**10. Cytotoxicity of African medicinal plants**

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 consum-

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 hypoglyce-

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,

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 gen-

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

Traditional medicines are increasingly being used outside the confines of traditional cultures and far beyond geographical areas without proper knowledge of their use and the underlying principles [8]. They are therefore practiced in ways that deviate from the traditional norm of practice within the specific traditional setting. Such deviations include the method of extraction—where highly efficient and sophisticated technological tools are frequently used for extracting medicinal plants and then reformulating the extract into a final product. Such an approach is entirely different from the hitherto traditional approaches of macerating

*B. chinense* which proved more serious than that caused by the water extract [28].

**9. Challenges of contemporary herbal medicine practice in Africa**

ers, and misuse and use over long periods even at tolerable dose [8, 29].

68 Herbal Medicine

mia if taken concomitantly with conventional antihyperglycaemic drugs [30].

such as corticosteroids and non-steroidal anti-inflammatory agents [8].

eration to generation has demonstrated their safety and efficacy [33].

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 cells to determine the cytotoxicity of especially African medicinal plants.

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


to acute lethality studies in rodents [36]. The selectivity exhibited by cytotoxic plants also underscores the need to distinguish highly active but toxic extracts from those that are selectively active against certain pathogens, diseased conditions and even cancerous cells. This provides good leads for continuous research on promising extracts, the sources of interesting biologically active and therapeutically useful compounds with excellent activity and low toxicity [37]. Toxicity testing at the cellular level is therefore very useful and recommended for all bioactive medicinal plants. Clearly, information on cytotoxicity of plants commonly used in traditional medicine in Africa is essential for assessing the quality, efficacy and safety of their preparations. Such knowledge is also critical in developing new

**Popular medicinal use Plant** 

gastrointestinal affections, hernia, febrifuge, anti-rheumatic, anthelmintic, antalgic, tonic, stomach pains, gastric hemorrhoids, diarrhea, **part**

http://dx.doi.org/10.5772/intechopen.72437

Toxicity and Safety Implications of Herbal Medicines Used in Africa

root bark [41]

**References**

71

In spite of the assumed safety of African medicinal plants, studies have shown that many plants used as food or traditional medicines are also potentially cytotoxic, mutagenic and carcinogenic [38–40]. A comprehensive survey by [37], for instance, recorded 400 plants of African origin with cytotoxic effects. These plant species, according to the study, are used to treat diseases of considerable economic burden to the African continent, of which malaria, leishmaniasis and sleeping sickness received much attention. The study, however, identified approximately 14 or 56% of the listed plant species as having significant cytotoxic activities (IC50 < 30 μg/ml) against some normal cells such as human normal lung fibroblast (MRC-5), human kidney epithelial and human monocytes. While the list compiled by McGaw et al. [37] comprised many species with high efficacy against cancerous cells or pathogens, it indicated

Although the above observation calls for great care in plant use and close monitoring of their potential side effects, there are also clear reasons why cytotoxicity results could not always be wholly extrapolated into safety prediction in TM: except when organotypic cultures are used [37].

There are some shortcomings to extrapolating cytotoxicity studies to the safety of herbal medicine used in traditional medicine. Among this is the fact that tissue responses due to *in vivo* toxicity cannot be addressed by toxic responses in cells [37]. According to McGraw et al. [37], a critical factor in toxicology is metabolism *in vivo*, as some substances lacking toxicity initially may produce toxic metabolites after being exposed to liver enzymes, while other

therapeutic products to ensure the safety of end users of herbal medicine.

that at least 14% of these African medicinal plants may be harmful to humans.

**11. Drawbacks of using cytotoxicity to predict safety of herbal**

**medicines in TM**

**Species Normal cell** 

**type**

*Quassia africana* MRC-5 cells Malaria, blenorragia, hypertension, scabies,

**Table 1.** Cytotoxic activities of aqueous extracts of African medicinal plants.

antiwounds


**Table 1.** Cytotoxic activities of aqueous extracts of African medicinal plants.

**Species Normal cell** 

Low cytotoxicity (>50 μg/ml)

70 Herbal Medicine

Moderate cytotoxicity (30–50 μg/ml)

High cytotoxicity (10–30 μg/ml)

Very high cytotoxicity (<5 μg/ml)

**type**

*Afrostyrax lepidophyllus* MRC-5 cells Anthelmintic, vomiting, urinary infections Stem

diarrhea

menstrual disorders

antihyperglycemia

cramps, malaria, rheumatism

kidney disease, aphrodisiac

filariasis, gastritis, epilepsy

gastrointestinal disorders, malaria.

fever, painful joints, diarrhea, ulcer, dysmenorrhea and edema

astringent, dysentery, diarrhea, constipation, diabetes, hepatitis, gonorrhea, diarrhea.

