*13.1.1. Animal and cell toxicity*

substances that are toxic in vitro may become detoxified. Other factors such as the capacity of the substance to penetrate the tissue, and clearance and excretion of the product cannot be accounted for using the cellular model. The time of exposure and the rate of change for these extracts are not the same in both *in vitro* and *in vivo* studies. Notwithstanding these limitations of cytotoxicity assay, it still needs to be an integral part of evaluating the safety of medicinal plants because they provide direct information at the cellular level which may be important

Other limitations in cytotoxicity studies with regard to safety prediction for herbal medicines is the use of organic solvent such as methanol, dichloromethane, petroleum ether, ethyl acetate, and so on extracts as against water decoctions/extracts. In situations like this, it is not reasonable to compare the cytotoxicity results of the organic solvent extract with what pertains in TM. Such studies are common because the focus of most cytotoxicity studies has not been the safety assessment of the plants as used in TM but to determine the fractions which contain the potentially safe and efficacious compounds. In some cases, while efficacy study was conducted for both organic solvent and aqueous extracts, cytotoxicity was determined for only the organic solvents. This makes it difficult to relate the toxicity of the plant to safety in traditional use. In most cases, the organic extracts tend to be more efficacious than the aqueous extracts. This could imply that the organic extracts are more cytotoxic than the aqueous extracts since, generally, they (organic extracts) tend to extract more active compounds,

**12. Some herbal medicine products clinically evaluated for safety**

There have been few reports of the clinical safety of herbal product used in TM.A coded herbal medicine made of *Saraca indica,* Foeniculum vulgare, Juniperus communis*, Mentha piperita* and Zingiber officinale used to treat dysmenorrhea was found to be safe from such toxic effects as hepatotoxicity, nephrotoxicity and other side effects such as menorrhagia, gastro-intestinal disturbance and palpitation in a random-controlled clinical trial [43]. Also an unnamed herbal product made of Capparis spinosa root, Cichorium intybus seed, whole plant of Solanum nigrum, *Terminalia arjuna* bark, Cassia occidentalis seed, aerial part of *Achillea millefolium* and whole plant of Tamarix gallica and used for the management of liver disorders evaluated clinically was well tolerated and did not produce any adverse event in participants [44]. Tetteh et al. [12] reported that a Ghanaian polyherbal medicine, Adutwumwaa malamix, used in the treatment of malaria did not show any hepatotoxic or hematotoxic effects nor any adverse complaint in the populations studied for its clinical effectiveness and safety. Turkson et al. also reported the safety of another Ghanaian herbal medicine for the treatment of malaria and indicated that kidney and liver function tests and full blood count were within normal range at the end of the study, an indication that the product is clinically safe [45]. The tea bag formulation of the root powder of C. sanguinolenta has effectively treated acute uncomplicated malaria on relatively short treatment regimens and did not show any toxicity in man [46]. This was against the fact that the aqueous extract of the root is genotoxic in the Chinese hamster lung fibroblast (V79) cell line [42, 47] and the ethanolic extract of the stem increased

in assessing the true toxicity of such plants.

72 Herbal Medicine

which are both efficacious and cytotoxic.

platelet counts in albino rats [48].

Acute and sub-acute oral toxicity evaluation of the aqueous extract of the root suggested general safety at oral dosages below 500 mg/kg in Sprague Dawley rats. The extract did not exhibit either physiological or behavioral abnormality [50]. However, the ethanolic extract of the stem demonstrated localized systemic acute and sub-chronic toxicity by selectively stimulating the bone marrow leading to an increase in platelet counts in albino rats [48]. On the other hand, the aqueous extract of the root demonstrated genotoxicity against the Chinese hamster lung fibroblast (V79) cell line inducing mutagenicity at high concentrations and causing DNA damage [42, 47]. The ethanolic extract of the stem thus poses hematological challenges to white blood cells and platelets and showed localized systemic toxicity by selectively stimulating the bone marrow.
