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Des sources du savoir aux médicaments du futur

Jacques Fleurentin
Jean-Marie Pelt
Guy Mazars

2. Études chimiques et pharmacologiques

Nootropic (medhya) plants from ayurvedic pharmacopoeia

Alexandre Maciuk, Marie-Jeanne Bouchet, Guy Mazars, B H Um et Robert Anton

Note de l’auteur

Note portant sur l'auteur1

Note portant sur l'auteur2

Note portant sur l'auteur3

Note portant sur l'auteur4

Note portant sur l'auteur5

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1In modern books of ayurvedic Materia Medica plants are often classified into different groups according to their prabhâva or "specific action". The prabhâva corresponds broadly to the western concept of pharmacological action (Mazars, 1995). Plants considered having a nootropic effect belong to the medhyâ (intellect promoting) group (from Sanskrit "medhâ", intellect). They are used as stimulants for the central nervous system, to improve memory and attention, or against epilepsy or insanity. Some of them might have an interest in the treatment of Alzheimer's disease (and Parkinson's disease when associated with Mucuna pruriens (L.) DC).

2In his book on Indian vegetable drugs P.V. Sharma (Sharma, 1987) deals with six "medhya" plants belonging to different families: Bacopa monnieri (L.) Pennell (Scrophulariaceae), Centella asiatica (L.) Urban (Apiaceae), Celastrus paniculatus Willd. (Celastraceae), Convolvulus pluricaulis Chois. (Convolvulaceae) and Benincasa hispida (Thunb.) Cogn. (Cucurbitaceae) have been used in Indian traditional medicine from very early times and are already mentioned in the Caraka-samhitâ, one of the two ancient Sanskrit medical treatises with Sushruta-samhitâ (1st century A.D.) (Sharma, 1983). As to Lavandula stoechas L. (Lamiaceae), it was borrowed from the Arabo-Persian pharmacopoeia. Except of Benincasa hispida and Lavandula stoechas these plants are used either alone or associated with other medhya plants in numerous Indian medicines (Giboin, 1949; Chopra et al., 1956; Dash, 1979; Sivarajan and Balachandran, 1994).

Botany, galenic, chemistry, pharmacology

3Bacopa monnieri is a creeping, glabrous, somewhat succulent herb growing in wet places. The plant is called Aindrî and Brâhmî in Sanskrit (Sharma, 1987).

4The fresh pure juice can be drunk, but a water extract or a lipidic decoction can be made to be mixed with other ingredients including medhya plants. The fat-soluble fraction would be the most active as a promoter of memory.

5B. monnieri is a saponin-rich plant. Most structures have already been isolated. The genins have been characterised as dammarane-type triterpenoids like protopanaxadiol and -triol glycosides from Panax ginseng (Araliaceae), and could be structurally related to jujubogenin, the major genin of Zizyphus jujuba Mill. (Rhamnaceae) (Garai et al., 1996a, 1996b; Jain and Kulshrestha, 1993; Mahato et al., 2000; Rastogi et al., 1994). (Table 1 and 2)

6Several studies have been done with an alcoholic extract. On rats, the extract increases both cognitive function and retention capacity, decreases retrograde amnesia and protects from phenytoin-induced cognitive deficit (Vohora et ai, 2000). The protein-kinase activity and the protein level were higher in the hippocampus. Other effects, like bronchodilatation and cardiovascular modifications were observed (Singh and Dahwan, 1997). In vitro, the extract showed a calcium antagonistic activity on vascular and intestinal smooth muscles of rabbit and guinea-pig (Dar and Channa, 1999), and a significant inhibition of the Sarcoma-180 cells growth (Elagovan et al., 1995).

7Centella asiatica is a slender, prostrate, glabrous herbaceous plant, rooting at the nodes. The leaves are simple, petiolate, palmately lobed (Kirtikar and Basu, 1935). The Sanskrit name of the plant is Mandûkaparnî. It is also called Brâhmî (Sharma, 1987).

8The plant is used for memory improvement, wound healing and as a cardiotonic. The galenic form is an extract of the whole plant.

9The major synthesized secondary metabolites are triterpenic acids and saponins. The essential oil (2-4 %) of this Apiaceae contains until to 37 different components, with numerous terpenes.