*Drypetes gossweileri* MRC-5 cells Anthelmintic, purgative, tonic, bronchitis,

*Napoleona vogelii* MRC-5 cells Dermatosis, sexual asthenia, stomach aches, diarrhea

*Tectona grandis* HUVECs Bronchitis, hyperacidity, dysentery,

*Cryptolepis sanguinolenta* V79 cells Fever, hepatitis, malaria, hypertension,

*Isolona hexaloba* (Rb) MRC-5 cells Pains, sexual weakness, headache, intestinal

*Phyllanthus fraternus* HUVECs Malaria, chronic pyrexia, chills, intermittent

*Psidium guajava* MRC-5 cells Antispasmodic, astringent, febrifuge, vulnerary,

*Terminalia ivorensis* HUVECs Wounds, hemorrhoids, infections, gonorrhea,

*Tetrapleura tetraptera* MRC-5 cells Enema, malaria, fungal infections, arthritis,

*Harungana madagascariensis* MRC-5 cells Anemia, venereal diseases, nephrosis,

*Enantia chlorantha* MRC-5 cells Intestinal worms, spasms malaria, sexual

*Piptadeniastrum africanum* MRC-5 cells Sexual asthenia, Constipation, intestinal

asthenia.

cramps, pain.

*Mammea africana* (Sb) MRC-5 cells Wounds, filariasis, mycosis, skin diseases Stem

**Popular medicinal use Plant** 

cough, pains, relieve urethral discharge,

verminosis, diabetes, leprosy, inflammation, skin diseases, pruritus, stomatitis, ulcers, hemorrhages, constipation, piles, leucoderma, headache, biliousness, anuria, urethral discharges, body swellings,

urinary and upper respiratory tract infections, colic, stomach complaints, amoebic dysentery, diarrhea, wounds, measles, hernia, snakebites, rheumatism, insomnia, antiplasmodial activity, anticancer, antifungal, antibacterial, hypotensive, antipyretic, anti-inflammation, **part**

bark

Stem bark

Stem bark

Leaf [11]

Root [42]

Root back

back

Whole plant

Leaf [41]

Leaf [11]

Fruit [41]

[41]

[41]

[41]

Stem bark

stem bark

stem bark

[41]

[41]

[11]

**References**

[41]

[41]

[41]

to acute lethality studies in rodents [36]. The selectivity exhibited by cytotoxic plants also underscores the need to distinguish highly active but toxic extracts from those that are selectively active against certain pathogens, diseased conditions and even cancerous cells. This provides good leads for continuous research on promising extracts, the sources of interesting biologically active and therapeutically useful compounds with excellent activity and low toxicity [37]. Toxicity testing at the cellular level is therefore very useful and recommended for all bioactive medicinal plants. Clearly, information on cytotoxicity of plants commonly used in traditional medicine in Africa is essential for assessing the quality, efficacy and safety of their preparations. Such knowledge is also critical in developing new therapeutic products to ensure the safety of end users of herbal medicine.

In spite of the assumed safety of African medicinal plants, studies have shown that many plants used as food or traditional medicines are also potentially cytotoxic, mutagenic and carcinogenic [38–40]. A comprehensive survey by [37], for instance, recorded 400 plants of African origin with cytotoxic effects. These plant species, according to the study, are used to treat diseases of considerable economic burden to the African continent, of which malaria, leishmaniasis and sleeping sickness received much attention. The study, however, identified approximately 14 or 56% of the listed plant species as having significant cytotoxic activities (IC50 < 30 μg/ml) against some normal cells such as human normal lung fibroblast (MRC-5), human kidney epithelial and human monocytes. While the list compiled by McGaw et al. [37] comprised many species with high efficacy against cancerous cells or pathogens, it indicated that at least 14% of these African medicinal plants may be harmful to humans.

Although the above observation calls for great care in plant use and close monitoring of their potential side effects, there are also clear reasons why cytotoxicity results could not always be wholly extrapolated into safety prediction in TM: except when organotypic cultures are used [37].
