Grape compounds marketed as antioxidants: Types and clinical evidence

Grape derivatives that are marketed as antioxidants are usually by-products of wine production: grapevine cane is used as a source of resveratrol; grape pomace (skin, seeds and lees), which accounts for 15-25% of the weight of the grape, is rich in phenolic compounds; and grape seeds contain proanthocyanidins, omega-6 fatty acids, phytosterols, and vitamin E. The content of antioxidant compounds depends on each grape variety.

Research has shown that oxidative stress is related to a number of diseases in both humans and animals.

Grape derivatives that are marketed as antioxidants are usually by-products of wine production: grapevine cane is used as a source of resveratrol; grape pomace (skin, seeds and lees), which accounts for 15-25% of the weight of the grape, is rich in phenolic compounds; and grape seeds contain proanthocyanidins, omega-6 fatty acids, phytosterols, and vitamin E. The content of antioxidant compounds depends on each grape variety.

An important advantage of antioxidants obtained from grapes is that their bioavailability is high compared to antioxidants obtained from other fruits, thanks to the low content of non-digestible carbohydrates and proteins, and their efficient gastrointestinal delivery.

Beneficial compounds contained in grapes and their biological functions

1. Polyphenols

Polyphenols are one of the most studied groups of secondary plant metabolites, thanks to their potential beneficial effects on human health. More than 8000 different polyphenols have been described, with very different molecular structures, biological effects, and bioavailability. They all have in common the fact that they have phenolic groups and a high antioxidant power.

They are classified as flavonoid (flavonols, flavones, flavanones, isoflavonoids, chalcones and anthocyanins) and non-flavonoid molecules (phenolic acids, stilbenoids and others). 

1.1 Flavonoids

Flavonoids are important secondary metabolites that play key roles in protecting plants against stresses. They are derived from the phenylpropanoid biosynthetic pathway, which results in the synthesis of resveratrol, and can be subclassified into flavonols, flavanols, proanthocyanidins, flavones, flavanones, isoflavonoids, chalcones and anthocyanins.

Flavonoids are concentrated mainly in the skin, as they are involved in the protection against UV light, the attraction of pollinators, and the defense against pathogens and predators. Their concentration depends on the berry variety, being higher in red grapes, and the developmental stage of the fruit.

Experimental results indicate that the bioavailability of flavonoids is very low. However, multiple studies confirm their biological effects, so it is hypothesized that they are transformed by the digestive flora into molecules with better bioavailability. Clinical studies in humans confirm their potential to prevent or treat memory decline, obesity, diabetes, and liver diseases.

The most common flavonols in grapes are quercetin, myricetin and rutin. In clinical studies, quercetin has shown potential to reduce cholesterol and blood pressure, as well as the symptoms of prostatitis.

Proanthocyanidins are polymers of flavanols. In the grape, the skin contains proanthocyanidins with a higher polymerization degree and lower bioavailability, while the seed has shorter polymers with better bioavailability. Clinical studies in humans confirm their potential to reduce blood pressure, to decrease the pigmentation in patients affected by chloasma, and to ameliorate the symptoms related to menopause.

Anthocyanins are responsible for the colour of grape berries and their products, such as wine and juice. They are concentrated in the skin of the berry, and are easily oxidized in the by-products obtained from grapes.

1.2 Non-flavonoids
1.2.1 Phenolic acids

Phenolic acids are characterized by the presence of one carboxylic acid, and are found in the plants as conjugates, rarely in free form. In in vitro tests, phenolic acids often show better antioxidant activity than well-known antioxidant vitamins.

Phenolic acids are present in the grape skin, and in lower amounts in pulp and seeds. They form stable pigments in red wine, and contribute to its astringency and bitterness.

They can be divided into two major sub classes:

  • Hydroxybenzoic acids: Possess a common structure derived from benzoic acid. They are found in soluble form, conjugated with sugars or organic acids. Grapes contain syringic acid, gallic acid, gentisic acid, ellagic acid, protocatechuic acid and vanillic acid.
  • Hydroxycinnamic acids: Derived from cinnamic acids, are found often in plants as simple esters with quinic acid or glucose. Caffeic acid, chlorogenic acid, coumaric acid, sinapic acid, and ferulic acid are present in grapes.

Both in vitro and in vivo experiments with isolated phenolic acids are rare; in most research projects, phenolic acids are used together with other compounds found in grapes.

