Because of its central importance as a universal regulator of metabolism and gene expression, systemic intervention of the cAMP metabolism is associated with numerous, sometimes considerable, side effects.


Forskolin Rescues cAMP Deficient Signaling

Forskolin is a naturally derived diterpenoid extracted from the roots of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations. Forskolin, which is a skin-permeable compound, directly activates adenylate cyclase to induce production of cAMP. Our laboratory was among the first to show that topical application of forskolin promoted UV-independent production of eumelanin in an MC1R-defective fair-skinned animal model [53], resulting in robust UV protection by interfering with epidermal penetration of UV photons [68]. Pharmacologic stimulation of cAMP using forskolin may protect the skin in ways other than through melanin induction. For example, cAMP provided enhancement of keratinocyte migration to promote wound healing [69] and it also decreased blister formation [70]. De Vries and co-workers proposed using a topical cAMP approach to regulate beta-adrenergic response in psoriasis patients [71]. Interestingly, cAMP stimulation has also been studied as an activator of hair follicle activity and has been considered as a therapy for age-related hair loss [72,73].


Pentacyclic Triterpene Distribution in Various Plants – Rich Sources for a New Group of Multi-Potent Plant Extracts

The pharmacological relevance of these triterpenes has increased during the last two decades demonstrating multi-target properties such as wound healing, anti-inflammatory, anti-bacterial, antiviral, hepatoprotective and anti-tumoral effects, combined with low toxicity.

Mediterranean spices and fruits contain, besides other nutraceuticals, pentacyclic triterpenes from the lupane, oleanane and ursane groups (see Figure 1 and Table 1), that are regularly isolated as active substances from these plants. For example, they can be found in rosemary and other spices of the Lamiaceae family as well as within olive leaves and fruit. Virgin olive oil contains up to 197 mg/kg triterpenes, indicating the importance of these substances as nutraceuticals [1-4]. Furthermore, the bioguided fractionation of several hundred plant extracts led to the isolation of betulinic acid (BA), oleanolic acid (OA) and ursolic acid (UA) as the active principles [5]. Apples are among the fruit most consumed worldwide and anti-tumoral effects from apples are correlated with the fruit peel [6] which contains OA, UA and maslinic acid (MA) [7]. Known sources for triterpenes are mainly plant surfaces such as stem bark or leaf and fruit waxes [8]. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations. The preparation of a semi-solid topical formulation of triterpenes is realised for instance with the above mentioned triterpene dry extract from the outer bark of birch. It has been used successfully in treating actinic keratoses.


S-Adenosyl-L-Methionine (AdoMet), S-Adenosyl- L-Homocysteine (AdoHcy), adenosine, trehalose and oleanolic acid were measured in six medicinal herbs and three spices. The findings showed that AdoMet content was forty six fold higher in the leaves of Catharanthus roseus as compared with average AdoMet content of rest of the plants.

AdoMet aka SAMe