. Astragaloside IV (AST) is one of these saponins that has been shown to decrease MMP-1 activity caused by UV damage (1, 2, 6). When studying this effect, it was identified that MMP-1 expression was significantly lower in the AST group compared to the control, suggesting that AST is a significant inhibitor of UVinduced MMP-1 expression (1).

This saponin inhibits UV-induced collagen-1 breakdown by stimulating the same TGF-β/Smad signaling pathway as well as suppressing MMP-1 expression (1). Skin collagen is constantly being broken down and created, as with all cells within the body, but through the aging process the breakdown tends to outperform the synthesis leading to the overall loss of collagen due to aging. A. membranaceus’ effect of suppressing this overactive MMP-1 helps to return skin to a more youthful and balanced function.

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HYALURONIC ACID Not only can A. membranaceus decrease the breakdown of collagen, it has also been found to increase hyaluronic acid content within the skin. As many now know, hyaluronic acid is a naturally occurring substance in the skin that provides moisture and the full or plump appearance of youthful skin. Hyaluronic Acid (HA) is the key molecule for skin moisture due to its unique capacity to retain water (9). Unfortunately as the human body ages epidermal HA also decreases, resulting in a loss of moisture in the outer layer of our skin creating those visible signs of aging many work to avoid.

To combat this, many topical products now contain HA. The problem is HA has a rather large molecular size, making it difficult to absorb into the skin on its own when applied topically (9). Some products incorporate penetration enhancing ingredients to help combat this, but it is still limited due to its molecular size. Through a series of cell studies, A. membranaceus has been found to increase the content of hyaluronic acid by increasing hyaluronan synthase-3 and hyaluronan synthase-2 , the enzymes responsible for hyaluronic acid synthesis in the skin (7). This means A. membranaceus may have the ability to promote natural HA synthesis within the body leading to fuller more hydrated skin through the aging process.

MELANIN & HYPERPIGMENTATION As discussed previously, UV radiation can be extremely damaging to the skin. Not only can it damage collagen production pathways, it also creates unsightly dark patches due to an overproduction of melanin, the dark pigment in skin. This melanin production is your skin’s attempt at protecting itself against this damaging UV exposure. This can lead to patches of pigmentation commonly known as “sun spots” or “age spots”. These spots are a result of UV related tyrosinase activity, the enzyme that accelerates melanin synthesis. Tyrosinase not only causes browning in human and animal skin, but also the browning of some fruits and vegetables (3). Since many plants have this same browning enzyme, it makes sense that they would have a natural way to regulate the process.

After review of several medicinal herbs, it was found that Astragalus membranaceus shows some tyrosinase inhibitory activity (3). Not only does this mean A. membranaceus could help to correct dark spots due to UV exposure, but tyrosinase inhibitors have also become an important aspect of hyperpigmentation products. Hyperpigmentation is also due to an overproduction of melanin in certain areas of the skin.

The active compound isolated from A. membranaceus, calycosin, could be used as a natural depigmentation agent for people with hyperpigmentation (3). The major factor being calycosin, isolated from the roots of Astragalus membranaceus, decreasing melanin production through regulation of tyrosinase enzymes leading to an evening of skin tone appearance (3). This helps to reverse damage and discoloration due to UV exposure as well as a potential treatment for hyperpigmentation issues.

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WOUND HEALING The wound healing capabilities of this herb stem from its polysaccharide content. One of these (APS21) had a particular effect in this process. When studying cell cultures during the replication cycle of healing skin, this polysaccharide was found capable of promoting reepithelialization, revascularization, and cytokine secretion (8,10,11).

These steps include the final phase of healing where epithelial cells return to resurface the wound and complete the sealing process of the affected area, the restoration of the blood circulation to the area, and vital cell signaling of the TGF-β1 pathway (8,10,11). This is accomplished by downregulating cyclin D1, a protein required for progression through the G1 phase of the cell cycle, where RNA is produced and the cell ensures everything is set and ready for DNA to be duplicated in the next phase (S phase). This in turn shortens the G1/S stage and accelerates cell proliferation in the wound area to accelerate the healing process (11).