1.2.2 Stilbenes

Stilbenes are phytoalexins: antimicrobial and antioxidant substances, without a particular chemical structure, that are produced by plants in response to an environmental stress. Resveratrol is the most well-known stilbene, found in the epidermis of the leaves and in the skin of the grapes, particularly when the grapevine is infected with Botrytis cinerea.

Resveratrol’s in vitro properties as anticancer, anti-inflammatory, antiallergic, etc are widely studied. However, due to its poor solubility and low bioavailability, its in vivo activity is not so clear. Until now, resveratrol has shown clinical potential in the following applications: antiaging cosmetics, reduction of cholesterol and blood pressure, and cognitive decline.

2. Lipids

Grape seeds contain up to 16% of lipids, including fatty acids (linoleic, oleic, and palmatic acid), tocopherols, tocotrienols and phytosterols.

The lipid fraction is used as a comestic ingredient, and recent studies show that the supplementation with grapeseed oil improves diseases related to inflammation as well as insulin resistance.

The importance of the right dose

Polyphenols have a double action as reducing and oxidizing agents, depending on the circumstances.

In vitro, polyphenols from grapes show both antioxidant and prooxidant action. In example, an in vitro experiment showed that low concentrations of both grape seed extract and proanthocyanidin B2 reduced the levels of free radicals, while at concentrations 50 to 100 times higher both compounds induced the generation of free radicals.

There is less research about their pro-oxidative action in vivo. A variety of polyphenols, including gallic acid, ellagic acid, quercetin, myricetin, rutin, and resveratrol can act as pro-oxidants, depending on the dose, which is usually considerably higher than the dose required for the antioxidant activity. Other factors include the duration of administration, solubility, chelating behaviour, metal-reducing potential and pH at the site of action.

Generally speaking, their pro-oxidative activity leads to toxic effects, but there are exceptions: achieving toxic levels of free radicals exerts cytotoxic effects against cancer cells and modulates the antioxidant capacity of certain endogenous factors, protecting the body against severe oxidative stress.

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Tea tree oil for acne: How it works and how to use it

Galenolink, consultant, consultancy, plant extracts, essential oils, phytogenics, natural products, asia pacific, pharmaceutical, food, feed, phytogenic, animal health, cosmetics,

Tea tree essential oil (TTO) is one of the most widely used worldwide. It can be easily found in the form of pure essential oil in pharmacies, supermarkets, and specialty stores, and is used as an ingredient in many cosmetic products, due to its antibacterial and anti-inflammatory properties. 

TTO is obtained by steam distillation of the leaves and terminal branches of the Australian native plant Melaleuca alternifolia. The yield of oil is 1-2% of the wet plant material weight. It contains circa 100 constituents and there are six chemotypes, but only one is used commercially, the terpinene-4-ol, which contains 30-40% of this constituent. Within the terpinene-4-ol chemotype, there is a great chemical variability, but it has not been shown to impact the biological effects of the oil, neither in vitro nor in vivo.

Aboriginal Australians traditionally used the leaves of the tea tree to treat skin and respiratory diseases. In the 18th century, sailors arriving in Australia dubbed the plant a “tea tree”, because they used the leaves to make an infusion that smelled of nutmeg. It was not until the early twentieth century that it was discovered that essential oil had an antimicrobial capacity 11 times higher than phenol, the golden standard of the time, and its use became popular. 

Currently, multiple scientific studies document the effectiveness of TTO in the treatment of wounds, insect bites, lice, fungal infections affecting bones, nails and skin, dandruff, seborrheic dermatitis, chronic gingivitis and acne vulgaris.

TTO is considered safe, but it can cause contact dermatitis in some patients. Concentrations up to 10% have been tested with few side effects, but the continued use of such high concentrations is discouraged, and the direct application of the pure essential oil must be avoided. A concentration of 5% is recommended for shock treatments and below 2% for long-term treatments.

Like all essential oils, TTO is not soluble in water, which can make it difficult to formulate water-based products. In addition, it is volatile, and there are plastic materials that absorb it, so it is recommended to choose products that are well formulated and to be extremely careful with DIY recipes.

Mechanisms of action

TTO has a broad-spectrum antimicrobial activity, being effective against Gram-positive and Gram-negative bacteria, protozoa, fungi and virus. The mechanism of antibacterial action is through nonspecific damage to the bacterial cell membrane, which results in loss of intracellular material, inability to maintain homeostasis and inhibition of respiration. The main antibacterial activity is carried out by terpinen-4-ol and α-terpineol, but the other constituents of the oil also contribute to its effect.

