**1. Introduction**

Foodborne diseases are caused by consumption of microbial contaminated foods, herbs and beverages as well as hazardous chemicals including heavy metals, mycotoxins, bacterial toxins as well as fermentation byproducts like biogenic amines and ethyl carbamate [1–3]. Most these foodborne diseases are caused by pathogenic bacteria, viruses and parasites and are of global public health concern [4]. Each year about 600 million people are a ffected by foodborne diseases worldwide and about 420,000 people die due to these illnesses [5–8]. The most common symptoms associated with pathogens-induced foodborne diseases are vomiting, abdominal pain, diarrhea, fever and chills that may progress to severe complications such as life-threatening dehydration and hemolytic uremic syndrome (HUS) [9]. The bacterial-induced foodborne diseases are caused by infections with *Salmonella*, *Campylobacter* spp., *Escherichia coli*, *Shigella*, *Vibrio*, *Listeria monocytogenes* and *Clostridium botulinum* and *Clostridium perfringens* [4]. The commonly reported viruses are Norovirus and Hepatitis A, while the parasites involved are *Cryptosporidium* spp, *Giardia lamblia, Trichinella spiralis*, *Cyclospora* spp, *Toxoplasma canis* and *Entamoeba histolytica* [10,11] The toxins produced by *Staphylococcus aureus*, *Bacillus cereus* and *Clostridium perfringens* also prompt this debilitating disease [12]. Recently, there is a dramatic increase in the outbreak of foodborne disease, part of which is due to the emergence of pathogens resistance against current therapies and decontamination strategies [13]. Theses pathogens use food stu ff as carrier to ge<sup>t</sup> transferred from one host to another one [14]. The diseases caused by these pathogens are a major public health concern and globally produce a social and economic impact.

The proper handling, use of cold chain and addition of chemical preservatives are currently the mainstay to ensure the preservation and safety of food materials. However, the use of synthetic preservatives is associated with a high occurrence of side-e ffects, thereby raising the demand for the use of natural preservatives [15,16]. The main treatment options for foodborne diseases are systematic treatments like antidiarrheal and antiemetic medications, use of oral rehydration salts and the use of antibiotics [17]. However, the emergence of multi drug-resistant (MDR pathogens) is another global issue that requires the discovery of alternative antimicrobial agents [18–20].

Medicinal plants play a vital role in the treatment and prevention of various diseases and their promotion and there is growing interest in the search for new drugs from natural resources [21–26]. People living in many developing countries in Asia and Africa are mostly dependent on traditional medicines for healing purposes due to their limited access to modern medical facilities. They also have more cases of foodborne diseases because of their poor hygiene and exposure to contaminated drinking water and food materials [27,28]. Various studies have regularly reported the antimicrobial activities of traditional medicines from this part of the world. Medicinal plants o ffer a substantial opportunity as they contain various bioactive chemical constituents (phytochemicals) that can act as antimicrobial agents. Natural products are also reported to act as synergists along with many modern drugs to combat MDR pathogens [29]. Thus, the exploration of these natural antimicrobials is a hope to curtail foodborne diseases. Traditional medicines have long been used for treating diseases caused by foodborne pathogens and various studies have shown their e fficacy in the managemen<sup>t</sup> of foodborne diseases [30]. Recently, there is a greater interest in the naturally occurring preservatives due to the side-e ffects associated with the use of artificial preservatives in foodstu ffs. Crude plant materials including extracts, essential oils and isolated components have been extensively evaluated to prevent the invasion of pathogens responsible for food spoilage and therefore may limit the spread of foodborne infections [31].

Plants/plant-derived products inhibit/modify the growth of bacteria by several mechanisms. These may include, inhibiting the adherence of the pathogen to host cells [32], causing loss of osmoregulation of microbe and loss of transmembrane electrochemical gradient, increasing NO production thus causing lethal action [33], inhibition of synthesis of the cell wall, proteins and nucleic acids of the pathogen [34]. This review summarizes the therapeutic e ffectiveness of medicinal plants and isolated natural compounds against pathogens implicated in foodborne infections.

