Trifolium pratense L.

Last updated: 25 May 2017

Scientific Name

Trifolium pratense L.  

Synonyms

Trifolium borysthenicum Gruner, Trifolium bracteatum Schousb., Trifolium lenkoranicum (Grossh.) Roskov, Trifolium pratense var. lenkoranicum Grossh., Trifolium pratense var. pratense, Trifolium pratense f. pratense, Trifolium ukrainicum Opperman. [1]

Vernacular Name

English Cow clover, meadow clover, purple clover, red clover [2]
China Hong che zhou cao [2]
India Buksum, chit batto, kuth, mitla, treparta, trepatra [2]
Japan Murasaki-tsume-kusa, ake-tsume-kusa [2]
Mexico Guie tuu xtilla, quie too castilla [2].

Geographical Distributions

Trifolium pratense is commonly found in Mediterranean and Red Seas countries. [3]

Botanical Description

T. pratense is a member of Fabaceae family. It is a perennial herb, sparsely villous or glabrescent. [4]

Stems are nu­merous from crown, erect or ascending, 20-70 cm, and stout, stri­ate. [4]

Leaves are palmately 3-foliolate, basal and cauline, long petio­late in lower leaves, shortly petiolate in upper leaves; stipules ovate-lanceolate, membranous, base adnate to petiole, apex acu­minate-subulate; leaflets ovate-elliptic or obovate, rarely ellip­tic, 1.5-3.5(-5) × 1-2 cm, lateral veins 15, base broadly cu­neate, margins obscurely serrulate, apex obtuse, rarely retuse. [4]

Flowers are 30-70, in dense globose or ovoid, terminal, sessile to shortly pedunculate heads, subtended by involucre of stipules of reduced leaves. Calyx is slightly pubescent or glabrous, veins 10; teeth subulate, unequal, lower tooth ca. 2 × others. Corolla is pur­ple, rarely pink or white, 12-14(-18) mm; standard spatulate, apex rounded, retuse. Ovary is elliptic. [4]

Legume is ovoid. It has one seed that is yellow or brown and ovoid. [4]

Cultivation

T. pratense is cultivated and naturalized in woodland margins, wet meadows, and roadsides. It has been cultivated in Anhui, Fujian, Guangdong, Hebei, Heilongjiang, Henan, Hu­bei, Jiangsu, Jiangxi, Jilin, Liaoning, Shandong, Taiwan, Xinjiang, and Yun­nan. [4]

Chemical Constituent

T. pratense was found to contain flavonoid glycosides (e.g. isoflavones formononetin, daidzein, genistein, biochanin A, and the flavonoid quercetin), coumarins, and polysaccharides. [5]

Plant Part Used

Flowering tops/heads. [3]

Traditional Use

T. pratense has been used traditionally as a medicinal agent by Asian, European, and Native American cultures as an expectorant, in asthma, and as an alternative (blood purifier) to treat psoriasis, eczema, and other chronic skin conditions. [3]

Preclinical Data

Pharmacology

Estrogenic activity

T. pratenseisoflavones were shown to have oestrogenic effects [6]. They interact with human estrogen receptor sites [7] and their estrogenic effect relative to 17 beta-estradiol is between 1-5 x 10-3 [8].

T. pratense isoflavones also is effective in preventing postmenopausal osteoporosis [9]. Extract of T. pratense, standardized to the phytoestrogen content, has gained a great deal of attention in the management of menopause and related symptoms. Research has focused on the T. pratense extract, which contains four principle phytoestrogens (biochanin A, fomonontein, genistein, and daidzein), all with reported levels of estrogen-like activity [10].

Steroidogenesis activity

Isoflavones modulate a range of enzymes that regulate the production, metabolism, and function of steroidal hormones, including: inhibiting 17 beta-hydroxysteroid dehydrogenase which is involved in the synthesis of 17 beta-estradiol; [11] inhibiting aromatase which converts androstenedione to estrone; [12] and inhibiting 5-alpha-reductase which converts testosterone to dihydrotestosterone [13]. Other activities include inhibition of the oxidation of steroid hormones [11] and the promotion of the production of sex-hormone binding globulin (SHBG) by liver cells [14].

Antioxidant activity

Isoflavones extracted from T. pratense was found to exhibit antioxidant activity as well as promoting the activity of antioxidant enzymes in gut and skin. [15][16][17]

Calcium metabolism and bone turnover activity

Isoflavones isolated from T. pratense was found to promote calcium storage in cells, and inhibit osteoclast activity and differentiation by increasing apoptosis via caspase 3 pathway [18][19][20]. They may also maintain bone density, as reported in animal studies [21].

