The Genus Turnera.: A Review Update

ABSTRACT

The review includes 93 references on the genus Turnera., and comprises ethnopharmacology, morphology and microscopy, natural products, pharmacological studies, clinical studies, and toxicology of the prominent species of the genus Turnera.. Alkaloids, cyanogenic glycosides, flavonoids, and volatile oil constitute major classes of phytoconstituents of the genus. Few species of this genus have medicinal value, among these, Turnera aphrodisiaca. Ward is reputed throughout the world for its aphrodisiac and nervine tonic properties. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Turnera. species, especially T. aphrodisiaca., has been emphasized with a view to isolate bioactive moieties, which could be used for multifarious biological activities.

Keywords:

• Aphrodisiac
• Turnera
• Turnera aphrodisiaca
• Turnera ulmifolia

Introduction

This review emphasizes the traditional use and clinical potential of Turnera. species, especially T. aphrodisiaca.. Additionally, it raises a question on traditional claims of this species, which have not been proved scientifically. Through this review, the authors hope to attract the attention of natural products researchers throughout the world to focus on the unexplored potential of Turnera. species. This genus needs to be investigated systematically so that potential species can be exploited as therapeutic agents.

This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, King's American Dispensatory, Raintree Nutrition Incorporation, Henriette's Herbal Homepage, National Agricultural Library (AGRICOLA), Duke's Phytochemical and Ethnobotany database, UK Cropnet Ethnobotany database, Archives of American Folk Medicine, and USPTO Patent Full Text and Image database.

The available information on Turnera. has been divided into six sections, that is, ethnopharmacology, morphology and microscopy, natural products, pharmacological studies, clinical studies, and toxicology, covering prominent species of Turnera.. The ethnopharmacological section has been further subdivided into two sections, that is, traditional uses and alternative and complementary medicinal uses. The reports in which Turnera. species have been used as a domestic remedy by common men without any prescription for the treatment of various ailments have been discussed under traditional uses. The subhead “Alternative and complementary medicinal uses” highlights Turnera. species as medicine prescribed by medical practitioners for the treatment of various ailments. It also mentions uses for which Turnera. species or their preparations are available in the market. Under every section, Turnera. species have been arranged in alphabetical order.

The genus Turnera. belongs to the family Turneraceae and comprises about 85 species of tropical and subtropical American, African, and Madagascar plants that vary in habit from herbs, sub-shrubs, shrubs, or, rarely, to trees (Osol et al., 1947; Lawerence, 1951; Willis, 1957; Prain, 1981; The Wealth of India, 1996).

Ethnopharmacology

Traditional uses

Only a few species of Turnera. have been used as traditional remedies in various ailments. Turnera aphrodisiaca. Ward [Syn.: T. diffusa. Willd. (Jackson, 1946)], commonly known as Damiana, has been used as a stimulant, aphrodisiac, tonic, diuretic, nerve tonic, laxative, urinary antiseptic, testosteromimetic, and in kidney, menstrual, and pregnancy disorders (Petersen, 1905; Ellingwood, 1919; Timothy, 1954; Hocking & Thomas, 1955; Dominguez & Hinojosa, 1976; Braun & Malone, 1978; Stuart, 1979; Hoffman, 1991; Bradley, 1992; Grieve, 1994; Mills, 1994; Parfitt, 1999). A tea, made from Damiana, is used as a tonic beverage (UCLA Folklore Archives, 2001). Damiana is a folklore restorative remedy for curing masculine insufficiency (Young, 1967). Israel and Youngkin (1997) collected information on selected herbal therapies for perimenopausal and menopausal complaints based on scientific sources and reported that T. aphrodisiaca. has a primary reputation as an aphrodisiac due to testosterone-like properties from alkaloids in the plant.

