A review of the most important medicinal herbs affecting giardiasis

Introduction Giardiasis is a parasitic disease caused by a flagellated protozoa called Giardia lamblia, Giardia intestinalis or Giardia duodenalis (1,2). Infection caused by this parasite has been reported from all over the world, including various regions of Iran. Infection due to the Protozoa giardia is one of the most common parasitic infections in the world. Millions of people worldwide acquire this parasite every year (3). Transmission of this disease occurs through fecal-oral route, especially through contaminated food and water intake. The most important route of transmission is contaminated drinking water (4). The incidence of this infection has been observed in children more than other age groups (5). Prevalence of giardiasis, as with most intestinal diseases, varies depending on the health status and is more common in temperate and tropical climates than cold regions (6,7). The most common clinical symptoms of giardiasis include abdominal pain, bloating and diarrhea. Other symptoms include indigestion, epigastric pain, nausea, vomiting, and fatty stools with bad smell (8,9). Common medications for the treatment of this disease include nitroimidazole derivatives including tinidazole, ornidazole, metronidazole and nimorazole, benzimidazole http://www.herbmedpharmacol.com doi: 10.15171/jhp.2019.13


Introduction
Giardiasis is a parasitic disease caused by a flagellated protozoa called Giardia lamblia, Giardia intestinalis or Giardia duodenalis (1,2). Infection caused by this parasite has been reported from all over the world, including various regions of Iran. Infection due to the Protozoa giardia is one of the most common parasitic infections in the world. Millions of people worldwide acquire this parasite every year (3). Transmission of this disease occurs through fecal-oral route, especially through contaminated food and water intake. The most important route of transmission is contaminated drinking water (4). The incidence of this infection has been observed in children more than other age groups (5). Prevalence of giardiasis, as with most intestinal diseases, varies depending on the health status and is more common in temperate and tropical climates than cold regions (6,7). The most common clinical symptoms of giardiasis include abdominal pain, bloating and diarrhea. Other symptoms include indigestion, epigastric pain, nausea, vomiting, and fatty stools with bad smell (8,9).
Common medications for the treatment of this disease include nitroimidazole derivatives including tinidazole, ornidazole, metronidazole and nimorazole, benzimidazole derivatives such as mebendazole and albendazole, and other drugs such as quinacrine, furazolidone and paromomycin, among which metronidazole is a selective drug for the treatment of giardiasis. These drugs have unpleasant side effects such as an unpleasant taste in the mouth, gastrointestinal discomfort, nausea, headache and leukopenia. In addition, some of these drugs can lead to neurotoxic effects, restlessness, seizures and dizziness, and disrupt the process of the treatment. In addition, the mutagenic, carcinogenic, and adverse effects of some of them on the embryo have been demonstrated by studies on laboratory animals (10)(11)(12). As the giardiasis infection is transmitted and spread by cyst, different ways have been recommended to remove cyst, one of which is the use of plants and natural nutrients to eliminate the cyst of the parasite (13,14). Medicinal plants and plant products have always been used to treat pain and illnesses from the old times (15)(16)(17), because when chemical drugs were not available, humans used these natural and accessible sources for treatment (18)(19)(20)(21). Considering the importance of giardiasis, it is necessary to study the effect of anti-parasitic herbal drugs on the elimination of cystic and trophozoite forms of the disease. On the other hand, many herbal drugs have been discovered and used for the treatment of protozoan diseases. Therefore, it is particularly important to review such drugs, especially anti-giardia herbal drugs, because they can be used to produce effective natural drugs for this infectious agent. Hence, this article is aimed to report the medicinal plants that are used in Iranian traditional medicine against giardiasis

Methods
The information in this review study was obtained from scientific articles indexed in databases such as ISI, PubMed, Scopus, SID, Magiran and Google Scholar that were retrieved using the search terms giardia, protozoa, herbs, extracts and essential oils.

Lavandula stoechas L
This herbal plant belongs to Lamiaceae family. The results of the studies have shown that lavender plants are very effective in intravenous conditions and have a therapeutic potential for Giardia infection. So that the dose of 400 mg/mL of hydroalcoholic extract of lavender is effective against Giardia lamblia (22).

Ferula assa-foetida
This herbal plant belongs to Apiaceae family. Alcoholic and aqueous extracts of Ferula assa-foetida had positive effects on Giardia lamblia cysts. The effect of fecundity of the alcoholic extract was greater than that of the aqueous extract. The percentage of fecundity of the alcoholic extract of Ferula assa-foetida was 37% at a concentration of 20 mg/mL and at the fourth hour it was 100%. While the highest percentage of fecundity of the aqueous extract of Angus, at the same temperature and concentration in the fourth hour was 57.23 mg/mL (23). After 4 hours, the effect of the plant was 100%.

