BETTER THAN BOTOX – Herbs for Skin Rejuvenation

© Jillian E Stansbury

Perhaps because people liver longer and wrinkles and aged faces have more of a social impact, or perhaps because of a psychological ailment affecting the culture, there is more and more emergence of anti-aging as a science. Real and earnest research into how the skin ages and what can prevent and remedy it is turning this branch of medicine into an actual scientific discipline. Research into what agents moisturize and retain fluid the best has morphed into a vast science of excipients, liposomal delivery systems, and molecular mechanisms of action. Active ingredient research now goes well beyond simple emollient activity and into the realms of agents that promote enzymes involving collagen synthesis and turn off enzyme involved with fibrin deposition, agents that absorb UV radiation and imaging techniques to assess this, agents that increase intracellular content of nutrients and anti-oxidant nutrients and techniques to assess this, and many other arenas of investigation. Just as nutritional research has transformed the concept of vitamins into the concept of “nutraceuticals”, current research in topical applications for the skin is turning the concept of moisturizers into the concept of “cosmeceuticals.”

Modern dermatology and the burgeoning ranks of dermatologists’ and aestheticians’ clinical practices increasingly focus on anti-aging. While it might have been the rare movie star in the past, cosmetic surgery and anti-aging medicine is booming and the number of clinics, conferences, techniques, research, is the growing rapidly. The human focus on appearance however, rather than leading to a focus on true health, to maintain one’s vitality, and thereby youth and appearance, a large focus in the modern medical area is surgical and topical. It would be logical that first, a change of a person’s lifestyle such as sun behavior, nicotine abuse, nutrition, circulation, hydration, etc must take place. Only secondly would other more cosmetic methods be worth the effort. This discussion will assume that underlying diet, exercise, lifestyle, and nutritional or botanical therapies where indicated are being addressed as the first step.

The standard somewhat allopathic therapies for the skin include surgical approaches such as face lifts, lid lifts, chin tucks, etc. and a variety of minor surgical resurfacing techniques for the superficial dermis including laser techniques, chemical peels, topical retinoids, botulinum neurotoxin injections, soft tissue filler injections, and systemic endocrinological therapies, and phytohormones. The alternative include nutritional agents for oral ingestion that improve the integrity of the skin and antioxidant content over a lifetime, as well as nutritional and plant compounds that may be applied topically to protect and rejuvenate the skin. This article aims to look at some of the science and usefulness of the current therapies as well as explore some other research and alternative from the realms or botanical and nutritional medicine This article aims to look at some of the science and usefulness of the current therapies as well as explore some other research and alternative from the realms or botanical and nutritional medicine Antioxidant plant compounds include ascorbic acid, pycnogenol, ursolic acid, and the botanical isoflavones. Other antioxidant being investigated for either oral or topical use include, vitamin E, coenzyme Q10, lipoic acid, resveratorol, l-carnosine and taurine.

Basic Anti-Aging Protocol

Dermal Vasculature and Aging
Aging of the blood vessels is a part of normal chronological aging of the skin. Many elderly are noted to have reduced microvasculature in the dermis that contributes to loss of skin vitality and appearance. Thus agents that protect blood vessels over a lifetime and agents that promote angiogenesis are being explored for having positive effects on the skin. Paradoxically, UV light is noted to stimulate angiogenesis in the skin, yet chronic exposure to UV light results in photodamage of the skin.
Curcuma longa has been noted to have positive action vascularity and angiogenesis in the skin. . Curcumin has also been shown to have beneficial effect as a pro-angiogenic agent in wound-healing by inducing transforming growth factor-beta, which induces both angiogenesis and accumulation of extracellular matrix, which continues through the remodeling phase of wound repair. These studies suggest the beneficial effects of curcumin and the potential of this compound to be developed as a potent nontoxic agent for treating skin diseases.
Centella asiatica may be useful for improving cutaneous microcirculation. Diabetics with impaired microcirculation may benefit from Centella therapy and improved venoarteriolar response, blood gases, capillary permeability and general microcirculation have been reported in clinical trials.

Dermal Connective Tissue and Aging
Technically, there may be considered to be two types of aging of the skin – chronological aging and photoaging. While chronological aging is inevitable, photoaging is a somewhat avoidable phenomenon.
The main structural component of the dermal connective tissue matrix is Type I collagen and ultraviolet light is known to damage type I collagen in the dermis. A reduction in collagen allows for microscopic contraction in the dermal matrix, over time producing visible wrinkling of the skin, a phenomenon referred to as “photoaging”.
The damage to collagen by UV light involves blockage of transforming growth factor-beta. Transforming growth factor beta’s binding to its type II receptor is down-regulated, which in turn inhibits the synthesis of collagen precursors. Therefore, agents which inhibit down-regulation of these receptors might have an anti-aging effect. The bacterium Zymomoas mobilis, for example has been used to produce a fermentable metabolite that is noted to prevent loss of collagen synthesis by this mechanism. Hypericum is noted to promote collagen production by fibroblasts. Centella asiatica saponin asiaticoside has shown to induce type I collagen synthesis in human dermal fibroblast cells.  Centella has also been noted to reduce fibrotic process in the liver in animal studies.
Fibrillin, a desirable connective tissue component of the dermal matrix is sometimes used a marker in some research models used to assess an increase or decrease in fibrin formation following the application of a variety of topical and internal medications. For example, Retin A, the gold standard in anti-aging medication, is noted to increase fibrilin-1 deposition in the papillary dermis.
Collagen is the major structural protein of the skin. It acts as a glue, a scaffold, and structural strong-arm, yet is also electromagnetically active. Collagen is composed of three protein chains wound together in a tight triple helix having great tensile strength.    Around 1/3 of all the protein in the body is collagen. In bones collagen combines with calcium and phosphorus. The skin itself is around ¾ collagen, giving the skin its plump elastic character. Loss of collagen due to sun damage or simple aging is the cause of sagging of the skin, wrinkles and loss of volume to the cheeks, lips, and face.

Skin Generation Basics
The formation of both skin and bone involve the spontaneous organization of complex, alive, soluble, and electromagnetically active architecture primarily that then becomes ossified in the case of bone, and “collaganized” in the case of skin. The dynamic organization matrix is sometimes referred to as the “ground substance” and is composed of glycosamioglycan (GAG) molecules which “granulate” with the synthesis of more solid collagen and elastin by fibroblasts. The observable sequence in dermal synthesis is first the breakdown of GAG molecules involving sulfur based metabolism and sulfur metabolizing enzymes, followed by an increase in the glycohydrolase enzymes, the glucuronidases and glucosaminidases. Glycohydrolases are enzymes involved with a rapid cell turnover rate and indicate healthy regenerating tissue. Measurement of glycohydrolases is therefore sometimes used as a laboratory indicator of dermal regeneration. Aloe vera, for example may increase levels of glycohydrolases.
Collagen and elastin are synthesized by fibroblasts from glycosaminoglycans. Hyaluronic acid is one of the prime GAG molecules in the human body. The GAGs that compose ground substance hold water and provide the building blocks for connective tissue synthesis. Procollagen is highly soluble and easily manipulated within cells, being transported about by the network of microtubules. It is excreted into extracelluar spaces at specific sites as directed by the microtubules. Procollagen is formed into the more solid collagen strand within the golgi apparati of the ER. Procollagen has disulfide containing peptides on one end that are involved with linking up the three strands that ultimately become the triple helix of collagen. Proteinase enzyme remove peptide groups from the procollagen strands which are recycled back into cells playing a role in collagen synthesis feedback loop of sorts. The amino acids lysine and proline play roles in the hydroxylation of procollagen into hydroxylysine and hydroxyproline, a transformation requiring Vitamin C and Iron as cofactors. The hyroxylated strands then undergo glycosylation with the addition of sugar moieties, a process requiring manganese as a cofactor. Enzymes that enable hydroxylation and glycosylation are most active in youth and decline with age.