Essentially the main mechanism of action for the wound healing function of APS2-1 is related to the reduction of the inflammatory response, promotion of cell cycle progression, and the secretion of cytokines that stimulate this pathway to begin with and aid in the anti-inflammatory effect (5, 11).

ANTI-AGE CONCLUSION All of these together seem to paint the picture of a powerful anti-aging herb. By improving the skin’s own healing ability, it can recover from trauma more efficiently, with decreased collagen breakdown and increased hyaluronic acid, skin will be stronger and retain more moisture. Add this to the pigmentation element, that would make for more even, moist, strong skin. This plant as a whole has a general positive effect on health, but when the specific compounds are isolated, it can work wonders for the skin.

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Centella asiatica For youngevity & antioxidant support

Centella asiatica, also known as Gotu Kola, has a long history as a medicinal herb. It has been used for centuries in China, India, and Africa for its “longevityproducing” properties and long list of health promoting functions (7). Centella asiatica is a creeping “ground cover” plant, that continuously re-roots as it grows, and if grown in a greenhouse setting, will sneak down to reroot in the water draining from above (7).

Medicinally, this plant can be eaten whole, dried and taken as a powder, or used as a topical treatment for skin conditions (7). C. Asiatica has been used to treat skin conditions such as burns and wounds for centuries and was even sourced as a treatment for leprosy because of these wound healing properties (3, 7, 11).

Although this herb does have a deep history of medicinal use, it can also be found in many modern skincare products. Various studies have found that it has effective anti-aging, anti inflammatory, and antioxidant properties, as well as a skin barrier support which helps to defend against external factors (1, 2, 3, 7, 11).

Not only can this herb aid in skin strength and healing, it has also been shown provide moisture when used in cosmetic formulations for the treatment of dry sensitive skin (11). C. asiatica contains numerous compounds that help to stimulate certain body processes to accomplish these tasks. The most commonly isolated compounds are saponins including madecassoside, asiaticoside, centelloside, and asiatic acid (10). The following will discuss the specific pathways and mechanisms of action involved in C. asiatica’s skin care abilities.

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COLLAGEN PRODUCTION INCREASE One of the more frequent claims towards Centella and its skincare use would be its ability to stimulate collagen production. There have been numerous studies on different aspects of this herb in relation to collagen with many coming to the same positive conclusion: a statistically significant and dosedependent increase in collagen synthesis (2, 10, 11). Some even reporting visually improved skin texture and hydration along with a decrease in wrinkles and improved skin strength and “firmness” (10).

This process begins with Centella asiatica’s ability to activate the TGF-β/Smad signaling pathway (11).

TGF-β (Transforming growth factor-β) regulates fibroblast function which is responsible for collagen production while Smads signal for gene transcription to carry out this production (4). The activation of this pathway can then increase type I collagen production by promoting fibroblast generation and increasing the synthesis of collagen (3, 11).

Two compounds in particular are generally looked to for these actions: madecassoside and asiaticoside.

Madecassoside is known to induce collagen expression and modulate inflammatory mediators, while asiaticoside induces type I collagen synthesis in fibroblast cells (10). By activating these pathways, skin is able to produce its own collagen rather than using collagen supplements to create the firm and strong appearance of skin.

WOUND HEALING & TENSILE STRENGTH Along with the increased production of collagen comes C. asiatica’s wound healing capabilities.

Several saponins work together to accomplish this task. Madecassoside, asiaticoside, centelloside, and asiatic acid have been reported to increase granulation tissue levels, total collagen, and crosslinking of collagen for improved tensile strength of the newly healed area (5, 10, 11). Increased tensile strength means it will take more force to rupture the wound creating a stronger and faster overall healing process (2, 3).

These saponins have also shown evidence of faster progression through the phases of inflammation, proliferation, and maturation (10). The mechanism of action for this process again involves fibroblasts and the synthesis of collagen providing the necessary structural support. This in conjunction with increased production of granulation tissue, an important tissue for the repair of open wounds, along with decreased inflammation and increase tensile strength make this herb very influential for the wound healing process.