Tanacetum parthenium
This herbal plant belongs to Asteraceae family. Based on the results of a study, chloroform extract of Tanacetum parthenium, at a concentration of 100 mg/mL, was effective in the treatment of Giardia lamblia infection of Balb/C mice (24).

Allium paradoxum
This herbal plant belongs to Asteraceae family. Alcoholic hydroalcoholic extract of Allium paradoxum with 100 mg/ mL could eliminate Giardia lamblia cysts in Balb/C mice. Therefore, hydroalcoholic extracts of Allium paradoxum can be introduced as a natural anti-giardia compound (25).

Chenopodium botrys L
This herbal plant belongs to Amaranthaceae family. The results of a study showed that the alcoholic and aqueous extracts of Turkish Chenopodium botrys seeds in vitro had a deleterious effect on Giardia lamblia cysts. The harmful effect of the alcoholic extract of this plant was greater than its aqueous extract. The effect of Turkish Artemisia alcoholic extract at a temperature of 37°C, concentration of 20 mg/mL, at fourth hour was 100%. While the highest germination percentage of aqueous extract of Artemisia turkey with the same concentrations was 66.1 (26).

Carum copticum
This herbal plant belongs to Apiaceae family. The results of a study showed that its alcoholic extract as well as its essential oil had good effects on Giardia lamblia cysts under laboratory conditions. The results of this study showed that after 60 minutes contact of hydroalcoholic extract and essential oil on Giardia lamblia cysts, the MICs of Carum copticum were 100 and 8 mg/mL, respectively (27).

Eucalyptus globulus
Cineol (33) Lippia beriandievi Tannin and verinalin (34) Punica granatum Resin compounds (34) Scientific name Active ingredients Plant figure Table 1. Continued has been reported that Garlic extract is quite effective on Giardia cysts. Although the treatment of infected mice during 3 days at 20 and 40 mg/kg body weight of garlic extract did not completely improve all of the hair, the dose of 80 mg/kg of body weight during three days resulted in their complete recovery (28).

Artemisia annua
This herbal plant belongs to Asteraceae family. According to the results of a study, hydroalcoholic extract of Artemisia annua plant at a concentration of 100 mg/mL for 24 hours used as an effective compound for the elimination of giardia cysts (29).

Allium ascalonicum
The results of one study showed that Allium ascalonicum (0.2 mg/mL) inhibited Giardia. It is known that the main compounds of this plant are di sulfides (30).

ZizIphora clinopodioides
The inhibitory dose of ZizIphora clinopodioides (zircia) has been reported to be 0.015 mg/mL. It is known that the main compounds of this plant are thymol and phenols (31).
Zataria multiflorahad a dose of 0.01 mg/mL of Zataria multiflorahad has had anti-Giardia effects. The main components of this plant are thymol and carvacrol (32).

Eucalyptus globulus
Eucalyptus (Eucalyptus globulus) at a dose of 0.022 mg/mL has had anti-Giardia effect due to the presence of active substances such as cineol (33).

Lippia beriandievi
The Lippia beriandievi plant at a dose of 0.85 mg/mL has shown to possess anti-Giardia effect due to the presence of substances such as tannins and verinalin (34).

Punica granatum
The pomegranate at a dose of 17 mg/mL has anti-Giardia effect due to its peppery content (31). The marked mango is composed of resin compounds. Based on the results of a study, it has been determined that mangoes with a dose of 212 mg/mL has anti-Giardia effect (34).
One of the important compounds of Allium sativum is allicin (47). In traditional medicine, Artemisia annua was used as an anti-parasite and anti-malarial agents (48)(49)(50).
The most important compound that has been isolated from the Artemisia annua is artemisinin (51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Giardia is one of the most common gastrointestinal parasites that causes various personal and social problems. Drugs such as metronidazole, furazolidone and paramomycin are prescribed for giardia and its species. The exact mechanism actions of the medicinal plants are not clear. Metronidazole causes the death of microorganisms by preventing subsequent replication. Probably the herbal drugs and bioactive compounds of this study, through a mechanism similar to the metronidazole mechanism, caused the death of Giardia's parasite. It should be noted that polyphenols which are abundant in most of these plants have been shown to possess anti-giardiasis effects (31).

Conclusion
The medicinal plants can produce anti-parasitic effects due to their active ingredients and antioxidant compounds, and can be used as effective natural anti-giardiasis drugs.

Authors' contributions
All authors all contributed equally in planning and carrying out this study. All authors read the manuscript and confirmed the publication for final version.

Conflict of interest
None.

Ethical considerations
Not applicable.

Funding/Support
There is no financial support for this work.