Fibroblasts have membrane receptors that, when bound by fibroblast growth factors, cause the fibroblasts to synthesis collagen and other proteins. Procollagen is manufactured first, which is transported out of the fibroblast. Procollagen threads fuse together, with the support of Vitamin C as a cofactor to form collagen. Lack of Vitamin C, therefore, lead to a lack of collagen synthesis. Scurvy, for example, results in bleeding gums due to lack of collagen synthesis and thereby lack of structural integrity of the gums and all tissues. The application of specific peptides, which act as fibroblast receptor agonists may also be a way to stimulate collagen production.



While the levels of hyaluronic acid and GAGs enzymes may indicate skin regeneration and a desirable lab marker, when elevated hyaluronic acid and collagen are associated with keloid formation and the associated loss of vital tissue and replacement with fibrous tissue. Curcumin, from Curcuma longa has been noted to decrease the levels of collagen and elastin when excessive, decreasing the proliferation of fibrous tissues.
Dermal fibroblasts also produce eotaxin, a chemotactic factor acting on eosinophilis. Chemotaxis, the phenomenon whereby distant cells can be called or pulled to a specific site where they are needed, most likely has electromagnetically active collagen and microtubules as an underlying mechanism. Eotaxin released from fibroblasts may stimulate local collagen to put out a signal that draws eosinophils to a site of allergic inflammation. Scutellaria bacialensis, long used for allergies in TCM, has had recent research showing that the flavinoids baicalein and baicalin inhibit eotaxin production by fibroblasts. Scutellaria is well regarded in herbal medicine as an anti-inflammatory for vascular, allergic and other inflammatory disorders. Added to the list might be skin inflammation. Scutellaria bicailensis might both reduce inflammatory processes in the skin, including photoaging.


Protecting Collagen
Avoiding UV radiation and preventing free radical damage. A daily ritual of sunscreen application over a lifetime may do a great deal to protect from solar photoaging and loss of collagen. Oral and topical use of antioxidants can also help provide a good supply of nutrients in the skin that help protect collagen and fibroblasts from damage. A discussion of agents that protect collagen and the fibroblasts that produce it follows.

Promoting Collagen Synthesis
Vitamin C is needed for Collagen synthesis, so regular consumption of topical use of Vitamin C containing moisturizers may help promote collagen synthesis. Umbelliferone has been shown to have a normalizing effect on collagen, thus any number of the Apicaea family plants high in this coumarin compound might promote and protect collagen. Centella and Hypericum also promoted collagen synthesis and are discussed in more detail below. The use of these herbs, both internally and topically may benefit the health and appearance of the skin.

Hydroxyacids and Exfoliation
Alpha-hydroxy acids are known to loosen the connections between stratum corneum cells, which are more or less the most superficial and devitalized of the epidermal cells. Loosening the connections between them helps them to slough away more efficiently and allow moisturizers, such as Vitamin C to penetrate. However, somewhat paradoxically, promoting the sloughing of devitalized skin cells, often referred to as exfoliation is noted to stimulate the growth of new cells. Rather than thinning the skin, exfoliants have been noted to actually increase dermal thickness due to stimulation of GAGs formations and promotion of collagen synthesis.

Antioxidants to Protect From UV Radiation
Plants with significant antioxidant activity would be logical choices for both topical and internal use to protect the skin from photo-oxidation and provide some degree of anti-aging activity. Nutrients and phytochemical with antioxidant activity do so because of the ability to accept free electrons, free radicals, and reactive oxygen species into their own chemical structure without becoming damaged themselves. Such compounds are able to do this, in general, by distributing the charge of free radicals about gridwork. Thus, rather than firmly binding to a cellular membrane, or more specifically a molecule within the cellular membrane and oxidizing it, the electrical charge is moved rapidly from spot to spot to spot about a large molecular complex such that the free electrons or ionizing radiation never firmly binds. With this background explanation, it can be understood then why many of the most powerful antioxidant phytochemicals have large ring structures. When carbon atoms group together to form benzene rings, the electrons of the Carbon atoms are shared collectively with all the carbon atoms in the ring structures. When several benzene rings are grouped together by plants, as is the case with flavinoids molecules such as hypericin in Hypericum or the heterosides in Gingko, electrons are shared about an even larger collective molecular structure. Such molecules are able to absorb other electrons or UV radiation without damaging their own structures. Thus many nutritional and plant preparations are useful both internally and topically to protect from oxidative damage, and over a lifetime have an ability to slow the normal process of aging.
Sophisticated techniques exist for measuring how much UV radiation a cell, such as a fibroblast is able to absorb. One current research tool involves “matrix metalloproteinases” or MMPs. MMPs are presently being shown to play a role in aging by accepting the charge from UV radiation and mediating the breakdown and recycling of extracellular matrix proteins. Because of this activity, MMPs are being developed as a research tool in the assessment of plants and nutrients with potential anti-oxidant activity and anti-aging activity. Luciferase enzyme activity is another research tool.