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ANTI-INFLAMMATORY/ANTIOXIDANT C. asiatica’s anti-inflammatory properties aid in both this healing of wounds and the overall appearance of skin. In terms of wound healing, inflammation is a vital step to protect the injured area and stimulate the normal phases of healing.

Alternately when inflammation is prolonged or brought on by other factors like sun damage and other irritants, it can be damaging and lead to various skin ailments (8). Due to this damage, antiinflammatories are important tools for skincare. C. asiatica’s saponin content can help to combat this inflammation (11). The saponin in question is again asiaticoside, which has been shown to inhibit cyclooxygenase and lipoxygenase activity as well as proinflammatory cytokines leading to a decrease in inflammation (11). Activated cyclooxygenase leads to oxidation and free radical formation in the skin causing irritation and potential complications (11). Asiaticoside was found to inhibit this activation, meaning the irritation and inflammation is also inhibited. C. asiatica’s saponins and flavonoids were found to have both antioxidant and anti-inflammatory properties due to this inhibition of free-radical development and subsequent inflammation (11).

INCREASED MOISTURE Skin structure, strength, and inflammation levels are all important, but without moisture it is still left with a dull appearance and undesirable texture. Thankfully C. asiatica also has moisturizing capabilities. Multiple studies have examined this function and found consistent reports of increased moisture (9, 10, 11). One of which found Centella asiatica extract capable of increasing skin surface hydration and decreasing transepidermal water loss (TEWL) (11). Their study also found this herb to significantly increase hydration of the stratum corneum (the outermost layer of the skin) due to the presence of triterpene saponins that bind water within an occlusive layer (11).

Furthermore, extracts from C. asiatica were found to inhibit hyaluronidase enzyme activity responsible for the breakdown of hyaluronic acid (9). This prolongs the effect of hyaluronic acid and the moisture it provides in the skin. Together these studies show increased moisture through the binding of water molecules in the outermost layer of the skin as well as increased moisture in deeper layers by inhibiting the breakdown of hyaluronic acid.

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SKIN BARRIER SUPPORT All of these come together to create stronger and healthier skin, which lead to increased skin barrier function. Hydration, first, is a very important indicator of this function (9).

The health of the outermost layer of the skin is vital when it comes to barrier support. With increased moisture and decreased TEWL natural moisturizing enzymes are kept in and harmful biological or chemical irritants from the surrounding environment are kept out leading to an overall increased functioning and healthier skin (9, 11). Antioxidant and anti-inflammatory functions also play a role in skin barrier function.

The combination of reduced inflammation and increased moisture in the stratum corneum is associated with skins faster return to homeostasis after exposure to irritants (11). This means the layers of the skin will be better protected against damage, and when damage does occur, it will heal and return to its normal state of function much faster than skin lacking in this function.

CONCLUSION Centella asiatica has been found to increase collagen synthesis which aids in its anti-aging and wound healing properties and increased tensile strength in newly formed skin. This leads to stronger, fuller, and healthier skin structure (2, 1, 3, 5, 10, 11). Since Centella asiatica extract is so rich in saponins and other active compounds, it is seen a valuable raw material that can be used in a wide range of cosmetic products for positive effect (11).

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Skin Rejuvenating & Hydrating Phytocompound Although these are not the only herbs to benefit a skin care regimen, Centella asiatica and Astragalus membranaceus should definitely be taken into consideration.

These two herbs have deep roots in the world of Chinese medicine and have been used for centuries to treat an extensive list of conditions from immune function, to weight loss, to respiratory health and wound healing. This is due to the vast variety of active chemical compounds present in these plants. When certain compounds from these herbs are isolated and used topically they have a unique way of reacting with our largest organ, stimulating natural pathways to more youthful skin.

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ASTRAGALUS MEMBRANACEUS A. membranaceus has been shown to increase skin’s natural production of hyaluronic acid, decrease discoloration caused by UV damage, and decrease collagen breakdown within the skin (8, 10). It has also been found to have a positive effect when treating hyperpigmentation, and can aid in the wound healing process through the stimulation of certain pathways including the TGF-β/Smad signaling pathway (9).

