Authentic Ativisha (Aconitum heterophyllum) is a rare, endangered Himalayan species. Ayurveda classical texts of c. 15th–16th century, introduced “abhava-pratinidhi dravya” concept, wherein Ativisha was categorized as an abhava dravya (unavailable drug) and Musta (Cyperus rotundus) was suggested as a pratinidhi dravya (substitute) for it. C. rotundus is a weed, abundantly available pan-India. Cryptocoryne spiralis (Naattu Athividayam) and Cyperus scariosus (Nagarmotha) are also traded as Ativisha and Musta, respectively. Yet, there are no scientific studies to validate the use of substitutes. A. heterophyllum bears no similarity in terms of botanical classification with the other candidates. This article reviews published literature with an emphasis to look for similar phytochemicals or groups of phytochemicals in the species that could contribute to similar pharmacological activities, thereby supporting the drug substitution from a bio-medical perspective. Alkaloids like atisine were found to be the main focus of studies on A. heterophyllum, whereas for the Cyperus spp., it was terpenoids like cyperene. Although alkaloids and terpenoids were reported from both species, alkaloids in C. rotundus and terpenoids in A. heterophyllum were minor constituents. Reports on phytochemicals on Cryptocoryne spiralis and C. scariosus were very limited. Despite no significant similarities in chemical profiles reported, the dravyaguna (Ayurvedic drug classification) of Ativisha and Musta was quite similar warranting further exploration into the bio-functional aspects of the drug materials.

The Ayurvedic literature during the medieval period suggests the use of Musta (Cyperus rotundus), a common weed, as a pratinidhi dravya (substitute) for Ativisha (Aconitum heterophyllum), an endangered species. Contemporary Ayurvedic practice also uses Cryptocoryne spiralis, (known as Naattu Atividayam in South India) and Nagaramusta (Cyperus scariosus) as substitutes for Ativisha and Musta, respectively. This article reviews published literature on the pharmacology of the above four species. Both A. heterophyllum and C. rotundus are reported to possess antiinflammatory, antipyretic, antibacterial and antidiarrhoeal properties, while antiinflammatory and antibacterial activities are attributed to C. scariosus. No reports exist on the bioactivity of Cryptocoryne spiralis. It is interesting to note that other than the veerya which is different, the biological properties of Ativisha and Musta are similar according to Ayurvedic classification of dravyaguna. This is also supported by modern pharmacological studies, which show that, both A. heterophyllum and C. rotundus have antidiarrheal, antipyretic, antiinflammatory, antihyperlipidemic and hypoglycemic activities. However, the similarities between the discussed species cannot be attributed to their phytochemical composition or taxonomical classification as these are quite distinct. The dravyaguna method of classifying materials, which we are calling as “pharmaco-taxonomy”, offers a unique way of classifying those plant materials which lack similarity at the botanical or chemical level, but are similar at the level of biological functions.

A Phase 2 clinical trial with Black Cohosh and Red Clover was conceived in 2000 within our UIC/NIH Center for Botanical Dietary Supplement Research on Womenʼs Health. Prior to implementing the trial, a Phase 1 study was required and approval from FDA that an IND application was not required since the end point being measured was reduction in hot flashes in menopausal women. Menopause, for purposes of FDA is not considered a disease. The study was delayed for more than a year in order to prepare a botanically authenticated and chemically and biologically standardized extract. It was ascertained that the biological endpoint for purposes of the study would be interaction with certain serotonin receptors, in vitro. The study preparations had to be formulated and were subjected to accelerated stability studies. During the recruitment of suitable subjects the results of the WHI (Womenʼs Health Initiative) caused difficulty in the ability to recruit suitable women since the study had four arms, i.e. Black Cohosh, Red Clover, Placebo and Prempro and many women were reluctant to enter the trial if there was a possibility that there would be taking Prempro. Because of this, only 88 subjects were recruited of the 128 initially planned. However, the study was powered sufficiently if the dropout rate was less than 15 %. In the final analysis, Red Clover was shown to positively affect cognition but neither test preparation reduced hot flashes. A discussion of these results will be presented.