Antioxidant Phytochemicals and the Skin
Chemically, phytochemicals with multiple benzene ring structures are referred to as phenolics or polyphenols. All flavinoids can be placed under the phenolic chemical umbrella. Catechins in green tea are a type of phenolic having much research demonstrating significant antioxidant effects. Recent investigations are also showing anti-aging effects from green tea catechins when used topically. Brightly colored phenolic compounds in Sea Buckthorn (Hippophae rhamnoides) have been noted to speed wound healing and have significant antioxidant activity, and offer UV light protection. A partial explanation for the significant wound healing effects of Sea Buckthorn is the rich nutrient content including Vitamins A,C, and E and the minerals sulfur, selenium, zinc, and copper. Hydroxyproline, an important basic building component of bone, cartilage, and the skin’s connective tissue matrix, has been shown to increase with the topical application of Sea Buckthorn oil. Hexosamine, glutathione, Vitamin C, and catalase are also all noted to increase in the skin following topical use. Sea Buckthorn is also being reported to have an anti-cancer effect. Oral ingestion of the oil is noted to improve fatty acid composition of the skin in patients with atopic dermatitis.
Xanthines from plants include the stimulants caffeine, theophylline, and theobromine. Xanthines are a type of polyphenol, an enormous category of plant compounds, many of which have powerful antioxidant effects. Xanthines are noted to possess such free-radical scavenging effects and an ability to protect from UV radiation when used both orally and topically. It is known that caffeine, theophylline and theobromine are able to be absorbed into the skin and that oleic acid and other fatty vehicles enhance the absorption. Terpenes have also been demonstrated to enhance the absorption of xanthines including theophylline and green tea catechins into the skin. Since many essential oils are high in terpenes, the addition of such to herbal oils and aqueous preparation may improve penetration of medicines into the stratum corneum. The naturally occurring oxygen containing turpineols have been found to better vehicles that the petroleum-based hydrocarbon terpenes are less effective in enhancing absorption. Animal studies have shown that the topical application of caffeine to previously UV damaged skin prevents the subsequent development of squamous cell cancers. Even orally ingested caffeine, in the form of green tea of coffee has been shown to reduce cancerous changes in cells exposed to UV radiation. Apoptosis has been shown to be enhanced with the oral ingestion of caffeine which may reduce the tendency to actinic keratosis and squamous cell cancers by protecting from UV radiation.
The topical use of oil from a green tea plant, Camellia japonica is high in the above mentioned terpenoid catechins, displays an antioxidant effect resulting in improved type I procollagen synthesis and improved water retention. Hypericum flavinoids hypericin and hyperforin have been noted to limit the proliferation of lymphocytes in the skin following radiation exposure. Tannins from Hamamelis have been noted to have protective effects on dermal fibroblasts. Hamamelitannin and gallic acid both showed significant antioxidant and UV protective actions. Furthermore, glycosides in Hamamelis were noted to have an affinity for fibroblasts by binding to fibroblast cell surfaces via sugar molecules. Hamameli-tannin and its analogues gallic and syringic acid protect fibroblasts from oxidative damage and increase cell survival following radiation exposure.
Ionizing radiation damages cells directly as well as generates reactive oxygen species that can be inflaming and damaging systemically. Nineteen different carotenoids have been identified in Calendula, 10 of them occurring only in the orange variety. Calendula (and Hypericum) has been shown to possess significant antioxidant properties.
Centella asiatica at a dose of 100 mg per Kg has been shown to offer a protective effect to the liver when dosed prior to radiation exposure. Centella was also shown to have a protective effect from gamma radiation generated by radioactive Cobalt 60 increasing survival time and reducing radiation-induced weight loss. The most effective dose was 100 mg per kg. A broad survey of a variety of herbal medicines showed numerous plants to have radioprotective activity including Gingko biloba, Centella asiatica, Hippophae rhamnoides, Ocimum santum, Panax ginseng, Phylllanthus amarus, Piper longum, Mentha piperita, Syzygium cumini, and Zingiber officinalis.

Glutamine, Glucosamine and Glycosaminoglycans
Glucosamine products are popular for arthritis due to an ability to help regenerate osseous connective tissue. Glucosamine is similar to the basic building blocks of all connective tissue – the glycsoaminoglycans such as hyaluronic acid. The glycosaminoglycans are precursors for the proteoglycans which act as structural and elastic components of all connective tissue including the connective tissue matrix of the skin. Glucosamine protects chondron reducing inflammation in cartilage and connective tissue.
Glycosaminoglycans in the skin are noted to retain a substantial amount of water which helps protect the connective tissue from being damaged by mechanical pressures. This and the increased collagen production are most likely responsible for the anti-wrinkle effects of glucosamine. With greater skin matrix synthesis, aged skin is more likely to withstand skin injury and displays an improved appearance.
Similar to the research on osteoarthritis, glucosamine has been shown to stimulate hyaluronic acid and water retention of the skin. Glucosamine also is noted to reduce the activation of tyrosinase, the enzyme involved with melanin production in the skin. By this mechanism, glucosamine may also reduce age spots and hyperpigmentation in the skin.

L-Glutamine Glutamine is a low molecular weight small and simple amino acid used by the body to synthesize endogenous GAGs. Glutamine is used to form the amino portion of the proteoglycans. The synthesis requires the enzyme glucosamine synthetase. This enzyme appears widely distributed in the tissues and forms glucosamine as well as hyaluronic acid, L-Glutamine supplementation has also been shown to elevate human growth hormone. L-Glutamine may help heal digestive ulcers by this mechanism, as well promote the synthesis of all proteoglycans in the body. Aloe vera contains significant amounts of Glutamine. Much lesser amounts are found in Date Palms (Pheonix dactylifolia) and Orange fruit (Citrus sinensis), Currants (Ribes nigrum) and Pineapples (Ananas comosus), Onions (Allium cepa) and Celery (Apium graveolans).

Glucosamine sulfate Glucosamine is a glucose-based substance combined with an amino acid based substance occuring naturally in animals as a component of the proteoglycans in cartilage. Glucosamine forms glycosaminoglycans (GAGS), a type of proteoglycan having ability to absorb water, become compressed without damage by loosing water, and acting as a resilient shock absorber in cartilage and connective tissue. Studies have shown glucosamine to rebuild cartilage.
The commercially available glucosamine is derived from the exoskeletons of shellfish such as crabs. Chondroitin is similar to glucosamine but of animal origin such bovine sources. There are claims that glucosamine is better absorbed than chondroitin, but little published investigation. Glucosamine does appear well absorbed in the intestines , and is observed to concentrate mostly in the cartilage with lesser amounts in the liver.
Present research has suggested that abnormalities in the connective tissue matrix necessary to regenerate the bladder mucosa, as well as maintain the integrity of the bladder is impaired in cases of interstitial cystitis. Aberrations in glycosaminoglycans (GAGS), a major component of the basement membrane of the urinary mucosa have been reported. , The GAGS serve to form a junction between the mucosal cells and prevent the entry of undesirable compounds from penetrating the mucosal cells and entering local tissues. If made incompetent due to toxic or inflammatory processes, weakened GAG metabolism may be involved with a cascade of physiologic changes resulting in the symptoms of interstitial cystitis.



Glucosamine sulfate and chondroitin are also being investigated to see whether it might also improve IC. These animal derived biopolymers are types of glycosamineglycans (GAGs) thought to be utilized by cells to generate proteoglycans. Proteoglycans are the basis of connective tissues, and the ingestion of glucosamine sulfate and chondroitin may stimulate repair and regeneration of these tissues. Most studies for arthritis, but glucosamine and chondroitin may benefit bruising and inflammation in soft tissues as well. Local application of another sulphate, DMSO, has been instilled in the bladder during cystoscopy where it may act as a methyl donor and assist mucosal repair. Methionine, s-adenylmethionine (SaMe), N-acetylcysteine (N-AC), choline, phosphotidylcholine, lecithin, and MSM are used in complementary medicine to reduce inflammation in connective tissue, as well as provide detoxifying support for the liver and central nervous system. These supplements may also prove valuable for IC by acting as sources of sulfur to help restore GAGs. Current research on GAG is also noting a correlation between potassium levels locally, and increased mucosal sensitivity. Abnormally elevated potassium levels may induce heightened nervous and electrical sensitivity.  Kava (Piper methysticum) has been noted to affect potassium channel activity.

