An Overview on Toxicity, Adverse Effects and Therapeutic Properties of Some Medicinal Plants

Plants with rich sources of secondary metabolites, pharmacological and therapeutic effects, have been considered by patients, traditional therapists and even modern medicine. This indicates the important role of medicinal plants and their compounds (3). In the most of studies on medicinal plants have addressed to their therapeutic and protective properties, and there is less research on the toxicity and adverse effects of these plants. In this article, with a brief description of the possible sources of plant toxicities production, ten medicinal plants have been reviewed that are widely used in traditional Iranian medicine, includes: Lemon balm, Watercress, Borage, Ginger, Cinnamon, Psyllium, Rosemary, Chicory, Valerian, Camel thorn.

Data collection was done by searching authentic databases (includes: Scopus, PubMed, Medline, SID, Google Scholar, Magiran and Science Direct) with related keywords in scientific articles and books. The time interval considered for review, was1991-2022. An initial search of 210 articles was made available. Finally, 122 articles were selected that they had inclusion criteria in this study.

The results of this study showed that many plant toxins are composed of alkaloids, glycosides, organic acids, resins, resinoids and mineral compounds which depending on the type of toxin may affect various organs of the body (15). Compounds such as pyrrolizidine alkaloids(PAs) that found in some plants kind of Borago officinalis L. and Senecio sp. from Boraginaceae and Asteraceae family, in above doses may cause diseases such as liver injuries and ascites (21, 23). Sesquiterpene lactones (SLs), which have been reported in some plants such as Taraxacum officinale and Laurus nobilis from Asteraceae and Lauraceae family, may be pathogenic to humans and animals (26, 27).A study on laboratory animals in lemon balm plant have shown that consumption of this plant in above doses (1350 mg / kg body weight) has caused toxic effects on liver tissue cells and as a result of liver damage and changes in liver enzymes (17). In other research on the alcoholic extract of watercress (Nasturtium officinale) showed that this plant has antioxidant potential in high concentrations in vitro. However, based on the results of LD50 test at a dose higher than 80 mg / kg, a relatively toxic substance has been reported (46).Laboratory studies on Borage (Borago officinalis L.) have shown that the alcoholic extract of this plant at a dose of 200 mg / kg causes a significant increase in ALT and AST enzymes compared to the control group, and this indicates possible damage to liver cells at high doses (86). Studies have shown that the toxicity of Ginger is very low and LD50 test of oral   its oil in lab different animals has been reported to be more than 5 g / kg body weight and no unpleasant side effects have been reported from Ginger consumption in humans (88).Compounds such as flavonoids in psyllium (Plantago psyllium) reduce blood levels of triglycerides, cholesterol, urea, creatinine and uric acid in patients with hyperlipidemia and hyperuricemia (5). However, there are reports of allergies and anaphylaxis like of chest congestion, tears from the eyes and sneezing with the use of psyllium (104, 105). Results of in vivo in the study of Cinnamon toxicity have shown that the toxicity of its is low to moderate, and the LD50 tests confirms this result and nomortality has been reported in laboratory animals (114). In a study on Rosemary hydroalcoholic extract in rats, was low acute toxicity, and lethal oral dose (LD50) was reported of more than 2000 mg / kg body weight (49).Some studies have shown that the use of Chicory (Cichorium intybus) reduces hepatotoxicity in side effects of synthetic drugs such as carbamazepine (127). However, in one study, it was shown that peritoneal injection of the extract of this plant at a dose of 400 mg / kg had a toxic effect and caused the death of laboratory animals (45). Some studies of lab have reported that aqueous and alcoholic extracts of Valerian are slightly toxic and  its LD50 (580 mg / kg body weight) is high  (134). It also lowers the seizure threshold by intensifying the inhibitory process and reducing the excitatory transmission (86). Therefore, its concomitant use with antiepileptic drugs in the form of synergistic effects may cause drug interactions. In the study in vivo of acute poisoning of aqueous extract of Camel thorn, it was found that this extract has no toxic effects or mortality up to a dose of 10 g / kg body weight (47). Meanwhile, the hydroalcoholic extract of the aerial parts of Camel thornplant can prevent side effects on the urinary system of rats against acute nephrotoxicity induced by gentamicin (142).

The most of plants studied in this research have different mechanisms and therapeutic properties, incuding: antispasmodic, sedative and analgesic (Borago officinalis and Valeriana officinalis); anti-inflammatory, antibacterial, antifungal, antiviral and anti-tumor (Nastutium officinale and Rosemarinus officinalis);  Anti-allergy and anti-inflammatory (Melissa officinalis and Alhahi maurorum); appetite stimulant, expectorant and liver and kidney protection properties (Cichorium intybus and Plantago psyllium), antioxidants, free radical scavenger and Strengthen  immune system (Zingiber officinale and Cinnamomum zeylanicum). By inducing these properties, they produce pharmacological effects against diseases. Also, under the influence of the appropriate dose of the plant in the treatment of diseases such as gout, rheumatism, diabetes, colds, hypertension, cough, infection, heart disorders, kidney and liver diseases, gastrointestinal diseases and other diseases have therapeutic effects. Despite all the important therapeutic properties and effects; the study of active ingredients of the plant that may cause poisoning in living organisms, including the plant itself, is of particular importance. As described in this article, medicinal plants such as lemon balm borage, valerian, chicory and rosemary, their chemical compounds may cause toxicity and drug interactions in long-term use or in high doses (45, 61, 86, 121).Due to the wide range of chemical compounds in medicinal plants; consumption of these compounds, which seem natural, may be associated with plant adverse effects and toxicity. As a result, through this study and investigation of therapeutic properties, biochemical, toxicity and determining the toxic dose of medicinal plants, the assurance of consumption or warning in the use of these high-consumption plant resources was determined.