r doses used in the study. More detailed or critical analysis of available information on bioactivities and safety of Fumaria indica extracts and their bioactive constituents is beyond the scope of this communication. For such purposes a recent review [13] and several monographs now available on the plant can be consulted.

6. Psychopharmacological Aspects

Initial reports on psychopharmacology of Fumaria indica dealt mainly with the CNS function modulating effects of its alkaloids. Amongst them the so called benzylisoquinoline alkaloid protopine is one of the more well studied one, and it is also one of the quantitatively major alkaloid of Fumaria indica. Protopine was first

Table 3. Marketed formulations containing Fumaria indica extracts.

Table 4. Reported pharmacological activities of secondary plant metabolites isolated from Fumaria indica.

isolated from opium during 1875, and since then it has been detected in numerous other medicinal plants, including several of them commonly used in TCM (Table 6 [82-120]). During more recent decades diverse therapeutically interesting pharmacological properties of protopine have been identified, and many analogous activities have also been reported for extracts of diverse other protopine producing plants. One such report dealing with antidepressant like properties of the alkaloid revealed that it is a potent inhibitor of neuronal serotonin and noradrenaline transporter, and does not have any effects on dopamine or GABA transporters [50]. Despite extensive efforts though, no antidepressant like activity of a hydro alcoholic Fumaria indica extract could be detected in rodent behavioural models commonly used for detecting such activities of synaptic serotonin and noradrenaline reuptake inhibitors [74]. Since protopine content of the tested extract is not known, no definitive statements on the role of protopine in psychotherapeutic potentially of Fumaria indica extracts can yet be made.

However, more recent efforts in our laboratories have revealed diverse therapeutically interesting psychopharmacological activities of hydro alcoholic extracts of Fumaria indica. They include their mental stress alleviating

Table 5. Reported pharmacological activities of Fumaria indica extracts.

[76], anti-aggressive [77], and anxiolytic [74,78] activities. During the course of these studies it became apparent also that the psychopharmacological activity profile of a given Fumaria indica extract depends largely on the functional state of the central nervous system. Thus for example, although no antidepressant like effects of a

Table 6. Some plants known to contain protopine and other Fumaria alkaloids.

hydro alcoholic Fumaria indica extract were detectable in non-stressed animals [74], such effects of the same extract was apparent in the same tests using mentally stressed animals [76]. It must be mentioned also that anxiolytics like and diverse other psychopharmacological activities of Fumaria indica extracts can be observed after their repeated daily doses only, and that their efficacies increase with the number of their daily oral doses administered. These and many other observations made to date with diverse types of Fumaria indica extracts and their bioactive constituents clearly reveal that their pharmacological targets and modes of actions are not like those of any known psychoactive drugs and other bioactive agents studied to date. It was only by the use of appropriate holistic psychopharmacological strategy, and proper choices of plant materials and extraction procedures, that these conclusions could be reached with certainty.

7. Concluding Remarks

It cannot be overemphasized that like many other medicinal plants Fumaria indica also produces structurally and functionally diverse bioactive secondary plant metabolites, not all of which can be extracted by a single solvent or extraction procedure. Moreover, therapeutically interesting bio-activity profile of a given plant extract is not only a resultant of the combined effects of all bioactive ingredients present in it, but also depends on its treatment regimen used to define its activity profile. Complexities arising from these facts clearly indicate that translation of traditional knowledge on medicinal uses of Fumaria indica, or of any other medicinal plant, in terms of modern medical sciences is possible only when the plant is considered as a whole, and its diverse types of extracts are tested in a battery of therapy relevant animal models. Hereupon, due attention has to be paid to the psychopharmacological activity profiles of the extracts.

It is now well established that all chronic diseases, or illnesses, always causes mental health problems, and that bi-directional interactions between mental health problems and physical health is a common feature of almost all socioeconomically important health problems. Unfortunately, even today, modern medicinal phyto-chemists and pharmacologists pay little attention to these facts and continue to explore traditionally known medicinal plants as sources for structurally and functionally novel therapeutic lead molecules only. Lessons learned and experiences gained from extensive efforts made since decades in our laboratories and elsewhere strongly suggest that Fumaria indica could be a valuable tool for identifying novel pharmacological targets and mechanisms potentially useful for achieving better and reproducible successes with phyto-pharmaceuticals containing its extracts as active ingredients. Since Fumaria indica is a weed, and holistic pharmacological strategies can easily be practiced in many developing and underdeveloped countries, efforts to better understand and more precisely define its therapeutic potentials can be strongly recommended. Moreover, since the lists of plants producing the same or structurally analogous bioactive secondary metabolites of Fumaria indica are long (for example see Table 6)know how gained from the efforts to properly decode its pharmacology will certainly be useful for decoding medicinal values of many other as yet underexplored ones. In any case, experiences gained with Fumaria indica strongly suggest that repeated oral dose studies with psychoactive alkaloid containing plants could be the more appropriate ones for properly evaluating their psychotherapeutic potentials.

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NOTES

*Former Head of the Pharmacological Research Laboratories, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany.

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