Allium cepa and Allium sativum may provide sulfur, promote detoxification, have anti-allergy effects and support GAG. Sulfur links the longitudinal threads together helping to give connective tissue its flexibility and resiliency. Dermatan sulfate, a ground substance sulfur molecule is sometimes used as a laboratory indicator of skin regeneration. Part of the efficacy of glucosamine, bromelain, and some amino acids is that they contain sulfur in an absorbable form helping to regenerate connective tissues. Sulfur is difficult for some to absorb, and in the form of amino acids or sugar-linked molecules as occur in some plants are most easily assimilated. Sulfur is found in high amounts in the following order: Brassica oleracea varieties (Cabbage and Cauliflower), Anethum graveolans (Dill), Pastinaca sativa (Parsnip), Armoracia rusticana (Horseradish), Petasites japonica (Butterbur), Urtica dioica (Nettle), and Raphanus sativus (Radishes). Lesser amounts are found in black pepper, spinach, puslane, cucumbers, turnips, sunflower seeds, cashews, oats, parsley, onions,and soybeans, in that order.

Asparagine and Allantoin and Plant Glycoproteins
The closest compounds in plants to the animal-based GAGs molecules are the glycoproteins. Some complex polysaccharides in plants may have an amino acid component allowing them to be considered glycoproteins. Arabinogalactan from the Larch tree for example appears to have mucous membrane and connective tissue enhancing effects.
Aspargine, form asparagus also appears to help heal urinary ulcers and have a restorative effect on animal mucous membranes, particularly in the GI tract. Asparagine is also found in Achillea millefolium, Apium graveolans, Salvia officinalis, Allium cepa, Camellia sinensis, Armoracia, Coffea, Gingko, Humulus, Lycium, Fragaria, Panax, Oryza, and Phaseolus varieties.
Allantoin, an imidizole alkaloid, acts as a cell proliferating agent has a GAGs-like chemical make-up. Allantoin is produced endogenously by animals and appears to be involved with rapid growth. It is observed to increase in the serum of pregnant women and is decreased in cases of placental insufficiency.
A plant with a notably high allantoin composition is Aloe vera. Aloe vera research has noted the plant to promote the formation of ground substance associated with measurable increases in hyaluronic acid and dermatan sulphate. Hyaluronic acid and dermatan sulphate levels are noted to be increased with both topical and internal use of Aloe.
Symphytum has the highest known content of allantoin, being present in both the leaf and root. Beet root, Beta vulgaris, Plantago, Pueraria, Solanum tuberosum, Aesculus hippocastanum, Arctostaphylos uva ursi, and Camellia sinensis, also contain allantoin. Many legumes contain allantoin including, Trifolium, Pisum and Glycine max, as do the grains Zea mays, Triticum,and Oryza.

Other polysaccharides in plants may have an affinity for certain glycoprotein receptors on skin and mucous membrane cell membranes, giving them wound healing or anti-inflammatory effects on the skin. Animal studies have shown that polysccharides from Opuntia have wound healing effects. Research has shown that topical application has resulted in accelerated re-epithelization of cutaneous lesions.
Sulfur containing plant oligosaccharides appear to influence metabolism of hyaluronidases enzymes. Sulphated oligosaccarhides include verbascose and plantose, both 100 to 500 times more potent than the weak hyaluronidase inhibitor, apigenin. A glycoprotein from Withania somnifera has been shown to inhibit hyaluronidase, the enzyme that breaks down hyaluronic acid. Echinacea polysaccarhides have been credited with the same activity. This has mainly been discussed in term of preventing the dissemination of snake venom throughout the tissues as venom contains hyaluronidase. However, these plants might also be included in skin care routines in order to help protect the integrity of hyaluronic acid.

Other plants still may promote glucosamine synthesis without being glycan-like substances themselves. The Noni fruit, Morinda citrifolia has been noted to up regulate the biosynthesis of collagen and glycosaminoglycans by human fiboblasts making it a logical addition to topical and internal formula for wrinkles and skin aging. Soy milk and cultured soy products are shown to enhance the production of hyaluronic acid.when applied topically. The proposed mechanism is the release of genistein and daidzein. These Legume family isoflavones have been shown to promote hyaluronic acid production in the skin when topically applied. Research on these isoflavones and their effect on hyaluronic acid suggest their utility for cosmetic applications. Soy is also noted to be very high in sulfur which may promote collagen cross-linking and general metabolism within the dermis.
Boswellic acids from Boswellia serrata have an influence of the sulfation of glycosaminoglycans. The uptake of sulfate molecules, in a variety of cell types including the skin, has been shown to increase under the influence of Boswellia. In keeping with the known sequence of dermal synthesis, breakdown of glycosaminoglycan molecules by sulfur based metabolism, and sulfur metabolizing enzymes, is followed by an increase in the glycohydrolase enzymes, the glucuronidases and glucosaminidases.


Calendula officinalis – Pot Marigold contains sterols, flavonols, and triterpenes having antiinflammatory and wound healing effects. Calendula extracts have been used topically and internally for centuries to promote healing. Modern studies have noted stimulation of glycoprotein and collagen metabolism locally after topical application to surgical wounds.

Centella asiatica or Gotu Kola is a nourishing succulent green leafy native to India. Centella has been used traditionally as something of panacea for general strength and longeveity. Centella has been widely used for wound healing including bone, skin, joint, and other tissues. Centella has also been specifically recommended for ulcerative and inflammatory conditions of the cystic, gastric, esophogeal, intestinal, rectal, and oral mucosal surfaces. Centella has been noted to promote healing of bladder ulcers specifically. , Skin injuries including burns, lacerations, keloid formation, excema, psoriasis and other forms of dermatitis may also respond to Centella. Recently, Centalla has been reported to improve abberant fibroblast activity in the skin and connective tissue as seen with scleroderma, Lupus and other auto-immune diseases. Earlier research has shown Centella to promote formation of new connective tissue, hyalronic acid, and chondrotin sulfate. , For this history as an ulcer and mucous membrane remedy, plus possible immune and inflammatory stabilization, Centella may benefit IC.

Equisetum arvense – Horsetail
Equisetum is noted to contain the anti-inflammatory and anti-allergic flavonoids, quercitin, isoquercitin and equicetrin which may reduce allergic phenomena. Hydroalcoholic extracts of a variety of Equisetum species have demonstrated antioxidant and antimicrobial activity. Topical application in the form of tub soaks and sitz baths has been used historically for musculoskeletal, arthritic, and auto-immune disorders. The silica and silicic acid that Equisetum is notably high in (6.0% and 0.6% respectively) is thought to enhance connective tissue restoration. Silica may also help the kidneys excrete heavy metals and others waste, and thereby improve toxicity, hypersensitivity, and autoimmune reactivity.