### **2. Materials and Methods**

Published literature related to the role of phytochemicals in foodborne infections was collected using di fferent search engines like PubMed, Google Scholar, SciFinder, Scopus, Web of Science, EBSCO, PROTA and JSTOR. Only in-depth, well designed (having control groups) studies reporting mechanistic results and published in journals of good quality were included in the manuscript.

### **3. Plant Extracts and Phytochemicals against Bacteria Causing Foodborne Diseases**

### *3.1. Campylobacter Species*

*Campylobacter jejuni* is a Gram-negative, non-spore-forming and non-fermenting bacteria. It is one of the most common causes of foodborne diseases in the US and Europe. Humans are usually infected by the ingestion of contaminated food, milk, water or interaction with animals [35]. Globally, about 9.6 million people are infected by *C. jejuni* annually [36]. For the treatment of *C. jejuni* infection, tetracyclines and fluoroquinolones are the drugs of choice; however, these days they are associated with a high degree of antibiotic-resistance [37,38]. Alternatively, phytochemicals can be utilized as they have the potential to combat foodborne diseases caused by *C. jejuni*. Dholvitayakhun et al. reported the inhibitory activity of extracts of *Adenanthera pavonina* L., *Moringa oleifera* Lam. and *Annona squamosa* L. against *C. jejuni* [39]. In these plants, among the flavonoids, kaempferol, quercetin and rutin are present which possess strong antimicrobial properties [40]. *Mammea africana* Sabine is used traditionally for the treatment of infections, stomach pain and skin ailments in Africa [41]. A coumarin, mammea A/AA was isolated by Canning et al. from *Mammea africana* and evaluated its activity against *C. jejuni*. It was found to be very potent with a minimum inhibitory concentration (MIC) value of 0.25 μg/mL [42]. Castillo et al. evaluated 28 plants against *C. jejuni*, out of which 21 were active. Of these 21 active plants, 4 plants including *Artemisia ludoviciana* Nutt., *Acacia farnesiana* (L.) Willd. *Opuntia ficus-indica* (L.) Mill. and *Cynara scolymus* L. were most potent having minimal bactericidal concentration (MBC) values of 0.5, 0.3, 0.4 and 2 mg/mL, respectively. They also tested the anti-adherence activity of these 4 plants against *C. jejuni,* as adherence of the microbe to mucosal cells is important for its virulence. The results proved that extracts were able to inhibit the attachment of *C. jejuni* [32]. Another mechanism of *C. jejuni* pathogenicity is cell lysis, entry into the host cell and production of a virulent cytotoxin, cytolethal distending toxin (CDT) [43]. Extracts of *A. ludoviciana* and *A. farnesiana* were shown to prevent the production of CDT along with a decrease in cytoplasmic pH and cellular ATP concentration and damages the bacterial cell membrane [44]. Moreover, motility also contributes to the virulence of *C. jejuni*. The subinhibitory concentrations of natural compounds, i.e., carvacrol (0.002%), *trans*-cinnamaldehyde (0.01%) and eugenol 0.01%) prominently decrease the motility of *C. jejuni*. Furthermore, these natural compounds also reduce other virulence potentials of this pathogen [45].

Several researchers have reported the potential antibacterial activity of essential oils (EO) of various plants against *C. jejuni* that are commonly used in the traditional system of medicine. These plants include *Syzygium aromaticum* (L.) Merr. & L.M.Perry [46,47], *Citrus limon* (L.) Osbeck and *Citrus bergamia* Risso [48], tea tree oil, Leptospermum oil [49], coriander (*Coriandrum sativum* L.) [50], *Daucus carota* L. [51], *Cuminum cyminum* L. [52], garlic (*Allium sativum* L.) [53], clove (*Syzygium aromaticum*), thyme (*Thymus vulgaris* L.) [54], eucalyptus (*Eucalyptus globulus* Labill.), sage (*Salvia o*ffi*cinalis* L.), rosemary (*Rosmarinus o*ffi*cinalis* L.), juniper (*Juniperus communis* L.), lavender (*Lavandula o*ffi*cinalis* Chaix), *Myrtus communis* L., *Laurus nobilis* L., pine oil (*Pinus brutia*) [55], *Juniperus excelsa* M.Bieb. [56], *Inula helenium* L [52], marigold (*Calendula o*ffi*cinalis* L.), ginger (*Zingiber o*ffi*cinale* L.), patchouli (*Pogostemon cablin*), gardenia (*Gardenia jasminoides* (Blanco) Benth.), cedarwood (*Cedrus atlantica* (Endl.) Manetti ex Carrière), carrot seed (*Daucus carota* L.), celery seed (*Apium graveolens* L.), mugwor<sup>t</sup> (*Artemisia vulgaris* L.), spikenard (*Nardostachys jatamansi* (D.Don) DC.), orange bitter oils (*Citrus* x *aurantium* subsp. *amara* (Link) Engl.), etc [47].

