{this is extracted from a report by Janna Weiss to the Israeli government and posted here for scientific and informational purposes only. ]

1. Identity and ingredients of the product:

Product description Name: Mamejava

Latin names: Enicostema littorale Blume (=Enicostema axillare subsp. littorale (Blume) A. Raynal), Enicostema axillare (Lam.) A. Raynal, Family: Gentianaceae (Gentian Family)

Part used: Whole plant

Clear description of the product. The product is a whole plant native to tropical Africa, India, Southeast Asia and Malaysia (Struwe 2004; Africa to Lesser Sunda Islands, Mabberley 1987:205).

Detailed description of the plant. Erect perennial herb, 5–30 cm. tall, simple or branched at the base. Stem cylindric, glabrous with a decurrent ridge below each leaf. Leaves sessile (sometimes narrowed into a petiole-like base), longer than the internodes; lamina (1)5–8 x 0.3–1 cm., linear to lanceolate or narrowly oblong, entire, obtuse and mucronate at the apex, somewhat narrowing towards the base, 3-nerved from the base, glabrous. Inflorescence in many flowered axillary clusters, numerous in the axils of each pair of leaves. Flowers white with green lines, drying yellowish, sessile or subsessile; bracts long, shorter than the calyx, lanceolate-acuminate, carinate. Calyx tube 1–2 mm. long; lobes usually unequal, 0.7–1.5(2) x 0.4–0.7 mm., triangular to lanceolate, acute at the apex and narrowly scarious at the margin, or obovate to subcircular, obtuse and mucronate at the apex, with wide scarious margin. Corolla tube 3.5–6 mm. long; lobes 1.5–2 x 0.7–1 mm., ovate and abruptly narrowing to an acute or mucronate apex. Stamens inserted below the sinuses, just above the middle of the tube; filaments 1.5–2.3 mm. long, with a double hood at the insertion point; anthers. 1 mm. long, erect, shortly apiculate. Ovary 5–6 x 1 mm., ovoid; style 2–2.5 mm. long, subulate; stigma subcapitate. Capsule 3–4.5 x 2–2.5 mm., obovoid. Seeds 0.4–0.5 mm. in diam., subglobose, reticulate faveolate. (Paivera and Noguiera 1990)

Product composition. The product consists of the whole dried plant only.

Generic synonyms for Enicostema: Adenema G. Don Enicostemma Stead. Henicostemma Endl. Hipponium Kuntze

Common names (Nadkarni 1976: 485): Ayurvedic medical: Mamejava , Mamejav, Mamejavo, Mamjjak, Mamejva; Hindi/Hindustani: Kariyatu, Chota-kirayat, Chota-chiretta, Chota-chirayata; Bombay: Kada-vinayi, Manucha; Tamil: Vallari Telugu: Nela-guli, Nela-gulimidi; Additional names: Gormadi koora (In the UK product description for Glucostat, Maharishi Ayurveda Products (2006), incorrectly refers to E. littorale as Indian Gentian; this English common name generally refers to Swertia spp. Whitehead is a common name that applies to E. verticillatum, in the New World.)

Other species known by these names (and can cause confusion): E. verticillatum is a New World species whose name is sometimes confused with E. littorale, but is unlikely to contaminate E. littorale originating in India, Africa or Malaysia.
    Methods of preventing this kind of confusion in the process of manufacturing and preventive measures in the contamination of the product: Adherence to nomenclatural accuracy should resolve any confusion regarding this plant.

Description of the plant parts in the ingredients: The whole plant may contain stems, leaves, fruits, flowers, and roots.

Plant extracts: The product consists of the whole dried plant in its natural form; there is no extraction process.

Animal, micoorganismal, fungal or algal components: The product is a plant and does not consist of any animals, microorganisms, fungi or algae or parts thereof.

Chemical components: The product is a plant and is not a chemical component.

2. Legislative status in country of origin (if product is being imported) and from other countries:
"Certificate of free sale" from the origin country of manufacturing – Not known.

List or countries that prohibit or restrict the usage of this ingredient: No prohibition or restriction was found in the following regulatory lists: Australian Pharmacopeia Danish Pharmacopoeia European Pharmacopoeia Japanese Pharmacopoeia

3. Purpose of the product and its ingredients:
The plant is included in plant mixtures intended as a food or food supplement. There are no chemical manufacturing processes involved in the use of the dried whole plant.

4. Proof of an existing usage in foods:
 Enicostema littorale is an uncultivated leafy green eaten in southern India as a source of iron and calcium (Dalit Database 2006). Greens (quelites) are important supplemental sources of nutrients such as iron, calcium, magnesium, vitamin C, B vitamins, betacaroten, in traditional societies (Deccan Development Society 2002). E. littorale, locally known as gorumadi, or gorumadi koora, is eaten as a curry with pulses or other greens (Dalit Database 2006).
    In a clinical trial with 84 diabetic patients who ingested 2g of E. littorale per day for 3 months, no adverse side effects were reported (Upadhyay and Goyal 2004).