Alpha ketoglutarate is involved with glutamic acid metabolism, using the amino acid glutamine in the synthesis of ground substance. Alpha-ketoglutarate, a krebs cycle intermediate, in known to play a role in the synthesis of proline by serving as a cofactor to the synthesis enzyme, prolyl-4-hydroxylase. Alpha-ketoglutarate has been noted to increase proline availability and promote it’s transformation into collagen. Since collagen loss and damage is part of the mechanism of skin aging, alpha-ketoglutarate is being explored as a possible anti-aging substance. Experiments have shown the topical use of alpha-ketoglutarate to stimulate dermal fibroblasts and protect from UV radiation. Longterm use is reported to reduce wrinkle formation and protect from photodamage by enhancing collagen synthesis via proline stimulation. Grape seed proanthocyanidins have been noted to decrease the breakdown of alpha ketoglutarate via decreasing alpha-ketoglutarate dehydrogenase enzyme activity.
Alpha ketoglutarate may be oxidized in the mitochondria and involve lipoic-acid catalyzed pathways. The high protein plants Pisum sativum, Oryza sativa and Arabidopsis display this metabolic activity prominently. Ketoglutarase enzymes release lipoic acid that deaminates some amino acids including valine, leucine, and isoleucine. The breakdown of amino acids by this enzyme system may be involved with damage to muscle and other tissues.
The chemotherapy drug Adriamycin, commonly used for breast cancer is well known to be cardiotoxic via mitochondrial damage and associated with a decrease in alph-ketoglutarate. A decrease in alpha ketoglutarate is associated with mitochondrial damage. Both pre and co-treatment with Centella is shown to prevent the activation of ketoglutarate dehydrogenases.
Smoking is also noted to damage the structure and function of mitochondria. Bacopa monniera, long used in India for all types of dementia, is noted to protect mitochondria as measured by various enzymes including the ketoglutarate dehydrogenases. Thus Bacopa protects ketoglutarate levels in tissues.
A deficiency in the quantity and activity of alpha-ketoglutarate is also associated with Alzheimer’s disease, and is related to genetic abnormality with fibroblasts. The excessive accumulation of collagen is part of the pathophysiology of a variety of fibrotic diseases, in the central nervous system as well as the skin. Alpha ketoglutarate has been shown to inhibit enzymes involved with synthesizing procollagen and its precursor hydroxyproline.
Glutamate dehydrogenase, the enzyme that degrades glutamine is excessive in many cases of hyperinsulinemia. The excessive breakdown of this amino acid can lead to excessive ammonia and nitrogenous wastes in the blood. Cimicifuga heraclefolia may decrease the activity of this enzyme , providing yet another mechanism by where Cimicifuga may be appropriate for endocrine disorders associated with hyperinsuinsim. This also provides a rationale whereby Cimicifuga may support skin metabolism via endocrine and hormonal pathways. Just as Cimicifuga has been noted to reduce osteoporosis and support bone growth, it appears there is a central nervous system centered effect on insulin, supporting the evidence that Cimicifuga has endocrine effects via gonadotropins.


Topical Vitamin A Acids, Carboxylic Acids, and Other Acids
The retinoids are all vitamin A derivatives and some natural and some synthetic are presently being used in the practice of dermatology. Three different vitamin A acids occur in the skin naturally, and retinoic acid is the most potent. Retinoic acid helps regulate the proliferation and differentiation of epithelial cells. Retinoic acid also stimulates the biosynthesis of collagen types I and III. Because of these activities, the retinoids are used for acne, keratoses, and photodamage to the skin.
The carboxylic acids include the AHAs (alpha-hydroxy acids), the PHA’s (polyhydroxy acids), the ABA’s (aldobionic acid). The carboxylic acids are naturally occurring hydroxyacids that modulate skin keratinization and synthesis of dermal components. These acids have been used therapeutically for a variety of skin complaints including warts, excema, psoriasis, and cosmetic complaints and photo-aging.
Other important acids include retinoic acid, vitamin C, salicylic, and azeleic acid Salicylic acid is used more for acne than wrinkles due to its marked astringent effect. Vitamin C (Ascorbic Acid) is a water soluble acid that is recommend topically for the prevention of skin damage caused by UV radiation.


Retinoids and Photoaging
Three naturally occurring physiologic Vitamin A acids exist – retinoic acid and the natural retinols. The synthetic retinoids include Retin A (Tretinoin), Isotretinoin, Retin aldehyde and Retinol. Tretinoin is currently thought to be the most potent of the synthetic retinoids and is widely used for photoaging of the skin. Although they have some value, they are frequently irritating when used topically to the point of limiting their utility. Burning sensation, scaling of the skin, and full blown dermatitis are common and cause many users to abandon the products. Retin aldehyde and retinol are considerably less irritating, but the effects on the skin less marked. Present studies are investigating the use of liposomal delivery systems that may improve tolerance and thus efficacy.
The naturally occurring Vitamin A acids are available but can be irritating like the popular synthetics. Clinical trials using Topical Vitamin A or retinols on elderly, has been noted to reduce photodamage based on both visual assessment following treatment as well as biopsy assessment. The group treated with topical retinols showed significant increases in glycosaminoglycan and procollagen content compared to placebo treated controls.

Astringent Plant Acids
The astringent plant acids include Azelaic acid and Salicylic acid. Many many others would be appropriate to include on this list, but these two have reached the marketplace with a bit of research. Azelaic acid has been noted to normalize keratinization in the demal follicle, have activity against Propriobacterium associated with acne. Azelaic acid is also noted to inhibit the synthesis of melanin and thereby be useful for hyperpigmentation disorders.
Hormones and Skin Aging
Hormones are noted to have profound effects on the skin. From testosterone’s stimulation of sebum production, to the acceleration of aging following menopause, hormones have wide and powerful activities on the dermis, connective tissue matrix, and skin vasculature. Delayed wound healing in the elderly may have both vascular and hormonal mechanisms underlying. Estrogens have been identified as playing roles in wound healing, while androgens actually slow healing by interfering with the accumulation of the structural proteins that reconstitute the damaged dermis. Thus estrogens are most investigated for wound healing and anti-aging actions.
Estrogens are noted to increase the thickness of the dermis and promote hydration. A decline in estrogen menopausally is associated with thinning of the skin, loss of moisture retention, and accelerated aging. A side affect of HRT is often skin benefits, though due to the numerous side affects and cancer concerns, estrogen can hardly be recommended for enhancing the skin alone. However phytoestrogens, the topical use of estrogens, and the judicious use of some of the bioidentical estrogens may have a role in cosmetic applications. The ingestion of whole plants having estrogenic and hormone supportive effects would be the best considerations of all. Rhodiola, Panax, Cimicifuga, Medicago, and Foeniculum would be just a few of the many whole plants to consider for providing phytosterols support to the skin and entire endocrine system.