CENTELLA ASIATICA C. asiatica has been used to treat skin conditions such as burns and wounds for centuries and was even sourced as a treatment for leprosy because of these wound healing properties (1, 4, 11). It has been found to be an effective anti-aging, anti inflammatory, and antioxidant; as well as a skin barrier support which helps to defend against external factors (1, 2, 3, 4, 11). It has additionally been discovered to increase collagen synthesis and increase tensile strength in newly formed skin, potentially reducing stretch mark formation (2, 3, 4, 5, 10, 11). Not only can this herb aid in skin strength and healing, it has also been shown increase moisture by inhibiting the breakdown of hyaluronic acid and supporting hydration of the outermost layer of the skin (11).

SO WHY ARE THESE SO BENEFICIAL? Skin aging is both intrinsic (part of the natural aging process) and extrinsic (due to external factors). Naturally through the years the skin produces less collagen leading to loose, saggy, or wrinkled skin. Moisture transfer between the layers of the skin slows, elastin fibers start to break and clump together, leading to a loss of elasticity and natural moisture in the skin (6).

This is compounded with exposure to environmental factors, or extrinsic damage. Extrinsic damage leads to many issues including thickening and discoloration of the outermost layer of the skin, possible skin cancers, deep wrinkles, and spider veins to name a few. This can be brought on by UV exposure, smoking, alcohol consumption, poor nutrition, chemical exposure, or harsh climates (6). Thankfully many of these can be controlled for, and when combined with access to powerful plant extracts, both intrinsic and extrinsic factors of aging can be managed.

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MARKET OPPORTUNITY: ASTRION™ TO THE RESCUE The combination of Centella asiatica and Astragalus membranaceus creates an impressive and effective aging skin remedy. Together these herbs increase skin’s own ability to produce both hyaluronic acid and collagen, while decreasing excessive collagen and hyaluronic acid breakdown. This protects the structure, elasticity, and moisture of the skin, decreasing fine lines and wrinkles and providing a hydrated glow.

This combination also provides anti-inflammatory and antioxidant functions while also aiding in the repair of damaged tissue. The increase moisture, structure and wound healing also work to improve the skin barrier function leading to a faster return to homeostasis after irritation (11). It also works to protect against UV damage while helping to correct previous discoloration due to overexposure of the elements. This leads to healthier functioning, looking, and feeling skin!

NuLiv Science, through meticulous research, has developed this patented skincare ingredient to take advantage of these amazing properties and bring life back into the skin in a completely natural and holistic way. Astrion™ is entirely plant-based and cruelty-free phytocompound, proven through in-vitro and human clinical studies to improve skin through various internal pathways without the risk of unfortunate side effects. Plus, consumers want more youthful appearing and feeling skin.

There’s incredible potential in the consumer market’s beauty-from-within niche and skin rejuvenating supplement users. Eastern markets already know the benefits of eastern botanical solutions. What’s fresh wihtin the western market and the beauty-from-within approach is the effect after oral intake. Astrion™ addresses both outer skin rejuvenation, and healthy support for skin internally.

In terms of cosemeceutical functions, Astrion™ promotes the synthesis of collagen type I and II and hyaluronic acid in dermal and epidermal skin cells. Furthermore, the phytocompound increases the absorption of proline, a building block of collagen, and the absorption of glucosamine, a building block of hyaluronic acid, and at the same time, reduces the breakdown of existing collagen by inhibiting the production of MMP’s (matrix metalloproteinases) to minimize the destructive effect of UV light to the skin.

Astrion™ can be delivered to the epidermis, dermis, and subcutaneous layers through transcellular, transfollicular, stratum, and sweet duct, and diffusion between cells because of its lipophilic-hydrophilic supporting properties.