*Terminalia macroptera* Guill. & Perr. has been used for treating various infectious diseases in West Africa. Silva et al. subjected 100 clinical isolates of *C. jejuni* to the ethanolic extract of *T. macroptera* and recorded a MIC value as low as 6.25 μg/mL, which was similar to that of co-trimoxazole, used as the positive control, therefore suggests a therapeutic potential of *T. macroptera* in foodborne disease caused by *C. jejuni* [57]. In South Africa, Samie et al. conducted a study on clinically isolated *C. jejuni* from stool samples (*n* = 110) to find a complementary therapeutic remedy for this infection. They tested extracts of 18 plants i.e., *Annona* sp., *Bauhinia galpinii* N.E.Br., *Bridelia micrantha* (Hochst.) Baill., *Carissa edulis* (Forssk.) Vahl, *Cissampelos torulosa* E.Mey. ex Harv. & Sond., *Elaeodendron transvaalensis* (Burtt Davy) R.H.Archer, *Ficus sycomorus* L., *Lippia javanica* (Burm.f.) Spreng., *Momordica balsamina* L., *Mucuna coriacea* Baker, *Peltophorum africanum* Sond., *Pouzolzia mixta* Solms, *Pterocarpus angolensis* DC, *Rhoicissus tridentate* (L.f.) Wild & R.B.Drumm., *Sida alba* L., *Syzygium cordatum* Hochst. ex Krauss, *Ximenia ca*ff*ra* Sond. and *Zornia milneana* Mohlenbr. on these isolated bacterial strain. All the extracts were active, but potent activity was observed with the extracts of *P. angolensis* and *L. javanica* having an MIC of 90 μg/mL [58]. The extract of *Cryptolepis sanguinolenta* (Lindl.) is used traditionally for treating different infections in Guinea Bissau. An alkaloid cryptolepine has been isolated from this plant. When tested on a collection of 106 clinical strains of *C. jejuni* by Paulo et al. in Portugal, it was found to be very effective. They recorded MIC50 of this alkaloid was equal to that of ampicillin in their study [59]. Jarriyawattanachaikul et al. in Thailand, evaluated 26 Thai plants against *C. jejuni* in search of complementary therapy for infection caused by this bacterium. They found 7 active plants, i.e., taew kaao (*Cratoxylum formosum* (Jacq.) Benth. & Hook.f. ex Dyer), golden shower (*Cassia fistula* L.), mangosteen (*Garcinia mangostana* L.), ginger (*Zingiber o*ffi*cinale* Roscoe), garlic (*Allium sativum* L.), onion (*Allium cepa* L.) and shallot (*Allium ascalonicum* L.), among which *C. formosum* possesses the strongest antibacterial activity as observed from its MIC of 0.3 mg/mL [60]. A traditional beverage, kombucha, showed strong activity against *C. jejuni* [61]. Black and green tea, which are the most widely consumed beverages in the world also have confirmed antibacterial propensity against *C. jejuni* [62]. Aslim et al. have obtained convincing results of the essential oil of *Origanum minutiflorum* O.Schwarz & P.H.Davis against a ciprofloxacin-resistant strain of *C. jejuni*. [63]. Many Australians plants possess antimicrobial properties and have been utilized by the native populations for centuries as traditional medicines for GIT diseases. In a study by Kurekci et al., 109 plants from Australia were tested against *C. jejuni*. Most of these plants were active as their MICs fall between 32 and 1024 μg/mL. *Eucalyptus occidentalis* Endl. was the most active plant reported with MIC of 32 μg/mL [64].