Growth Factors and Aging
Dermal growth factors play a role in both chronological and photo and environmental aging of the skin. Both types of aging involve oxidative processes in the intra- and extracellular matrices of the skin which over time damage collagen and elastin webs. Human growth factors have been noted to increase dermal collagen synthesis thereby reducing the effects of aging. Growth factors play a role in wound healing in the skin having cell proliferating and collagen-stimulating activities. One pilot study assessed a topical growth factor containing cream on the chin and around the eyes and mouth for two months and reported beneficial results based on subjective opinion. Thus, agents or topicals which promote the quantity and activity of dermal growth factors may help reduce the aging process in the skin.

B Vitamins
Nicotinic acid and derivatives are being investigated for repair of and protection against photoaging. Myristyl nicotinate, a nicotinic acid derivative is noted to increase epithelial NAD (nicotinamine adenine dinucleoutide) content by a full 25%, increase stratum corneum thickness by 70% and epidermal thickness by 20%. Myristyl nicotinate also improves water retention by the skin.


Misc Connective Tissue Effectors in the Skin
Elastase inhibition has been investigated to help retain the elasticity of the skin. Korean research has reported a Korean plant Persicaria hydropiper to be a potent elastase inhibitor. Plants inhibiting the deposition of inelastic fibrin are also being investigated to help retain the youthful elastic quality of the skin. Persicaria hydropiper, Filipendula glaberrina root, Nymphaea tetragona root and Camellia japonica leaf preparation have been shown to inhibit fibroblast activity. The Korean plant Melothria heterophylla has been shown to have antioxidant effects as well as an ability to limit excessive fibrin formation.


Laser Therapy
Sometimes referred to as “optical skin rejuvenation” in the literature, this discipline is used to resurface the facial skin. All sorts of lasers, frequencies, and techniques, as well as combining with other topical applications simultaneously are being explored with entire medical journals dedicated to the art of laser surgery. Lasers can be used with such precision that they can be used to kill only the most superficial living skin, which will then flake and shed like a sunburn, revealing younger, temporarily less wrinkled and photodamaged skin. The results are not dramatic but are pleasing enough to a large number of people that the practice and specialty is growing. Research on using anti-inflammatory, antioxidant, tissue-protective topical applications is underway to suggest what agents will reduce side-affects, and what agents can help prevent the newly emerging skin from aging rapidly. Very detailed research involving liposomal agents, optimal dose and saturation time, methods of delivery, techniques for assessing cellular absorbtion, and so on are underway and part of the current practice of laser surgery.


Soft Tissue Fillers, Injections
Injecting a variety of substances into facial pits, scars, and wrinkles is another cosmetic possibility. The difficulty is that the skin does not usually leave such injected material lie, and it is slowly metabolized, assimilated, and the lesion reemerges, necessitating repeated injections. None the less, for individuals with facial lesions, receiving injections every few months to maintain the effect, remains an attractive option.
Potential side affects of these injections are local inflammation and increased sensitivity with repeated therapy. All possible are the rare local necrosis and systemic reaction. The search for the optimal substances is ongoing. Hyaluronic acid injections are among the more “natural” agents used for this purpose, but even this may promote the rare inflammation of blood vessels to the point of occluding them and leading to necrosis.