TTO shows anti-inflammatory action, impacting a range of immune responses, and decreasing the production of free radicals.

Use of tea tree oil to treat acne

Acne vulgaris is a chronic skin disease that occurs when hair follicles are blocked with dead skin cells, bacteria, and oil (sebum). The blocked follicles cause lesions on the skin, including pimples, blackheads, whiteheads, papules, nodules, and cysts. The cause of the disease is multifactorial, including excessive sebum production, low desquamation rate of the follicular epithelium, inflammation, and the presence of the acne-causing bacteria Cutibacterium acnes.

Conventional antiacne treatments include the following mechanisms of action:

  1. Antibacterial activity, especially against Cutibacterium acnes (antibiotics, benzoyl peroxide)
  2. Antiinflammatory (retinoids)
  3. Normalization of the keratinization of the follicles (retinoids)
  4. Reduction of sebum production (retinoids)
  5. Keratolytic activity (beta hydroxy acids, in example salicylic acid)

TTO is present in many over the counter anti-acne products, and it is often chosen by patients who decide to self-treat. As explained above, TTO only works through mechanisms of action 1 and 2 (antibacterial and anti-inflammatory). However, several studies have shown that TTO reduces the number of lesions in patients with mild to moderate acne:

  • A study showed that TTO was better than placebo
  • Another study showed that TTO was equivalent to 5% benzoyl peroxide and 2% topical erythromycin
  • Another study showed that a face wash and a facial gel reduced lesion counts and were safe to use.
  • A study demonstrated that 5% TTO had similar effectiveness as 5% benzoyl peroxide, with less side effects, although the TTO treatment was slower.
  • An investigation showed the effectiveness of topical TTO alone and in combination with an oral Ayurvedic treatment.
  • Two studies demonstrated the effectiveness of TTO combined with other natural ingredients.

All these research studies show that TTO is an effective and safe alternative for the treatment of moderate acne, and that it satisfies the patient’s willingness to use natural products to solve common health problems. 

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Use of Saint John’s Wort in skin care

St. John’s wort (Hypericum perforatum), also known as goat weed or enola weed, it’s a perennial flowering herb belonging to the Clusiaceae family. The name of the specie, “perforatum”, refers to small translucent spots that are evident when the leaves are held up to the light.

It has been used since Ancient Greece both externally as a macerated oil to treat wounds, burns, bruises, cuts, and pain and internally in infusion against stomach ulcers, neuralgia, anxiety, and insomnia.

The herb produces golden yellow flowers that, according to the traditional recipe, must be left to macerate for 40 days in olive oil and exposed to direct sunlight. Legend has it that the oil is more effective if flowers are collected on Saint John’s Day (June 24) and left to macerate until the day of the Saint’s beheading (August 29). The resulting oil is red, which is also associated with the color of St. John’s blood.

The red color of the oil is due to the presence of hypericin, an anthraquinone-derived pigment, belonging to the naphthodianthrones chemical family. Due to its chemical structure, with two oxygen atoms very close to each other sharing a mobile hydrogen atom, hypericin is very reactive to light.

The macerated oil contains other naphthodianthrones such as pseudohypericin, isophypericin, and protohypericin, together with other lipophilic compounds such as hyperforin (another photoreactive compound), adhyperforin and furohyperforin.

Hypericin and hyperforin are antioxidant and anti-inflammatory. Hyperforin stimulates the growth and differentiation of keratinocytes. St. John’s wort extract enhances collagen production and activates the fibroblasts that is responsible for wound closure.

Hyperforin has been shown to inhibit the growth of certain bacteria and viruses.

St. John’s wort extracts and macerated oils are used in skin care products to;

  • Prevent fine lines
  • Treat acne
  • Soothe reddened, burnt, or sunburned skin
  • Reduce itching, irritation, eczema, and inflammation
  • Treat psoriasis or dermatitis
  • Regenerate the skin in case of minor wounds, bruises, and dry skin
  • Promote recovery after a tattoo

Due to the high photoreactivity of hypericin and hyperforin, St. John’s wort extracts and macerated oils are mildly phototoxic. Phototoxicity is a chemically induced skin irritation that takes place when the skin is exposed to the sun. It is advised not to expose the skin to the sun after using skin care products containing St. John’s wort extracts or macerated oils and apply them preferably at night.

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