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References Astragalus membranaceus: Herbal Skincare to Rejuvenate & Restore 1. Chen, B., Li, R., Yan, N., Chen, G., Qian, W., Jiang, H., . . . Bi, Z. (2015). Astragaloside IV controls collagen reduction in photoaging skin by improving transforming growth factor-β/Smad signaling suppression and inhibiting matrix metalloproteinase-1. Molecular Medicine Reports,11(5), 3344-3348. doi:10.3892/mmr.2015.3212 2. Curnow, A., & Owen, S. J. (2016). An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations. Oxidative Medicine and Cellular Longevity,2016, 1-9. doi:10.1155/2016/7053897 3. Gene Family: SMAD family (SMAD). (n.d.). Retrieved from https://www.genenames.org/cgi-bin/ genefamilies/set/750 4. Hong, M. J., Ko, E. B., Park, S. K., & Chang, M. S. (2012). Inhibitory effect of Astragalus membranaceus root on matrix metalloproteinase-1 collagenase expression and procollagen destruction in ultraviolet B-irradiated human dermal fibroblasts by suppressing nuclear factor kappa-β activity. Journal of Pharmacy and Pharmacology,65(1), 142-148. doi:10.1111/j.2042-7158.2012.01570.x 5. Kim, B., Oh, I., Kim, J., Jeon, J., Jeon, B., Shin, J., & Kim, T. (2014). Anti-inflammatory activity of compounds isolated from Astragalus sinicus L. in cytokine-induced keratinocytes and skin. Experimental & Molecular Medicine,46(3). doi:10.1038/emm.2013.157 6. Kim, J. H., Kim, M. R., Lee, E. S., & Lee, C. H. (2009). Inhibitory Effects of Calycosin Isolated from the Root of Astragalus membranaceus on Melanin Biosynthesis. Biological & Pharmaceutical Bulletin,32(2), 264-268. doi:10.1248/bpb.32.264 7. Liu, P., Zhao, H., & Luo, Y. (2017). Anti-Aging Implications of Astragalus membranaceus (Huangqi): A Well-Known Chinese Tonic. Aging and Disease,8(6), 868. doi:10.14336/ad.2017.0816 8. Mukherjee, P. K., Maity, N., Nema, N. K., & Sarkar, B. K. (2011). Bioactive compounds from natural resources against skin aging. Phytomedicine,19(1), 64-73. doi:10.1016/j.phymed.2011.10.003 9. Papakonstantinou, E., Roth, M., & Karakiulakis, G. (2012). Hyaluronic acid: A key molecule in skin aging.

Dermato-Endocrinology,4(3), 253-258. doi:10.4161/derm.21923 10. Wound Care Tips for the Proliferation Phase of Healing. (2015, December 21). Retrieved from https:// www.advancedtissue.com/wound-care-tips-for-the-proliferation-phase-of-wound-healing/ 11. Zhao, B., Zhang, X., Han, W., Cheng, J., & Qin, Y. (2017). Wound healing effect of an Astragalus membranaceus polysaccharide and its mechanism. Molecular Medicine Reports,15(6), 4077-4083. doi:10.3892/mmr.2017.6488