Cell growth and differentiation activity

Genistein is an inhibitor of a range of enzymes that modulate cell transduction processes involved in cell growth and differentiation; the principal enzymes are protein tyrosine kinases, and DNA topoisomerases [22][23][24]. Genistein blocks the growth of normal human lymphocytes and human leukemic cells by arresting growth in the G2/M phase of the cell cycle [25]. Genistein induces terminal differentiation and inhibits proliferation of rodent leukemic and melanoma cells and it also induces apoptosis of mouse leukemic cells in vivo [26].

Anticancer activity

Isoflavones (mostly genistein) have been reported to be inhibitory in vitro to the following human cell lines; melanoma [27], breast cancer [28][29], and neuroblastoma cells [30].

Antiproliferative activity

T. pratense extract was found to reduce endometrial proliferation of Wistar rats in comparison to the placebo group. [31]

Procoagulant activity

Isoflavones also inhibit nitric oxide production by macrophages [32] and the procoagulant activity of activated adherent monocytes [33].

Neuroprotective activity

Isoflavones from T. pratense exert neuroprotective effect on human cortical neurons from glutamate toxicity, probably due to their antioxidant and oestrogenic properties. [34]

Isoflavones from T. pratense also protected dopaminergic neurons from lipopolysaccharide-induced damage by inhibiting microglia activation and generation of pro-inflammatory factors. [35]

Toxicity

No documentation.

Clinical Data

Clinical findings

Anticholesterol activity

Isolated isoflavones from T. pratense enriched in biochanin (genistein precursor) but not in formononetin (daidzein precursor), lowered LDL-C in men. [36]

Phytoestrogens and ascorbic acid was found to inhibit LDL oxidation that involves interaction with apoB-100. [37]

A proprietary extract of T. pratense has been reported to raise HDL cholesterol and decrease ApoB. [38]

Authors reported that supplementation with isoflavones from T. pratense did not significantly alter total plasma cholesterol, LDL cholesterol, HDL cholesterol or plasma triglyceride levels levels [39], while others showed a reduction in total cholesterol [40], LDL cholesterol and triglycerides [41], and an increase in HDL levels [42].

Calcium metabolism and bone turnover activity

Human studies reported that isoflavones from T. pratense selectively increased cortical bone density of the proximal radius and ulna. [43]

Anticancer activity

Genistein induces terminal differentiation and inhibits proliferation of human lymphoblastic leukemia. [44]

In human study, it showed no increase in endometrial thickness in postmenopausal women after supplementation of isoflavones from T. partense extract. [45]

Anticardiovascular activity

A study reported that T. pratense isoflavones reduce cardiovascular risks by reducing arterial elasticity in menopausal women. [46]

Postmenopausal activity

A meta-analysis on clinical trials reported that T. pratense isoflavones supplementation produced a marginal significant effect in treating hot flushes symptom. [47]

However, this result is in contrast with another systematic review and meta-analysis which reported no significant reduction in hot flushes frequency. [48]

Neuroprotective activity

Isoflavones from T. pratense extract was shown to reduce anxiety and depressive symptoms among postmenopausal women. [49]

Precautions

No documentation.

Side effects

T. pratense contains coumarins. Although no adverse effects related to the coumarins have been reported, large doses may alter the course of therapy in patients with bleeding or clotting disorders. [3]

Pregnancy/Breast Feeding

No documentation.

Age limitation

No documentation.

Adverse reaction

No documentation.

Interaction & Depletion

Interaction with drug

This dietary supplement is reported to contain ingredients similar to those contained in these medications. Though no adverse effects have been reported, large doses of this dietary supplement may alter the effects of these medications and possibly the dose needed for treatment. These drugs include warfarin, heparin, dalteparin, tinzaparin, enoxaparin, danaparoid sodium, antithrombin III, lipirudin, argatroban, and bivalirudin. Use with caution. [3]

T. pratense has hormonal-like activity, which may alter the effects of these medications and possibly the dose needed for treatment. These drugs include conjugated estrogens, estradiol, estrone, esterified estrogens, estropipate, ethinyl estradiol, raloxifene, transdermal estradiol, vaginal estrogens, norethindrone, ethynodiol diacetate, norgestrel, norgestimate, ethinyl estradiol, drospirenone, desogestrel, and levonorgestrel. Use with caution. [7][50]

Interaction with other Herbs

No documentation.

Contraindications

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

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  2. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume V R-Z. Boca Raton, Florida: CRC Press, 2012; p. 629-630.
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  4. Flora of China. Trifolium pratense Linnaeus. [homepage on the Internet]. No date [cited 2017 May 25]. Available from: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200012343.
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