5. Proof of other usage, including medical usage:
Israeli legislative status E. littorale does not appear on the Israeli Ministry of Health medicinal plant, food or toxic substance lists.

Traditional medical use E. littorale is traditionally used in India as a stomachic, bitter tonic, laxative, carminative (Nadkarni 1976:485), to reduce fever and as a “tonic” for appetite loss (Jensen and Schripsema 2002:611-612). Many other genera in the gentian family have similar traditional uses worldwide (Jensen and Schripsema 2002:611-612 lists species with similar uses worldwide; Weiss 1988:40-42 describes uses of European Gentian spp.). In Ayurvedic (India) medicine, E. littorale is taken in combination with other herbs, especially for diabetes (Upadhyay and Goyal 2004).
    Medicinal use or other non-nutrition purposes of the ingredients - Clinical trial E. littorale was administered in Ayurvedic pill form (known as ghavantis) at a daily dosage of 2000 mg for three months to 84 patients with Type 2 Diabetes. E. littorale reduced blood glucose and serum insulin levels, and significantly improved kidney function, lipid profile, systolic and diastolic blood pressure and pulse rate (Upadhyay and Goyal 2004). No side effects were reported in this study.

6. Possible side-effects from the product or its ingredients.

6.1 Known pharmacological effects and mechanisms Pharmacological activity: E. littorale is known to have antibacterial (Patel and Trivedi 1957), antiinflammatory (Maroo et al. 2002, Sadique et al. 1987, van Rietschoten 1990), anti-cancer (Kavimani et al. 2000, Maroo et al. 2002) and antidiabetic activity (Maroo et al. 2002). Maroo et al. (2002) found that E. littorale enhances glucose-dependent insulin release. Swertiamarin, a secondary compound present in E. littorale (Rai and Thakar 1966, Anwar et al. 1996), has antispasmodic and anticholinergic activity (Yamahara et a. 1991). Outcome of a human clinical study with E. littorale demonstrated significant hypotensive, hypoglycemic, and hypolipidemic effects (Upadhyay and Goyal 2004). Swertiamarin has demonstrated antibacterial activity in vitro (Kumarasamy et al. 2003).

Animal trials E. littorale has demonstrated antiinflammatory activity (Sadique et al. 1987) and tumor inhibition (Kavimani et al. 2000) in rats. Swertiamarin may have a CNS depressant effect in rats (Bhattacharya et al. 1976). There are no reported symptoms of overdose.

Chemical substances which belong to the product include: secoiridoid compounds (not specified, Jensen and Schripsema 2002:612) C-glucosides (not specified, Jensen and Schripsema 2002:612) erythrocentaurin (Ghosal et al. 1974 cited in Jensen and Schripsema 2002:612) swertiamarin (Rai and Thakar 1966, Anwar et al. 1996) .
   Swertiamarin exhibited significant general toxicity in brine shrimp lethality bioassay and the LD50 value was 8.0 microg/ml, whereas that of the positive control podophyllotoxin, a well known cytotoxic lignan, was 2.79 microg/ml (Kumarasamy et al. 2003). Swertiamarin is metabolized by human intestinal bacteria. Erythrocentaurin is one of the swertiamarin intestinal metabolites (el-Sedawy et al. 1989). (For Gentiana lutea, with related compounds, general recommendations (Newall et al. 1996:134) are that gentian is “best avoided in pregnancy and lactation” and “excessive doses should be avoided in view of the lack of toxicity data.” Tyler (1994:43-45) recommends up to 4 g. of gentian tea daily.)

7. Daily consumption, recommended or expected, of the product.
Recommended and expected daily dose Recommended dose is 2g per day (based on Upadhyay and Goyal 2004). Expected daily dose in DBCare is 300mg.

Nutritional information: According to a nutritional analysis of E. littorale by the National Institute of Nutrition, Indian Council of Medical Research, 100g fresh E. littorale greens contain 140 Kcal energy, 7g protein, 0.7g fat, 26.5g carbohydrates, 4.2g fiber, 8.4g minerals, 49.9mg iron, 1,641mg calcium, 81mg phosphorous, and 53.2g moisture (Dalit Database 2006). Based on this analysis, 100g of fresh E. littorale daily would be highly nutritious and recommended.

Possible exposure sources for the ingredient: There are no other possible exposure sources to swertiamarin or secoiridoids, except other plants in the Gentianaceae, not normally encountered or ingested in foods or other commercial products.

8. Possible contaminants in the product or its ingredients, and the control methods regarding them:
There are no known contaminants.

References and publications: 

Anwar, M., Ahmad, M., Aslam, M., Aftab, K. Enicostema littorale: a new source of swertiamarin. Pakistani Journal of Pharmaceutical Sciences 9: 29-35. 1996.

Bhattacharya, S.K., Reddy, P.K., Ghosal, S., Singh A.K., Sharma, P.V. Chemical constituents of Gentianaceae XIX: CNS-depressant effects of swertiamarin. Journal of Pharmaceutical Sciences. 65:1547-1549. 1976.

Dalit Database. Community Food System Data Table #200. Quebec, Canada: McGill University Centre for Indigenous Nutrition and Environment (CINE). 2006.