J Dermatol. 2007 Sep;34(9):593-600. Angiogenesis in skin aging and photoaging.Chung JH, Eun HC.Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Can J Physiol Pharmacol. 2007 Sep;85(9):943-51. XP-828L (Dermylex), a new whey protein extract with potential benefit for mild to moderate psoriasis.Drouin R, Lamiot E, Cantin K, Gauthier SF, Pouliot Y, Poubelle PE, Juneau C. Advitech Inc., 1165, boulevard Lebourgneuf, Suite 140, Québec, QC G2K2C9
Int J Low Extrem Wounds. 2006 Sep;5(3):169-80. A review of the microcirculation in skin in patients with chronic venous insufficiency: the problem and the evidence available for therapeutic options.Wollina U, Abdel-Naser MB, Mani R.
Angiology. 2001 Oct;52 Suppl 2:S49-54.Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model.Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Bavera P, Bucci M, Ippolito E
Arch Dermatol Res. 2007 Nov 30 Fermentable metabolite of Zymomonas mobilis controls collagen reduction in photoaging skin by improving TGF-beta/Smad signaling suppression.Tanaka H, Yamaba H, Kosugi N, Mizutani H, Nakata S.
J Ethnopharmacol. 2007 Apr 20;111(1):33-9. Wound-healing activity of St. John’s Wort (Hypericum perforatum L.) on chicken embryonic fibroblasts.Oztürk N, Korkmaz S, Oztürk Y.
Planta Med. 2006 Mar;72(4):324-8. Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling.Lee J, Jung E, Kim Y, Park J, Park J, Hong S, Kim J, Hyun C, Kim YS, Park D.
Int J Dermatol. 2004 Nov;43(11):801-7. Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts.Lu L, Ying K, Wei S, Fang Y, Liu Y, Lin H, Ma L, Mao Y.
Br J Dermatol. 2004 Sep;151(3):571-8. LDermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis.Lu L, Ying K, Wei S, Liu Y, Lin H, Mao Y.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Aug;24(8):731-4.Effect of total glucosides of Centella asiatica on antagonizing liver fibrosis induced by dimethylnitrosamine in rats. Ming ZJ, Liu SZ, Cao L.
Br J Dermatol. 2007 Dec 6 Repair of photoaged dermal matrix by topical application of a cosmetic ‘antiageing’ product.Watson RE, Long SP, Bowden JJ, Bastrilles JY, Barton SP, Griffiths CE. Dermatological Sciences Research Group, The University of Manchester, Manchester M13 9PT, U.K.
J Ethnopharmacol. 1998 Jan;59(3):179-86. Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. Chithra P, Sajithlal GB, Chandrakasan G.
Zhongguo Zhong Yao Za Zhi. 2006 Apr;31(7):570-3. Experimental study on protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats. Zhou G, Wang JF, Niu JZ, Lu YS, Chen WT, Li ZH, Lin TX.
Planta Med. 2001 Mar;67(2):132-5.Inhibitory effect of baicalein, a flavonoid in Scutellaria Root, on eotaxin production by human dermal fibroblasts.Nakajima T, Imanishi M, Yamamoto K, Cyong JC, Hirai K.
Basic Clin Pharmacol Toxicol. 2007 Aug;101(2):73-7. Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocin-diabetic rats.Ramesh B, Pugalendi KV.
J Am Acad Dermatol. 2005 Jun;52(6):1049-59. Green tea and the skin.Hsu S.
Khirurgiia (Sofiia). 1995;48(3):30-3. The effect of an extract of sea buckthorn (Hippophae rhamnoides L.) on the healing of experimental skin wounds in rats [Article in Bulgarian]
Mol Cell Biochem. 2006 Oct;290(1-2):193-8. Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound healing in rats.Gupta A, Kumar R, Pal K, Singh V, Banerjee PK, Sawhney RC
J Agric Food Chem. 1999 Sep;47(9):3480-8. Sea buckthorn products: manufacture and composition.Beveridge T, Li TS, Oomah BD, Smith A.
Int J Low Extrem Wounds. 2005 Jun;4(2):88-92. A preclinical study of the effects of seabuckthorn (Hippophae rhamnoides L.) leaf extract on cutaneous wound healing in albino rats.Gupta A, Kumar R, Pal K, Banerjee PK, Sawhney RC.
Nutr Cancer. 2005;51(1):59-67. Chemoprevention by Hippophae rhamnoides: effects on tumorigenesis, phase II and antioxidant enzymes, and IRF-1 transcription factor.Padmavathi B, Upreti M, Singh V, Rao AR, Singh RP, Rath PC.
J Nutr Biochem. 2000 Jun;11(6):338-40. Effect of dietary supplementation with sea buckthorn (Hippophaë rhamnoides) seed and pulp oils on the fatty acid composition of skin glycerophospholipids of patients with atopic dermatitis.Yang B, Kalimo KO, Tahvonen RL, Mattila LM, Katajisto JK, Kallio HP.
Photodermatol Photoimmunol Photomed. 2007 Apr-Jun;23(2-3):86-94. Topical application of plant extracts containing xanthine derivatives can prevent UV-induced wrinkle formation in hairless mice.Mitani H, Ryu A, Suzuki T, Yamashita M, Arakane K, Koide C.
Drug Dev Ind Pharm. 2007 May;33(5):513-21.Transdermal and buccal delivery of methylxanthines through human tissue in vitro.Thakur RA, Michniak BB, Meidan VM.
Biol Pharm Bull. 2007 Feb;30(2):343-9. Transdermal delivery of tea catechins and theophylline enhanced by terpenes: a mechanistic study.Fang JY, Tsai TH, Lin YY, Wong WW, Wang MN, Huang JF.
Br J Dermatol. 2007 May;156(5):957-64. Protection from photodamage by topical application of caffeine after ultraviolet irradiation.Koo SW, Hirakawa S, Fujii S, Kawasumi M, Nghiem P
Carcinogenesis. 2007 Jan;28(1):199-206. Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice.Lu YP, Lou YR, Xie JG, Peng QY, Zhou S, Lin Y, Shih WJ, Conney AH.
Toxicol Appl Pharmacol. 2007 Nov 1;224(3):209-13.Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice.Conney AH, Zhou S, Lee MJ, Xie JG, Yang CS, Lou YR, Lu Y.
J Ethnopharmacol. 2007 May 30;112(1):127-31.Effect of Camellia japonica oil on human type I procollagen production and skin barrier function.Jung E, Lee J, Baek J, Jung K, Lee J, Huh S, Kim S, Koh J, Park D.
Br J Dermatol. 2000 May;142(5):979-84. Topical application of St John’s wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells.Schempp CM, Winghofer B, Lüdtke R, Simon-Haarhaus B, Schöpf E, Simon JC
J Dermatol Sci. 1995 Jul;10(1):25-34. Protective activity of hamamelitannin on cell damage of murine skin fibroblasts induced by UVB irradiation.Masaki H, Atsumi T, Sakurai H.
Biol Pharm Bull. 1995 Jan;18(1):59-63.Protective activity of hamamelitannin on cell damage induced by superoxide anion radicals in murine dermal fibroblasts.Masaki H, Atsumi T, Sakurai H.
Biosci Biotechnol Biochem. 2005 Nov;69(11):2122-8. Analysis of carotenoid composition in petals of calendula (Calendula officinalis L.).Kishimoto S, Maoka T, Sumitomo K, Ohmiya A.
Roum Arch Microbiol Immunol. 2003 Jul-Dec;62(3-4):217-27.Antioxidant properties of some hydroalcoholic plant extracts with antiinflammatory activity.Herold A, Cremer L, Calugăru A, Tamaş V, Ionescu F, Manea S, Szegli G.
Phytother Res. 2005 Jul;19(7):605-11. Modification of gamma ray induced changes in the mouse hepatocytes by Centella asiatica extract: in vivo studies.Sharma R, Sharma J.
Phytother Res. 2002 Dec;16(8):785-6. Radioprotection of Swiss albino mouse by Centella asiatica extract.Sharma J, Sharma R.
J Clin Biochem Nutr. 2007 Mar;40(2):74-81. Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation.C Jagetia G
J Cosmet Dermatol. 2006 Dec;5(4):309-15.Glucosamine: an ingredient with skin and other benefits.Bissett DL.
Pharmatherapeutica 2(8):504-508;1981 M “Glucosamine sulphate, a controlled investigation in arthrosis”
Setnikar I, Pacini MA, RevelL, “Antiarthritic Effects of Glucosamine sulfate studied in animal models” Arnzeim-Forsch 45(5):542;1991 D’Ambrosio E, Casa B, Bompani G, Scali
Welbourne TC “Increased plasms bicarbonate and growth hormone after an oral glutamine load” Am J Clin Nutrition 61(5):1048-61 May 1995
Dovanti A, Baignamini AA, Rovati AL “Therapeutic activity of ofal glucosamine sulphate in osterorthritis: A placebo controlled double blind investigation” Clin Ther 3:266-272, 1980
Setnikar I, Giachetti C, Zanolo G “Absorption, distribution, and excretion of readioactivity after a single iv or oral administration of [14C] glucosamine to the rat” Pharmatherapeutica 3(8):538-550;1984
Setnikar I, Giachettia C, Zanolo G “Pharmacokeinetic of glucosamine in the Dog and in Man” Arnzeim-forsch 36;729-733;1986
Nickel JC et al, “The bladder mucus glycosaminoglycan layer in interstitial cystitis” Urology 1995; 149:716-718
Wilson CB et al, “Selective type IV collagen defects in the urothelial basement membrane in interstitial cystitis” J Urology 1995;154: 1222-1226
Mateu J et al, “Ann Pharmacother 1994 Nove;28:1243-44, and Jul-Aug;28;967-68,
Payne CK et al. “Graded potassium chloride testing in Interstitial Cystitis” J Urology 1996; 155-158
Parsons CL, “Potassium Sensitivity Test. Techniques in Urology” J Urology 996;171-173
J Ocul Pharmacol Ther. 2007 Dec;23(6):541-50. Larch arabinogalactan for dry eye protection and treatment of corneal lesions: investigations in rabbits.Burgalassi S, Nicosia N, Monti D, Falcone G, Boldrini E, Chetoni P.
Izv Akad Nauk Ser Biol. 2006 Sep-Oct;(5):541-5.Biological functions of allantoin. Shestopalov AV, Shkurat TP, Mikashinovich ZI, Kryzhanovskaia IO, Bogacheva MA, Lomteva SV, Prokof’ev VP, Gus’kov EP.
J Ethnopharmacol. 1998 Jan;59(3):179-86. Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. Chithra P, Sajithlal GB, Chandrakasan G.
Phytomedicine. 2006 May;13(5):352-8.Effect of polysaccharides from Opuntia ficus-indica (L.) cladodes on the healing of dermal wounds in the rat.Trombetta D, Puglia C, Perri D, Licata A, Pergolizzi S, Lauriano ER, De Pasquale A, Saija A, Bonina FP.
Planta Med. 2005 Aug;71(8):727-32. Sulphated oligosaccharides as inhibitors of hyaluronidases from bovine testis, bee venom and Streptococcus agalactiae.Salmen S, Hoechstetter J, Käsbauer C, Paper DH, Bernhardt G, Buschauer A.
Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jun;143(2):158-61 A glycoprotein from a folk medicinal plant, Withania somnifera, inhibits hyaluronidase activity of snake venoms.Machiah DK, Girish KS, Gowda TV.
J Med Food. 2005 Winter;8(4):552-5.Induction of extracellular matrix synthesis in normal human fibroblasts by anthraquinone isolated from Morinda citrifolia (Noni) fruit.Kim SW, Jo BK, Jeong JH, Choi SU, Hwang YI.
Skin Pharmacol Appl Skin Physiol. 2003 Mar-Apr;16(2):108-16. Bifidobacterium-fermented soy milk extract stimulates hyaluronic acid production in human skin cells and hairless mouse skin.Miyazaki K, Hanamizu T, Iizuka R, Chiba K.
Skin Pharmacol Appl Skin Physiol. 2002 May-Jun;15(3):175-83.Genistein and daidzein stimulate hyaluronic acid production in transformed human keratinocyte culture and hairless mouse skin.Miyazaki K, Hanamizu T, Iizuka R, Chiba K.
Biochem Pharmacol. 1989 Oct 15;38(20):3527-34. Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents.Reddy GK, Chandrakasan G, Dhar SC.
Kloucheck-Popava E, et al Acta Pharmacol Bulg 1982;8:63
Etrebi A, Ibrahim A, and Zaki K, “Treatment of bladder ulcer with asiaticoside” J Egypt Med Assoc 58(1975):324-7
Aziz-Fam, A, “Use of titrated extract of centella asiatica (TECA) in bilharzial bladder lesions” Int Surg 58 (1973):324-7
Monograph: Centella asiatica Indena S.p.A., Milan, Italy, 1987
European Journal Pharmacol 1:414-24, 1967
Plant Foods Hum Nutr. 2007 Sep;62(3):113-9. Antioxidant, antimicrobial and genotoxicity screening of hydro-alcoholic extracts of five serbian Equisetum species.Milovanović V, Radulović N, Todorović Z, Stanković M, Stojanović G.
Biol Pharm Bull. 2007 Aug;30(8):1395-9. Alpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts, and decreases UVB-induced wrinkle formation following topical application on the dorsal skin of hairless mice.Son ED, Choi GH, Kim H, Lee B, Chang IS, Hwang JS.
Life Sci. 2007 Nov 30;81(23-24):1615-21.Grape seed proanthocyanidins ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes: an in vivo study.Karthikeyan K, Sarala Bai BR, Niranjali Devaraj S.
Plant Physiol. 2004 Feb;134(2):838-48. Lipoic acid-dependent oxidative catabolism of alpha-keto acids in mitochondria provides evidence for branched-chain amino acid catabolism in Arabidopsis.Taylor NL, Heazlewood JL, Day DA, Millar AH.
Mol Cell Biochem. 2007 Jan;294(1-2):55-63.induced myocardial failure in rats: protective role of Centella asiatica.Gnanapragasam A, Yogeeta S, Subhashini R, Ebenezar KK, Sathish V, Devaki T.
J Environ Pathol Toxicol Oncol. 2005;24(3):225-34. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats.Anbarasi K, Vani G, Devi CS.
Ann Neurol. 1994 Mar;35(3):312-8.Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer’s disease.Sheu KF, Cooper AJ, Koike K, Koike M, Lindsay JG, Blass JP.
J Biol Chem. 1987 Jul 5;262(19):9397-403. Reduction of collagen production in keloid fibroblast cultures by ethyl-3,4-dihydroxybenzoate. Inhibition of prolyl hydroxylase activity as a mechanism of action.Sasaki T, Majamaa K, Uitto J.
Mol Cells. 2004 Jun 30;17(3):509-14. Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets.Lee KH, Lee WJ, Yang SJ, Huh JW, Choi J, Hong HN, Hwang O, Cho SW.
Clin Interv Aging. 2006;1(4):327-48. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety.Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G.
Arch Dermatol. 2007 May;143(5):606-12. Improvement of naturally aged skin with vitamin A (retinol).Kafi R, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S.
J Cosmet Dermatol. 2004 Apr;3(2):76-87.Alpha-hydroxyacids and carboxylic acids.Yu RJ, Van Scott EJ.Chalfont, Pennsylvania, USA.

