Journal of Ethnopharmacology, 4 (1981) 229 - 232

0 Elsevier Sequoia S.A., Lausanne - Printed in The Netherlands

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Short Communication

Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs

C. K. ATAL, USHA ZUTSHI and P. G. RAO

Regional Research Laboratory, Jammu-Tawi (J&K) (India)

(Received March 7, 1980; in revised form August 14, 1980)

Summary

Experiments were conducted to evaluate the scientific basis of the use of the trikatu group of acrids (long pepper, black pepper and ginger) in the large number of prescriptions in Ayurveda. [ 3H] vasicine and [ 3H] sparteine were taken as test drugs. Piper Zongum (long pepper) increased the blood levels of vasicine by nearly 233%. Under the influence of piperine, the active principle of Piper species, sparteine blood levels increased more than 100%. The results suggest that these acrids have the capacity to increase the bioavail- ability of certain drugs. It appears that the trikutu group of drugs increase bioavailability either by promoting rapid absorption from the gastrointestinal tract, or by protecting the drug from being metabolised/oxidised in its first passage through the liver after being absorbed, or by a combination of these two mechanisms.

In Ayurveda, black pepper (Piper nigrum Linn.), long pepper (Piper longurn Linn.) and ginger (Zingiber officinalis Rose.) are collectively termed trikatu, a Sanskrit word meaning three acrids. The ancient documented Ayurvedic materia medicu mention these three drugs as essential ingredients of numerous prescriptions and formulations, used for a wide range of diseases. These documents date back to the period between the sixth century A.D. and the third century B.C. (Charakaet al., 1941; Kaviraj, 1963; Vagbhat, 1962). If the claims (Raj and Nagarsheth, 1978) made about the use of individual members of the trikutu group are examined, it is amazing to find that the single entities have been shown to be a panacea for numerous ills. One wonders, therefore, whether these “acrids” have some unique inherent prop- erty to cure avariety of ailments or a role other than their therapeutic action.

Some modern Ayurvedic practitioners have tried to explain the scien- tific basis underlying the use of these herbals. According to Dutt and King (1900) these herbals are added to formulations “often without reason and

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sometimes only for the sake of rhyme”. Lakshmipathi (1946) reported that these acrids are useful in restoring the balance of kapha, uata and pitta, which according to Ayurvedic concept represent the three humours of the body, the imbalance of which causes all disease. Only Bose (1928), while describing the anti-asthmatic property of vasaka leaves (Adhatoda uasica), makes a positive mention that the addition of long pepper to vasaka increases its efficacy.

We therefore, became interested in investigating the possible scientific basis for the extensive usage of these three herbals.

Female rats weighing between 50 and 80 g, were used for the study. The animals were fasted for 24 h and water made freely available. Five animals per data point were employed (a total of 30 animals for each set of measurements). Distilled water was used as dosing vehicle. The alkaloids vasicine (ex. Adhatoda uasica) and sparteine (ex. Spartium junceum) were taken as test drugs. The alkaloids were radio-labelled (tritium) and adminis- tered orally (10 mg/kg) to the animals

TIME IN HOURS

Fig. 1. Comparison of plasma drug concentration uersus time after oral administration of vasicine alone (0) and of vasicine plus long pepper, (0).

Vusicine. Two sets of experiments were organised. In one, vasicine was given orally alone and in another vasicine was administered with a suspension of finely powdered long-pepper fruits (250 mg/kg). Blood samples were taken at different time intervals. The processed samples were counted, after the addition of 10 ml of Bray’s fluid, in a Beckman liquid scintillation system LS 3150 P using an external standard. The vasicine concentration in circulating blood thus monitored at different time intervals is presented in Fig. 1. It can be inferred from the data that long pepper can play a significant role in in- creasing bioavailability. The total area under the plasma concentration-time

curve increased from 61.3 to 204.4 pg h ml-‘. It is also clear from the curve that serum levels of vasicine are maintained for a longer period when vasicine is administered with long pepper. Quantitatively, there is more than a 200% increase in bioavailability of vasicine under the influence of co-administered suspensions of long pepper. The quantitative increase in bioavailability was computed by the procedure adopted by Wagner (1975).

Fig. 2. Comparison of drug concentration versus time after oral administration of sparteine alone (0) and of sparteine plus piperine, (0).

Sparteine. In this case piperine, one of the main chemical components of both black and long pepper, was given in a 30 mg/kg dose along with the test drug. Figure 2 shows that under the influence of piperine the area under the concentration curve increases from 54.8 to 113.4 pg h ml-‘. This shows an increase in bioavailability of sparteine of more than 100% under the influence of piperine.

These results show that such herbal drugs or their active principles such piperine were not included in Ayurvedic prescriptions just for the sake of rhyme but that they have a definite and important role to play in increasing drug bioavailability when given orally. It is believed that these findings will open a new chapter in both research and application of these agents in the

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pharmaceutical industry. Improved bioavailability through the oral route can eliminate the need, in many cases, to administer the drug by the more painful parenteral route. It can also mean elimination of the risk of infection, hyper- sensitivity and anaphylactic shock which is associated with the parenteral administration of certain drugs. Further work on the mode of action of these herbals and their pure constituents is now being conducted. However, at this stage we believe that the trikatu group of drugs increases bioavailability either by (1) promoting absorption from the gastrointestinal tract, (2) pro- tecting the drug from being metabolised/oxidised in the first passage through liver after being absorbed, (3) a combination of these two mechanisms, or (4) causing increased production of bile.

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References

Bose, K. G., Pharmacopoeia Indica, Bose Laboratories, Calcutta, 1928. Charaka, et al., Charak Samhita, 3rd edn., Nirnaya Sagar Press Bombay, 1941, (in

Sanskrit). Dutt, U. C. and King G., Materia Medica of Hindus, Calcutta, 1900. Kaviraj, K. B., Sushruta Samhita, 2nd edn., Chowkhamba Sanskrit Series, Vol. 3,

Varanasi, India, 1963. Lakshmipathi, A., One Hundred Useful Drugs, 3rd edn., Arogya Ashram Samithi,

Madras, 1946. Raj, K. P. S. and Nagarsheth, H. K., Indian Drugs, 16 (1978) 199-203. Vagbhat, Ashtang Hridaya, Chowkhamba Sanskrit Series, Varanasi, India, 1962,

(in Sanskrit). Wagner, J. G., Fundamentals of Clinical Pharmacokinetics, Drug Intelligence Publications

Inc., Hamilton, IL, 1975, pp. 173-229.