T. aphrodisiaca. has been used extensively in the traditional system of therapeutics of many countries (Raintree Nutrition Incorporation, 1999). In the ancient Mayan civilization, Damiana was used for “giddiness and loss of balance” and as an aphrodisiac. In the Bahamas, the plant is used for headache and enuresis. Damiana is applied as a plaster for lumbago and is ingested as a decoction for parturition in California (Campa, 1950). In France, the plant is used as an aphrodisiac. In Germany, the leaves of the plant are used to relieve nervous debility and for a tonic action on the hormonal and central nervous system. In Haiti, the plant is used as an aphrodisiac, tonic, liqueur, and in intestinal diseases. In Holland, Damiana is known for its sexual enhancing properties and tonic effect on the reproductive organs. In Mexico, the plant is used in amaurosis, stomachache, diabetes, dysentery, dyspepsia, malaria, paralysis, rhinitis, syphilis, intestinal diseases, and as an aphrodisiac, astringent, diuretic, and tonic. The plant has been used by Mexicans to treat gastrointestinal diseases (Hernandez et al., 2003). In the United States, the plant is used as an aphrodisiac, astringent, expectorant, laxative, stimulant, tonic, and in dysmenorrhea (Raintree Nutrition Incorporation, 1999). The midwives and women of loose morals of western Mexico also attribute emmenagogue properties to it (Ellingwood, 1919). Damiana has achieved some repute in the treatment of sexual impotence, but it is always given in conjunction with strychnine, phosphorus, or some other stimulant (Culbreth, 1927; Osol et al., 1947). Damiana is one of the common ingredients of traditional herbal remedies used as alternatives for treating menopausal symptoms (Duke, 1985; Zava et al., 1998). It also maintains normal menstruation at puberty (Priest & Priest, 1982). The leaf infusion of Damiana has been used in diseases related to the gastrointestinal, and respiratory systems (Caceres, 1996), and reproductive organs (Saggese, 1959; Tilgner, 1999) and for gonorrhea treatment (Koch, 1936).

The infusion of fresh leaves of Turnera guaianensis. Aubl. is indicated to treat inflammatory diseases and as an immunomodulator, while the decoction of its dried leaves is employed to treat furunculosis (Pio Correa, 1984). In Mexico, Turnera pringei. has been used for hangovers (UK Cropnet, 2003). Turnera subulata. Smith has been used to treat boils. Poultices made from the roots of Turnera trioniflora. Sims are applied to boils (The Wealth of India, 1996). Turnera ulmifolia. Linn. has been used in indigestion, bronchitis, and as a tonic (Bradley, 1992). The plant is used for the management of weakness, cold, fever, and boils (Beckwith, 1928). In India, it has been used for chest ailments, indigestion, biliousness, and rheumatism (The Wealth of India, 1996). In the Bahamas, it is used for melroxenia, sore throat, cold, and as an emmenagogue (UK Cropnet, 2003). In Haiti, it is used in vertigo, dysmenorrhea, hemorrhage, toothache, metrorrhagia, lumbago, and dyspepsia. In Java, the plant has been used for dysentery. In Mexico, the plant is used as tonic and for dyspepsia.

Alternative and complementary medicinal uses

Among various species of the genus Turnera., T. aphrodisiaca. is the only one that is extensively used clinically throughout the world. T. aphrodisiaca. was first introduced as a drug in 1874 by Dr. F.O. St. Clair and first appeared in the form of a tincture from the firm of Messers Helmick and Co. of Washington, D.C. (Felter & Lloyd, 1898). The product was promoted as a powerful aphrodisiac, and to give increased tone and activity to all secretions in that vicinity.

Damiana has been prescribed in all conditions where a general tonic is needed, especially for weakness of the central nervous system (Ellingwood, 1919; Hoffman, 1992). The drug is useful in some cases of chronic cystic and renal catarrh. It relieves irritation of the urinary mucous membranes, improves digestion, and overcomes constipation. In respiratory disorders, it is employed to relieve irritation and cough, and due to its tonic properties, to check hypersecretion from the broncho-pulmonic membranes. In reproductive disorders, it is used to treat dysmenorrhea, headache at the menstrual epoch, bad complexion, rough or discolored patches on the skin with acne, especially of severe type, depending on uterine irritation, delayed or suppressed menstruation, and amenorrhea in very young girls. Damiana has been prescribed in young girls with menstrual complaints. The remedy must be given in full doses, i.e., 5 to 10 grains of the extract 3 or 4 times a day to accomplish these results. As a nerve tonic, it is often used with oats. Depending on the situation, it combines well with Kola or Skullcap (Scutellaria lateriflora.).

