**8. Safety of medicinal plants and herbal medicines used in traditional medicine**

Generally, plants used in traditional medicines have been considered safe as a result of the long history of use in the treatment of diseases based on knowledge accumulated over several centuries. In many cultural settings, toxic fatalities have been rare due to systematic selection of medicinal plants for use. While thousands of people die each year from even supposedly 'safe' over-the-counter remedies, deaths or hospitalizations due to herbs are so rare that they are hard to find; not even the United States National Poison Control Centers have a category in their database for adverse reactions to herbs [17].

When used appropriately as dietary supplements, food supplements or medicines, traditional medicines are generally regarded as safe. However, there are instances where adverse events ascribed to herbal medicines used have been reported in both humans and animals. For example, Barbosa et al. [25] reported clinical and pathological neurological disorders in horses following a large intake of fresh *Bambusa vulgaris* leaves. Paradoxically, the aqueous decoction is a popular antimalarial medicine in Ghana [11, 21] and this has been used without any report of adverse reaction. Besides, the aqueous extract of the leaves did not cause cytotoxicity in normal human cells [11, 21]. In these situations, the dose of the constituents administered is of great importance; as stated by Paracelsus that, 'All substances are poisons; there is none, which is not a poison. The right dose differentiates a poison and a remedy' [26]. This is to say that the toxicity of any substance, including medicinal plants and even food, is largely dependent on the amount or dose used. A non-toxic substance can be toxic at a high dose, and a very toxic substance can be considered safe if the dose is low [27]. Over-dosage in the course of treatment is bound to pose safety problems. The dose-toxicity relationship was illustrated by the toxicity of *Bupleuri chinense* in which the toxic dose was about 21 times than the common clinical dose of 9 g/60 kg [28].

Apart from an overdose, adverse events may also arise from the misidentification of medicinal plants, errors in the use of herbal medicines both by health-care providers and by consumers, and misuse and use over long periods even at tolerable dose [8, 29].

the plant materials either dried or fresh often in boiling water to produce decoctions, which are then administered. This traditional approach therefore tends to make the herbal medicine safe since potentially toxic compounds are not extracted due to the inherent inefficiency in the aqueous extraction method (preparation of the decoction). Also, doses employed in contemporary practice often tend to be different from the traditional doses, which were systematically established over several years of practice and proven to be safe. Besides, herbal medicines are used for non-traditional indications in recent years. A typical example is the use of herbal medicines for relieving constipation but abused as an abortifacient by the youth due to its induced contractive effect on smooth muscles such as the endometrial muscles. The concomitant use of traditional medicines with other types of medicines is quite outside the

Toxicity and Safety Implications of Herbal Medicines Used in Africa

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Another challenge posed to the practice is the lack of appropriate foundational knowledge in traditional medicine practice and the herbal medicines used to treat diseases. This is a common occurrence among many contemporary practitioners, especially those in urban and cosmopolitan areas. The work of such practitioners is based on information gathered from indirect sources such as the Internet or from reading books and therefore lacking in specific knowledge. These 'neo-herbalists' most often lack the expertise and basic principles necessary for the use of herbal medicines. Their practice may therefore not be entirely safe and can put

Besides, documented knowledge about medicinal plants and their uses within cultural settings rarely contains information on potential toxicity of the plants. This is because many ethnopharmacologists tend to focus more on the therapeutic property of the plants and hence do not inventory their toxicological information. This failure to document and contextualize potential toxicity of plants in the perspective of local healing traditions and healing practitioners' methods and approaches to treatment does not promote the safe use of medicinal plants

Cytotoxicity refers to the ability of a substance to interfere with cell attachment, alter its growth, proliferation and or cause death [34]. Accurate determination of cytotoxicity is necessary to identify compounds or effective parts that might pose health risks to humans. Surprisingly, most cytotoxic assays are geared toward screening only bioactive compounds that can kill rapidly dividing cancer cells. Cytotoxic substances may destroy living cells via either necrosis/ lysis (i.e. accidental cell death) or apoptosis (i.e. programmed cell death) [35]. In cancer drug discovery, for example, potential cytotoxic agents induce apoptosis instead of necrosis with very low or no toxicity toward normal cells. Only few case studies have investigated normal

Toxicity studies on most medicinal plants using animal models have provided results that strengthen their use among humans; however, many such plants could be associated with some cytotoxicity (**Table 1**). As a consequence, researchers have supported the use of human cell lines for *in vitro* cytotoxicity assays in predicting human acute toxicity as alternatives

traditional context and has become a matter of particular safety concern [8].

outside the boundaries of the cultures where the medicinal plants are used.

cells to determine the cytotoxicity of especially African medicinal plants.

**10. Cytotoxicity of African medicinal plants**

patrons at risk of adverse reactions.

Interactions between herbs (herbal medicines) and drugs (allopathic medicines) may increase or decrease the pharmacological or toxicological effects of either component. Thus, synergistic therapeutic effects may complicate the administration of medications for chronic diseases, for example, herbs traditionally used to treat diabetes could theoretically lead to hypoglycemia if taken concomitantly with conventional antihyperglycaemic drugs [30].

In the formal herbal industry, the toxicity problems of medicinal plants could be attributable to insufficient quality assurance and non-compliance with the standards of good manufacturing practice [8, 31], and also inadequate access to the information required for the effective use of herbal medicines and inappropriate approaches to their use. Furthermore, the problem could be complicated by adulteration of herbal remedies by the addition of synthetic drugs and other potentially toxic compounds such as other botanicals, pathogenic microorganisms, toxins, pesticides and fumigants agrochemical residues or heavy metals [8, 29, 32]. The majority of adverse events related to the use of herbal products are attributable to weak quality control systems leading either to poor product quality [8]. According to WHO [8], poor regulatory measures and largely uncontrolled distribution channels could partly account for such events. These give rise to poor quality products arising from such situations as adulteration of herbal products with other undeclared medicines and potent pharmaceutical substances, such as corticosteroids and non-steroidal anti-inflammatory agents [8].

Usually, it is difficult to identify genuine adverse reactions to herbal medicines and herbal products until the cause of such events has been established. When appropriately employed, herbal medicines are relatively safe. Long historical including experience passed on from generation to generation has demonstrated their safety and efficacy [33].

It is worth noting that toxicity results of many medicinal plants are very often misinterpreted and wrong conclusions drawn with regard to traditional practices. Many toxicity studies were conducted on medicinal plants extracted in organic solvents such as methanol, dichloromethane, and so on other than aqueous extracts as used in traditional medicine practice. This was the case as reported in the degree of hepatotoxicity damage caused by the alcohol extracted *B. chinense* which proved more serious than that caused by the water extract [28].
