Coleus spp.

The Genus Coleus

More than 300 species belong to the genus Coleus, a member of the family Lamiaceae. Coleus species are native to tropical and subtropical regions of Africa, Australia, the East Indies, the Malay Archipelago, and the Philippines. Some species, especially those with showy colorful foliage, are grown as ornamentals all over the world. In India, tubers of some Coleus species, namely, C. tuberosus and C. forskohlii, are eaten as vegetables and pickles, leaves of other Coleus species (e.g. C. amboinicus) are used as spices. Preparations from several Coleus species are used in Ayurvedic medicine in India, e.g., preparations from C. amboinicus are active against skin problems and worms. Other preparations from Coleus are traditionally used against heart diseases, abdominal colic, respiratory disorders, painful micturition, insomnia, and convulsions. The genus Coleus was first described by de Loureiro in 1790. The name Coleus is derived from the Greek work koleos, which means sheath. This relates to a typical characteristic of Coleus, where the four filaments fuse at the bottom to form a sheath around the style (de Loureiro 1790).

Plants of the genus Coleus grow as herbaceous perennials, subshrubs, and low shrubs. They have square stems, opposite, toothed, stalked, or stalkless leaves and asymmetrical flowers. These flowers are mostly blue or lilac-blue and grow in terminal spikelike racemes or panicles. The blooms have a five-toothed calyx and tubular, two-lipped corolla. The upper lip is often two-lobed, the lower longer, often three-lobed, and frequently contains the two pairs of deflexed stamens and style. The stalks of the stamens are united at their bases into a tube encircling the style. The anthers are joined. The only style has two stigmas. The fruits are of four seedlike nutlets.

Coleus forskohlii and Forskolin

Coleus forskohlii Briq. is also known under the name Coleus barbatus Briq., which is the legitimate name. The plant originated from the Indian subcontinent, but has been distributed to Egypt, Arabia, Ethiopia, East Africa, and Brazil. It is a perennial aromatic plant with a height of 40-60 cm. The root system forms tubers, which are eaten as a vegetable in India. During screening programs for useful medicinal plants in India, two different groups independently discovered roots of C. forskohlii as a source for a potential drug. The tuberous roots contain a labdane diterpene which was called coleonol by one group and forskolin by the other.

Forskolin has a number of promising pharmacological effects and has become an important research tool since its discovery. It activates the catalytic subunit of the enzyme adenylate cyclase in eukaryotes, and also potentiates the hormonal response of this enzyme in a new and unique manner. Therefore, forskolin is used to study the role of adenylate cyclase and cyclic AMP in eukaryotic systems all over the world. The pharmacological effects reported for forskolin may also base on this activity on adenylate cyclase. The compound is able to lower hypertension by decreasing the peripheral resistance, and it also has a positive inotropic effect on the heart muscle. Therefore, it may be used to treat congestive heart failure. Moreover, forskolin has been studied as a bronchodilator in asthmatics and for lowering intraocular pressure, thus treating glaucoma. It also acts as an anti-inflammatory drug, and may be used to treat thromboembolic platelet disorders and tumor metastases of certain cancers. Since the acute toxicity of forskolin is much lower than the therapeutic range, this compound or semi-synthetic derivatives may be promising drugs of the future.

The demand for forskolin was mainly satisfied by large-scale and indiscriminate collections of C. forskohlii from wild habitats. Since C. forskohlii up to now is the only known plant source for forskolin, this has led to a severe depletion of the plant, and C.forskohlii is listed as one of the endangered plant species in India. Today, large-scale field cultivation of C. forskohlii is used in India to produce large amounts of plant material for the isolation of forskolin.

Coleus blumei and Rosmarinic Acid

The origin and nomenclature of Coleus blumei is not very clear, since different names are currently used for the same species, which might be a natural hybrid with origin in Southeast Asia. The first description of this plant was by Linnaeus (1763), who gave the name Ocimum scutellarioides. Later, Brown (1810) reclassified this species as Plectranthus scutellarioides, and this name was also used by Blume (1826) for another specimen which was similar to the one of Linnaeus. Bentham (1832-1836) considered these two plants as different species and placed them into the genus Coleus, with the names C. blumei and C. scutellarioides. In 1896, Siebert and Voss placed C. blumei, C. scutellarioides, C. atropurpureus, C. bicolor, C. verschaffelti, and C. hybridus as subspecies into the species C. scutellarioides. Therefore, the legitimate name for the plant is Coleus scutellarioides (L.) Bentham. Nevertheless, numerous publications on this species use the name C. blumei, namely, reports on the production of rosmarinic acid by this species. Therefore this name is also used in this chapter. Coleus blumei () is grown as an ornamental plant all over the world in an enormous number of different cultivars which vary in the color and shape of the leaves. The first plant was brought to Europe from Java in 1851 and the species became very popular as an ornamental plant (Gardener 1855). It is used as a medicinal plant in India, Indonesia, and Mexico.