10Numerous unsaturated fatty alcohols, flavonols, amino-acids, steroids and vitamins have been identified. The major genins and saponins are given on the tables 3 and 4 (Chapmann, 1982-2000; Dev et al., 1989; Holeman et al., 1994; Mahato et al., 1987; Pinhas et al., 1967; Pinhas and Bondiu, 1967; Sahu et al., 1989; Singh and Rastogi, 1967). (Table 3 and 4)

11The topical properties of C. asiatica extracts have been well documented. It is the only one of these medhya plants used in western medicine, as a cicatrising ointment (Bonte et al., 1993; Inamdar et al., 1996; Shukla et al., 1999). Nevertheless, the nootropic potentialities of C. asiatica have been assessed in pharmacological and behavioral trials in rats. The administration of aqueous or ethanolic extract showed an antistress activity by reducing stress-induced ulcerization and by inducing a state of non-specifically increased resistance. These effects were comparable to those of diazepam (Sarma et al., 1995; 1996; Valsala, 1998). A sedative and anti- convulsivant effect beside a low toxicity has been noticed, indicating a high therapeutic index (De Lucia et al., 1997). C. asiatica causes an overall decrease in the turnover of central monoamines norepinephrine, dopamine and serotonine, known to be implicated in learning and memory process (Nalini et al., 1992).

12Celastrus paniculatus is a climber with stems up to 23 cm of diameter and 18 m high, with broadly elliptic ovate leaves. The seeds are enclosed in an orange-red aril, and taste bitter (Kirtikar and Basu, 1935; Sharma, 1987).

13The oil is used in colleges by Indian teachers to increase the intelligence of their pupils.

14This oil contains several terpenoids like paniculatadiol, b-sitosterol, celastrol, b-amyrin, pristimerin, but its most investigated components are its many sesquiterpenoids, dihydroagarofuran-type poly- ols or esters, presented in Table 5,6 and 7 (Brijning and Wagner, 1978; Hong et al., 1991; Tu et al., 1991; Tu and Yao, 1993). (Table 6 and 7)

15Pharmacological studies on mice and rats showed that the seed oil increases the pentobarbital-induced narcosis time (Ahumada et al., 1991). A delay is required to get a reversal of scopolamine-induced deficit in memory performance. This effect suggests cognitive enhancing properties, but the mechanism of action is not related to an anticholinesterase-like action, as the current anti-Alzheimer's disease do (Gattu et al., 1997). On the brain level, the seed oil of C. paniculatus increases the myelinisation and the protein content and decreases the dopamine turnover in rats, suggesting an increased mental activity linked to memory (Bidwai et al., 1987; Nalini et al.,1995). The same decrease on dopamine turnover is described for man (Nalini et al., 1986).

16Toxicological studies showed an antispermatogenic action and reversible fatty degeneration of liver and tubular damage in kidneys (Bidwai et al., 1990a; 1990b).

17Convolvulus pluricaulis is a hairy perennial herb growing throughout the plains of India, with white to light pink flowers. One of its common Indian name is the Sanskrit name Shamkhapushpi (Kirtikar and Basu, 1935; Sharma, 1987).

18The whole plant is used as a rejuvenating and as a nervine tonic in epilepsy and insanity.

19It contains various products like scopoletin (a coumarin), b-sitosterol, fatty acids, fatty alcohols and sugars (Srivastava and Deshpande, 1975). The most notable constituents are tropane alkaloids. Only convolamine has been identified (Basu et al., 1948), but other alkaloids (convoline, convolidine, convolvine, confoline, convosine, etc.) found in other species from this family are probably present beside to convolamine (Lounasmaa, 1988). Structures are presented in table 8.

20Pharmacological studies on the alcoholic extract noticed an antagonist effect against amphetamines and tremorine, a potentiation of acetylcholine effect, of pentobarbitone-induced hypnosis and morphine analgesia, without having own sedative properties. A protective action on muscle against electroshocks has been showed (Barar and Sharma, 1966; Mudgal, 1975; Sharma et al., 1965). The specific pharmacological action of convolvine has been investigated. It is a specific blocker of M2 and M4 cholinergic muscarinic receptors. Convolvine also potentiates the effects of arecoline, a muscarinic memory enhancer that ameliorates cognitive deficits in Alzheimer's disease (Asthana et al., 1996; Mirzaev and Aripova, 1998).