Balch and Phyllis (1999) report that damiana relieves headaches, controls bed-wetting, and stimulates muscular contractions of the intestinal tract and further comment that damiana interferes with iron absorption when taken internally.

The British Herbal Pharmacopoeia (1983) lists the specific indications for Damiana as anxiety neurosis associated with impotency and lists other indications as depression, nervous dyspepsia, atonic constipation, and coital inadequacy. Mother tincture (ethanol extract) of Damiana is an important homeopathic medicine for the treatment of sexual debility and nervous prostration (Boericke, 1988). Homeopathic materia medica mentions use of Damiana tincture in sexual neurasthemia, impotency, renal and cystic catarrh, frigidity of females, and to maintain normal menstrual flow in young girls (Boericke, 1999).

It has been reported that herbal narcotic distillates, which are used for smoking purposes, contain T. aphrodisiaca. (Huang et al., 1982). Ingestion of an infusion of Damiana leaves, or alternatively smoking the leaves, produces a feeling of euphoria characterized by relaxation and increased imagination (Tyler, 1980). A herbal preparation containing Damiana as one of the ingredients has been reported to exhibit favorable effects on the symptoms of irritable bladder associated with functional and neurohormonal disorders and on bacterial bladder infections (Westendorf, 1982). These reactions are supposedly more pronounced in women.

Damiana is one of the constituents of a breast-enhancing oral formulation that is used as a dietary supplement (Ernest & Smith, 2001). Damiana is included in a number of herbal formulations that are used to treat menopausal symptoms (Morrow, 1998), diabetic male sexual dysfunction (Shlyankevich, 1996), impotence (McLeod, 1993), and to improve sexual response and psychological effects (Heleen, 2002).

Morphology and Microscopy

A survey of the literature revealed that detailed accounts of morphology and microscopy of the genus Turnera. are missing. Preliminary information on habits of the following species is available: T. acutasrena. (Brittonia, 1957), T.. amapaensiscowan. (Brittonia, 1957), T. angustifolia. Mills. (Curtis, 1794), and T. trioniflora. (The Wealth of India, 1996). However, somewhat detailed notes on morphological aspects of T. aphrodisiaca. and T. ulmifolia. have been reported. T.. aphrodisiaca. is a robustly growing, spreading plant that consists of herbaceous stems and is indigenous to southwestern Texas and Mexico (Felter & Lloyd, 1898; The British Pharmaceutical Codex, 1911; Culbreth, 1927; Perez et al., 1984; Hoffman, 1991; Raintree Nutrition Incorporation, 1999). T. aphrodisiaca. stem is small, reddish-brown, woody; leaves pale green or yellow green in color, 10–25 mm long, 4–10 mm broad, broadly lanceolate, short petioled, acute tip, cuneate base, serrate margin, smooth surface, lower surface glabrous with few hairs on ribs, and prominent veins on the under surface; branches have reddish-brown bark; flowers yellow, globose pods, 8–12 mm long with 5 yellowish petals and 5 styles; fruits small capsules (Fig. 1).

Figure 1 T. aphrodisiaca. aerial parts.

T. ulmifolia. is a polymorphic perennial herb, often woody at base, up to 1.5 m in height. The stem is bright green, covered with short hairs; buds small, vegetative, borne singly at the nodes; leaves alternate, 5–8 cm long, broadly lanceolate-oblong, short thick petiole, tip acute to acuminate crowded at the shoot apex, base cuneate, margins very coarsely, lobately serrated, rather flaccid and pendent, pinnately veined, two glands located near the intersection of the blade and petiole; stipules small, subulate and decidous; flowers fragrant, solitary, axillary, on a short peduncle about the length of petiole; calyx of five, deep, lanceolate segments; corolla full yellow, of five, nearly rotundate, shortly unguiculated; petals spreading; stamens five, yellow; filaments short; anthers subulate; ovary ovate, one-celled, with three parietal placentae and many ovules; styles three, erect; stigmas penicillate; fruits small capsule filled with tiny seeds (Hooker, 1845; Brouwer & Stahlin, 1955; Arnold, 2002) (Fig. 2).