Deccan Development Society. Uncultivated foods and the poor. India Together 2002.(http://www.indiatogether.org/agriculture/dds/uncultivated.htm (Retrieved November 8, 2006)

el-Sedawy, A.I., Shu Y.Z., Hattori, M., Kobashi K., Namba T. Metabolism of swertiamarin from Swertia japonica by human intestinal bacteria. Planta Medica 55:147-150. 1989.

Ghosal, S., Singh, A. K., Sharma, P. V., Chaudhuri, R. H. Chemical constituents of Gentianaceae. IX. Natural occurrence of erythrocentaurin in Enicostemma hyssopifolium and Swertia lawii. Journal of Pharmaceutical Sciences 63: 944-945. 1974.

Jensen, S.R., Schripsema, J. Chemotaxonomy and pharmacology of Gentianaceae. In Gentianaceae: Systematics and Natural History, Struwe, L., Albert V., eds. Cambridge, UK: Cambridge University Press. 2002.

Kavimani, S., Manisenthlkumar, K. T. Effect of methanolic extract of Enicostemma littorale on Dalton's ascitic lymphoma. Journal of Ethnopharmacology 71:349-352. 2000.

Kumarasamy, Y., Nahar, L., Cox, P. J., Jaspars, M., Sarker, S. D. Bioactivity of secoiridoid glycosides from Centaurium erythraea. Phytomedicine 10:344-7. 2003. h

Maharishi Ayurveda Products. Ayurveda Ltd. Lancashire, UK. 2006. http://www.maharishi.co.uk/productinfo/91407.pdf (Retrieved November 7, 2006)

Mabberley, D. J. The Plant Book. Cambridge, UK: Cambridge University Press.

Maroo, J., Vasu, V.T., Aalinkeel, R., Gupta, S. Glucose lowering effect of aqueous extract of Enicostemma littorale Blume in diabetes: a possible mechanism of action. Journal of Ethnopharmacology 81: 317-20. 2002. 

Missouri Botanical Garden (MOBOT) TROPICOS VAST (VAScular Tropicos) Nomenclatural Database. 2006. http://mobot.mobot.org/ (Retrieved November 7, 2006)

Nadkarni, A.K. Dr. K. M. Nadkarni’s Indian Materia Medica, Vol. 1. Bombay: Popular Prakashan Private Ltd. 1976.

Newall, C.A., Anderson, L.A., Phillipson, J.D. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press. 1996.

Paivera, J., Nogueira, I. Gentianaceae. Flora Zambesica, Vol. 7, Part 4. Kew, UK: Royal Botanical Gardens. 1990. http://www.kew.org/efloras/namedetail.do?flora=fz&taxon=5776&nameid=14645 (Retrieved November 7, 2006)

Patel, R.P., Trivedi, B.M. The in vitro antibacterial activity of extracts from Enicostema littorale. Indian Journal of Medical Science 11: 887-91. 1957.

Rai, J. Thakar, K. A. Chemical investigation of Enicostemma Littorale [sic] Blume. Current Science 35:148-149. 1966.

Sadique, J., Chandra, T., Thenmozhi, V., Elango, V. The anti-inflammatory activity of Enicostemma littorale and Mollugo cerviana. Biochemical Medicine and Metabolic Biology 37:167-176. 1987.

M. Srinivasan, M., Padmanabhan, M., Prince, P. S. M. Effect of aqueous Enicostemma littorale Blume extract on key carbohydrate metabolic enzymes, lipid peroxides and antioxidants in alloxan-induced diabetic rats. Journal of Pharmacy and Pharmacology 57:497-504. 2005.

Tyler, V.E. Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York: Haworth Press. 1994.

United States Department of Agriculture (USDA) Germplasm Resources Information Network (GRIN). Enicostema axillare. 2006. http://www.ars-grin.gov/cgi-bin/npgs/html/splist.pl?4274 (Retrieved November 8, 2006)

United States Department of Agriculture (USDA) Natural Resources Conservation Service (NRCS) Plants Database. Enicostema vercillatum. 2006. http://plants.usda.gov/java/profile?symbol=ENVE (Retrieved November 8, 2006)

Upadhyay, U.M., Goyal, R.K. Efficacy of Enicostemma littorale in type 2 diabetic patients. Phytotherapy Research 18: 233-235. 2004. van Rietschoten, K. Plants with anti-inflammatory action. British Journal of Phytotherapy 1: 11-18. 1990.

Weiss, R.F. Herbal Medicine. Gothenburg, Sweden: AB Arcanum. 1988.

Yamahara, J., Kobayashi, M., Matsuda, H., Aoki, S. Anticholinergic action of Swertia japonica and an active constituent. Journal of Ethnopharmacology 33:31-35. 1991.

Note:  The GENTIAN RESEARCH NETWORK do not endorse or encourage the use of gentians or gentian-derived products for any medicinal purposes or as a cure for specific diseases and ailments.  The information is listed here for educational purposes only. The health value and safety of any of these plants and products has not been evaluated by us and we do not recommend any of them for medicinal use.