21Benincasa hispida is a climbing gourd cultivated in all Asia as vegetable. The fruit, broadly cylindrical, is covered with a waxy bloom, explaining the name of "wax gourd" (Kirtikar and Basu, 1935; Petelot, 1952; Sharma, 1987).

22The fresh juice is used in insanity, epilepsy and other nervous diseases, and as an antidote for many kinds of poisoning.

23The flesh (96 % water) has a good nutritive value, and contains many fatty acids, sugars, aminoacids, vitamins and minerals (Duke, 1999). b-sitosterol, lupeol, alnusenol and n-triacontanol have been found in the juice, and isomultiflorenyl acetate in the wax (Faure and Gaydou, 1991; Lakshmi and Mitra, 1976) (Figure 1).

24The B. hispida juice injected intra-peritonally showed a depressive action on the CNS, a potentiation of the pentobarbitone-induced narcosis and hypothalamus-related hypothermia. It acts as a cholinergic and a-adrenergic agonist (Ramesh et al., 1989).

25Lavandula stoechas forms a pretty little shrub, with narrow leaves and very small, dark violet flowers, terminated with a tuft of bright- coloured leaflets. This was probably the lavender so extensively used in classical times by the Romans and the Libyans, as a perfume for the bath. The odour is more akin to rosemary than to ordinary lavender.

26The Yûnânî (Greco-Arabian) medicine calls it Ustukhudus and uses it by smoking or decoction as an expectorant, antispasmodic, against headache and nerve affections. In India, Yûnânî medicine practitioners use the powder of its dried flowers and leaves as a nerve tonic, intellect promoter (Cazin, 1997; Kirtikar and Basu, 1935).

27The essential oil of L stoechas contains more than 50 different terpenes: mainly fenchone (15-70 %), camphor (2-56 %), 1,8-cineole, eucalyptol, pinocarvyl acetate, myrthenol, etc. (Kokkalou, 1988; Ristorcelli et al., 1998; Valentini et al., 1993). Triterpenoids (oleano- lic acid, ursolic acid, vergatic acid, b-sitosterol, a-amyrine, a- amyrine acetate, lupeol, erythrodiol) and flavonoids (luteoline, acacetine, vitexine) have also been isolated (Ulubelen and Olcay, 1988). (Table 9 and Figure 2).

28The crude extract of L. stoechas and pure ursolic acid produced hypotension in rats, decreased the rate and contraction of isolated atrium and produced vasorelaxation in isolated aorta. The authors suggested that the hypotensive and bradycardic effects were due to the ursolic acid constituent (Aftab et al., 1997). Scientific investigations have been led on lavender essential oil, showing a quantifiable sedative effect on man (Jellinek, 1998; Manley, 1996). However, no influence on cognitive performances has been pointed out (Ludvigson and Rottman, 1989). The aqueous-methanolic extract exhibited anti- convulsivant and antispasmodic activities, probably due to its calcium channel blocking property (Gilani et al., 2000).

Current ayurvedic medicine

29Many intellect-promoting medicines are currently available in India, mixing numerous plant extracts or powders with two or three medhya plants. This is why the formulations and preparations of compound medicines are very complex and involve a number of processes and apparatus. This complexity is explained by the care taken to combine ingredients in order to counterbalance, enhance or prolong the effects of some ingredients through the effects of others (Mazars, 1998; 1999). Some of them have been subjected to clinical trials. Some examples are given here. The botanical names are those indicated by the manufacturers:

30REMEM (Zydus Industries, India): syrup, tablets. 10 species:

31Centella asiatica - Celastrus paniculatus - Convolvulus pluricaulis - Asparagus racemosus - Acorus calamus - Embelia ribes - Tinospora cordifolia - Achyrantes aspera - Terminalia chebula - Saussurea lappa.

32TIRUKATI: 13 species:

33Bacopa monnieri - Convolvulus pluricaulis - Centella asiatica - Asparagus racemosus - Valeriana wallichii - Rueraria tuberosa - Saussurea lappa - Embelia ribes - Tinospora cordifolia - Operculina turpethum - Pavonia odorata - Caryophyllus aromaticus - Foeniculum vulgare.