Figure 2 T. ulmifolia. aerial parts.

Solereder (1908) has compiled whatever little information is available on leaf anatomy of T. annularis. Urban, T. aphrodisiaca., T. blanchetiana. Urban, T. calyptrocarpa. Urban, T. cearensis. Urban, T. chamaedrifolia. Cambess, T. hebepetala. Urban, T.. hermannioides. Cambess, T. incana. Cambess, T. lamiifolia. Cambess, T. longiflora. Cambess, T. melochioides. Cambess, T. sidioide.s Linn., T. stachydifolia. Urban, T. ulmifolia., and stem anatomy of T. odorata. Vahl. and T. optifera. Benth.

Natural Products

Eighty species of Turneraceae have been tested and found to contain cyanogenic constituents (Spencer et al., 1985). Analysis by HPLC, NMR, and paper chromatography data showed all to possess tetraphyllin A (1) and B (2), epitetraphyllin B, and deidaclin (3) (Fig. 3). Table 1 summarizes phytoconstituents reported from various species of Turnera..

Figure 3 Various phytoconstituents of the genus Turnera..

Table 1.. Phytoconstituents of various species of Turnera..

Species	Phytoconstituents
T. angustifolia. Mills.	Cyanohydrin glucoside linamarin (4) (Olafsdottir et al., 1990; Jaroszewski et al., 1995); cyanogenic glucoside deidaclin (3) (Olafsdottir et al., 1992).
T. aphrodisiaca. Ward (Syn. T. diffusa. Willd.)	Cyanogenic glucoside tetraphyllin B (2) (Spencer & Seigler, 1981); flavonoid gonzalitosin I (5) (Dominguez & Hinojosa, 1976); arbutin (6) (Auterhoff & Hackle, 1968; Piacente et al., 2002); damianin (Steinmetz, 1960); tricosan-2-one (Fryer, 1965); hexacosanol-1; volatile oil containing α.-pinene, β.-pinene, p.-cymene, 1,8-cineole, opopienone, cadalene, and epi-cubenol (Auterhoff & Hackle, 1968; Bicchi et al., 2003); caffeine (Huang et al., 1982); β.-sitosterol (Jaroszewski et al., 1995); resin; tannin (Steinmetz, 1960).
T. caerulea. Moc. & Sesse	Cyanohydrin glucoside linamarin (4) (Olafsdottir et al., 1990); essential oil containing γ.-cadinene and β.-caryophyllene (Morais et al., 1994).
T. calyptrocarpa. Urban	Essential oil containing β.-elemene, β.-caryophyllene, γ-cadinene, and curzerene (Morais et al., 1994).
T. chamaedrifolia. Cambess	Cyanohydrin glucoside linamarin (4) (Olafsdottir et al., 1990).
T. diffusa. Willd.	See T. aphrodisiaca..
T. hassleriana. Urban	Cyanohydrin glucoside linamarin (4) (Olafsdottir et al., 1990).
T. krapovicksii. Arbo.	Proteins (Athanasiou & Shore, 1997).
T. scabra. Millsp.	Proteins (Athanasiou & Shore, 1997).
T. subulata. Smith	Proteins (Bahadur & Swamy, 1983; Athanasiou & Shore, 1997); sugars; nucleic acids (Bahadur & Swamy, 1983).
T. ulmifolia. Linn.	Cyanogenic glucosides deidaclin (3) (Spencer & Seigler, 1980; Tober & Conn, 1985), tetraphyllin A (1), epi-tetraphyllin B and tetraphyllin B (2) (Tober & Conn, 1985); essential oil containing α.-elemene, trans-caryophyllene, lineol, pinene (Lima et al., 2000); caffeine (Tarar & Patil, 1979); fatty acids uernolic acid, malvalic acid, and sterculic acid (Hosamani, 1993).