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Centella asiatica: Skincare Solutions 1. Bodeker, G., & Ryan, T. J., Volk, A., Harris J., Burford, G. (2006). Integrative Skin Care: Dermatology and Traditional and Complementary Medicine. The Journal of Alternative and Complementary Medicine. Vol. 23, No. 6. doi:10.1142/9781860949135_0014 2. Brinkhaus, B., Lindner, M., Schuppan, D., & Hahn, E. (2000). Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine,7(5), 427-448. doi:10.1016/ s0944-7113(00)80065-3 3. Bylka, W., Znajdek-Awiżeń, P., Studzińska-Sroka, E., & Brzezińska, M. (2013). Centella asiatica in cosmetology. Advances in Dermatology and Allergology,1, 46-49. doi:10.5114/pdia.2013.33378 4. Gene Family: SMAD family (SMAD). (n.d.). Retrieved from https://www.genenames.org/cgi-bin/ genefamilies/set/750 5. Gohil, K., Patel, J., & Gajjar, A. (2010). Pharmacological review on Centella asiatica: A potential herbal cure-all. Indian Journal of Pharmaceutical Sciences,72(5), 546. doi:10.4103/0250-474x.78519 6. Gotu Kola. (n.d.). Retrieved from http://healthlibrary.epnet.com/GetContent.aspx?token=e0498803-7f624563-8d47-5fe33da65dd4&chunkiid=21763#ref3 7. Gotu Kola | Centella asiatica. (n.d.). Retrieved from http://ayurveda.alandiashram.org/ayurvedic-herbs/ gotu-kola-centella-asiatica 8. Kim, B., Oh, I., Kim, J., Jeon, J., Jeon, B., Shin, J., & Kim, T. (2014). Anti-inflammatory activity of compounds isolated from Astragalus sinicus L. in cytokine-induced keratinocytes and skin. Experimental & Molecular Medicine,46(3). doi:10.1038/emm.2013.157 9. Milani, M., & Sparavigna, A. (2017). The 24-hour skin hydration and barrier function effects of a hyaluronic 1%, glycerin 5%, and Centella asiatica stem cells extract moisturizing fluid: An intra-subject, randomized, assessor-blinded study. Clinical, Cosmetic and Investigational Dermatology,Volume 10, 311315. doi:10.2147/ccid.s144180 10. Mukherjee, P. K., Maity, N., Nema, N. K., & Sarkar, B. K. (2011). Bioactive compounds from natural resources against skin aging. Phytomedicine,19(1), 64-73. doi:10.1016/j.phymed.2011.10.003 11. Ratz-Lyko, A., Arct, J., & Pytkowska, K. (2016). Moisturizing and antiinflammatory properties of cosmetic formulations containing Centella asiatica extract. Indian Journal of Pharmaceutical Sciences,78(1), 27. doi:10.4103/0250-474x.180247

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Astrion™: A Botanical Skincare Solution 1. Alandi Ashram. (n.d.). Gotu Kola | Centella asiatica. Retrieved from http://ayurveda.alandiashram.org/ ayurvedic-herbs/gotu-kola-centella-asiatica 2. Brinkhaus, B., Lindner, M., Schuppan, D., & Hahn, E. (2000). Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine, 7(5), 427-448. doi:10.1016/ s0944-7113(00)80065-3 3. Burford, G., Bodeker, G., & Ryan, T. J. (2006). Skin And Wound Care: Traditional, Complementary And Alternative Medicine In Public Health Dermatology. Traditional, Complementary and Alternative Medicine,311-348. doi:10.1142/9781860949135_0014 4. Bylka, W., Znajdek-Awiżeń, P., Studzińska-Sroka, E., & Brzezińska, M. (2013). Centella asiatica in cosmetology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834700/ 5. Gohil, K. J., Patel, J. A., & Gajjar, A. K. (2010). Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116297/ 6. Carrillo Leal, A. (2013, January 29). Why Does Your Skin Age? Retrieved from http://dujs.dartmouth. edu/2013/01/why-does-your-skin-age/#.Wsz9xy7waiM 7. Gotu Kola. (2015, December 15). Retrieved from http://healthlibrary.epnet.com/GetContent. aspx?token=e0498803-7f62-4563-8d47-5fe33da65dd4&chunkiid=21763#ref3 8. Hong, M. J., Ko, E. B., Park, S. K., & Chang, M. S. (2012). Inhibitory effect of Astragalus membranaceus root on matrix metalloproteinase-1 collagenase expression and procollagen destruction in ultraviolet B-irradiated human dermal fibroblasts by suppressing nuclear factor kappa-B activity. Journal of Pharmacy and Pharmacology,65(1), 142-148. doi:10.1111/j.2042-7158.2012.01570.x 9. Liu, P., Zhao, H., & Luo, Y. (2017). Anti-Aging Implications of Astragalus membranaceus (Huangqi): A Well-Known Chinese Tonic. Aging and Disease,8(6), 868. doi:10.14336/ad.2017.0816 10. Mukherjee, P. K., Maity, N., Nema, N. K., & Sarkar, B. K. (2011). Bioactive compounds from natural resources against skin aging. Phytomedicine,19(1), 64-73. doi:10.1016/j.phymed.2011.10.003 11. Ratz-Lyko, A., Arct, J., & Pytkowska, K. (2016). Moisturizing and antiinflammatory properties of cosmetic formulations containing Centella asiatica extract. Indian Journal of Pharmaceutical Sciences,78(1), 27. doi:10.4103/0250-474x.180247

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