34AYUMEMO (Welexlabs, India): 5 species:

35Centella asiatica - Convolvulus pluricaulis - Celastrus paniculatus - Withania somnifera - Asparagus racemosus.

36ABANA (The Himalaya Drug and Co, India): syrup, tablets. 19 species:

37Centella asiatica - Convolvulus pluricaulis - Celastrus paniculatus - Balsamodedron mukul - Ocimum sanctum - Nardostachys jatamansi - Piper longum - Carum copticum - Zingiber officinalis - Cyperus rotundus - Acorus calamus - Embelia ribes - Syzygium aromaticum - Santalum album - Elettaria cardamomum - Foeniculum vulgare - Rosa damascena - Cinnamomum cassis - Crocus sativus.

38LEARNOL-PLUS (Dalmia Industries, India): syrup. 3 species:

39Bacopa monnieri - Celastrus paniculatus - Acorus calamus.

40TEJRAS (Sandu Brothers, India): syrup. 12 species:

41Centella asiatica - Convolvulus pluricaulis - Celastrus paniculatus - Eclipta alba - Cynodon dactylon - Asparagus racemosus - Withania somnifera - Nardostachys jatamansi - Acorus calamus - Zingiber officinalis - Vetiveria zizanoides.

42ALERT (Vasu Pharmaceutical PVT. LTD., Bajua (Vadodara), India): Capsules.

43Celastrus paniculatus seed oil - Cow ghee.

44Showed to reduce liver glycogen depletion after swimming in rats (Kakrani et al., 1985).

45BRAHMIGHRITHAM: tablets. 3 species:

46Bacopa monnieri - Cyperus rotundus - Saussurea lappa.

47Showed to have a protective action against chemical-induced seizures (Shanmugasundaram et al., 1991).

48BRAHMI RASAYAN: tablets. 4 species:

49Bacopa monnieri - Eugenia caryophyllus - Piper longum - Elettaria cardamomum.

50Showed to have an antinociceptive action, and to protect mice from electroshocks and chemoconvulsions, suggesting a GABA-agonist profile (Shukia et al., 1987).

51GERIFORTE (The Himalaya Drug and Co, India): tablets. 35 species:

52Centella asiatica - Celastrus paniculatus - Mucuna pruriens - Capparis spinosa - Cichorium intybus - Solanum nigrum - Cassia occidentalis - Terminalia arjuna - Terminalia chebula - Achillea millefolium - Tamarix gallica - Saffron (Crocus sativus) - Asparagus adscendens - Caesalpinia digyna - Asparagus racemosus - Withania somnlfera - Glycyrrhiza glabra - Myristica fragans - Piper longum - Eugenia caryophyllata - Elettaria cardamomum - Carum copticum - Curcuma longa - Berberis aristata - Adhatoda vasica - Eclipta alba - Argyreia speciosa - Phyllanthus emblica - Allium cepa - Allium sativum - Phyllanthus niruri - Boerhaavia diffusa - Tinospora cordifolia - Raphanus sativus - Tribulus terrestris.

53Showed to have tranquillising properties, and to improve cognitive performance in people suffering from neurosis (Gupta et al., 1979).

54SHANKHAPUSHPI (Unjha Pharmacy, India): syrup. 6 species:

55Convolvulus pluricaulis - Centella asiatica - Nardostachys jatamansi - Nepeta hindostana - Nepeta elliptica - Onosma brateatum. Shows an anti-epileptic activity (Dandekar et al., 1992).

56MENTAT or BR-16 (The Himalaya Drug and Co, India): syrup, tablets. 24 species:

57Bacopa monnieri - Centella asiatica - Celastrus paniculatus - Mucuna pruriens - Withania somnifera - Evolvulus alsinoides - Acorus calamus - Nardostachys jatamansi - Zingiber officinalis - Valeriana wallichi - Prunus amygdalus - Orchis mascula - Syzygium aromaticum - Embelia ribes - Terminalia chebula - Terminalia arjuna - Terminalia bellerica - Emblica officinalis - Tinospora cordifolia - Oroxylum indicum -Elettaria cardamomum - Foeniculum vulgare - Ipomoea digitata - Myristica fragrans.