Pharmacological Studies

An aqueous extract of T. diffusa. has been reported to exhibit sexual stimulating activity in sexually sluggish male rats at a dose of 1 ml/kg (Arletti et al., 1999). The plant extract improved copulatory behavior of impotent rats and also increased the percentage of rats achieving ejaculation. Aqueous extract of whole plant of T. diffusa. has been reported to exhibit significant hypoglycemic activity in alloxan-diabetic male mice (Perez et al., 1984). A glucose tolerance test performed on rabbits by Alarcon et al. (1998) showed significant hypoglycemic activity in the orally administered decoction of leaves of T. diffusa.. Contrary to these reports, Alarcon et al. (2002) recently reported that hydro-alcoholic extract of T. diffusa. is devoid of any hypoglycemic activity. Dichloromethane and methanol extracts of T. diffusa. exhibited relaxant effect on the smooth muscle of the corpus cavernosum of guinea pig (Hnatyszyn et al., 2003). Hexane extract of T. aphrodisiaca. exhibited antibacterial activity against Gram-positive and Gram-negative bacteria (Hernandez et al., 2003).

An exhaustive pharmacological study was performed on T. ulmifolia. aerial parts by two Brazilian researchers (Antonio & Brito, 1998). They have attributed anti-inflammatory as well as antiulcerogenic activity of the plant to hydro-alcoholic extract and its partitioned fractions. The crude hydro-alcoholic extract (1000 mg/kg) and its partitioned fractions, viz., the aqueous, ethyl acetate, and ethanol fractions (100 mg/kg), inhibited carrageenan-induced edema in male rats. Due to nonavailability of sufficient quantity of aqueous, ethyl acetate, and ethanol fractions, only hydro-alcoholic extract was assessed for anti-inflammatory activity using other experimental models. Hydro-alcoholic extract inhibited the cotton pellet granuloma and the increase of vascular permeability induced by histamine, 5-hydroxytryptamine, and prostaglandin E₂. The hydro-alcoholic extract and ethanol fraction inhibited the appearance of gastric lesions induced by indomethacin, ethanol, and pylorus ligature but not those induced by stress, thus, confirming its antiulcerogenic activity. The extract and the fraction were also evaluated for analgesic activity in the writhing test using acetic acid, but both did not exhibit any activity. Another Brazilian group of researchers (Gracioso et al., 2002) evaluated an aqueous fraction (AqF) of the aerial parts of T. ulmifolia. for its antiulcerogenic activity on gastric and duodenal mucosa in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration as well as lesions induced by a combination of indomethacin and bethanechol at doses of 500 mg/kg and 1000 mg/kg. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250, 500, and 1000 mg/kg, respectively. Okoli et al. (2003) also reported the use of T. ulmifolia. in the treatment of inflammatory disorders in various in vivo. and in vitro. inflammatory models. The highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH and decreasing the acid output in pyloric ligature experiment. Essential oil of T. ulmifolia. has been reported to exhibit excellent antifungal activity against dermatophyte species (Lima et al., 2000). Petroleum ether extract of T. ulmifolia. has been reported to exhibit mild larvicidal activity against Cutex quinquefasciatus, Anopheles stephensi., and Aedes aegypii. (Kalyanasundarum & Das, 1985).

