Toxicology and Clinical Applications of Black Pepper

2015

Toxicology of Black Pepper

There are no data available on the acute or chronic toxicologic aspects of pepper and/ or its constituents. Pepper constituents are not used therapeutically in the allopathic system. Pepper has been in use since very early times as a spice and food additive. No health hazard or untoward action may arise in the concentrations used. The total contents of piperine and associated phenolic amides are of the order of 7–9 per cent w/w and that of the volatile oil are 2–4 per cent. At this level the actual doses of the different constituents available from the quantity of pepper powder, oleoresin or extractive used, will be very little to elicit any toxic reactions. Moreover, the pungent taste of piperine and flavour of the volatile oil constituents will themselves serve as a limiting factor for the intake of high doses. No acceptable daily intake (ADI) has been prescribed by the Joint FAO/WHO Experts Committee on Food Additives for piperine and/or the volatile principles. The major untoward action of pepper is the gastric mucosal injury at a dose of 1.5 g/kg food. There are a few reports about the carcinogenic potential of piperine. It enhances the DNA adduct formation, and extract of pepper produces an increased incidence of cancer in mice. El Mofty et al. reported the formation of hepatocellular carcinoma, lymphosarcoma and fibrosarcoma in Egyptian toad by force feeding them with an extract of black pepper. However, large number of studies prove the anticarcinogenic effects. Anyway, to establish the carcinogenicity or anticarcinogenicity unequivocally, piperine has to be subjected to further screening. The observation that it enhances the liver microsomal enzyme activity also has to be investigated further. This is to ascertain whether constant use of pepper can produce any nonspecific enzyme induction.

Clinical Applications of Black Pepper

Clinical applications are not reported for black pepper or any of its constituent in Allopathic Medicine. However, in the Indian systems, Ayurveda, Sidha and Unani, pepper has been used in many clinical applications. But in any of these applications, piperine or other phenolic amides or the volatile oil constituents as such are not being used. Black pepper in the dried form along with other medicinal plants are used for preparing the particular formulations. Some important preparations used in Ayurveda are Dasamulakatutrayadi Kasayam, a formulation used for the treatment of Asthma, Astacurnam — used for dyspepsia and flatulence and as stomachic and carminative effect, Amirtaristam — for fever as an antipyretic, and as an antiperiodic, Muricadi Tailam — for inflammations and rheumatic pain, Dasamularasayanam — for cough and bronchitis, Gulgulutiktaka ghrtamanalgesic and antiinflammatery effect.

The varied type of pharmacological activities of black pepper and its constituents justifiy many of its therapeutic uses in Ayurveda, even though an active constituent-dependent action and therapeutic effect is not the basis in this system. For pepper and its constituents to be used in the allopathic system, there is a long road to travel. However, pepper provides natural compounds with analgesic, antipyretic and antinflammatory activities which are promising areas demanding further investigation. Similarly, the use in malarial fever also needs more study. The antioxidant and antimicrobial activities are beneficial properties and support the use of pepper as an important spice and food additive. Moreover, pepper has good dietary value also. Umapradeep et al. () reported that it has a high dietary fibre content (15–53%), iron (54–62 mg/100 g), calcium (1.0–1.5%) and also appreciable amounts of essential amino acids. Pepper has long been used as a digestive aid and is good for gastrointestinal upsets and flatulence (excessive gas in the body). The carminative property of pepper have been known since ancient times. Excessive gas in the alimentary tract is characteristic of many health disorders. Flatulence can cause pain and discomfort in other parts of the body. Pepper increases salivary flow and the secretion of the enzyme amylase which helps in the proper digestion of starch.

Insecticidal Activity

Plants have been used for pest control from time immemorial. Many of the plant derived insecticidal compounds have the added advantage that while being toxic to the pest they are nontoxic to humans. The extract, the volatile oil and the various phenolic amides present in pepper have shown to exhibit insecticidal and/or insect repellent and ovicidal activities to different insects and pests harmful to mankind. The major alkaloid piperine was more toxic than pyrethrine, a standard insecticide, to house flies. In many of the cases the insecticidal/repellent activity was obtained at low concentrations. Hence, this aspect of the biological activity of pepper is a very promising area which could be exploited in the field of insect control. The volatile oil of pepper was found to cause mortality to Lasioderma serricorne (cigarette beetle). The effect of the alcoholic extract of pepper was investigated by several groups and found that this was effective against cotton ball weevil, rice weevil and Drosophila (). The LD50 for topical application of the crude and purified extracts, obtained from 24 h dosage mortality were 3.4 µg and 4.8 µg/insect for adult Sitophilus oryzae and 4.5 µg and 7.2 µg/insect for adult Callosobrunchus maculatus. Acetone and petroleum ether extracts were also investigated for insecticidal properties by Samuel et al. (), Su and Sondengum and Su. At moderate to low doses both the extracts were lethal to the storage insects like rice weevil (Sitophilus oryzae), pulse beetle (Callosobrunchus chinensis) and repellent to flour beetle (Tribolaum castaneum). This was also found to be ovicidal for Tetranychus and toxic to the eggs of rice armyworm (Spodoptera). Topical application of acetone extract caused high mortality of rice weevil, red flour beetle, cowpea weevil, lesser grain borer (Rhizoperpta dominica) and ricemooth. The oleoresin, piperine and other amides were found to inflict lethality to culex mosquito (Culex pipiens) and also to pulse weevil. Piperonal, piperine, piperoline, pellitorine, pepercide and dihydropipercide also were investigated by Miya Kado et al. (), Masakazu et al. () and Desmukh et al. () and found that all these pepper amides possess good insecticidal activity towards pulse beetle, rice weevil, and Drosophila (growth inhibition of larva). The larvicidal activity of the acetone extract of pepper on Anopheles subpietus larvae was shown by Desai et al. (). The larvae showed 100 per cent mortality within 24 hours at 80 ppm.

Pepper is an essential ingredient in the Indian system of medicine, but plays no role in the allopathic or modern medicine. Only in China a compound from pepper is widely used for treatment against epilepsy in hospitals. Pepper and pepper components to be useful in modern medicine, there is a long road to travel. Recently a U.S. firm has taken a patent for the use of piperine for enhancing the bioavailability of drugs. Compound formulations with piperine will be more readily absorbed and hence will be useful in oral drug formulations. Further pharmacological studies are needed to asses the biological effects of various pepper constituents.

 

Selections from the book: “Black Pepper. Piper nigrum”. Edited by P.N.Ravindran. Series: “Medicinal and Aromatic Plants — Industrial Profiles”. 2000.