58Mentat is the most clinically studied among the Indian nootropic medicines. It is prescribed for the treatment of memory disturbances (Kulkarni, 1996; Agrawal et al., 1990), behavioural disorders (Patel and Pereira., 1991), mental retardation (Quadri, 1993; Dixit et al., 1992; Dave et al., 1993), psychiatric problems (Dixit et al., 1993; Das and De Sousza, 1989). Many double blind clinical studies have been done to assess the different effects of the drug (Singh and Dhawan, 1997).


59Western medicine has to face emerging demand of drugs able to treat diseases related to aging or poor coping with modern life. In this matter (and in others) the knowledge accumulated over 2000 years by some traditional medicines like the Indian Ayurveda could be very useful. This rational medicine selected some plants by virtue of their effects on man. The traditional therapeutical use deals with plants extracts or powder mixtures, which efficacy is often confirmed by scientific trials. Efforts remain to be done to explore the precise pharmacological actions of the different active molecules. Furthermore, confronted to traditional phytotherapies, western science should accept to question its Cartesian dogma that " the whole equals the sum of the parts ", and to explore the pharmacological or pharmacokinetic role played by the combination of different molecules belonging to the whole extract of the plant, phenomenon which has been called "totum-effect".

Table I. Jujubogenin-saponins from Bacopa monnieri

Table I. Jujubogenin-saponins from Bacopa monnieri

Table II. Pseudojujubogenin-saponins from Bacopa monnieri

Table II. Pseudojujubogenin-saponins from Bacopa monnieri

Table III. Triterpenic acids from Centella asiatica

Table III. Triterpenic acids from Centella asiatica

Table IV. Saponins from Centella asiatica

Table IV. Saponins from Centella asiatica

Table V. Polyalcohols from Celastrus paniculatus

Table V. Polyalcohols from Celastrus paniculatus

Table VI. Sesquiterpene alkaloïds from Celastrus paniculatus

Table VI. Sesquiterpene alkaloïds from Celastrus paniculatus

Table VII. Polyesters of Celastrus paniculatus

Table VII. Polyesters of Celastrus paniculatus

Table VIII. Tropane alkaloids from Convolvulus sp

Table VIII. Tropane alkaloids from Convolvulus sp

Table IX. Triterpenes of Lavandula stoechas

Table IX. Triterpenes of Lavandula stoechas

Figure 1. Some components of Benincasa hispida

Figure 2. Major terpenes of Lavandula stoechas



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Notes de fin

1 Faculté des Sciences Pharmaceutiques, Université Louis Pasteur, F-67401 lllkirch-Graffenstaden

2 Faculté des Sciences Pharmaceutiques, Université Louis Pasteur, F-67401 lllkirch-Graffenstaden

3 Institut d'Histoire des Sciences, Université Louis Pasteur, F-67070 Strasbourg Cedex. Centre de Recherches Interdisciplinaires en Anthropologie, Université Marc Bloch, F-67084 Strasbourg Cedex Email:
To whom the correspondence should be sent.

4 Faculté des Sciences Pharmaceutiques, Université Louis Pasteur, F-67401 lllkirch-Graffenstaden

5 Faculté des Sciences Pharmaceutiques, Université Louis Pasteur, F-67401 lllkirch-Graffenstaden

Table des illustrations

Titre Table I. Jujubogenin-saponins from Bacopa monnieri
Fichier image/jpeg, 356k
Titre Table II. Pseudojujubogenin-saponins from Bacopa monnieri
Fichier image/jpeg, 240k
Titre Table III. Triterpenic acids from Centella asiatica
Fichier image/jpeg, 332k
Titre Table IV. Saponins from Centella asiatica
Fichier image/jpeg, 172k
Titre Table V. Polyalcohols from Celastrus paniculatus
Fichier image/jpeg, 256k
Titre Table VI. Sesquiterpene alkaloïds from Celastrus paniculatus
Fichier image/jpeg, 116k
Titre Table VII. Polyesters of Celastrus paniculatus
Fichier image/jpeg, 384k
Titre Table VIII. Tropane alkaloids from Convolvulus sp
Fichier image/jpeg, 196k
Titre Table IX. Triterpenes of Lavandula stoechas
Fichier image/jpeg, 172k
Légende Figure 1. Some components of Benincasa hispida
Fichier image/jpeg, 152k
Légende Figure 2. Major terpenes of Lavandula stoechas
Fichier image/jpeg, 68k

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