Clinical Studies

In a double-blind placebo-controlled study, Argin Max (a nutritional supplement for the enhancement of female sex function) containing Damiana as one of the constituents was given to 34 women for 4 weeks (Ito et al., 2001). It showed improvement in sexual desire, reduction of vaginal dryness, increase in sexual intercourse and orgasm, and improvement in clitoral sensation. Argin Max did not exhibit estrogenic activity with an in vitro. estrogen bioassay, which was performed using a human endometrial adenocarcinoma cell line, Ishikawa, which contains an alkaline phosphatase enzyme sensitive to estrogen stimulation (Polan et al., 2004). A double-blind placebo-controlled study was performed on a herbal preparation “YGD” containing leaves of Ilex paraguayenia., seeds of Paullinia cupana., and leaves of T. diffusa. to determine the effect on gastric emptying and weight loss over 10 days and 45 days (Andersen & Fogh, 2001). The preparation significantly delayed gastric emptying and induced significant weight loss over 45 days in overweight patients. Fifteen patients were administered twice a day an appetite-suppressant composition containing Damiana as one of the ingredients (Mann, 1993). Significant weight loss was observed in all the patients at the end of the 42 days. In a separate set of double-blind randomized crossover studies performed on 47 patients using Damiana containing herbal formulation, a significant decrease in body weight was observed after 45 days of treatment (Hessel & Lundsgaard, 1999).

Toxicology

Due to occurrence of cyanogenic constituents in Turnera. species, their toxicity cannot be ruled out. There has been a report of a case of poisoning of an individual who consumed 8 ounces of an extract of Damiana and who underwent tetanus-like convulsions and paroxysms, which resulted in symptoms like those of strychnine poisoning (Dominguez & Hinojosa, 1976). This may have occurred due to cyanide poisoning. The alcoholic extracts of the roots of Turnera. species have been reported to exhibit oxytocic activity, and, hence, should be avoided during pregnancy (Vieira et al., 1968). The leaves have a slight laxative effect and may cause loosening of the stools at higher amounts (Mills, 1991).

Conclusions

About 85 species of the genus Turnera. have been reported in various floras. An exhaustive survey of the literature on this genus revealed that sporadic information is available only on 27 species. Among these 27 species, ethnopharmacological reports are available on, and little pharmacological studies have been carried out only on, two species, viz., T. aphrodisiaca. and T. ulmifolia.. Further, only 10 species of Turnera. (Table 1) have been partially investigated for their phytoconstituents.

A close scrutiny of the available literature on Turnera. reveals that T. aphrodisiaca. is the most reputed plant throughout the world for its medicinal properties. The plant has been used traditionally in various traditional as well as alternative and complementary systems of therapeutics as an aphrodisiac, nerve tonic, and in various other ailments. The plant has also been available commercially in the United States since 1874 and has been approved by the FDA as a food additive (Abby's Herbal Newsletter Archives, 1998). Still, no systematic work has been carried out on T. aphrodisiaca. as is evident from the availability of sporadic pharmacological reports on this plant, and most of these reports are contradictory. The pharmacological studies section of this review reveals that three groups of researchers have worked on T. aphrodisiaca. to evaluate the plant for hypoglycemic activity in alloxan-induced diabetes and glucose tolerance test. Two groups reported that the plant possesses hypoglycemic activity, whereas third group contradicts the reports. The authors suggest that improper selection of the plant material, geographical or seasonal variation, and wrong time of collection might be responsible for these controversial reports. Various pharmacognostic standards, viz., morphological, microscopic characters, and physicochemical parameters, should be generated to select authentic plant. The authors have established pharmacognostic standards for T. aphrodisiaca. (Kumar et al., 2003). By resorting to these parameters, only authentic plant should be evaluated systematically for antidiabetic and other bioactivities. Even the authors of the German Commission E monographs feel that the traditional use of this plant has not been justified by modern research (Blumenthal et al., 1998).

Keeping in mind the traditional and alternative and complementary medicinal uses, sporadic phytochemical and pharmacological reports, and low toxicity, T. aphrodisiaca. seems to hold great potential for in-depth investigation for various biological activities, especially its effect on the reproductive and central nervous systems. The authors are involved in bioactivity-directed extraction and fractionation of this plant with a view toward isolating bioactive fraction/constituent(s).

Acknowledgment

The authors acknowledge the financial assistance provided by University Grants Commission, New Delhi, to Suresh Kumar for the compilation of this review.