Coleus blumei is not used for medicinal purposes but there is a high demand for this plant as an ornamental. Certain varieties with striking foliage can only be propagated by cuttings that can be easily rooted. Other varieties are reproduced by seeds.

Commercial Aspects

Up to now, none of the mentioned secondary compounds which can be produced by in vitro cultures of Coleus are in any commercial use as pure substances. Forskolin, which was detected only quite recently as a promising drug because of its activity towards adenylate cyclase, is used as a research tool for studying the function of this enzyme. Also clinical studies have been performed with forskolin and semisynthetic derivatives of this compound and are still being published numerously. The low water solubility to forskolin has made a direct application of forskolin impossible. Today, more soluble semi-synthetic derivatives are produced with plant-derived forskolin as basic molecule and used for clinical studies in Japan for treatment of cardiac disorders. About the same is true for rosmarinic acid. RA-containing herbal extracts from well-known medicinal plants such as Mentha, Melissa, Salvia, Thymus, Rosmarinus, Symphytum, and many others are used in folk medicine and also in commercial medicaments. However, rosmarinic acid (RA) as a pure compound has never been used despite its promising properties for pharmaceutical and food-preserving purposes.

In India, C. forskohlii is now being cultivated in fields on a large scale to obtain the plant material for the isolation of forskolin. The production of forskolin by in vitro cultures of C. forskohlii can yield about the same amounts of forskolin in the dry mass as the wild-growing plant, therefore this procedure might become feasible if the productivity could be further optimized.

A large-scale production of rosmarinic acid by suspension cultures of C. blumei has been successfully performed with a yield of more than 20% of the cell dry weight as rosmarinic acid. Therefore, large amounts of rosmarinic acid could be produced by in vitro cultures; however, a market for rosmarinic acid does not exist at the moment, and the commercial value of this compound is therefore low. Since RA has a number of interesting pharmacological activities, a future use of rosmarinic acid in pharmacy, medicine, or the food industry cannot be excluded.

Coleus spp.: Conclusions and Prospects

Members of the genus Coleus produce interesting secondary compounds from very different classes, e.g., C. blumei synthesizes rosmarinic acid and C. forskohlii forskolin, which belong to the caffeic acid esters and the diterpenoids respectively. Rosmarinic acid is found not only in the plant, but is also produced in undifferentiated cell cultures which even have a much higher content. Cell cultures of C. blumei accumulate up to 21% of the cell dry weight as rosmarinic acid, which is one of the highest accumulation levels of secondary products in plant cell cultures ever found, compared to 2-3% in the plant. This is not the rule, since a number of secondary compounds of higher plants are not produced in cell cultures at all or only in very low concentrations. Technical production of RA in cell cultures of C. blumei could be economically feasible. Unfortunately, despite the interesting pharmacological activities and the low toxicity of RA, the pure compound is not used for medicinal purposes and therefore a market for rosmarinic acid does not exist. As a result, attempts at a large-scale production of RA were not continued. However, RA-producing cell cultures of C. blumei have become a useful system for basic research concerning the regulation of secondary product biosysnthesis. With easy manipulations of the culture medium, the biosynthesis of RA can be stimulated. A high amount of rosmarinic acid is accumulated in only a few days at the end of the growth phase of the cell cultures. At this time the activities of the enzymes involved in the biosynthetic pathway of rosmarinic acid are very high and also the genes encoding these enzymes are supposed to be active. Since only eight enzymes are involved in the biosynthetic pathway, all of which are known now, this system is very suitable to study the regulation of this pathway. Knowledge of the regulatory principles of one secondary pathway could help us in future to understand why some cultures do not produce the secondary compounds which are found in the plant. This could show us how to manipulate these cultures in a direction where secondary compound production starts. An example for this is the production of forskolin by cell cultures of C. forskohlii. Undifferentiated suspension cultures of this plant do not produce forskolin, which is mainly accumulated in the roots of the plant, but can be detected in all organs. In an induction medium which promotes differentiation in direction of root formation, root-like structures are formed and forskolin accumulation can be observed. Also more or less differentiated axenic cultures, namely transformed and untransformed root cultures, shoot cultures, and shoot-forming callus cultures, were reported to produce forskolin. The highest forskolin production in tissue and organ cultures was in about the same range as in the plant material. The synthesis of forskolin seems to be coupled to some state of differentiation; however, this correlation is not as strict as in other systems, where absolutely no secondary compounds are formed in undifferentiated cells. The production of forskolin by in vitro cultures is under investigation only for some years now and further optimization of the culture systems might lead to higher contents of forskolin. The interesting activity of forskolin and semisynthetic derivatives on adenylate cyclase and the resulting multiple pharmacological activities are still under investigation. The plant-derived forskolin is used as basic molecule for semisynthetic derivatives. If the production of forskolin by cell or organ cultures could be further optimized, these in vitro cultures might become a further source for forskolin besides field-grown plants.

Selections from the book: “Medicinal and Aromatic Plants VI”, 1994.