Climacteric. 2007 Aug;10(4):276-88. Sex steroids and cutaneous wound healing: the contrasting influences of estrogens and androgens.Gilliver SC, Ashcroft GS.
Climacteric. 2007 Aug;10(4):289-97. Effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators.Verdier-Sévrain S. Bio-Hybrid, LLC, West Palm Beach, Florida, USA.
Dermatol Ther. 2007 Sep-Oct;20(5):350-9. Endogenous growth factors as cosmeceuticals.Mehta RC, Fitzpatrick RE.
Research and Development, SkinMedica, Inc., Carlsbad, California, USA
J Drugs Dermatol. 2007 Oct;6(10):1018-23. Human growth factor and cytokine skin cream for facial skin rejuvenation as assessed by 3D in vivo optical skin imaging.Gold MH, Goldman MP, Biron J.
J Drugs Dermatol. 2007 Feb;6(2):197-201.Efficacy of novel skin cream containing mixture of human growth factors and cytokines for skin rejuvenation.Gold MH, Goldman MP, Biron J.
Exp Dermatol. 2007 Jun;16(6):490-9. A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin.Jacobson EL, Kim H, Kim M, Williams JD, Coyle DL, Coyle WR, Grove G, Rizer RL, Stratton MS, Jacobson MK.Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85724, USA
J Cosmet Sci. 2007 Jan-Feb;58(1):19-33.Inhibitory effects of natural plants of Jeju Island on elastase and MMP-1 expression.Kim YH, Kim KS, Han CS, Yang HC, Park SH, Ko KI, Lee SH, Kim KH, Lee NH, Kim JM, Son KH.
J Cosmet Sci. 2006 Jul-Aug;57(4):279-89.Inhibitory effects of antioxidant constituents from Melothria heterophylla on matrix metalloproteinase-1 expression in UVA-irradiated human dermal fibroblasts.Cho YH, Kim JH, Sim GS, Lee BC, Pyo HB, Park HD.

Lasers Surg Med. 2007 Apr;39(4):302-10. 5-ALA for photodynamic photorejuvenation–optimization of treatment regime based on normal-skin fluorescence measurements.Christiansen K, Bjerring P, Troilius A.
J Drugs Dermatol. 2007 Mar;6(3):325-8.Comment in:J Drugs Dermatol. 2007 Jun;6(6):581; author reply 581.
Delayed presentation of impending necrosis following soft tissue augmentation with hyaluronic acid and successful management with hyaluronidase.Hirsch RJ, Lupo M, Cohen JL, Duffy D.


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