Mrs ir. Elzbieta E.Brand-Garnys and Dr ir. Hans M.Brand, Elzbieta Cosmetics BV
Dr Horst Denzer and Dr Hamke Meijer, KAO Chemicals GmbH

Flavonoids are frequently recognised as “flower pigments” in angiosperm plants. Their occurrence is not restricted to flowers; they are also found in all other parts of plants. Approximately 5000 flavonoids have been reported in the literature. Most of them have a molecular skeleton composed of 15 carbon atoms, subdivided in {6+9} carbon atoms. The molecular part with 6 carbon atoms is made up from a phenolic moiety, substituted with one or more hydroxy or methoxy functionalities. The second part has a cinnamic acid moiety as the building block, also substituted with one or more hydroxy or methoxy functionalities. The hydroxy groups may be glycosylated; the sugar moiety may be a neutral sugar or an acidic sugar although the last group less frequently occurs. We previously reported in an extensive review on the chemical identity of flavonoids (E.E.Brand-Garnys, et al., Cosmetics and Toiletries Manufacturing Worldwide, Aston Publishing, London, 2001).

Virtually all flavonoids exhibit physiological activity and their properties are undergoing research for pharmaceutical applications. Their application in personal care and cosmetic products is useful, and ground-breaking. It should be emphasised that the use of flavonoids as anti-oxidants is inferior to their other properties; many flavonoids are antiviral agents and are able to manipulate enzyme activity. This property is frequently utilised in anti-ageing products. Furthermore flavonoids have been shown to affect various cancer lines and are currently undergoing clinical testing, frequently with unexpectedly positive results.

Sometimes flavonoids also show adverse reactions, particularly in the presence of sunlight. Psoralens such as angelicin, bergapten and imperatorin are particularly notorious. These are subject to [2+2] photochemical cycloadditions to genetic material, disabling cell reproduction. The use of Peru Balsam (Myroxylon Toluifera Pereirae) is too well-known to require further documentation. Tangerine oil, cassia oil, grapefruit oil, parsley oil, rue oil, styrax, oakmoss extract and marigold oil are less well known for their psoralen content. These products are restricted to topical use when a direct interaction with sunlight can be expected. There is a strict prohibition on the use of melissa oil, verbena oil, costus oil, fig leaf absolute and opoponax oil.

1. Baicalein/baicalin: antiviral properties

Baicalein (5,6,7-trihydroxyflavone) is a flavon found in Scutellaria baicalensis (Baikal skullcap), largely as its glycoside with glucuronic acid (coupled on the 7-postion; baicalin). Baikal skullcap is used in gardens because of its beautiful flowers though despite its relationship with the mint family both flowers and leaves are virtually odour-free.

Baicalein/baicalin have been described as the most significant non-nucleoside reverse transcriptase inhibitors (NNRTI). Reverse transcriptases are enzymes that enable viruses to invade healthy cells and duplicate themselves. Inhibition of reverse transcriptases can be inhibited by nucleotide analogues (NRTI’s; FDA approved since 1985). Baicalein and baicalin have also been shown to inhibit reverse transcriptases, such as in the case of HIV-1, without side reactions.

Viruses actually use only two enzymes; reverse transcriptases and integrases. Integrases enable the integration of the viral DNA with the host chromosome. Like reverse transcriptases, integrases are vulnerable to inhibition (E.E.Brand-Garnys, H.M.Brand, SPC, 2003). Chlorogenic acids (CA) are precursors for flavonoids; 3,5-Dicaffeoyl quinic acid (a CA) found in Carqueja (Baccharis trimera) was reported to be a potent inhibitor of HIV-1 integrase in vitro at dosages as low as 1 mcg/ml (W.E.Robinson, et al., Proc.Natl.Acad. Sci.USA 93, 6326, (1996)).

The usable part of Baikal skullcap is the root. The pharmacological activity has been attributed to baicalin, baicalein, and to a lesser extent to wogonin and scutellarein. These flavonoids all appear to bind to particular receptors with benzodiazepine-like effects (K.M.Hui, X.H.Wang, H.Xue. Planta Med., 66,91,2000; J.F.Liao, H.H.Wang, M.C.Chen, Planta Med., 64,571,1998). Baicalein has weak antipyretic properties and there are indications that it also has anti-mutagenic alpha-glucosidase activity.

Baicalin has potent anti-inflammatory and anti-tumour properties. Some evidence suggests it can inhibit tumour growth and suppress carcinoma cell proliferation. Baicalein and baicalin are reported to be far more active as free-radical scavengers than e.g., d,l-α-tocopherol. Baikal skullcap has antibacterial and antiviral properties, as well as antifungal activity, particularly against Candida albicans. It has been suggested that Scutellaria extract can be used as preservative, although broad spectrum activity is subject to discussion.

Baikal skullcap, usually addressed a Scutellaria, has been listed in the Chinese Pharmacopoeia for centuries. Its dried roots, better known as ‘Oughon’, were valued for their anti-inflammatory action. Oughon was much sought after by noblewomen, as its helped to give them a radiant, porcelain-like complexion. Today, it is still used in cosmetology for this reason (citation: Clarins).

Baikal skullcap can probably be considered to be the flagship, but there are many other flavonoids that also exhibit antiviral properties. (An incomplete anthology is given in Table 1.). In spite of this, it should be noted that flavonoids are not usually suitable for the treatment of viral infections. The elapsed time for the activity of flavonoids to become noticeable or measurable is usually longer than the response time of the human body to produce antibodies to eliminate viruses. However, from a prophylactic point of view flavonoids are extremely powerful and totally ignored by traditional medicine.

Naturally occurring flavonoids with antiviral activity have been recognized since the 1940s. In recent times attempts have been made to modify naturally occurring flavonoids to improve antiviral activity. Quercetin, morin, rutin, taxifolin, dihydrofisetin, apigenin charts:

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